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['PMC5894974']
|
['29641522']
|
['pone.0193441.t001', 'pone.0193441.t002']
|
We included 398 patients, who all completed measurement at baseline while 383 (96%) completed measurement at follow-up. The study population had more males (56%) than females, and most of the patients were Dutch (94%). The majority (60%) lived together with a partner, and approximately half of the patients had children. About two thirds reported being non-religious. A total of 270 patients (68%) had a middle level of education whereas lower but similar numbers of patients had low (n= 63) and high (n= 65) levels of education. Three quarters of the patients were employed. The median age was 36.7 years, the median BMI ((body weight in kilograms)/(body height in meters)2) was 24.6, and the median preoperative HR (beats per minute) was 69 (Table 1). Mean anxiety scores (STAI-State, STAI-Trait and HADS-A) decreased after surgery whereas the mean values for aggression scores (STAS-State and STAS-Trait) and depression scores (HADS-D) remained about the same over time (Table 2). Mean fatigue scores (MFI) increased postoperatively. The differences across time were not tested for statistical significance.
|
PMC5894974
|
Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry
| null | 29,641,522
|
Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework
|
Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW.
|
PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018.
|
Mijderwijk H
|
PLoS One
| 2,018
|
2018/04/12
|
PMC5894974
| null |
10.1371/journal.pone.0193441
|
oa_comm/txt/all/PMC5894974.txt
|
2ab04bb2a251199ccc7bdda01c13474f
|
PLoS One. 2018 Apr 11; 13(4):e0193441
|
2021-06-18 17:06:35
|
CC BY
|
no
|
['PMC5894974']
|
['29641522']
|
['pone.0193441.t003', 'pone.0193441.t003']
|
At T0 (baseline), the highest correlations were found between HADS-A and STAI-Trait (r = 0.66) and HADS-A and STAI-State (r = 0.66;Table 3). Also, STAI-Trait correlated substantially with STAI-State (r = 0.52), MFI (r = 0.54) and HADS-D (r = 0.55). At T1 (seventh day after surgery), the intercorrelations were substantial. The highest correlations were found between STAI-State and STAI-Trait (r = 0.76) and between STAI-State and HADS-A (r = 0.71). STAI-Trait had a correlation of 0.71 with HADS-A. The intracorrelations over time of most of the psychological outcome variables varied from moderate to substantial: STAI-State (r = 0.42), STAI-Trait (r = 0.79), HADS-A (r = 0.59), MFI (r = 0.54), STAS-Trait (r = 0.68), and HADS-D (r = 0.55). STAS-State showed a correlation of only 0.16 (Table 3).
|
PMC5894974
|
Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry
| null | 29,641,522
|
Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework
|
Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW.
|
PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018.
|
Mijderwijk H
|
PLoS One
| 2,018
|
2018/04/12
|
PMC5894974
| null |
10.1371/journal.pone.0193441
|
oa_comm/txt/all/PMC5894974.txt
|
2ab04bb2a251199ccc7bdda01c13474f
|
PLoS One. 2018 Apr 11; 13(4):e0193441
|
2021-06-18 17:06:35
|
CC BY
|
no
|
['PMC5894974']
|
['29641522']
|
['pone.0193441.t004', 'pone.0193441.t005', 'pone.0193441.t006', 'pone.0193441.g002']
|
The final model comprised the following predictors: sex, having children, STAI-State, STAI-Trait, HADS-A, MFI, STAS-State, STAS-Trait, HADS-D, and GSES. Nationality, marital status, religion, educational level, employment, age, BMI, HR, RSES and type of intervention as randomized were fixed at zero. The performance measures all showed adequate values: using the MLR as the estimation method, the P value for the chi-square for model fit (98.99; df = 77) turned out to be just significant (P = 0.05) while the ML estimation method yielded a chi-square value of 97.36 (df = 77; P = 0.06). The chi-square/degrees of freedom ratio was 1.29. The comparative fit index was 0.99, and the Tucker–Lewis Index was 0.98. RMSEA was 0.03 (90% confidence interval: 0.004 to 0.042) and the SRMR was 0.02. The demographic variables had minor effects in the final model, and adding the medical variables did not affect the performance of the final model. In contrast, the prognostic potential of psychological baseline measurements was substantial. The adjusted explained variances (R2adjusted) ranged from 0.15 for State aggression (STAS-State) to 0.66 for Trait anxiety (STAI-Trait). STAI-State, HADS-A, MFI, STAS-Trait and HADS-D showed R2adjusted scores of 0.44, 0.45, 0.31, 0.54 and 0.38, respectively. In all, with the exception of aggression, the outcome variables were substantially predictable (Table 4). For each outcome variable, on the seventh day after surgery (T1), we considered the important prognostic variables according to the standardized estimates (B), as shown in Tables5and6. We focused on standardized estimates with a value of ≥ 0.20 only (Fig 2). For STAI-State, baseline STAI-Trait was the most important predictor (B = 0.36), followed by MFI (B = 0.23). In contrast, the baseline assessment of STAI-State had no high prognostic impact. For STAI-Trait, only baseline STAI-Trait was important (B = 0.52). For HADS-A, baseline HADS-A had the highest prognostic effect (B = 0.41), followed by STAI-Trait (B = 0.27). For MFI, only baseline MFI was of high prognostic relevance (B = 0.50). For STAS-State, HADS-A had substantial prognostic effect (B = 0.24). In contrast, the baseline assessment of STAS-State had no high prognostic impact. For STAS-Trait, baseline STAS-Trait dominated the prognostic variables (B = 0.57). STAI-Trait was also an important prognostic variable (B = 0.25). For HADS-D, two predictor variables were of prognostic importance: HADS-D (B = 0.36) and STAI-Trait (B = 0.26). The residuals of the outcomes were moderately interrelated (intercorrelations between 0.15 and 0.54).
|
PMC5894974
|
Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry
| null | 29,641,522
|
Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework
|
Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW.
|
PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018.
|
Mijderwijk H
|
PLoS One
| 2,018
|
2018/04/12
|
PMC5894974
| null |
10.1371/journal.pone.0193441
|
oa_comm/txt/all/PMC5894974.txt
|
2ab04bb2a251199ccc7bdda01c13474f
|
PLoS One. 2018 Apr 11; 13(4):e0193441
|
2021-06-18 17:06:35
|
CC BY
|
no
|
['PMC5894974']
|
['29641522']
|
['pone.0193441.ref034', 'pone.0193441.ref035', 'pone.0193441.ref034', 'pone.0193441.ref036', 'pone.0193441.ref037', 'pone.0193441.ref036', 'pone.0193441.ref038']
|
We developed a prognostic model using sociodemographic, medical, and psychological variables assessed just before day-case surgery that predicts multiple psychological outcomes after day-case surgery. Overall, apart from state aggression, the psychological outcome variables could be adequately predicted using the identified prognostic model. Sociodemographic and medical variables were of minor importance, with the exception of sex (females are at higher risk for a poor psychological outcome) and having children. In contrast, the psychological variables as assessed at baseline were of prominent importance. This model is of interest for improving patients’ quality of recovery and is useful for preoperative decision making. The model can be easily applied in the clinical setting because the parameters can all be completed by patient self-assessment. In the next step, the model results give healthcare professionals the possibility of identifying patients at risk for poor psychological outcomes after the surgical procedure. After identification, patients at risk can be guided in adequate follow-up or–in a worst-case scenario–can be unselected for day-case surgery. We believe that such a prognostic model can be of substantial additional benefit in prehabilitation programs. Recently, prehabilitation programs have showed that optimal preoperative preparation leads to better postoperative outcomes [34], and these programs improve postoperative outcomes by using preoperative interventions. Surgical procedures in day-case surgery are electively planned, so the preoperative period can be used to implement intervention within a prehabilitation program framework. Prehabilitation programs may differ for different surgical populations [35], and should therefore be tailored to the population of interest. One thing that should be developed in every single prehabilitation program is a preoperative prognostic model directed to vulnerable patients [34]. The provided preoperative prognostic model in this study enables simultaneously prediction of multiple outcomes of interest in day-case surgery by means of only one prognostic model. Accordingly, identification and management of patients at risk becomes feasible, which could lead to better postoperative psychological outcomes together with a reduction in negative socioeconomic effects. The model is also of interest for prognosis-related research dealing with psychological outcomes. First, from a clinical–theoretical perspective, the STAI-Trait questionnaire score showed to be a valuable prognostic variable for almost all psychological outcome variables expect postoperative fatigue (B > 0.20), although it was not powerful enough to replace the model. Sensitivity analysis that included only STAI-Trait as the prognostic variable showed that only anxiety (STAI-State and STAI-Trait) as outcome variable was still adequately predicted, R2equalled 0.37 and 0.62 respectively. Concerning aggression and depression, the reduction in R2was considered too steep, i.e. R2percentage reduction of > 20%. That the STAI-Trait was not an important variable for predicting fatigue (R2< 0.20) is in line with earlier findings [36], but understanding why postoperative fatigue does not follow the mechanisms of other psychological factors requires further study. Christensen et al. have suggested that the mechanisms cannot be explained by psychological factors [37]. More recently, though, it has been postulated that the underlying mechanism should be explained by psychological factors and mainly by its measurement itself [36]. Our results support the latter. Second, from a statistical modeling perspective, here we have applied SEM, a strong statistical approach, to evaluate the joint potentialities of several variables in predicting several outcomes. This joint analysis is especially preferred because psychological outcome variables are likely to interact with one another [38], which also was observed in the present study. Next to this theoretical rationale of an integral analysis, SEM has a couple of additional advantages. It enables achieving a consistent set of predictors for all outcomes and accordingly enables comparison of the regression weights for the different outcome variables, which is difficult and time consuming with a conventional analysis (i.e., predicting each outcome individually). Furthermore, SEM tests if the prediction model adequately represents the data structure, with random fluctuation, and gives insight into the related (residual) intercorrelations of the outcomes. If these residual intercorrelations were to be high for some or all outcome variables, a principal component analysis or a partial least squares regression analysis would be indicated. This information would be missed in case of individual outcome analysis. It has to be noted that ideally, a latent modeling approach seems indicated for analyzing the joint prediction of observed variables. However, we have refrained from using this approach because in clinical practice, it is not plausible to obtain the measurements without error.
|
PMC5894974
|
Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry
| null | 29,641,522
|
Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework
|
Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW.
|
PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018.
|
Mijderwijk H
|
PLoS One
| 2,018
|
2018/04/12
|
PMC5894974
| null |
10.1371/journal.pone.0193441
|
oa_comm/txt/all/PMC5894974.txt
|
2ab04bb2a251199ccc7bdda01c13474f
|
PLoS One. 2018 Apr 11; 13(4):e0193441
|
2021-06-18 17:06:35
|
CC BY
|
no
|
['PMC5894974']
|
['29641522']
|
['pone.0193441.ref039', 'pone.0193441.ref040', 'pone.0193441.ref041', 'pone.0193441.ref042']
|
Of the psychological outcomes analyzed, the explained variances (R2) were substantial for the anxiety scales (STAI-State, STAI-Trait and HADS-A), the depression scale (HADS-D), the fatigue scale (MFI), and the trait component of aggression regulation (STAS-Trait). However, state aggression (STAS-State) was only moderately predictive. Although we found substantial explained variances as the criterion for assessing the performance of the individual outcomes in the current model, a number of variances still remain unexplained. This result could arise from the fallibility of the measurements. To assess such fallibility we evaluated the internal consistency of the measurements using Cronbach’s α, both at baseline and at 1 week after surgery. According to the commonly accepted criteria [39], we concluded that internal consistency was satisfactory for all measurements (for the majority of the used scales Cronbach’s α ≥ 0.85, four scales were in the range of 0.73 to 0.79), except for HADS-D assessed at baseline (Cronbach’s α = 0.60). In this study, we used two measurements for anxiety and found the interrelationships of STAI and HADS-A to be non-perfect, in line with previous research [40]. This discrepancy suggests that the different instruments for anxiety have common and unique elements. In addition, the model might be mis-specified in principle, but we firmly believe that this possibility is not realistic. It is also possible that the phenomenon of omitted variables have played a role in this study. Other unmeasured or as-yet-unknown variables may be relevant and consequently, when added, enhance the prognostic performance of the model. Our study comprises only intrapersonal characteristics, but interpersonal characteristics may also be important. For example, recent research has shown that negative dyadic coping (collaborative coping/dealing with stress within a couple) is associated with a higher degree of psychological distress [41]. Positive dyadic coping seems to be effective in dealing with problems surrounding illness, especially in older couples [42]. Such positive interpersonal variables could also help people cope in a perioperative setting. Environmental variables (e.g., living in suburbs), economic variables (e.g., economic crisis, being unemployed), and cultural variables could also be of interest. Adding such variables to our model may increase its prognostic performance.
|
PMC5894974
|
Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry
| null | 29,641,522
|
Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework
|
Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW.
|
PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018.
|
Mijderwijk H
|
PLoS One
| 2,018
|
2018/04/12
|
PMC5894974
| null |
10.1371/journal.pone.0193441
|
oa_comm/txt/all/PMC5894974.txt
|
2ab04bb2a251199ccc7bdda01c13474f
|
PLoS One. 2018 Apr 11; 13(4):e0193441
|
2021-06-18 17:06:35
|
CC BY
|
no
|
['PMC5894974']
|
['29641522']
|
['pone.0193441.ref005']
|
First, a limitation of this study was that the assessments were conducted at a single center, which means that further external validation is needed. Second, because we excluded patients who were taking psychopharmaceuticals and those with psychological disorders [5], we can assume that the level of psychological dysfunction after day-case surgery could well be higher. This effect might bias our findings negatively, or strengthen them. Third, the majority of our study population was Dutch, so different results may be obtained when considering broader nationalities or ethnical and sociocultural groups. Despite these limitations, the fact that our data were obtained in a randomized controlled trial implies their high quality. Another strength of the study is the use of SEM, which appears to be a powerful approach that is suitable for conducting research on optimizing medical decision making using multiple outcome criteria.
|
PMC5894974
|
Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry
| null | 29,641,522
|
Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework
|
Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW.
|
PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018.
|
Mijderwijk H
|
PLoS One
| 2,018
|
2018/04/12
|
PMC5894974
| null |
10.1371/journal.pone.0193441
|
oa_comm/txt/all/PMC5894974.txt
|
2ab04bb2a251199ccc7bdda01c13474f
|
PLoS One. 2018 Apr 11; 13(4):e0193441
|
2021-06-18 17:06:35
|
CC BY
|
no
|
['PMC5894974']
|
['29641522']
|
[]
|
We provide a prognostic model, using a structural equation modeling framework, that adequately predicts multiple outcomes in day-case surgery. The final model comprised the following prognostic variables: anxiety (STAI-State/Trait, HADS-A), fatigue (MFI), depression (HADS-D), aggression (STAS-State/Trait), self-efficacy, sex, and having children. Overall, it enables timely identification of vulnerable patients who may require additional medical or psychological preventive treatment, or–in a worst-case scenario–could be unselected for day-case surgery.
|
PMC5894974
|
Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry
| null | 29,641,522
|
Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework
|
Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW.
|
PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018.
|
Mijderwijk H
|
PLoS One
| 2,018
|
2018/04/12
|
PMC5894974
| null |
10.1371/journal.pone.0193441
|
oa_comm/txt/all/PMC5894974.txt
|
2ab04bb2a251199ccc7bdda01c13474f
|
PLoS One. 2018 Apr 11; 13(4):e0193441
|
2021-06-18 17:06:35
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR1', 'CR2', 'CR2', 'CR3', 'CR5', 'CR6', 'CR7', 'CR8', 'CR10', 'CR10', 'CR12', 'CR13', 'CR15', 'CR16', 'CR17', 'CR17', 'CR18', 'CR19', 'CR20', 'CR21', 'CR22']
|
Common mental disorders (CMDs) such as stress-related ill health, depression and anxiety disorders, are an increasing universal burden not only for the affected individuals but for the society at large [1,2]. The total costs of mental ill health (CMDs) are estimated at over EUR 600 billion across the 28 European member states [2]. In working age groups, loss of income, labour and productivity, and marginalisation as well as increased strain on the welfare systems, are only a few aspects related to mental ill health and subsequent sickness absence [3–5]. Mental ill health has a multifactorial background, and the workplace or the working situation are in many cases the cause of the ill health [6]. Stress, anxiety or depression is the most mentioned work-related health issue in the majority of the EU countries according to a European survey conducted in 2014 [7]. Previous research has investigated which work factors promote or hinder a good working climate and work health [8–10]. It is well established that high work burden with minimal possibility to control or influence the work situation, as well as existing conflicts, can lead to distress and increases the risk for future ill health [10–12]. Most people with mental distress consult their primary healthcare physician with their symptoms as an initial contact with the health system [13–15]. A Swedish cross-sectional study [16] conducted in primary healthcare (PHC) revealed that 59% of all patients aged 18–65 seeking care at a primary healthcare centre (PHCC), regardless of cause, reported high mental stress levels. Another study found that individuals with continued stress, without possibility for recovery, often seek care repeatedly with an increasing symptom burden before they receive the right care [17]. In some cases, the underlying stress is not identified by the healthcare service until very late in the care process, when sick listing has become unavoidable [17]. There are several questionnaires available that are developed for either screening or diagnostic assessments in the PHC [18]. However, these questionnaires mostly cover depression and/or anxiety and are not aimed towards work-related stress and stressors in the working situation. Since stress that is directly related to the work situation is an increasing issue, there could be benefits, such as earlier and better adjusted care, in introducing a new questionnaire that functions as both a screening tool and a diagnostic instrument in primary healthcare. The Work Stress Questionnaire (WSQ) was developed in PHC to identify early symptoms of work-related stress in PHC [19]. The WSQ is based on previous research and on the experiences of women on sick leave because of work-related stress [20]. The WSQ takes into consideration organisational and environmental issues at work and individual factors such as high commitment and engagement in work. Earlier studies with the WSQ conducted in PHC showed that the questionnaire predicted future sick leave at follow-up among the participants who scored high stress levels at baseline [21]. The next step was therefore to evaluate the practicability of the WSQ as a screening and diagnostic instrument for physicians in their consultation and treatment of their patients [22]. In Sweden, the healthcare system is tax-funded with universal coverage for the whole population. Private care providers are also mainly tax-funded and thus reimbursed by the county. There are two levels of care: primary healthcare (including child, youth and maternity healthcare) and specialist hospital care (outpatient and inpatient care). Each patient needs to pay a fee (out-of-pocket payment), currently EUR 9.5 (SEK 100) for a visit to a PHC physician or psychotherapist, EUR 7.6 (SEK 80) for a visit to an occupational therapist or physiotherapist and EUR 28.4 (SEK 300) for visits to specialist outpatient care. Patient fees are the same in both public and private PHCCs. There is protection against high costs for outpatient care; when the patient has accumulated out-of-pocket payments of EUR 108.9 (SEK 1150) during a 12-month period, further healthcare visits during that time period are free of charge for the individual. Our aim with this study was to evaluate whether responding to the WSQ in combination with feedback of the results from the physician would lead to differences in healthcare use and treatment compared to treatment as usual (TAU) in patients reporting high stress. Our hypothesis was that patients receiving the intervention (responding to the WSQ plus physician’s feedback) would generate more visits to rehabilitation providers, that is, psychologists/psychotherapists and occupational therapists/physiotherapists, during the year after inclusion compared to control patients receiving TAU. Our aim was also to assess whether the intervention would result in care measures more in line with established national treatment guidelines.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
This study is part of the research project ‘Early Identification of Work-related Stress’ titled TIDAS in the research programme “New ways: Mental health at work” at the Sahlgrenska Academy, University of Gothenburg (www.epso.gu.se/newways).
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR23', 'CR23']
|
This study was conducted in the primary healthcare in South-West Sweden in the Region Västra Götaland (VGR). VGR, with its 1.7 million residents (approx. 17% of the Swedish population), has about 200 PHCCs, of which 52% are public and 48% are private (both are reimbursed by VGR). During 2017, 71% of the population in VGR visited the PHC at least once [23]. On average, 3.6 visits per inhabitant were made to the PHC, which corresponds to over 4 million visits to the region’s PHCCs [23].
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR24', 'CR22']
|
This study was designed as a randomised controlled trial (RCT) in accordance with the CONSORT® guidelines [24]. The RCT study was conducted at public and private PHCCs in VGR and is presented in full in a previously published study protocol [22]. Recruitment of the PHCCs was conducted between May 2015 and November 2015. Fifty-one of 200 PHCCs were asked to participate in the study. Seven PHCCs accepted participation (four public and three private). The main reasons for the high number of refusals from the PHCCs were either that the PHCC had implemented primary care triage (in which a nurse assesses each patient case and triages the patient to a suitable care provider), or had a lack of time, and/or already had an ongoing research project. A research assistant on site was responsible for identification and recruitment of participants. The PHCCs were financially reimbursed for each patient, both intervention and control, recruited to the study.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR25', 'CR26', 'CR27', 'CR29', 'Tab1']
|
As research has found that work-related stressors result in numerous mental and physical health complaints [25,26], the target group for this study were non-sick-listed employed persons between 18 and 64 years of age who sought care for physical and/or mental complaints at their PHCC [27–29]. In line with the purpose of the RCT to early identify people with work-related stress, patients with established diagnoses were excluded. The full inclusion and exclusion criteria are listed in Table1.Table 1Inclusion and Exclusion CriteriaInclusion criteriaPatients seeking care for:• depression• anxiety• musculoskeletal disorders• gastro-intestinal• cardiovascular conditions• other potentially stress related symptomsExclusion criteriaPatients with:• ≥7 days sickness absence the last month• sickness or activity benefits• ongoing pregnancy (due to risk of pregnancy-related healthcare contacts)Patients seeking care for:• psychiatric conditions (e.g. schizophrenia, bipolar disorder)• diabetes• urinary tract infection (UTI)• infections (cold, sore throat)• fractures• lumps and spots• allergy• prolonging of sick leave• medical check-ups• chronic obstructive pulmonary disease (COPD)
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR20', 'CR21', 'CR30', 'CR19', 'CR31', 'CR19', 'CR22']
|
The instrument in focus for this study was the WSQ. The WSQ was developed from a qualitative study of former long-term sick-listed women who emphasised the combined importance of organisational and individual factors for the progression from health to sick leave [20]. The WSQ has been used in PHC studies [21] and population studies [30]. The psychometric properties of the WSQ have been assessed with test-retest reliability and face validity with satisfying results [19,31]. The questionnaire consists of 21 questions grouped into four categories. The categories aim to identify stress in relation to (1) Influence over work situation, (2) Indistinct organisation and conflicts, (3) High work commitment, and (4) Work interference with leisure time. Responses to each item are given on a four-point ordinal scale: “Not at all stressful”, “Less stressful”, “Stressful”, and “Very stressful”. For more details, see Holmgren et al. 2009 [19] and 2016 [22].
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
Randomisation was done on the physician level meaning that the physicians at the same participating PHCCs were randomised to either conduct the intervention or belong to the control group. After the randomisation of the physicians, the research team visited the PHCCs and presented the study to the staff and informed them which physicians were randomised to each group.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
The intervention physicians got a short training about the WSQ, on how to interpret the WSQ and how to give feedback based on the WSQ’s result. Moreover, the intervention physicians received a list of healthcare providers and other relevant rehabilitation providers for possible patient referrals. The research team stressed that the intervention physician first should address the health complaint for which the patient sought care and as a next step address the result from the WSQ, and, if work-related stress was identified, give recommendations for further care (like referrals to other healthcare professions). The short training was given either one on one or in a group depending on what the physicians’ schedule permitted. The physicians randomised to the control group were instructed to carry on as usual, that is, giving the care that the patients were entitled to.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
The research assistant on site was given permission from the head of the PHCC to, in collaboration with personnel, identify eligible patients from the electronic patient record system. After identifying possible eligible patients (based on the inclusion and exclusion criteria), the research assistant or the personnel contacted the patients, either on site or by telephone, and gave information about the study and invited them to participate. If the patients were interested in participating in the study, they gave their informed written consent. Patients who had an appointment with an intervention physician filled in the WSQ questionnaire before the consultation, together with some questions on background characteristics. The WSQ was compiled by the research assistant and given to the treating physician. If work-related stress was identified, the intervention physician gave recommendations for further care, departing from the patient’s illness and from the specific work-related problems detected by the WSQ. If the results from the WSQ indicated lack of stress in all four categories, no further feedback from the intervention physician was given. Participants who had an appointment with a control physician received TAU and then filled in the questionnaire (WSQ and background characteristics) after their visit to the physician. This was done to make sure that we later could compare the controls with the intervention participants.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
The intervention periods were 4 to 8 weeks at each PHCC and lasted from May 2015 to the end of January 2016. An exception was one PHCC that had two intervention periods over a period of 12 weeks.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['Tab1']
|
Data from the questionnaire, filled in by the patients at the PHCC, included both the WSQ and information on background characteristics such as age, sex, employment status et cetera. Data on healthcare contacts were obtained from VGR’s healthcare database, VEGA, which includes information on hospital and primary care consumption by VGR inhabitants both within and outside the region. The objective of the database is to be a tool for uniform care assessment and follow-up. The information collected consisted of healthcare level, private or public management, inpatient care, care provider, number of visits and care measures. Healthcare levels included PHC, specialised healthcare at a county hospital and national/regional specialised healthcare. Due to having few participants in the category national/regional specialised healthcare, this healthcare level was excluded from the analyses but is available from the authors on request. We excluded measures not relevant for our research question and those that were listed as exclusion criteria at inclusion (Table1). Patients seeking care for these measures were not the target group for this study. The categorisation of care measures was based on the guidelines from the National Board of Health and Welfare (Socialstyrelsen) and was divided into four categories: (1) Diagnostics/Assessments, (2) Treatment, (3) Information/Education and (4) Collaborative Care. One participant in the intervention group had an incorrect/not interpretable social security number and therefore had only self-reported baseline data and no register data. Data from 12 months pre-inclusion and from index date and 12 months post-inclusion were collected. The register data was merged with the questionnaire data.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
This study applied methods commonly used for descriptive statistics. For the analyses, Fisher’s exact test was performed for a group-wise comparison. Subgroup analyses were made with the participants (in both groups) reporting high stress in order to distinguish the effect of the intervention. Because of the very skewed data material, the presentation of the data is in proportions instead of means or medians. The software used for the statistical analyses was IBM SPSS Statistics® version 25. The level of statistical significance was set atp< 0.05 (95%).
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
Prior to the inclusion, each patient was given oral and written information from the research assistant about the study and the possibility of withdrawing from participation at any stage without jeopardising their care at the PHCC. Each participating patient gave informed consent. This study was approved by the regional ethical review board in Gothenburg, Sweden (Dnr: 125–15; T131–17). Registered at ClinicalTrials.gov (Identifier: NCT02480855).
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['Fig1', 'Tab2']
|
Information about number of involved physicians and participating patients is found in Fig.1. Descriptive characteristics of the study participants is presented in Table2. Hereafter the participants who received the intervention will be referred to as WSQ-IG (WSQ intervention group), and the participants who received TAU will be referred to as controls.Fig. 1Flowchart of recruited physicians and participantsTable 2Baseline characteristics of study participantsa, data from self-reported questionnaire,n= 271WSQ-IGb% (n= 132)Controls% (n= 139)SexWomen67 (88)70 (97)Men33 (44)30 (42)Age categories19–30 years16 (21)19 (26)31–50 years44 (58)54 (76)51–64 years40 (53)27 (37)Civil statusSingle25 (33)18 (25)Married/cohabitant69 (91)76 (106)In a relationship, live-apart5 (7)5 (7)Educational levelCompulsory schooling10 (13)11 (15)Secondary school46 (61)42 (59)University or higher44 (57)47 (65)Occupational classSkilled/unskilled manual37 (49)42 (58)Medium/low non-manual46 (60)41 (56)High-level non-manual17 (23)17 (24)Main type of employmentEmployed until further notice79 (105)80 (112)Project employee2 (3)1 (1)Substitute2 (3)3 (4)Employed by the hour4 (5)5 (7)Self-employed6 (8)5 (7)Other type of employment6 (8)5 (7)Scope of workFull-time76 (100)77 (107)Part-time, ≥ 15 h/week24 (31)22 (30)Reason for consultationcMental or behavioral57 (75)50 (69)Musculoskeletal47 (62)32 (44)Gastrointestinal20 (26)20 (28)Cardiovascular12 (16)11 (16)Other22 (29)19 (27)High WSQ-valuesdLow influence over work situation41 (54)39 (54)Indistinct organisation and conflicts21 (28)19 (26)High work commitment48 (63)45 (62)Work interference with leisure time41 (54)40 (55)aSome baseline characteristics are also published in the study protocol by Holmgren et al. [22]bWSQ-IG = the group that received the WSQ interventioncMultiple answers were possibledParticipants that scored values of 3 (stressful) and 4 (very stressful) on the Work Stress Questionnaire (WSQ)
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['Tab2']
|
No distinct differences in perceived stress between the WSQ-IG and controls were found in either of the two time periods (Table2). The highest frequency of perceived stress, among both groups, was in the categoryHigh work commitment(63% among WSQ-IG and 62% among controls).
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['Tab3']
|
No significant differences in types of healthcare use (i.e. healthcare level, public/private care, outpatient/inpatient care) were found between the WSQ-IG participants and the controls that reported high perceived stress. Information on visits to different care providers among the participants with perceived stress can be found in Table3. Visits to psychologist/psychotherapist was significantly higher among the stressed WSQ-IG (20%) in the post-inclusion period compared to the stressed controls (7%) (p< 0.05). Visits to occupational therapists and physiotherapists were 43% among the WSQ-IG with high stress levels and 32% among the corresponding controls during follow-up. The difference between the two groups was not statistically significant (p= 0.38).Table 3Visits to care providers among WSQ intervention group and controls reporting high stressaBefore inclusion (< 12 months)Follow-up (≥12 months)WSQ-IG% (n= 84b)Control% (n= 92b)p-valueWSQ-IG% (n= 87b)Control% (n= 97b)p-valueVisits toPhysician.94.38020 (17)22 (20)3 (3)0 (0)1–555 (46)50 (46)48 (42)47 (46)6–1016 (13)17 (16)25 (22)27 (26)> 1110 (8)11 (10)23 (20)26 (25)Nurse.32.5506 (5)3 (3)13 (11)13 (13)1–571 (60)67 (62)55 (48)54 (52)6–1014 (12)24 (22)17 (15)24 (23)> 118 (7)5 (5)15 (13)9 (9)Psychologist/Psychotherapist.86.048†094 (79)96 (88)81 (70)93 (90)1–55 (4)4 (4)12 (10)6 (6)6–101 (1)0 (0)2 (2)0 (0)> 110 (0)0 (0)6 (5)1 (1)Occupational therapist/Physiotherapist.59.38063 (83)73 (102)58 (50)68 (66)1–517 (23)11 (15)15 (13)8 (8)6–104 (5)6 (8)7 (6)7 (7)> 119 (12)5 (7)21 (18)17 (16)aParticipants that scored values of 3 (stressful) and 4 (very stressful) in at least one of the four categories in the WSQbNumber of valid observationsFisher’s Exact Test was performed with a significance level of .05 (95%).†Statistically significant difference (p< 0.05) between groups
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['Tab4', 'MOESM1']
|
Treatment was the most frequent care measure category in both groups with high stress levels irrespective of time period (12 months pre-inclusion and from index date and 12 months after) (Table4). The WSQ-IG with perceived stress received much more collaborative care measures during follow-up (23% vs 2% before inclusion). Among the stressed controls, this category changed from 2 to 11%. The inter-comparison analysis resulted in a statistically significant difference between the two groups (p< 0.05).Table 4Healthcare treatments among WSQ intervention group and controls reporting high stressaBefore inclusion (< 12 months)Follow-up (≥12 months)WSQ-IG% (n= 84b)Control% (n= 92b)p-valueWSQ-IG% (n= 87b)Control% (n= 97b)p-valueHealthcare treatmentDiagnostics/Assessments8 (7)8 (8)117 (15)12 (12).41Treatment10 (8)14 (13).3628 (24)26 (25).87Information/Education4 (3)4 (4)19 (8)5 (5).39Collaborative care2 (2)2 (2)123 (20)11 (11).048†aParticipants that scored values of 3 (stressful) and 4 (very stressful) in at least one of the four categories in the WSQbNumber of valid observationsFisher’s Exact Test was performed with a significance level of .05 (95%).†Statistically significant difference (p< 0.05) between groups Information and counselling with patient over telephonewas the most common care measure among the WSQ-IG and controls with high perceived stress in the pre-inclusion period (26% among WSQ-IG and 12% among controls) (Additional file1). In the WSQ-IG, the most frequent care measure during follow-up wasCognitive behavioural therapy(CBT) (16% compared to 5% before inclusion). For the controls, amount of CBT had not changed between the two time periods and was about 10%.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
In this study we investigated whether the patients with perceived high stress, as measured by the WSQ, and receiving feedback from a physician would have more rehabilitative healthcare visits and treatments post-intervention compared to controls receiving TAU. Significant differences were found between the WSQ intervention group and controls who reported high perceived stress, in visits to psychologists and in amount of received collaborative care. A difference between the two groups was also found in amount of received CBT. This confirms our hypothesis that the intervention with physicians giving feedback from the WSQ can result in increased numbers of rehabilitative measures at an earlier stage in the care process compared to TAU. However, with a small sample size, caution must be applied, as the findings might not be robust or persist in future studies with larger study populations or in other healthcare systems.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR32', 'CR33', 'CR32', 'CR34']
|
According to both the Swedish and British national guidelines, evidence-based treatments for CMDs are psychological measures such as CBT and interpersonal therapy, among others [32,33]. Furthermore, in the latest and revised national guidelines for treatment of CMDs [32] the Swedish National Board of Health and Welfare emphasisedcollaborative and structural care by a care manageras a point of recommendation for treatment of patients diagnosed with a CMD. In other words, we could see that the intervention group reporting high perceived stress levels did receive care measures more in line with established clinical treatment guidelines compared to the stressed controls. This indicates that adherence to guidelines could be more effective when a CMD has been identified by the physician, as also confirmed in a study by Smolders et al. [34].
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR35', 'CR36', 'CR23', 'CR23', 'CR37']
|
To the best of our knowledge, there have been no or few studies that have investigated the use of a self-administered work stress questionnaire in combination with physicians’ feedback in relation to our outcomes: healthcare use and treatment. Our first major finding was the higher frequency of visits to psychologists/psychotherapists among the stressed WSQ-IG. This result indicates that the intervention could have improved the physicians’ recognition of patients in need of psychological treatment. Our findings reflect those of Magruber-Habib et al. [35] who showed that the recognition rate of patients with depression increased when physicians used a screening instrument (for depression) with feedback of the results, with more initiated treatments as an effect. Another finding relating to the previous one, was the higher amount of received CBT among the stressed WSQ-IG compared to the stressed controls. As the WSQ-IG participants had more visits to psychologists/psychotherapists, it is logical that this group also received more CBT treatment, as psychologists/psychotherapists are the ones authorised to give the treatment. Our study also showed that the WSQ-IG with high stress had a higher proportion of received collaborative care compared to the corresponding controls. Collaborative care has in an earlier review study [36] been shown to be an important part for a successful recognition and management of depression in studies that used screening questionnaires in combination with feedback of results. Finally, one finding that was not statistically significant was the difference in frequency of visits to occupational therapists and physiotherapists between the two groups. The visits to occupational therapists/physiotherapists increased in both groups reporting high stress levels, during the 12-month follow-up period. The increase appeared to be greater among the WSQ-IG, although no statistical significance was reached. In 2014, Sweden introduced a new healthcare reform called “Vårdval Rehab” (Choice of care rehab) [23]. This reform aimed to increase the access to rehabilitative care providers, as the population could then freely choose a rehabilitation provider without the need of a referral note from their physician. Since then, there has been a gradual increase each year in visits to rehabilitation providers such as occupational therapists and physiotherapists [23]. The introduction of this reform could partly explain the overall increase in visits among both participant groups, but not the seemingly higher increase among the intervention group. The observed differences between the intervention group and the controls could be explained by the fact that the intervention led to the physicians being more observant/aware of the patients’ problems and need of care. This could, in turn, have resulted in the physicians referring the patients to more suitable treatments of which they (the physicians) have had good experience and which are available in the PHC organisation. An earlier study has shown that through a structured approach, physicians become aware of their patients’ occupations and of factors in the working situation that can cause stress, and that by becoming aware of work-related risks of ill health, physicians can advise their patients and refer them to more adjusted measures and to other care providers [37].
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
['CR24', 'CR38', 'CR39', 'CR29']
|
A strength of the study is the predefined study protocol outlined in accordance with strictly controlled guidelines, in this case the CONSORT guidelines [24]. Another strength is the use of register data for follow-up. The strength of using data on healthcare contacts from the VEGA database is that it is systematic, comprehensive and up to date (data are updated on a monthly basis). The PHCCs with contracts with the region (VGR) have an obligation to send in their patient information for the database. The database is one of a kind in Sweden when it comes to collecting PHC data. A possible limitation with our choice to randomise on the physician level could be the spillover effect, meaning that intervention physicians could talk about the study procedure with their colleagues randomised to the control group. We anticipated this risk to be low, as the physicians are autonomous and work independently from one another, and because of the brief intervention that was imbedded in their everyday routine. Also, the time period at each centre was short. The reason behind this randomisation was to avoid large variations in sociodemographic and socioeconomic factors between participants. Including both intervention and control physicians at the same PHCC would minimise this risk and was therefore seen as the more advantageous choice. Another methodological consideration important to acknowledge is the lack of data from the occupational health service. Since our target group were employed persons with possible work-related stress, we can conclude that some of the participants could have been referred to their occupational health service (OHS) by the primary care physician. The VEGA database does not cover healthcare data from occupational providers, and there are no other databases in Sweden that collect data from these care providers. The lack of follow-up data from the OHS could have influenced our result, as measures relevant for our study could have been prescribed to patients in the OHS and not in ordinary healthcare. As a result, the effect of the intervention risks being attenuated. However, only about 65% of the working population have access to an OHS, with one third of these only having access “on paper” [38]. Therefore, we believe the risk of a weaker intervention effect to be rather small. All in all, we found only small differences between the WSQ intervention group who perceived themselves as stressed and the control group (with stress) who received TAU. The lack of statistically significant differences in most of the analyses between the intervention group and the controls could be because the compared groups were quite small, which affects the likelihood of identifying existing significant differences. As a further consequence of the small sample, there were limitations in the available choices of statistical methods and also in the possibility to conduct stratified analyses on different background characteristics. Although we saw an effect regarding differences in healthcare treatment between the intervention group and the controls, we cannot say with absolute certainty what actually caused the effect. In another published article [39] based on the same RCT as this one, with the outcome measurenumber of sick leave days, no differences were detected. Possible explanations for the lack of effect in that study were low power or that the time period for follow-up was too short [29]. Thus, there is a need for future studies to investigate this effect with larger study samples, which also would enable more in-depth analyses.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC7339485']
|
['32631243']
|
[]
|
The intervention group that used the WSQ with physicians’ feedback had an increased number of rehabilitative measures and treatment more in line with established guidelines compared to treatment as usual. Findings of the study indicate that the WSQ can assist in identifying work stress in primary healthcare and contribute to physicians’ recommendation of suitable rehabilitative measures at an earlier stage compared to treatment as usual.
|
PMC7339485
|
Research Article
| null | 32,631,243
|
Effects of a work stress intervention on healthcare use and treatment compared to treatment as usual: a randomised controlled trial in Swedish primary healthcare
|
Sandheimer C, Hedenrud T, Hensing G, Holmgren K.
|
BMC Fam Pract. 2020 Jul 6;21(1):133. doi: 10.1186/s12875-020-01210-0.
|
Sandheimer C
|
BMC Fam Pract
| 2,020
|
2020/07/08
|
PMC7339485
| null |
10.1186/s12875-020-01210-0
|
oa_comm/txt/all/PMC7339485.txt
|
1ab4aa1e5148bf95e23619748c69e030
|
BMC Fam Pract. 2020 Jul 6; 21:133
|
2021-06-19 05:46:31
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['CR1', 'CR2', 'CR3', 'CR3', 'CR5', 'CR6', 'CR7', 'CR8', 'CR9']
|
From late 2019 when first cases of pneumonia of unknown etiology were described, the new fast spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) became the major newsmaker and a great challenge for all the humanity [1]. An extremely extensive research program provided permanently growing amount of data but still left some knowledge gaps in COVID-19 pathogenesis and immunological mechanisms of defense. The natural course of COVID-19 in most cases present as asymptomatic or mild disease limited to replication of SARS-CoV-2 in epithelial cells of the respiratory tract which induces limited innate immune response. However, in approximately 20% of cases COVID-19 may progress to severe disease caused by the exaggerated immune response to the virus, diffuse alveolar damage, poorly controlled release of proinflammatory cytokines, development of acute respiratory distress syndrome, multiple organ failure and coagulation abnormalities [2,3]. Increased level of proinflammatory cytokines is associated with high viral load, lung injury, disease severity and poor outcome [3–5]. Assuming that subjects with severe infection can benefit from suppression of cytokine release syndrome, a large number of clinical trials aimed to investigate the efficacy of anti-inflammatory therapy including anti-IL-1, anti-IL-6 agents and steroids in patients with COVID-19 were started [6]. Levilimab (LVL) is an original monoclonal antibody that binds to the alpha subunit of the IL-6 receptor (IL-6R) and blocks the transmission of IL-6 signal into cells. In a phase I clinical study LVL was well tolerated, showed favorable safety profile and low immunogenicity in doses ranged from 0.006 mg/kg to 2.9 mg/kg in healthy volunteers [7]. A phase II placebo-controlled clinical study showed that LVL 162 mg administered subcutaneously (SC) either once weekly (QW) or once every 2 weeks (Q2W) plus methotrexate (MTX) was superior to MTX alone in patients with active rheumatoid arthritis (RA) and inadequate response to MTX (NCT03455842) [8]. Considering the role of IL-6 pathway in the pathogenesis of severe COVID-19 and the confirmed LVL ability to block the IL-6 signaling, as well as its safety and good tolerability, we conducted a phase III clinical study to evaluate the efficacy and safety of LVL in subjects with severe COVID-19 [9].
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
CORONA was a multicenter, comparative, randomized (1:1), double-blind, placebo-controlled, parallel groups phase III clinical trial conducted at 12 investigational sites in the Russian Federation in accordance with the Declaration of Helsinki and International Council for Harmonization E6 Guideline for Good Clinical Practice. The study was approved by the Central Regulatory Authority of the Russian Federation and Ethical Review Boards of each of the participating sites. The sponsor designed the trial, was responsible for the monitoring, collected the data, and performed the data analysis. Patients or their legally authorized representatives provided written informed consent (IC) to participate in the study. If a patient was unable to give consent due to the current health status, a council of three independent physicians could make the decision to enroll the patient in the study, and the patient or his/her legally authorized representative was notified about the study as soon as possible. After the improvement in clinical status written IC was obtained. CORONA clinical study had an adaptive design with the pre-planned opportunity to modify the endpoints, LVL doses, sample size, or the size of the study groups.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
Eligible were men and non-pregnant women aged 18 years or older, positive for SARS-CoV-2 RNA, hospitalized with radiologically confirmed pneumonia with at least one criteria of disease severity (respiratory rate > 30/min, SpO2≤ 93%; PaO2/FiO2≤ 300 mmHg; increase of the lung involvement by more than 50% after 24–48 h; decreased consciousness level; agitation; unstable hemodynamics; arterial blood lactate > 2 mmol/L; quick sequential organ failure assessment score (qSOFA) > 2, defined by the presence of any two symptoms of the following: systolic blood pressure ≤ 100 mm Hg; respiratory rate ≥ 22/min; Glasgow Coma Scale score ≤ 14). Patients with a critical form of COVID-19 (defined by the presence of any of the following: respiratory failure and need of the invasive mechanical ventilation; septic shock; multiple organ failure); suspected active bacterial, fungal, viral, or other infection (besides COVID-19); confirmed active tuberculosis; life expectancy < 24 h, in the opinion of the investigator or who were unlikely to remain at the investigational site beyond 48 h; treated with other monoclonal antibodies, immunosuppressive agents or participating in a clinical trials of other drug; history of allergic reaction to monoclonal antibodies; who have any illness or laboratory findings that, in the opinion of the study investigator, might pose an additional risk to the patient by their participation in the study; pregnant or breastfeeding women were not eligible. Laboratory exclusion criteria were: ALT and/or AST levels > 10 × ULN, platelet count < 50 × 109/L, absolute neutrophil count < 1.0 × 109/L. The use of other monoclonal antibodies for the treatment of COVID-19 was not allowed.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
Eligible patients were stratified according to the C-reactive protein (CRP) level (CRP ≤ 7 mg/L; CRP > 7 mg/L) and then randomized at a 1:1 ratio to receive either LVL 324 mg SC (LVL group) or placebo (placebo group) on Day 1 at the investigational site. Single LVL 324 mg administration was performed as two SC injections of LVL 162 mg at a time. During the study all patients continued to receive the standard of care therapy (SOC) in accordance with the National clinical guidelines of the Ministry of Health of the Russian Federation, which included symptomatic treatment, antiviral agents, anticoagulants, supportive care, etc. In case of worsening of clinical status (increased SOFA score ≥ 2 and/or deterioration of respiratory or oxygenation parameters, blood pressure, vital signs, etc.) the investigator could give the subject a single open-label SC administration of LVL 324 mg as the rescue therapy. Health status of the study subjects was assessed for the 30 days of the main study period or until the subject was discharged or until death, whichever occurred first. The follow-up telephone contact was performed on Day 60.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
Randomization was performed centrally. After the investigator entered the eligibility screening data, the central electronic system generated a unique subject identifier (subject ID) and a unique investigational product (IP) lot number. The investigator and patients were blinded to the treatment allocation. LVL and placebo were provided in identical primary and secondary packages with identical labels. LVL intended for use as rescue therapy was provided unblinded and was labeled “rescue therapy”. All randomized patients received the study treatment according to the intervention they were allocated.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
The Independent Data Monitoring Committee (IDMC) included three independent medical specialists. Sponsor’s representatives were not IDMC members, had no access to the blinded data, and did not participate in voting. IDMC was involved in the assessment of the risk/benefit ratio of LVL in patients with severe COVID-19.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
The initial primary endpoint was the overall mortality (the proportion of subjects who died in each group). Observed mortality rate in the study population was significantly lower than the assumed value. Thus, the study had not enough power to detect the difference between the groups using overall mortality. The primary efficacy endpoint was changed to the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14 after the IP administration. This outcome is suggested by FDA for the assessment of clinical efficacy of therapy in COVID-19 trials. The 7-category ordinal scale includes the following categories: 1—not hospitalized/discharged, 2—hospitalized, not requiring oxygen therapy or other medical care, 3—hospitalized, not requiring oxygen therapy, requiring other medical care (related or unrelated to COVID-19), 4—hospitalized, requiring oxygen therapy, 5—hospitalized, requiring high-flow oxygen therapy or non-invasive ventilation, 6—hospitalized, requiring mechanical ventilation or extracorporeal membrane oxygenation, 7—death. Sustained clinical improvement was defined as ≥ 2-category improvement in clinical status relative to baseline on the 7-category ordinal scale or reaching the clinical status of categories 1 or 2. The key secondary efficacy endpoint was the proportion of patients with each of the outcomes of the 7-category ordinal scale. Other secondary efficacy endpoints included: the proportion of patients transferred to the Intensive Care Unit (ICU), duration of fever (body temperature > 38 °C; for survivors) and hospitalization (for survivors) after the IP administration, change from baseline in the Erythrocyte Sedimentation Rate (ESR), CRP, and IL-6. Safety assessment was based on the proportion of patients with the adverse drug reactions (ADRs), grade ≥ 3 ADRs, serious ADRs, frequency of systemic or opportunistic infections, grade 4 neutropenia, hypersensitivity, and injection site reactions. ADRs were reported according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. Adverse events (AEs) data was coded using Medical Dictionary for Regulatory Activities (MedDRA) v. 23.0. ESR, CRP, and IL-6 levels, as well as all safety-related laboratory parameters, were measured at local clinical laboratories of trial sites using routine methods.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['CR10', 'CR12']
|
The study hypothesis was that the efficacy of LVL in combination with SOC is superior to placebo in combination with SOC. To calculate the sample size, we used the published data on the proportion of patients with sustained clinical improvement on the 7-category ordinal scale 14 days after the other IL-6R inhibitors administration [10–12]. It was estimated that at least 93 patients had to be randomized to each study group to provide 80% power to detect the treatment effect of 20% (54% vs 34%) between the LVL and the placebo groups with the superiority hypothesis (ɛ> 0) at a one-sided 2.5% type I error rate.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['Fig1']
|
The main efficacy analysis was performed in the population of all randomized patients (full analysis set, FAS,n= 206). In patients who received rescue therapy, all efficacy data obtained after the rescue therapy administration were considered missing. In the primary efficacy analysis patients with missing data were classified as non-responders. The efficacy analysis for the key secondary endpoint and other secondary endpoints was performed without missing data imputation (complete case analysis). The safety population included all randomized patients who received study therapy (n= 204). The safety analysis was performed using all the collected data, regardless of the use of rescue therapy (complete case analysis), in the LVL and placebo groups. To test the hypothesis of the LVL superiority over placebo, a one-sided 97.5% Wilson confidence interval (CI) was calculated with the established superiority margin Δ = 0.Pvalue for the primary endpoint was calculated for one-sided hypothesis at a statistical significance level of 0.025. Two-sided hypothesis tests with the statistical significance level set at 0.05 were conducted for the key secondary and secondary efficacy endpoints, as well as the safety analysis. The categorical data were compared using Pearson’s chi-squared test or Fisher’s exact test. The quantitative data was compared with Mann–Whitney test. To confirm the validity of classifying patients who received rescue therapy as non-responders the supportive efficacy analysis was performed in as-treated groups (Fig.1) based on the initial assignment and prescription of rescue therapy, using all collected efficacy data, regardless of the prescription of rescue therapy (without replacing the data obtained after the start of rescue therapy with missing data).Fig. 1Patients flow diagram.LVLlevilimab,ICinformed consent,IPinvestigational product (LVL/placebo) The changes of the initial clinical study plan were described in protocol amendments approved by the Central Regulatory Authority of the Russian Federation. The statistical analysis was conducted using SAS®9.4 and the programming language R.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['Fig1']
|
The study was conducted from April 2020 to August 2020. A total of 217 patients were enrolled in the study. Overall, 206 patients were randomized (1:1): LVL group (n= 103) and placebo group (n= 103); 2 patients in the placebo group withdrew consent before the IP administration and 204 patients received the IP (103—LVL, 101—placebo). During the main study period 8 patients died (4 patients in each group), 2 patients were prematurely withdrawn from the study: 1 patient in the LVL group was withdrawn due to the major protocol deviation and 1 patient in the placebo group was lost to follow-up. 98 patients in the LVL group and 96 patients in the placebo group completed the main study period. During the follow-up period 1 patient in the placebo group was lost to follow-up. Thus, 98 patients in the LVL group and 95 patients in the placebo group completed the follow-up period. 13 patients in the LVL group (LVL + LVL) and 42 patients in the placebo group (placebo + LVL) received rescue therapy (Fig.1).
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['Tab1']
|
The baseline demographics, clinical characteristics and the range of concomitant diseases were almost consistent across the LVL and placebo groups. The mean age of patients was 58.5 ± 12.9 years in the LVL group and 58.2 ± 10.8 years in the placebo group, but the proportion of patients aged ≥ 75 years was higher in the LVL group than in the placebo group (11.7% (12/103) vs. 3.9% (4/103), respectively). 48.5% (50/103) and 39.8% (41/103) of patients in each group had concomitant vascular disorders and metabolism and nutrition disorders, respectively, 19.4% (20/103) of patients in the LVL group and 11.7% (12/103) of patients in the placebo group had cardiac disorders. The clinical status assessed by the 7-category ordinal scale was similar between the LVL and the placebo groups. Most patients met categories 3 and 4. The duration of fever and hospital stay were similar between the groups. The most prescribed treatment for COVID-19 was hydroxychloroquine, anticoagulants, and antibacterials. 4.9% (5/103) of patients in the LVL group and 8.7% (9/103) of patients in the placebo group received corticosteroids (Table1).Table 1Baseline characteristics of patients included in CORONA clinical studyParameterGroups“as randomized”Groups“as treated”LVL(n= 103)Placebo(n= 103)LVL(n= 90)Placebo + LVL(n= 42)LVL + LVL(n= 13)Placebo(n= 61)Age, yearsMean (SD)58.5 (12.9)58.2 (10.8)58.0 (11.9)58.4 (11.7)61.9 (18.5)58.1 (10.3)≥ 18 and < 40 years,n(%)8 (7.8)7 (6.8)6 (6.7)3 (7.1)2 (15.4)4 (6.6)≥ 40 and < 65 years,n(%)67 (65.1)67 (65.1)61 (67.8)27 (64.3)6 (46.2)40 (65.6)≥ 65 and < 75 years,n(%)16 (15.5)25 (24.3)16 (17.8)11 (26.2)014 (23)≥ 75 years,n(%)12 (11.7)4 (3.9)7 (7.8)1 (2.4)5 (38.5)3 (4.9)Male gender,n(%)58 (56.3)51 (49.5)47 (52.2)18 (42.9)11 (84.6)33 (54.1)BMI, kg/m2Median [IQR]28.1 [25.5–31.6]28.7 [25.5–31.6]28.2 [25.3–31.6]27.5 [25.1–31]26.5 [25.9–32.3]29.4 [26.8–32.1]SpO2, %Median [IQR]91.0 [90.0–92.0]91.0 [90.0–92.0]91.0 [90.0–92.0]90.5 [90.0–92.0]90.0 [89.0–92.0]91.0 [90.0–92.0]7-point ordinal scale category at screening,n(%)Category 5Hospitalized, requiring high-flow oxygen therapy or non-invasive ventilation,n(%)2 (1.9)1 (1)1 (1.1)01 (7.7)1 (1.6)Category 4Hospitalized, requiring oxygen therapy,n(%)60 (58.3)63 (61.2)52 (57.8)21 (50)8 (61.5)42 (68.9)Category 3Hospitalized, not requiring oxygen therapy, requiring other medical care,n(%)40 (38.8)39 (37.9)36 (40)21 (50)4 (30.8)18 (29.5)Category 2Hospitalized, not requiring oxygen therapy, not requiring other medical care,n(%)1 (1)01 (1.1)000Concomitant diseases (> 10% of patients at least in one of the groups, LVL or placebo),n(%)Vascular disorders50 (48.5)50 (48.5)43 (47.8)22 (52.4)7 (53.9)28 (45.9)Metabolism and nutrition disorders41 (39.8)41 (39.8)35 (38.9)17 (40.5)6 (46.2)24 (39.3)Surgical and medical procedures19 (18.5)17 (16.5)17 (18.9)9 (21.4)2 (15.4)8 (13.1)Cardiac disorders20 (19.4)12 (11.7)15 (16.7)7 (16.7)5 (38.5)5 (8.2)Gastrointestinal disorders15 (14.6)10 (9.7)12 (13.3)6 (14.3)3 (23.1)4 (6.6)Neoplasms benign, malignant, and unspecified13 (12.6)8 (7.8)9 (10)5 (11.9)4 (30.8)3 (4.9)Main disease characteristicsFever,n(%)99 (96.1)102 (99)17 (18.9)9 (21.4)2 (15.4)8 (13.1)Duration of fever, days from onset to Day 1Median [IQR]9 [7–13]9 [7–13]9 [7–13]8 [6–11]8 [7–12]10 [8–14]Duration of hospital stay, days to Day 1Median [IQR]3 [2–6]3 [2–5]3 [2–6]3 [2, 3]2 [2–4]4 [2–7]Concomitant corticosteroidsDexamethasone5 (4.9)5 (4.9)5 (5.6)2 (4.8)03 (4.9)Methylprednisolone04 (3.9)02 (4.8)02 (3.3)Prednisolone01 (1)01 (2.4)00Other concomitant therapy (> 20% of patients at least in one of the groups, LVL or placebo),n(%)Hydroxychloroquine74 (71.9)65 (63.1)65 (72.2)28 (66.7)9 (69.2)37 (60.7)Antithrombotic agents70 (68)67 (65.1)62 (68.9)33 (78.6)8 (61.5)34 (55.7)Macrolides and lincosamides70 (68)67 (65.1)60 (66.7)33 (78.6)10 (76.9)34 (55.7)Other beta-lactam antibacterials40 (38.8)40 (38.8)35 (38.9)13 (31)5 (38.5)27 (44.3)Direct acting antiviral agents27 (26.2)25 (24.3)26 (28.9)11 (26.2)1 (7.7)14 (23)Quinolone antibacterials23 (22.3)21 (20.4)21 (23.3)4 (9.5)2 (15.4)17 (27.9)β-blocking agents22 (21.4)20 (19.4)18 (20)8 (19.1)4 (30.8)12 (19.7)Other analgesics and antipyretics19 (18.5)23 (22.3)18 (20)10 (23.8)1 (7)13 (21.3)Inflammatory markers at screeningIL-6, pg/mlMedian [IQR]11.2 [2.7–25]9.4 [1.7–32.2]11 [2.5–20.9]10.1 [4.6–32.2]15.4 [9.7–37.7]4.2 [1.2–34.8]CRP, mg/lMedian [IQR]39.8 [20–76]46 [18–78.4]35.9 [20–72.5]45.7 [18.2–80.5]45.6 [41–76]46 [17–76]ESR, mm/hMedian [IQR]29.5 [18–45]35 [21–50]28 [18–45]40 [24–51]39 [26–48]33 [20–50]LVLlevilimab,IL-6interleukin 6,CRPC-reactive protein,ESRErythrocyte Sedimentation Rate
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
The proportion of patients who achieved the sustained clinical improvement on Day 14 and not required rescue therapy was significantly higher in the LVL group than in the placebo group (63.1% (65/103) vs. 42.7% (44/103);P= 0.0017). The difference in sustained clinical improvement rate between the LVL and the placebo groups was 20.4% with one-sided 97.5% CI (7–100) (P= 0.0017) with its lower limit above the established superiority margin. Thus, the hypothesis of superiority of the efficacy of LVL over placebo has been confirmed. The number of patients with sustained clinical improvement and not required rescue therapy increased in both groups throughout the main period of the study with a statistically significant predominance in the LVL group. Overall, on Day 30 84.5% (87/103) of patients in LVL group and 55.3% (57/103) of patients in placebo group met the criteria of sustained clinical improvement without rescue therapy (P< 0.0001).
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['Fig2', 'Fig3', 'Fig3', 'Fig3']
|
From Day 1 to Day 4 there was no statistically significant difference between the LVL and the placebo groups in the number of patients meeting each of the categories of the 7-category ordinal scale and not requiring rescue therapy. On Day 5 significantly more patients treated with LVL did not require oxygen therapy (met category 3) without rescue therapy compared to the patients receiving placebo (41.8% (43/103) vs. 26.2% (27/103);P= 0.0186). These differences were clear until Day 12. From Day 13 and to the end of the main study period, the proportion of discharged patients (category 1) who did not require rescue therapy was significantly higher in the LVL group than in the placebo group. On Day 30, 84.5% (87/103) of patients in the LVL group and 55.3% (57/103) of patients in the placebo group were discharged (P< 0.0001) with no additional LVL administration (Fig.2).Fig. 2The proportion of discharged patients.LVLlevilimab. Stars indicate the statistical significance of difference between groups as per legend. *P< .05; **P< .01; ***P< .001 The number of patients who met categories 4–7 without rescue therapy was comparable between the LVL and the placebo groups throughout the main study period. Thus, on Day 30, none of the patients required mechanical ventilation or extracorporeal membrane oxygenation, high flow oxygen therapy or non-invasive ventilation, less than 1% (1/103) of patients in the placebo group and none of the patients in the LVL group required oxygen therapy, 1.9% (2/103) of patients in the LVL group and less than 1% (1/103) of patients in the placebo group died (P= 1.0000 for all the comparisons). During the main study period fewer patients in the LVL group (3/103, 2.9%) than in the placebo group (10/103, 9.7%) were transferred to the ICU without rescue therapy (P= 0.0449). After the IP administration, the duration of fever was rather short in both groups. The duration of hospital stay was also comparable between the LVL and the placebo groups. However, in patients who received rescue therapy, efficacy data obtained after the rescue therapy administration was considered missing thus the analysis of the duration of fever and hospital stay performed in subgroups (as treated) is more significant and the results are presented below. We evaluated the dynamics of ESR and CRP as the main inflammatory markers. After the IP administration on Day 1, the ESR distinctly decreased, but more rapidly in the LVL group: on Days 3, 5, and 7 the ESR was significantly lower in the LVL group compared to the placebo group (Fig.3).Fig. 3The dynamics of inflammatory markers. A. ESR, B. CRP. C. IL-6.ESRErythrocyte Sedimentation Rate,CRPC-reactive protein,IL-6interleukin 6,LVLlevilimab. Dots indicate medians and whiskers indicate upper and lower quartiles. Stars indicate the statistical significance of difference in changes from baseline of inflammation markers level between groups as per legend. *P< .05; **P< .01; ***P< .001 We observed a gradual decrease of CRP level. The CRP level was significantly lower in the LVL group compared to the placebo group on Days 3, 5 and 7 (P< 0.0001 for all the comparisons, Fig.3). The dynamics of IL-6 serum concentrations was strikingly different in the LVL and placebo groups. After the LVL administration we detected a rapid significant increase in IL-6 concentration with a slight further decline due to IL-6 inhibition representing the LVL pharmacodynamics. In the placebo group, the IL-6 concentration increased slightly until Day 2, and then decreased significantly due to clinical improvement in this group. The differences in the change of IL-6 level was statistically significant during the entire evaluation period except the Day 14 (Fig.3).
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['Tab2']
|
The number of patients who required rescue therapy due to the worsening of the clinical status was significantly greater in the placebo group compared to the LVL group: 40.8% (42/103) vs. 12.6% (13/103), respectively (P< 0.0001). The median time to the rescue therapy administration was 3 [IQR 2–3] days in both LVL and placebo groups (P= 0.7030). On Day 14, the sustained clinical improvement rate was higher in patients who did not receive rescue therapy compared to those who received it: 72.2% (65/90), 45.2% (19/42), 53.9% (7/13), and 72.1% (44/61) of patients in the LVL, placebo + LVL, LVL + LVL, and placebo groups, respectively (P= 0.0105). The differences between rescue therapy and non-rescue therapy groups were seen in the proportion of discharged patients and in the proportion of patients requiring oxygen therapy starting from Day 9. On Day 9, the proportion of discharged patients was 38.9% (35/90) and 44.3% (27/61) in the LVL and the placebo groups and 9.5% (4/42) and 23.1% (3/13) placebo + LVL and LVL + LVL groups, respectively (P= 0.0006). These differences were statistically significant throughout most of the main study period. At the same time, on Day 9, the proportion of patients requiring oxygen therapy was 38.1% (16/42) and 38.5% (5/13) in placebo + LVL and LVL + LVL groups and 16.7% (15/90) and 13.1% (8/61) in LVL and placebo groups, respectively (P= 0.0068). These differences remained statistically significant on Days 10, 11, 14, 15, 18. Significantly more patients were transferred to the ICU in rescue therapy groups compared to non-rescue therapy groups: 21.4% (9/42) and 15.4% (2/13) in the placebo + LVL and LVL + LVL groups and 2.2% (2/90) and 4.9% (3/61) in the LVL and the placebo groups, respectively (P= 0.0006). There was a trend to a longer fever in patients who received rescue therapy compared to patients who received the IP only, but the differences did not reach statistical significance (P= 0.1507). The patients who initially received LVL stayed in hospital for 3 days less than the patients who initially received placebo and required rescue therapy thereafter (P= 0.0391, Table2).Table 2Efficacy of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation (main secondary efficacy endpoints)ParameterGroups “as randomized”Groups “as treated”LVL(n= 103)n(%)Placebo(n= 103)n(%)PvalueLVL(n= 90)Placebo + LVL(n= 42)LVL + LVL(n= 13)Placebo(n= 61)Patients with sustained clinical improvement,n(%)Day 76 (5.8)6 (5.8)1.0000a6 (6.7)1 (2.4)06 (9.9)Day 1465 (63.1)44 (42.7).0017b65 (72.2)19 (45.2)7 (53.9)44 (72.1)Day 2179 (76.7)49 (47.6)<.0001a79 (87.8)31 (73.8)8 (61.5)49 (80.3)Day 2887 (84.5)57 (55.3)<.0001a87 (96.7)38 (90.5)10 (76.9)57 (93.4)Day 3087 (84.5)57 (55.3)<.0001a87 (96.7)38 (90.5)10 (76.9)57 (93.4)Patients transferred to the ICU,n(%)3 (2.9)10 (9.7).0449a2 (2.2)9 (21.4)2 (15.4)3 (4.9)Duration of fever, days after IP administrationMedian [IQR]1 [1–3]2 [1–3].1065c1 [1, 2]2 [1–3]1[1–3]1 [1, 2]Duration of hospital stay, days after IP administrationMedian [IQR]11 [8–16]11 [7–18].4852c10 [7.5–15.5]14 [10–19]12.5 [8–21]9 [7–13]ESR, mm/hDay 3Median [IQR]30 [18–44.5]38 [23–56].0035c29.5 [18–43.5]45.5 [32.5–57]30.5 [19.5–53.5]35.5 [21–54]Day 5Median [IQR]25 [15–41]40 [24–55].0002c24 [15–42]42 [27–57]29 [16–38]31 [21–53]Day 7Median [IQR]23.0 [15–36]31.0 [21–45].0009c23 [15–36.5]34 [21–43]27 [14–36]30.5 [20–49]CRP, mg/LDay 3Median [IQR]14.6 [5.1–29.8]31.7 [12–62.6]< .0001c12.9 [4.9–28.6]50.8 [30–108]28 [8.9–61]22.4 [6–47.4]Day 5Median [IQR]5.3 [1.5–15]17.7 [6.9–44]< .0001c5 [1.5–12.1]22.2 [10.5–57]8.4 [2.8–23]14.5 [5.5–27.9]Day 7Median [IQR]3.9 [1.3–8.4]9.2 [4.1–19]< .0001c3.8 [1.3–8.4]9.7 [4.7–19]4.6 [2.2–24]8.5 [3.8–18.2]IL-6, pg/mlDay 3Median [IQR]65.9 [16.5–201]16.4 [3.9–80.4].0017c56.6 [14.8–144]51.7 [14–163.8]205.8 [92.4–300]5.3 [0.7–16.7]Day 4Median [IQR]64.2 [18.3–247.1]20.1 [1.5–119.1].0121c48.2 [16.2–138]78.2 [22.9–297]300 [123.4–300]1.5 [0.8–16.9]Day 14Median [IQR]25.4 [12.6–77.8]108.7 [22.1–10.5]1.0000c25.1 [1.5–62.2]33.2 [13.5–150.7]119.2 [12.6–300]4.6 [0.1–9.1]IPinvestigational product,ICUintensive care unit,LVLlevilimab,IL-6interleukin 6,CRPC-reactive protein,ESRErythrocyte Sedimentation RateaTwo-sided Pearson’s chi-squared testbOne-sided Pearson’s chi-squared testcMann–Whitney testP< 0.05 marked in bold
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['Tab3']
|
During the 60 days of the study, ADRs were reported in 27.2% (28/103) and 23.8% (24/101) of patients in the LVL and placebo groups, respectively (P= 0.5750) and severe ADRs (grade ≥ 3, CTCAE 5.0) were reported in 9.7% (10/103) and 6.9% (7/101) of patients in the LVL and the placebo groups, respectively (P= 0.4279). Overall, 3 serious adverse events (SAEs) were reported during the study (1 in the LVL group and 2 in the placebo group); none of them were considered treatment related. In the LVL group (LVL + LVL), a 53-year-old male with a history of long-lasting hypertension and type 2 diabetes mellitus presented with unstable angina pectoris 4 days after he was discharged, he was re-hospitalized, and improved after treatment. In the placebo group (placebo + LVL), 2 patients died: a 69-year-old female with a history of chronic heart disease, atherosclerosis and type 2 diabetes mellitus presented with cardiac rhythm disturbances and a 52-year-old male progressed to respiratory failure, pulmonary thromboembolism, and respiratory distress syndrome; both deaths were considered not related to the IP in both investigator’s and Sponsor’s opinion. 6 deaths were related to the course of COVID-19 and were not reported as SAEs according to the protocol: 4 cases in the LVL group (2 cases in the LVL group and 2 cases in the LVL + LVL group) and 2 cases in the placebo group (1 case in the placebo group and 1 case in the placebo + LVL group). Overall, 2 patients had systemic/opportunistic infections (less than 1% of patients in both the LVL and the placebo groups): 1 patient in the LVL group had grade 1 positive blood culture test and 1 patient in the placebo group had grade 2 bacteremia and grade 2 vulvovaginal candidiasis. There were no cases of grade 4 neutropenia, hypersensitivity, or injection site reactions. Laboratory abnormalities were the most common adverse events (AEs) during the study and were reported in 61.2% and 55.5% of patients in the LVL and the placebo groups, respectively (Table3).Table 3Safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilationParameterLVL(n= 103)n(%)Placebo(n= 101)n(%)Proportion of subjects with ADRs,n(%)28 (27.2)24 (23.8)Proportion of subjects with grade ≥ 3 ADRs,n(%)10 (9.7)7 (6.9)Proportion of subjects with serious ADRs,n(%)00Systemic or opportunistic infections,n(%)1 (0.97)1 (0.99)Grade 4 neutropenia,n(%)00Hypersensitivity reactions, local reactions to the IP,n(%)00Summary of most common AEs (> 5% of patients)ALT increasedGrade 17 (6.8)4 (4)Grade 215 (14.6)13 (12.9)Grade 311 (10.7)6 (6)AST increasedGrade 15 (4.9)4 (4)Grade 212 (11.7)7 (6.9)Grade 37 (6.8)4 (4)Blood pressure increasedGrade 213 (12.6)9 (8.9)Grade 39 (8.7)10 (9.9)Diastolic blood pressure increasedGrade 217 (16.5)13 (12.9)Systolic blood pressure increasedGrade 210 (9.7)14 (13.9)Grade 33 (2.9)0Neutrophil count decreasedGrade 25 (4.9)0Grade 31 (1)2 (2)Summary of ADRsALT increasedGrade 13 (2.9)2 (2)Grade 213 (12.6)10 (9.9)Grade 37 (6.8)6 (5.9)AST increasedGrade 14 (3.9)3 (3)Grade 29 (8.7)6 (5.9)Grade 37 (6.8)4 (4)Neutrophil count decreasedGrade 22 (1.9)0Grade 301 (1)Blood pressure increasedGrade 202 (2)Grade 31 (1)0Diastolic blood pressure increasedGrade 21 (1)1 (1)Systolic blood pressure increasedGrade 31 (1)0Bilirubin increasedGrade 201 (1)Grade 301 (1)Lymphocytes count decreasedGrade 201 (1)Toxic hepatitisGrade 21 (1)0AE grades are presented according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0ADRsadverse drug reactions,AEsadverse events,ALTalanine aminotransferase,ASTaspartate aminotransferase,IPinvestigational product,LVLlevilimab The range of ADRs was consistent with the known safety profiles of other anti-IL-6R monoclonal antibodies, as well as the safety information of levilimab obtained in the previous phase I-II clinical studies. Therefore, all ADRs were expected. No cases of early withdrawal due to safety reasons were reported.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
['CR4', 'CR13', 'CR20', 'CR4', 'CR13', 'CR14', 'CR16', 'CR13', 'CR17', 'CR21', 'CR22']
|
During 1 year of COVID-19 pandemic multiple studies evaluating the effects of IL-6 inhibitors tocilizumab and sarilumab in COVID-19 patients showed controversial and sometimes disappointing results [4,13–20]. The range of the placebo-controlled trials of tocilizumab failed to meet the primary efficacy endpoints such as the clinical status according to the 7-category ordinal scale within 28 days, intubation or death, number of patients requiring non-invasive or mechanical ventilation or survival [4,13,14,16]. At the same time the COVACTA trial revealed the benefits of tocilizumab administration according to the other assessed outcomes: decrease of the length of the hospital stay and the decreased risk of progression to mechanical ventilation and ICU transfer. In EMPACTA trial tocilizumab administration reduced risk of start of mechanical ventilation or death [13]. Recently the REMAP-CAP trial provided new evidence of the efficacy of both tocilizumab and sarilumab based on the increased number of organ support free days and reduced mortality in critically ill ICU patients [17]. In the RECOVERY trial patients allocated to tocilizumab were more likely to be discharged from the hospital alive within 28 days and had a lower risk of invasive mechanical ventilation or death [21]. Overall, based on the results of REMAP-CAP and RECOVERY trials the use of tocilizumab and sarilumab in combination with dexamethasone was recommended in certain hospitalized patients who are exhibiting rapid respiratory decompensation due to COVID-19 [22]. It can be assumed that the diversity of the efficacy endpoints and heterogeneity of the populations with wide range of disease severity and significant differences in concomitant medication including corticosteroids could be considered the main reasons for these uncertainties. The results of CORONA study are important and contribute to the data about the effects of anti-IL6R therapy in severely but not critically ill COVID-19 patients. Due to the ethical concerns of depriving patients in the placebo group of potentially effective treatment, open label LVL administration was used as rescue therapy in patients with worsening condition according to the pre-specified criteria. It is worth mentioning that the rescue therapy was prescribed more than 3 times less frequently in the LVL group than in the placebo group illustrating the benefit of early LVL administration. In the CORONA study, only 5 patients in LVL group and 9 in placebo group received glucocorticoids as concomitant medication, which did not allow to perform specific subgroup analysis. Single LVL administration in combination with SOC resulted in an increased sustained clinical improvement rate without requirement of rescue therapy in overweighted (BMI > 28) males and females, aged > 40 years old, with vascular and metabolism/nutrition disorders as main comorbidities, who have radiologically confirmed SARS-CoV-2 pneumonia with no signs of other active infection, requiring or not oxygen therapy (but not ventilation) with median saturation 91% [90.0–92.0] and increased CRP, ESR and IL-6 blood concentrations. As early as the first week after the IP administration the LVL and placebo groups were significantly different in the distribution of patients according to the ordinal scale categories. During the first 2 weeks of therapy (from Day 5 to Day 12) significantly more patients who received LVL did not need oxygen therapy compared to placebo without need of rescue therapy. After 2 weeks of therapy (IP combined with SOC) more patients were discharged in the LVL group than in the placebo group without need of rescue therapy. Patients who received LVL were transferred to the ICU 3 times less frequently than patients in the placebo group without additional LVL administration. The supportive analysis confirmed that the rescue therapy was administered to the patients with worse course of the disease and validity of classification those who required rescue therapy as non-responders. Although the groups of patients who received and did not receive rescue therapy were similar in their demographic and clinical characteristics at screening, significantly more patients who initially received LVL and did not require rescue therapy (72.2%) demonstrated sustained clinical improvement on Day 14 than patients who initially received placebo and then required additional LVL administration (45.2%) as well as patients who received placebo.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC8479713']
|
['34586459']
|
[]
|
CORONA study had multicenter design, centrally performed randomization, the double-blinding of the allocated therapy was maintained throughout the study. The study included the homogeneous population of severely ill COVID-19 patients not requiring mechanical ventilation. The sample size was enough to test the hypothesis. IDMC was involved in the assessment of the risk/benefit ratio of LVL in patients with severe COVID-19. Thus, the risk of bias can be considered as low. Administration of LVL + SOC resulted in an increase of sustained clinical improvement rate and decreased frequency of the ICU transfer without requirement of rescue therapy in subjects with radiologically confirmed SARS-CoV-2 pneumonia requiring or not oxygen therapy (but not ventilation) with no signs of other active infection. The rescue therapy was prescribed more frequently in the placebo group than in the LVL group suggesting the benefit of early LVL administration. Thus, the data support that administration of LVL results in more favorable course of the disease, earlier oxygen withdrawal, and increase of sustained clinical improvement rate.
|
PMC8479713
|
Original Research Article
| null | 34,586,459
|
The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study
|
Lomakin NV, Bakirov BA, Protsenko DN, Mazurov VI, Musaev GH, Moiseeva OM, Pasechnik ES, Popov VV, Smolyarchuk EA, Gordeev IG, Gilyarov MY, Fomina DS, Seleznev AI, Linkova YN, Dokukina EA, Eremeeva AV, Pukhtinskaia PS, Morozova MA, Zinkina-Orikhan AV, Lutckii AA.
|
Inflamm Res. 2021 Dec;70(10-12):1233-1246. doi: 10.1007/s00011-021-01507-5. Epub 2021 Sep 29.
|
Lomakin NV
|
Inflamm Res
| 2,021
|
2021/09/29
|
PMC8479713
| null |
10.1007/s00011-021-01507-5
|
oa_comm/txt/all/PMC8479713.txt
|
d50320f9df832e6419b2e7a868deb5ca
|
Inflamm Res. 2021 Sep 29; 70(10-12):1233-1246
|
2021-12-11 07:50:25
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
['CR1', 'CR2', 'CR4', 'CR5', 'CR6', 'CR7', 'CR9', 'CR10', 'CR11', 'CR12', 'CR13']
|
Herniorrhaphies are performed 800.000 times a year in the U.S. A male person in the industrialized world faces an up to 27% lifetime risk of requiring surgery for his inguinal hernia [1]. Some 10–12% of these patients were found to report moderate to severe chronic pain after the operation [2–4]. Chronic postherniorrhapy inguinal pain may be caused by nociceptive, inflammatory or neuropathic changes, the latter depending on whether inguinal nerves are affected. A comparably related pain syndrome may occur after nerve entrapment following a lower abdominal pfannenstiel incision [5]. Both pain entities are also referred to as chronic post-surgical inguinal pain (PSIP) syndromes. Recently, a consensus was proposed concerning the management of chronic postherniorrhapy inguinal pain [6]. If non-surgical options failed, a triple neurectomy with inguinal nerves removal via an inguinal approach is suggested. Success rates range from 50 to 100%, depending on surgical technique (open or laparoscopic) and definitions of outcome measures [7–9]. However, the suggested consensus did not address alternative treatment options once a patient was an all options non-responder. Interestingly, a recent study showed that the number needed to harm, defined as patients who had an increase > 25% of pain compared to preoperatively, was 1 of 8 patients at a 3 year follow up when a selective neurectomy accompanied by mesh removal was performed. [10] Currently, few therapeutic options are available for patients demonstrating limited (or no) success after neurectomy. A promising new treatment tool is spinal cord stimulation (SCS) of the dorsal root ganglion. This novel variant of traditional SCS is claimed to effectively target the groin and has proved to be a safe and efficaous therapy in small, heterogeneous case series of patients with PSIP [11,12]. In order to evaluate whether this therapy is an effective treatment option for PSIP, a randomized clinical trial comparing SCS to conventional medical management is proposed. [13] Aim of the present article is to report on characteristics regarding the set-up of this randomized clinical trial.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
[]
|
The SMASHING (Spinal Modulation After failed Surgery for chronic pain following Hernia treatment in INGuinal area) trial is a randomized, cross-over, multicenter study. The protocol is approved by the Regional Ethics Committee of the Máxima Medical Center, Veldhoven, The Netherlands (no. 1435). The objective is to evaluate the efficacy of SCS of the DRG with an Axium® SCS System of Spinal Modulation Inc. in patients with post-surgical pain after a hernia repair or pfannenstiel incision who did not favorably respond to a neurectomy. Clinical results of the Axium arm are compared with those in a CMM arm. Patient enrolment has started in February, 2015. The study protocol is registered at the NIH Clinical Trials Registry (http://clinicaltrial.gov,ClinicalTrials.govidentifier: NCT02349659).
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
['CR6']
|
Adults (18 years or older) of either gender suffering from persistent inguinal pain (minimum duration of 6 months) following either open or laparoscopic inguinal hernia repair surgery or a Pfannenstiel incision who have subsequently undergone and failed to respond to a neurectomy procedure will be considered for inclusion. Failure to benefit from additional treatment options such as peripheral nerve blocks, physical therapy, minimally invasive interventional pain procedures and medical regimens with at least a tricyclic antidepressant or similar neuropathic pain agents is required. Patients should have a minimum daily average baseline pain rating of 5 out of 10 in the inguinal area on an 11-point NPRS. Patients should be able to operate the device. Inclusion criteria as set out by the Dutch Neuromodulation Society should be met. A psychologist will screen patients and assess for suitability within a multidisciplinary team including an anesthesiologist or pain specialist and a surgeon-herniologist. [6] Patients are excluded if there are contra-indications for device implantation such as pregnancy, ongoing infection, coagulation disorders, previous spinal surgery at or between vertebral levels T10-L2, the presence of other active implantable devices or a condition which will require MRI investigations. Patients are not allowed to undergo injection therapy or radiofrequency treatment at the target neural structure in the 3 months prior to inclusion. An escalating or changing pain condition and a diagnosis of cancer in the past 2 years are also considered as exclusion criteria.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
[]
|
Patients are considered for the trial if all criteria are satisfied. After suitability within is confirmed by the multidisciplinary team, informed consent is signed after patient is adequately informed and has agreed upon participation. Patients will be randomized in a 1:1 ratio to either arm. An independent statistician will generate and hold the allocation sequence, concealed from those involved in assessing eligibility and recruiting subjects.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
['Fig1', 'CR11', 'CR12', 'Fig1']
|
The SCS group (Axium® Group, Fig.1) receives an Axium® SCS System within 4 weeks after randomization. Implantation is performed in one of the participating centers by an experienced anesthesiologist or neurosurgeon. Electrodes are placed in the epidural space near the targeted DRG under sedation in a surgical theatre, using a transforaminal, fluoroscopy checked approach. During the procedure, the patient is asked if paresthesia elicited by stimulation covers the painful area. If so, electrodes are connected to an external stimulator if a trial phase is deemed needed. After a successful trial (defined as reaching adequate pain relief upon stimulation), a fully implantable device will be placed in a second session some 2–3 weeks later on as earlier suggested. [11,12] After implantation, patient will be subjected to a standard follow-up schedule as dictated by the implanting center plus additional trial visits if needed.Fig. 1Basic design and follow-up schedule. Seven analysis groups are indicated (‘AG’) to refer to groups at several time points After randomization, the CMM (CMM group, Fig.1) will continue with prior pain treatments as previously initiated by their general practitioner or pain specialist. This regimen will generally comprise physical therapy and medications such as a tricyclic antidepressant (amitriptyline) and/or anticonvulsants (pregabalin, gabapentin, valproic acid), opioids or other analgesics, as is the standard protocol for neuropathic pain. Use and adjustment of pain medication is allowed and monitored. There are no restrictions to dosage and sort of pain medication including opioids. However, interventional pain techniques are not allowed during this time period. If (pulsed) radiofrequency, epidural or peripheral injection or infusion therapy with analgesic agents or any other form of neurostimulation (traditional SCS, Deep Brain Stimulation, TENS) are performed, these treatments are considered as a protocol violation. After 6 months, patients will be offered to cross-over to the Axium ® Group. They will then receive treatment and follow-up as previously described.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
[]
|
Patients of both groups will undergo a follow-up visit after 2 weeks, 1 month, 3 months, 6 months and 12 months postrandomisation. Standardized questionnaires investigating quality of life, physical impairment, health resources utilization, subject satisfaction and adverse events will be completed. Validated questionnaires such as the EQ-5D, BPI, NPSI (Neuropathic Pain Symptoms Inventory) and a 7 point Likert Scale will be used. Pain and sleep will be evaluated using a pain-sleep interference diary containing an NPRS and DSIS over a 7-day period. Measures of average, worst and least pain during the previous 24 h are obtained using this diary. Primary analysis is conducted on average pain intensity scores. Physical examination will be performed in order to assess changes in neuropathic pain symptoms.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
['Fig2']
|
The primary outcome is percentage of subjects experiencing a minimal 50% reduction in average daily pain intensity as measured using the average NPRS as noted in pain diaries in the Axium® group as compared to the CMM group. Group differences in the change in pain intensity scores (NPRS) at the 6-month FU visit are also calculated. The analysis will be done following an Intention to Treat (ITT) principle. Secondary outcomes are an ‘as treated’ analysis of the percentage of subjects experiencing a minimal 50% reduction in average daily pain intensity (NPRS) at 6 months and the mean difference in the change in pain intensity scores (NPRS) between the successfully trialed subjects with the Axium® arm as opposed to the CMM arm. This ‘as treated’ analysis is important as it reflects clinical convention i.e. utilization of a therapy trial (TNS) to improve changes of a successful outcome with the fully implantable system. A number needed to treat (NNT) analysis at the 6-months time point for ≥30% and ≥50% pain relief is also performed. However, reduction in pain intensity is not the only clinically relevant outcome in chronic pain patients. Changes in disability, pain interference, neuropathic pain symptoms, sleeping disorders and health resources utilization are also investigated using validated questionnaires at baseline and each follow-up visit. (Fig.2).Fig. 2SPIRIT Flow chart. The red star marks the cross-over option for the CMM group. *TNS: Trial stimulation phase (1 week) Total study duration is anticipated to be 2 years.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
['CR14', 'CR15', 'CR11', 'CR12']
|
Sample size estimation is based on a ‘responder’ analysis as recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) group recommendations [14]. The estimated proportion of responders (≥ 50% reduction in pain NPRS) in the CMM group is 10%, based upon data generated by a RCT on SCS in failed back surgery syndrome (FBSS) [15]. Expected effect size in the Axium® group is extrapolated from published literature [11,12]. The targeted effect size is a difference in proportion responding to treatment (Axium® vs. CMM) at the 6-month time point of 40%; i.e., 50% responding in Axium® group vs. 10% in the CMM group. With 90% power and 2p = 0.05, using a normal approximation with continuity correction, 31 subjects are required in each group at the 6 months primary endpoint analysis follow up point. With an allowance for attrition of 20% in both arms at 6-month follow-up, a total of 78 subjects is recruited (62/0.8 = 78). Sample size estimation was conducted using Stata software (version 13.1; StataCorp, College Station, TX). Figures were verified using Medcalc® software (v.14.8). There are no specific data to judge the effect size of CMM or the drop out rates in this specific study population.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
[]
|
The primary analysis is a comparison of the proportion of responders (≥ 50% pain relief) in the Axium® versus CMM group at the 6-months time point. The mean difference between proportions and 95% confidence intervals are calculated. A risk difference is obtained using generalized linear modeling with a binomial distribution and an identity link. Difference between groups in the change in pain score (6-months minus baseline), adjusted for any chance imbalance between groups at baseline (ANCOVA model) are also calculated. The mean treatment effect (Axium® minus CMM) together with its 95% confidence interval is obtained. NNT will also be calculated as the reciprocal of the difference in proportions of responders (Axium® minus CMM) and presented with its 95% confidence interval. All analyses are conducted both ‘as randomized’ (intention to treat principle) and ‘as treated’ (secondary).
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
['CR6', 'CR11', 'CR15', 'CR16', 'CR19']
|
The results of the presently proposed ´SMASHING´ trial may shed light on a possible viable alternative treatment option once other treatments have failed in therapy resistant patients with PSIP. A very recent consensus protocol does not address this group [6]. Based on a retrospective analysis of 10 CPIP patients who were implanted with DRG stimulation leads, the technique is very promising. Eight of these 10 patients reported > 50% pain relief whereas a 77% mean VAS reduction was attained. [11] However, it is obvious that a proper RCT is required using a cross-over design. Firstly, a placebo controlled setting is inappropriate as it is clearly noticeable for patients if a sham device is implanted because of the absence of paresthesia. Secondly, ethics direct that the control group is not to be denied access to the therapy for which a cross-over is offered. Thirdly, a control group is heterogeneous because of the often individually tailored treatments for these therapy-resistant patients. This heterogeneity however mirrors daily clinical practice, and therefore generalization of the forthcoming results will be realistic. Moreover, possible confounding variables are controlled with randomization. The PROCESS study used a similar construction [15]. It must be appreciated that the validation of various outcomes is of utmost importance in pain treatment studies. Pain reduction scores are subjective whereas the clinical relevance of a 30% or 50% pain reduction is debatable. The presently proposed outcome measurements are linked to improved patient satisfaction, diminished medication usage, daily functioning and sleeping quality and a positive expert’s opinion regarding patient’s improvement [16–19]. We will address these components as well as other secondary outcomes as all of these issues are indispensable for a thorough efficacy analysis of any type of novel pain treatment.
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC5872506']
|
['29587729']
|
['CR20']
|
Per 17-Jan-2017, sponsorship of the study has been transferred from St. Jude / Abbott to the Maxima Medical Center and primary investigator due to a slow inclusion rate. Analysis of the preliminary results of 18 patients enrolled from March 2015 to November 2016 is currently performed using repeated measures ANOVA on the primary outcome (number of patients with > 50% pain reduction and individual pain reduction). The original protocol did not describe regulations for interim analysis, but the authors will adhere to Bayesian approach as described in Li and Gates, 2013 [20].
|
PMC5872506
|
Study Protocol
| null | 29,587,729
|
Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial
|
Mol FMU, Roumen RM, Scheltinga MR.
|
BMC Surg. 2018 Mar 27;18(1):18. doi: 10.1186/s12893-018-0349-8.
|
Mol FMU
|
BMC Surg
| 2,018
|
2018/03/29
|
PMC5872506
| null |
10.1186/s12893-018-0349-8
|
oa_comm/txt/all/PMC5872506.txt
|
eef6652c068f975024a0e6ec1f1a7a3d
|
BMC Surg. 2018 Mar 27; 18:18
|
2021-06-18 17:03:27
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['CR1', 'CR3', 'CR4', 'CR5', 'CR6', 'CR7', 'CR8', 'CR9', 'CR11', 'CR12', 'CR13', 'CR14', 'CR15']
|
The prevalence of obesity has increased rapidly worldwide recently [1–3]. In addition, the epidemic of childhood obesity is becoming one of the most crucial public health challenges globally [4,5]. Childhood obesity may increase the risk of adult obesity, which likely increases the burdens of several diseases including diabetes, cardiovascular diseases, and other noncommunicable diseases in later life [6]. The increasing prevalence of childhood obesity is also a major economic concern that may produce severe adverse consequences, such as lower skill attainment, poor academic outcomes, reduced labor productivity, and increased health care cost [7]. The prevalence of childhood obesity in China increased nearly 50-fold, from 0.15 to 7.3%, between 1985 and 2014 [8]. To develop the most effective intervention strategy, an increasing number of childhood obesity intervention studies have been implemented in China [9–11]. From a policy development perspective, the cost per quality-adjusted life year (QALY) to the health care system is of particular interest. Because of the wide range of health-related, societal, and economic consequences, policy makers and intervention providers urgently need evidence-based obesity prevention programs. Although systematic reviews of economic evaluations of pediatric health promotion programs have been performed, most of them evaluated the school-based programs in developed countries [12,13], though some school-based obesity intervention programs have been carried out in China, most of them focused on effects evaluation and rare on economic evaluation. To evaluate the effects and cost-effectiveness of a school-based comprehensive intervention program for childhood obesity, we conducted the nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC). The NISCOC comprised two trials. One trial was a cluster-randomized controlled trial of separate nutrition education (NE) and physical activity (PA) interventions. In Beijing, eight randomly selected schools were divided into three intervention groups (three schools for NE, three schools for PA, and two schools as shared controls). The other trial was a multicenter cluster-randomized controlled trial of comprehensive interventions including both nutrition education and physical activity (CNP) in five cities: Shanghai, Chongqing, Guangzhou, Jinan, and Harbin. Six schools from each city were randomly assigned to one of two groups (three to CNP and three to control). In total, 38 primary schools were included in this trial. The program was implemented for two semesters from May 2009 to May 2010. NE was targeted toward parents, teachers, and health workers in treatment group schools [14]. Our analysis indicated that CNP could produce a greater preventative effect against childhood obesity than the other two single interventions [15]. The present study performed cost–utility and cost–benefit analyses of the NISCOC childhood obesity interventions.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
[]
|
This analysis was conducted from a societal perspective to the health outcome and costs that are attributable to the intervention. The costs of three childhood obesity interventions (CNP intervention, single NE intervention, and single PA intervention) were estimated separately. The QALYs saved from adult (≥ 40 years old) obesity cases prevented were used as the health outcome. The medical and productivity loss costs associated with cases of adulthood obesity that were averted as a result of intervention were estimated. To correspond with the timing of the intervention, all costs were calculated in 2009 RMB, and then translated into 2019 RMB and 2019 US dollars ($1 equals to ¥6.99 in 2019). The imputation began at 10 years old (in 2010). All costs averted and QALYs saved over a 25-year period, 40 to 65 years of age, were calculated and discounted at an annual rate of 3%. Missing data were replaced using imputation methods, some records with missing data of BMI or sex were not included for analysis. This study was approved by the Ethical Review Committee of National Institute for Nutrition and Food Safety. The informed consent voluntarily was signed by participants’ parents or their guardians.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['CR16', 'CR15', 'CR17']
|
In NE intervention schools, one nutrition education handbook was developed [16] for the students, courses on nutrition and health for the students, parents, teachers and health workers were designed separately. Furthermore, “Dietary Pagoda for Chinese people” posters were displayed in the classrooms. In PA intervention schools, the “Happy 10”, which was a classroom-based physical activity program for primary school students, was used [15,17]. Furthermore, students, parents, health workers and teachers received the PA education from the program. The parents were also involved for improving the home environment, including but not limited to sending them physical activity education bulletins. In CNP schools, all above interventions including both NE and PA were implemented. The supervisors from project office went to each center to carry out project supervision during the program period.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['Tab1']
|
The intervention costs were collected through both accounting records and retrospective methods. Both monetary and labor costs were included in the total intervention costs. Monetary costs comprised the monetary investment during program implementation, and the labor costs refer to transforming labor investment into currency. The intervention costs included different funds and resources spent on project initiation, training, implementation, and supervision. The total costs of CNP, NE and PA were ¥398,851.8 ($57,060.3), ¥63,679.4 ($9110.1) and ¥58,345.1 ($8346.9), respectively (Table1).Table 1The intervention costs of three intervention measures in NISCOC (¥ ($))ItemResourceCNPNEPAMaterial and bullet developmentLabor10,579.0 (1513.4)2023 (289.4)1840.5 (263.3)Money43,908.4 (6281.6)8509.8 (1217.4)5258.0 (752.2)Training and experienceLabor1099.6 (157.3)00Money23,622.7 (3379.5)3714.3 (531.4)3379.1 (483.4)Transport feeMoney27,139.3 (3882.6)4942.0 (707.0)4496.0 (643.2)The other cost for implementionLabor247,044.0 (35,342.5)18,865.1 (2698.9)20,059.1 (2869.7)Money45,459.0 (6503.4)25,625.1 (3666)23,312.5 (3335.1)Total398,851.8 (57,060.3)63,679.4 (9110.1)58,345.1 (8346.9)CNPcomprehensive interventions including both nutrition education and physical activity,NEnutrition education,PAphysical activity,NISCOCthe nutrition-based comprehensive intervention study on childhood obesity in China
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['CR15', 'CR18', 'Tab2', 'CR19', 'CR20', 'MOESM1']
|
The cases of overweight and obesity being prevented in this program was calculated according to the intervention effects on prevalence of overweight and obesity [15]. Height and overnight fasting body weight were measured during physical examination in school at baseline and end. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared (kg/m2). Childhood overweight was defined as a BMI between the 85th and 95th percentiles, whereas childhood obesity was defined as a BMI in the 95th percentile or above, according to the age- and sex-specific BMI cutoffs developed by the Working Group for Obesity in China [18]. The cases of overweight and obesity prevented by three interventions after this program was calculated respectively as1\documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$ {N}_{2 ij}={N}_t\left(\left({P}_{1b}-{P}_{1e}\right)-\left({P}_{2b}-{P}_{2e}\right)\right), $$\end{document}N2ij=NtP1b−P1e−P2b−P2e, Where i=m,f, indicating male or female, respectively, j=ow,ob, representing overweight or obesity, respectively, N2ij= Cases of overweight or obesity prevented at the end of this study (at age 10), Nt= The total participants received the intervention, P1b= prevalence of overweight or obesity at baseline in intervention group, P1e= prevalence of overweight or obesity after intervention in intervention group, P2b= prevalence of overweight or obesity at baseline in control group, P2e= prevalence of overweight or obesity after intervention in control group. The cases of overweight and obesity prevented in the program and after 40 years old were shown in Table2. The literature data was used to estimate the probability of progressing from overweight or obese child to obese adult. A two-stage overweight/obesity progression model was used to predict adult cases with obesity by age 40. First, the probability at 10 years old of children developing overweight or obesity at ages 21 to 29 was estimated with literature data [19]. Second, the obesity cases averted at ages 40 to 65 were estimated according to the probability of developing obesity at these ages conditional upon obesity at age 21 to 29 [20]. We assumed that adults who developed obesity by age 40 in this model would remain obese until age 65. The obesity progression model was inAppendix.Table 2The cases of overweight and obesity prevented at the end of the programCNPNEPACases of overweight or obesity prevented after the program (measured)OverweightAll83.926.48.2Boy022.48.2Girl83.94.00ObesityAll46.36.714.5Boy46.301.4Girl06.713.1Cases of obesity prevented ≥40 years old (predicted)Male20.20.03.6Female34.34.90.0CNPcomprehensive interventions including both nutrition education and physical activity,NEnutrition education,PAphysical activity
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['CR20', 'CR21', 'CR22', 'MOESM1']
|
The equations for QALY saved estimation and other parameters in our study were drawn from studies by Brown [20], Erickson [21], and Peeters [22]. QALYs saved are the additional QALYs gained by avoiding adult obesity, the data used for the estimate of QALYs saved was from literature. Activity scales were used in QALY estimation to weight and quality-adjust values, with a health status value ranging from 0.10 (limited with poor health) to 1.00 (no limitations with excellent health). The equation used to estimate QALYs saved was inAppendix.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['CR20', 'CR23', 'MOESM1']
|
The averted costs from productivity loss included those costs averted that were associated with losses attributed to impaired work ability for obesity-related morbidity and mortality. The life expectancy, mortality, and additional sick days for 40-year-old individuals with and without obesity who die before 65 were calculated according to literature [20], which used 2002 American National Health Interview Survey data. Wages in the six cities where the program was implemented were used to place value on the productivity lost due to obesity-related illness. The mean annual and daily earnings of full-time workers in the six cities were calculated according to data from the National Bureau of Statistics of China [23]. Equations used to estimate the costs of labor productivity loss per participant were inAppendix.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['CR24', 'CR25', 'CR26', 'CR27', 'MOESM1']
|
The prediction model for medical costs averted was developed following Brown and Wang [24]. The data used to estimate the medical costs averted after obesity avoided were drawn from Zhao’s study [25], which calculated the total medical costs from four chronic diseases—hypertension, type 2 diabetes, coronary heart disease, and stroke—attributable to overweight and obesity in China. These costs were estimated using data from the 2002 National Nutrition and Health Survey and 2003 Third National Health Service Survey [26,27]. The formulas for medical costs averted through adult obesity prevention were inAppendix.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
[]
|
Cost–utility and cost–benefit analyses were applied on the outcomes of the interventions. A cost–utility ratio (CUR), which was defined as the net intervention costs per QALY saved by the intervention, and cost–benefit ratio (CBR), defined as the ratio of intervention costs to the sum of medical and productivity loss costs averted, were used for intervention assessment. CUR can be written as2\documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$ CUR=\left(C-{N}_{1i}{B}_3\right)/{N}_{1i}Q $$\end{document}CUR=C−N1iB3/N1iQand the CBR can be written as3\documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$$ CBR=C/\left({N}_{1i}B+{N}_{1i}{B}_3\right) $$\end{document}CBR=C/N1iB+N1iB3where C= cost of intervention, N1i= number of cases of adult obesity prevented, Q= QALYs saved per case of obesity prevented, B= productivity loss costs averted per case of obesity prevented, B3= medical costs averted per case of obesity prevented. The incremental cost-effectiveness ratio (ICER), the difference in cost (USD) divided by the difference in utility (QALYs gained) between the two interventions, was calculated.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
[]
|
Sensitivity analysis was conducted to evaluate the extent to which the results were dependent on the intervention effect and cost parameters used and assess the robustness of cost-utility. A Bayesian multivariate probabilistic sensitivity analysis was performed with 10,000 Monte Carlo simulations, using physical activity intervention as the reference arm. For costs, a gamma distribution was used, and for transition probabilities and utilities a beta distribution was used.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['Tab3', 'Tab4', 'Tab3', 'Tab4', 'Fig1']
|
The results of the cost–utility and cost–benefit analyses are displayed in Tables3and4, respectively. The analyses estimated that 30.3 QALYs saved and cost of ¥11,505.9 ($1646.0) per QALY by the CNP intervention, 2.8 QALYs saved and cost of ¥21,316.4 ($3049.6) per QALY by the NE intervention, and 1.9 QALYs saved and cost of ¥28,417.1 ($4065.4) per QALY by the PA intervention. Compared with PA intervention, the ICERs were ¥10,335.2 ($1478.6) and 4626.3 ($661.8) for CNP and NE respectively (Table3). The CBR was ¥1.2, 0.7, and 0.4 benefits per ¥1 cost for CNP, NE, and PA interventions, respectively. Net estimated savings were achieved only through CNP intervention, amounting to ¥73,659.6 ($10,537.9) (Table4). Our probabilistic sensitivity analysis revealed that in most of the simulations, the CNP remained cost-effective with 1.0 at a willingness-to-pay threshold of $5000/QALY. (Fig.1).Table 3The cost-utility analysis for 3 interventionsCNPNEPAQALY savedBoy10.80.01.9Girl19.52.80.0Total30.32.81.9Intervention cost (C, ¥ ($))398,851.8 (57,060.3)63,679.4 (9110.1)58,345.2 (8346.9)Medical Care Costs Averted (B3, ¥ ($))50,327.0 (7199.9)4511.5 (645.4)3341.0 (478.0)CUR (¥ ($))11,505.9 (1646.0)21,316.4 (3049.6)28,417.1 (4065.4)ICER (¥ ($))10,335.2 (1478.6)4626.3 (661.8)–CNPcomprehensive interventions including both nutrition education and physical activity,NEnutrition education,PAphysical activity,Ccost,CURcost–utility ratio,ICERincremental cost-effectiveness ratioTable 4The cost-benefit analysis for 3 different interventionsIntervention typeIntervention costs (¥ ($))Costs of lost productivity averted (¥ ($))Medical care costs averted (¥ ($))Net benefit (¥ ($))Cost-benefit ratioCNP398,851.8 (57,060.3)422,184.4 (60,398.3)50,327.0 (7199.9)73,659.6 (10,537.9)1:1.2NE63,679.4 (9110.1)42,654.0 (6102.1)4511.5 (645.4)−16,513.9(− 2362.5)1:0.7PA58,345.2 (8346.9)22,028.9 (3151.5)3341.0 (478.0)−32,975.3(− 4717.5)1:0.4CNPcomprehensive interventions including both nutrition education and physical activity,NEnutrition education,PAphysical activityFig. 1The cost-effective acceptability curve for three interventions
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
['CR15', 'CR28', 'CR30', 'CR31', 'CR32', 'CR33', 'CR24', 'CR34', 'CR20', 'CR35', 'CR19', 'CR22', 'CR24']
|
Though two single interventions were negative for the net benefit, all three school-based intervention measures for childhood obesity prevention were cost-effective by cost-utility in this study. Economic analyses revealed that the comprehensive intervention was cost saving, and the cost per QALY saved was less than that of the other two interventions. Effect evaluation of this childhood obesity intervention indicated that comprehensive childhood obesity intervention could significantly control childhood obesity [15]. To perform economic evaluation of obesity interventions, we implemented this study using a life-course approach. To our knowledge, this is the first study to perform cost–utility and cost–benefit analyses of school-based childhood obesity interventions in China. Although the findings are particularly relevant to public health decision-makers in China, they are also valuable for other countries in similar situations. The comprehensive intervention was net beneficial, whereas the other two were not. We therefore performed the sensitivity analysis on only the comprehensive intervention. Further promotion of the comprehensive intervention could increase the CBR to ¥1.50 benefit per 1 cost. This indicates that comprehensive intervention for preventing childhood obesity could become more beneficial and reduce development costs in further expansion of the program, thus improving the benefit. As noted, few evaluations of childhood obesity interventions include cost–utility and cost–benefit analyses and thus cannot easily be compared with ours; moreover, differences in the age of participants, country, intervention components, and outcome measures make comparison with other studies difficult. A threshold for cost-effectiveness is generally set to identify sufficiently effective interventions. Although there is no universally accepted standard, several thresholds have been used. Some experts consider health-related programs with CUR < US$30,000 per QALY saved are generally cost-effective [28–30]. The most commonly used cost-effectiveness thresholds are those based on a country’s per capita gross domestic product (GDP) [31]. According to the World Health Organization, interventions with an incremental cost-effectiveness ratio (ICER) per QALY less than one GDP per capita can be considered highly cost-effective. Those with an ICER 1–3 times GDP per capita can be considered cost-effective, and those with an ICER > 3 times the GDP per capita are not considered cost-effective [32]. China’s GDP per capita was ¥29,992(2019 $5599.4) in 2010 [33]. According to the aforementioned standards, the comprehensive intervention and two single interventions were cost-effective, and the comprehensive intervention was the most cost-effective. Compared with physical activity intervention, the ICERs for comprehensive intervention (US$1478.6/QALY) and nutrition education (US$661.8/QALY) were both lower than one GDP. The Planet Health program was a 2-year school-based intervention designed to reduce obesity rates among middle school students in the United States, but the prevalence of obesity only among girls was reduced significantly. The cost was US$4305 per QALY saved and the net savings was US$7313 to society among girls [24]. Although all scenarios were cost-effective and most were cost saving, compared with our results, the cost per QALY saved was greater. One randomized controlled trial enrolling 80 participants (aged 8–19 years) with severe obesity was implemented to conduct an economic evaluation in the Netherlands. Participants received an intensive 1-year lifestyle program with an inpatient period of either 2 months (short-stay group) or 6 months (long-stay group). The program focused on nutrition, PA, and behavior change and required active participation from parents and caregivers. Although the short-stay treatment was considered more cost-effective, the results indicated no difference in QALYs saved between the groups after 24 months [34]. The coordinated approach to child health (CATCH) intervention program promoted healthy eating and PA in US elementary schools between 2000 and 2002. CATCH was cost-effective and net beneficial, costing $900 per QALY saved, and the net benefit was $68,125 (2004 US dollars) [20], which was more cost-effective than our intervention. Generally, childhood obesity prevention is considered more cost-effective than adult obesity treating, and our study provides evidence to support this. Treating adult obesity with the drugs orlistat or sibutramine or through gastric bypass surgery costs US$8327, US$9299, and US$5000–$35,600 per QALY, respectively, and Wheeling Walks, a behavior modification program for sedentary adults, costs $14,286 per QALY [35]. These treatments were much more costly than the comprehensive childhood intervention evaluated here. Forecasting methods were used to predict the long-term obesity prevention effect [19–22,24]. By taking into account the natural risk of obesity in general cohort, it could exclude the probability of obesity under natural transition to predict the obesity processing rate in adulthood. In addition, the predictions of QALYs saved, medical cost averted and productivity losses averted were from the life perspective, which made the prediction results closer to the real situation. This study has some limitations to acknowledge. First, many factors of this cost-effectiveness analysis are unknown, such as how effectively participants-maintained weight loss over time. Second, some parameters used in QALY estimation were drawn from other countries. These countries may differ from China; however, no referred studies of a Chinese cohort were available. Third, the benefits evaluated were not comprehensive. The health benefits that may arise from improvements in health knowledge, attitudes, self-efficacy, and leadership of parents, teachers, and school canteen staff were not included. Therefore, our CUR per QALY gained estimates may be conservative.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC7585177']
|
['33097026']
|
[]
|
According to our model analysis, school-based comprehensive childhood obesity intervention is cost-effective for obesity prevention and reduction of lifetime chronic disease risk. Such school-based comprehensive programs are likely to reduce the public health care burden from obesity and chronic diseases.
|
PMC7585177
|
Research Article
| null | 33,097,026
|
Cost-utility and cost-benefit analyses of school-based obesity prevention program
|
Xu H, Li Y, Du S, Zhang Q, Liu A, Sun J, Ma G.
|
BMC Public Health. 2020 Oct 23;20(1):1608. doi: 10.1186/s12889-020-09718-x.
|
Xu H
|
BMC Public Health
| 2,020
|
2020/10/24
|
PMC7585177
| null |
10.1186/s12889-020-09718-x
|
oa_comm/txt/all/PMC7585177.txt
|
33357c9d4ad0c461cd299c2f4199a200
|
BMC Public Health. 2020 Oct 23; 20:1608
|
2021-06-19 06:25:18
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR1', 'CR2', 'CR3', 'CR4', 'CR5', 'CR4', 'CR6', 'CR7', 'CR8', 'CR9', 'CR9', 'CR10', 'CR10', 'CR3', 'CR8', 'CR11', 'CR13', 'CR9', 'CR10', 'CR14']
|
Diabetic foot ulceration is a complex condition, which requires regular clinical assessment, and wound management to prevent deterioration or infection with considerable cost to the National Health Service (NHS). The cost of wound care alone can range from £2140 to £8800 per diabetic foot ulcer, with much greater cost if this leads to amputation [1]. Foot orthoses are recommended to reduce forefoot plantar pressures in people with diabetes [2] and reducing peak plantar pressure to below 200 kPa is demonstrated to reduce the risk of re-ulceration [3]. The supply chain of customised foot orthoses includes an initial clinical decision making process to evaluate risk and to inform the specification and design of a product, followed by manufacture within physical (fit to shoe and fit to foot) and time constraints. This is driven by foot parameters (e.g. foot shape) and clinical information (e.g. risk status), but is also influenced by pragmatic issues such as material availability, cost and procurement constraints [4] and footwear choices made by patients [5]. These factors are known to influence the effects of foot orthoses and thus each part of the supply chain may impact on foot orthoses efficacy. In a traditional or manual, supply chain foot shape is captured using plaster of Paris or foam impression boxes [4]. However, in a digital supply chain the foot surface is digitally scanned, a processe that is more repeatable but produces different orthoses geometries than the manual techniques [6]. Owings et al. [7] integrated plantar pressure data with foot shape in a digital orthoses supply chain to produce superior forefoot off-loading. Other work used computational models to optimise pressure relief [8]. These digital approaches are impossible to implement using traditional supply chain processes, which rely on manual identification of anatomical features (e.g. metatarsal heads). It follows that if supply chains use different data and processes to inform orthoses design, then pressure relief might also vary. There are potential process benefits of using digital rather than traditional supply chains. Orthoses designs and processes are quantified, easier to control, adjust, and repeat, and data and information are permanently recorded and portable. Digital processes allow for standardised templates and design steps which can reduce the number of manual tasks and could be time saving if automated. There is also less physical waste and reduced space requirements (plaster, impression boxes, and storage of these). These potential advantages are only valuable, however, if the efficacy of the orthoses is not inferior to that of orthoses made through traditional manual processes. Whilst reduction in plantar pressure is the primary objective in using off-loading foot orthoses, this is assumed to be a pre cursor to reduced risk of ulceration and thereafter improvement in quality life [9]. Few studies have included these measures in their evaluation of foot orthoses designs and supply, though their inclusion has been advocated [9,10]. Digital processes also involve a different financial model, with need for equipment, software, space, and staff time and training at both clinical and production sites. Any benefits accrued, whether in orthosis efficacy or supply process, must justify any additional costs. Few studies have evaluated cost issues and none have considered these data alongside plantar pressure and quality of life data to evaluate the difference between traditional and digital foot orthoses supply chains. Only Paton [10] measured plantar pressure changes, quality of life and some aspects of supply chain economics, but this compared prefabricated to custom made foot orthoses for people with diabetes. Comparisons of digital and traditional foot orthoses supply processes have focused on the resultant orthoses geometry and immediate pressure relief, [3,8,11–13], with longitudinal studies limited to comparisons between traditional and sham or prefabricated orthoses [9,10,14]. The aim of this study was to compare, over 6 months, plantar pressure, health-related quality of life and health service use in patients receiving orthoses through a digital supply chain compared to a traditional orthotic supply chain.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
[]
|
This was a pragmatic parallel group randomised controlled trial with repeated measures assessing non-inferiority and cost-consequence analysis of traditional and digital foot orthoses production methods. Testing was conducted at the Royal Blackburn Hospital (East Lancashire NHS Trust) subsequent to ethical approval from institutional (HSCR15–89) and health service committees (REC ref.: 15/YH/0392) (registered trial, ISRCTN10978940).
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
[]
|
The primary outcome was the percentage reduction in peak plantar pressure at the site of highest forefoot plantar pressure. It was not ethical to provide a control orthotic on a longitudinal basis due to the high risk of ulceration in the cohort and as such a non-inferiority analysis was conducted. Secondary outcomes were the number of regions of interest (ROI) where plantar pressure was > 200 kPa; the percentage peak pressure reduction for all ROI; self-rated health-related quality of life and capability at 6 months; and service use costs at 6 months.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR15', 'CR11', 'CR13', 'CR16', 'MOESM1']
|
The use of the non-inferiority approach outlined here is in accordance with the FDA guidance for industry [15]. A non-inferiority margin (NIM) of 11.29% was established as a fixed margin in advance of data collection. The NIM was based on a pooled data analysis of prior studies which compared foot orthoses to flat control insoles [11,13,16], with an orthotic effect on peak pressure of 14.5% (95% Confidence Interval 11.29–17.77%). To ensure that the NIM represented the entire effect of orthoses in terms of pressure reduction the lower bound of the Confidence Interval (CI) was used, without the application of a clinically acceptable level of difference [see Additional file1].
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR17', 'CR18']
|
A priori power analysis for a non-inferiority test was based on data from previous work (n= 41) demonstrating an effect size of − 11.9% (standard deviation of difference = 15.2%) [17]. A sample size of 22 participants per arm was calculated (0.05 significance level, 80% power). Sample size was calculated using online software [18].
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR19']
|
Randomisation sequence was generated using a randomization plan generated using online software [19], in which 60 subjects were randomised into 10 blocks. This sequence was generated by a researcher independent of the trial team and a series of sealed envelopes were produced.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Fig1', 'Tab1', 'CR20', 'Tab2', 'CR21', 'CR22', 'CR23', 'CR22', 'CR23', 'MOESM2']
|
Records of existing service users were screened to identify patients with diabetes, peripheral neuropathy and a moderate/high risk of ulceration. Potential participants were invited to a screening appointment (Fig.1).Fig. 1Consort Diagram for progression of participants through the study The study comprised three visits: (1) potential participants were screened against inclusion/exclusion criteria (Table1) by an orthotist and thereafter provided informed consent. Demographic data were collected and foot risk status determined as either moderate (one of; loss of sensation, peripheral vascular disease or signs of callus or deformity) or high (previous ulceration or amputation or more than one moderate risk factor present) for each foot using the SCI-DC framework [20] (Table2). A foot related medical history was recorded (e.g prior ulceration, minor surgery, other interventions).Table 1Screening CriteriaInclusion CriteriaExclusion CriteriaAged between 40 and 85 yearsHave had prior foot or ankle surgeryHave Diabetes diagnosed by a medical practitionerHave had major injury to the lower limb (e.g. fracture)Have modular or bespoke footwearaHave had prior or active chronic foot or leg ulceration within last 2 yearsHave all normal foot structures presentRequire heel pressure reduction interventionBe able to walk without a stick for 100 mHave had prescription foot orthoses via the department in the last 12 monthsHave sensory neuropathybAbsence of foot pulses assessed via Doppler or palpationCapable of providing informed consent to participateComorbidities (Ischaemia, Renal, Charcot Arthropathyaprovided by the orthotics department,bassessed by 10 mg monofilament and vibratory perception at less than 3 out of 10 sites on the foot and ankleTable 2Point of supply and DemographicsTraditional Supply ChainDigital Supply ChainPatient Demographicsn2626Age(Years)61.4±10.066.3±10.5BMI(kg/m3)31.3±8.631.1±5.0Gender(M/F)23/322/4Clinical FactorsHistory of Smoking(No/Yes)17/916/10Previous Ulceration(No/Yes)12/1417/9Palpable foot pulsesa(No/Yes)24/222/4Foot Risk Status(Moderate/High)12/1414/12Neuropathic Symptoms Score(0–4)2.3±1.42.7±1.3Footwear and OrthoticsDuration in Orthotics Service(Years)6±4.56.4±4.9Footwear Used(Stock/Modular/Bespoke)5 / 19 / 21 / 23 / 2aPulses were detectable by Doppler in all cases (2) At a second visit the appropriate orthoses were fitted by an orthotist. Plantar pressure data was collected (Pedar insoles, Novel, Germany) whilst participants walked in their orthotic insoles and a control insole (flat 3 mm Poron). The order of testing was randomised. Walking speed was established using timing gates (Brower Timing Systems, Draper, Utah, USA) prior to data collection and maintained within +/− 5% [21]. A minimum of three 10 m walks were recorded in each of the two conditions, yielding approximately 30 steps per foot after excluding periods of acceleration/deceleration. The EQ-5D-5 L and the ICECAP-A were used to assess health-related quality of life (HRQoL) [22] and capability (well-being beyond health) [23] respectively. The EQ-5D is a generic, validated HRQoL measure [22]. The EQ-5D-5 L was analysed to produce an index score between 0 (state of death) and 1 (perfect health). The ICECAP-A is a validated capability measure focussing on well-being beyond health and is scored from 0 (no capability) to 1 (full capability) [23]. Participants took the orthoses home with instructions for use daily in everyday footwear. Adherence to use of orthoses was monitored by monthly telephone follow-up to ensure regular use with the intention to exclude participant data from subsequent analysis where there is an apparent substantial lack of use of the orthosis. (3) At a 6 month visit plantar pressure, EQ-5D-5 L, ICECAP-A and NHS service use was measured. NHS service use was examined using a client service receipt inventory (CSRI) and participants were asked to recall the last 6 month use of NHS services relating to foot conditions [see Additional file2]. To investigate economic differences in the two supply chains, clinical process times (excluding research activities) were documented and compared as part of a cost analysis.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Tab3', 'Tab3']
|
Orthotics in both supply chains were modifications of a foot size specific template. The template included: medium density EVA rearfoot (30–40 ShoreA) with minimum 6 mm thickness under the heel; a medial arch profile and heel cup (10 mm). The forefoot (area distal to the end of the medial arch) was a minimum of 6 mm Poron (20 ShoreA). Modifications to relieve pressure (cavities, material substitutions or additions) were made on a patient by patient basis to reflect real practice (Table3). All orthoses were finished with a leather top cover.Table 3Modifications to OrthoticsType of Orthotic ModificationTraditional Supply ChainDigital Supply ChainDesign ModificationLocal removal of material11Local softening of material23Addition of metatarsal pad or bar2Addition of Wedge or Skive2Maintenance and RepairRepair or Glue of top cover149Replacement of top cover1Insole Damaged/Replaced1Design modifications were made on a patient by patient basis to relieve pressure. Maintenance and repair was made when required to reflect normal practice within the Orthotics service For the traditional supply chain a foam impression box was used to capture foot shape at visit 1 and a written prescription form completed. Devices were manufactured by filling the impression box with plaster, heat moulding material to the cast, and hand finishing. Manufacture was external to the orthotics department and blind to the research study (Beagles Orthopaedic, UK). For the digital supply chain foot shape was captured using a weight bearing foot scan at visit 1 (Inescop, Spain). Static plantar pressure distribution data was recorded during barefoot standing (F-Mat, Tekscan, USA). These data were integrated in CAD software (iCAD Pan, Inescop, Spain) to allow adjustment of the orthotic template (from Salford Healthcare Ltd) by the orthotist on a patient by patient basis. Static pressure data was used to adjust the position of modifications (Table3). Digital models were used for CNC milling (Victor 1200, UK) and orthoses finished by hand. To allow for non-inferiority assessment a flat 3 mm Poron insert very similar to that used in studies which established efficacy of orthoses was used as a control.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR20', 'CR3', 'CR3']
|
Data for the foot which had the highest clinical risk status based on SCI-DC framework [20] was selected for analysis, when both feet had equal risk status the left foot data was used. Plantar pressure data was segmented with Matlab (MatWorks, Inc. Version 9.0, USA) into hallux, 1st metatarsal head, and metatarsal heads 2–5, consistent with [3]. Peak pressure was calculated for each region in each step and the mean calculated by averaging across all footsteps. For each participant the site of highest peak pressure in the control insole (flat Poron insole) was identified and compared to peak pressure at the same site when wearing the orthotic to determine an orthotic effect (% increase or decrease in peak pressure). For each participant all regions which had a mean peak pressure > 200 kPa in the control insole were designated as regions of interest (ROI) [3], with each participant having 0–3 ROIs. For each ROI the orthotic effect on peak pressure was determined.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR24', 'CR25', 'CR24']
|
Service use was costed using published national unit costs available at the time of data collection [24,25]. Staff costs were calculated using NHS Band 6 point 25 and Band 5 point 19, inflated by on-costs, overheads and capital overheads, as recommended by Curtis et al. [24]. Cost of the orthoses were £60 for traditional and £50 for digital supply chains.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR26', 'CR23']
|
The EQ-5D produces an index score between 0 (state of death) and 1 (perfect health). At the time of analysis, a validated UK value set was not available to score the EQ-5D-5 L, and therefore, a crosswalk value set was used to calculate utility values based on the EQ-5D-3 L scoring system [26]. ICECAP-A was used to produce a total capability score from 0 (no capability) to 1 (full capability) [23].
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR27', 'Fig1', 'Fig1']
|
Plantar pressure data was assessed per-protocol (completers) using SPSS (IBM SPSS Statistics: Version 24, USA). This approach ensured that comparisons made between groups at set time points were equivalent in terms of regular orthoses use. This further ensured that factors such as material performance, known to impact on biomechanical performance [27] and compliance did not bias the results. Post screening 57 participants were randomised to the digital (n= 28) or traditional (n= 29) supply chains, allowing for some expected drop out in each group. At fitting appointment 53 participants remained in the study (26 digital, 27 traditional supply chain) (Fig.1). At the 6 month visit 42 participants (19 digital, 23 traditional supply chain) had used the devices regularly, 11 had withdrawn (5 due to adverse events (4 digital, 1 traditional) and 6 lost to follow up (3 digital, 3 traditional) (Fig.1). Peak plantar pressure data in the control and orthotic insoles was not normally distributed.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR28']
|
Within supply chain analysis was conducted to compare control to orthotic using Wilkoxon signed ranks test. Between supply chains group variance was assessed using the Mann-Whitney U test, comparing control-to-control and orthotic-to-orthotic. Orthotic effect was calculated as the percentage change in peak pressure from control to orthotic insoles, this data was normally distributed and was compared between supply chains using independent t-tests. For each supply chain, the orthotic effect was assessed for non-inferiority against a pre-established NIM [28]. To establish non-inferiority the lower bound of the two-sided CI for the orthotic effect was compared to the NIM (11.29%). If the lower bound of CI is greater than the NIM then the orthotic effect is not inferior to the established effect of orthoses based on the literature.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR29', 'CR30']
|
A cost-consequence analysis was undertaken and service use was compared between the two supply chains. Mean differences in costs between the two interventions were calculated using nonparametric bootstrapping, and run on 5000 iterations, to produce 95% confidence intervals around these differences [29]. The analysis was undertaken from an NHS perspective. NICE recommend an NHS and personal and social services perspective, as the societal perspective risks bias against individuals who are retired or unable to work. The NHS perspective focuses on costs and benefits directly associated with health care treatment, disease management and associated administrative costs [30]. Discounting was not undertaken as the length of interventions did not exceed 12 months. Independent samples t-tests were used to assess differences in mean change (point of supply-6 month) in HRQoL and wellbeing between the two trial arms.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Fig1', 'Tab2', 'Tab4', 'Tab5']
|
Over the 6 months six participants were lost to follow up (3 in each arm), there were 4 unrelated adverse events (1 traditional, 3 digital) and one foot ulceration at a ROI (digital arm) a further 1 dataset was excluded from pressure data analysis due to corrupted files Fig.1. The groups were comparable in terms of clinical and risk status at the start of the trial (Table2) and there was no statistically significant difference between peak pressures for the control condition for either site of highest pressure or ROI analysis (Tables4and5), suggesting a comparable pressure profile across both groups. After 6 months a significantly increased peak pressure at the site of highest pressure for the digital group was found in both control and orthotic conditions compared to the traditional Group (p< 0.01), suggesting a change to the pressure profile.Table 4Pressures at ROIsnControlOrthoticOrthotic EffectMean (SD)Mean (SD)Mean (SD)95% CIWilcoxon Rank(kPa)(kPa)(%)(LB - UB)ZpTraditional Supply Chain0 M42307.92 (84.87)263.56 (98.19)↓13.85 (20.24)(7.55–20.16)−3.3950.0016 M25276.53 (53.78)240.96 (69.94)↓11.94 (24.11)(1.98–21.89)−2.7040.007Digital Supply Chain0 M42308.88 (88.93)244.08 (87.83)↓20.52 (15.79)(15.54–25.50)¥−5.2080.0006 M32298.95 (84.57)271.75 (80.49)↓8.01 (18.69)(1.27–14.75)−2.4310.015DifferenceT-DM-W UpT-DM-W UpT-Dtp95% CI0 M−0.968800.98619.4810010.287−6.671.675*0.098(−1.26 to 14.59)6 M−22.423430.359−30.792970.0983.930.693**0.491(−15.28 to 7.43)LBLower Bound, ↑: Increase in pressure for custom orthotics compared to flat control, ↓: Decrease in pressure for custom orthotics compared to flat control. Statistical significant difference between control and orthotic was assessed via related samples Wilcoxon Rank test ǂ:p< 0.05, ф:p< 0.01. T-D: Mean for Traditional group minus Mean for Digital Group. Non-Inferiority was assessed against a predefined margin of 11.29%. ¥:Lower bound of the 95% Confidence interval for the intervention effect was greater than the NI marginTable 5Site of Highest PressurenControlOrthoticOrthotic EffectMean (SD)Mean (SD)Mean (SD)95% CIWilcoxon Rank(kPa)(kPa)(%)(LB - UB)ZpTraditional Supply Chain0 M26309.67 (101.33)261.52 (110.67)↓14.91 (20.56)(5.89–22.87)−2.6790.0076 M22251.12 (64.98)209.84 (63.83)↓16.71 (17.25)(9.06–24.35)−3.6520.000Digital Supply Chain0 M26318.95 (109.78)240.03 (113.36)↓24.43 (20.18)(16.27–32.58)¥−4.0260.0006 M19321.32 (90.33)279.74 (90.05)↓12.41 (20.23)(2.65–22.16)−2.3340.020DifferenceT-DM-W UpT-DM-W UpT-Dtp95% CI0 M−9.283550.75621.492790.280−9.520−1.695**0.096(−20.80 to 1.76)6 M−70.203160.005−69.903120.0074.3000.726**0.473(−7.72 to 16.31)LBLower Bound, ↑: Increase in pressure for custom orthotics compared to flat control, ↓: Decrease in pressure for custom orthotics compared to flat control. Statistical significant difference between control and orthotic was assessed via related samples Wilcoxon Rank test ǂ:p< 0.05, ф:p< 0.01. T-D: Mean for Traditional group minus Mean for Digital Group. Non-Inferiority was assessed against a predefined margin of 11.29%. ¥:Lower bound of the 95% Confidence interval for the intervention effect was greater than the NI margin
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Tab4', 'Tab5', 'Fig2']
|
The orthotic effect in the traditional supply chain at the site of highest pressure and all ROI was inferior to the NIM at point of supply (Tables4and5). The orthotic effect of the digital supply chain was non-inferior to the NIM at point of supply and was superior (p< 0.1) to the traditional supply chain. However, at 6 months, the orthotic effect of both the traditional and digital supply chains was inferior to the NIM (Fig.2).Fig. 2Non-inferiority assessment of Orthotic Effect at Site of Highest Pressure. Error bars indicate 2-sided 95% CIs. The dashed line at x = − 11.29 indicates the non-inferiority margin (NIM). The yellow tinted region to the right of x = − 11.29 indicates the zone of inferiority. Digital at 0 M lies wholly left of zero indicating a reduction in pressure compared to control and wholly to the left of the NIM indicating that this is non-inferior. Digital at 6 M, Traditional at 0 M and Traditional at 6 M all lie left of zero indicating a reduction in pressure with orthotics but the lower boundary of their confidence intervals are to the right of the NIM meaning non-inferiority is not demonstrated
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Tab4', 'Fig3']
|
At the point of supply and at 6 months the effect of orthoses on peak pressure was statistically significant (p< 0.05), demonstrating a reduction of pressure with the orthotic insoles in both supply chains vs control insoles (Table4). At point of supply, peak pressure at the site of highest pressure was reduced below 200 kPa in 17 and 39% of participants in the traditional and digital groups respectively (Fig.3). This orthotic effect was not statistically significantly different between supply chains at the point of supply or 6 months.Fig. 3Orthotic effect at Site of Highest Pressure within the forefoot. Data for orthotic effect on peak pressure data at site of highest pressure in each particiant, ordered based on pressure measured without orthotic (control condition). Initial peak pressure recorded without orthotics (a) Digital supply chain at point of supply, (b) Digital Supply Chain at 6 Months, (c) Traditional supply chain at point of supply, (d) Traditional Supply Chain at 6 Months
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Tab5', 'Fig4']
|
For both the traditional and digital groups over 50% of regions assessed were considered to be high risk (> 200 kPa). The use of orthoses significantly reduced peak pressure by > 10% at point of supply and > 8% at 6 months for ROIs in both the traditional and digital supply chains (p < 0.05) (Table5). At point of supply, orthoses reduced the number of ROIs by 21% for the traditional group and 33% for the digital group. After 6 months, taking into account participant dropout, orthoses reduced the number of ROIs by 24% for the traditional group and 16% for the digital group (Fig.4).Fig. 4Orthotic effect on Region of Interests (Peak Pressure > 200 kPa) within the forefoot. Data for orthotic effect on peak pressure from all regions in which peak pressure was over 200 kPa in control condition, ordered based on pressure measured without orthotic (control condition) . Initial peak pressure recorded without orthotics (a) Digital supply chain at point of supply, (b) Digital Supply Chain at 6 Months, (c) Traditional supply chain at point of supply, (d) Traditional Supply Chain at 6 Months
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Tab6']
|
Participants in the traditional supply chain showed slightly better overall HRQoL and self-rated health status effects compared to the digital supply chain at 6 month follow-up, but vice versa for capability (Table6). The changes were not statistically significantly different between the supply chains.Table 6HRQoL and wellbeing: Effectiveness results and statistical significance for quality of life measuresTraditional Supply ChainaDigital Supply ChainbDigital v TraditionalPoint of supply (SD)6 month (SD)Mean change (SD)Point of supply (SD)6 month (SD)Mean change (SD)Mean effect at 6 monthsIndependent samplesttestEQ-5D0.645 (0.728)0.685 (0.261)0.040 (0.190)0.728 (0.239)0.671 (0.227)−0.057 (0.191)−0.097t(40) = 1.644,p= 0.108EQ-VAS63.91 (23.97)62.65 (21.13)−1.26 (19.78)71.05 (18.83)65.26 (19.33)−5.79 (21.62)−4.529t(40) = 0.708,p= 0.483ICECAP-A0.730 (0.181)0.693 (0.195)−0.037 (0.105)0.801 (0.173)0.829 (0.132)0.028 (0.107)0.064t(38) = −1.908,p= 0.064aN= 23 for EQ-5D and EQ-VAS, 22 for ICECAP-A,bN= 19 for EQ-5D and EQ-VAS, 18 for ICECAP-A. Due to a lack of statistical significance there is no indication that either intervention was effective at improving HRQoL, health status or capability in this study
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Tab7']
|
The traditional supply chain cost an average of £72.63 per participant and the digital £85.68 (difference of £13.17, Table7). The digital supply chain took over three times longer (53:10 min [23:08] versus 17:39 [11:04] respectively) and led to differences in staff time costs (£12.63 for traditional versus £35.68 for digital), partly offset by the higher orthotic cost in the traditional supply chain (£60 versus £50 in the digital).Table 7Staff time and costs for the two supply chainsStaff activityMean staff timea(SD)Mean staff CostMean total costbTraditional supply chain (n= 17)Clinical Assessmentc05:18 (01:46)£3.79Foot Shape Capturec00:56 (00:40)£0.67Written Prescriptionc01:49 (01:38)£1.31Medical Notesc09:32 (09:43)£6.82Modify Impression Boxc00:04 (00:15)£0.04Total17:39 (11:04)£12.63£72.63Digital supply chain (n= 18)Clinical Assessmentc06:43 (01:56)£4.81CAD Designc17:07 (11:09)£12.25Medical Notesc11:37 (11:21)£8.31Foot Shape Captured06:17 (04:56)£4.49Configure Scansd05:17 (03:33)£3.78Align Scansd06:10 (03:42)£4.41Total53:10 (23:08)£35.68£85.68atime format minutes:seconds (mm:ss),bincluding orthotic cost of £60 for TSC and £50 for DSC,cActivity completed by NHS Orthotist,dActivity completed by NHS Technician
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['Tab8']
|
On average participants in the traditional supply chain accessed an additional £194 worth of NHS services in the 6 month follow-up period (Table8) compared to those in the digital supply chain, though this was not statistically significant. Differences in inpatient service use explain the variance. Two participants’ accessed inpatient services, both in the traditional supply chain arm, and incurred high costs (£2116.04 each). Removing inpatient service use reduces the overall mean difference in service use costs to £17.79, remaining higher in the traditional supply chain arm.Table 8NHS service use costs relating to foot conditions or diabetes over 6 month follow-up periodService useTraditional Supply Chain (n= 24)Digital Supply Chain (n= 20)Mean difference (95% CIa)3 month (SD)6 month (SD)Total (SD)3 month (SD)6 month (SD)Total (SD)PRIMARY CARE AND COMMUNITY SERVICESGeneral Practitioner£22.46 (52.55)£28.58 (53.42)£51.04 (89.63)£4.90 (15.08)£30.63 (67.86)£35.53 (70.86)↓-£15.52Practice Nurse£5.58 (10.41)£6.75 (13.67)£12.33 (16.79)£3.91 (9.77)£5.58 (14.26)£9.49 (15.91)↓-£2.84District Nurse£0.93 (4.56)£0.00£0.93 (4.56)£0.00£0.00£0.00↓-£0.93Diabetes Specialist Nurse£0.00£3.39 (12.36)£3.39 (12.36)£4.38 (10.94)£6.25 (12.66)£10.63 (15.72)£7.24Chiropodist£9.00 (15.60)£13.13 (20.65)£22.13 (26.02)£7.50 (12.14)£11.40 (9.67)£18.90 (15.33)↓-£3.23Dietician£0.79 (3.88)£0.00£0.79 (3.88)£1.43 (6.37)£1.90 (6.20)£3.33 (8.56)£2.53Other£0.00£2.05 (7.09)£2.05 (7.09)£0.49 (2.20)£0.00£0.49 (2.20)↓-£1.56Total£38.76 (58.87)£53.89 (65.72)£92.65 (99.49)£22.60 (27.39)£55.76 (81.55)£78.36 (86.74)↓-£14.29 (−67.28 to 22.19)SECONDARY CARE: OUTPATIENTOrthotics Department£8.92 (30.21)£17.83 (40.73)£26.75 (27.33)£5.35 (23.93)£5.35 (23.93)£10.70 (32.93)↓-£16.05Chiropodist£1.50 (7.35)£0.00£1.50 (7.35)£0.00£0.00£0.00↓-£1.50Dietician£0.00£0.00£0.00£0.95 (4.25)£0.95 (4.25)£1.90 (8.50)£1.90Dietetics Department£0.00£0.00£0.00£3.45 (15.43)£0.00£3.45 (15.43)£3.45Diabetes Consultant£0.00£0.00£0.00£12.60 (56.35)£0.00£12.60 (56.35)£12.60Other£1.50 (7.35)£6.00 (13.71)£7.50 (18.32)£3.60 (11.08)£0.00£3.60 (11.08)↓-£3.90Total£11.92 (30.99)£23.83 (44.26)£35.75 (55.76)£25.95 (86.04)£6.30 (24.08)£32.25 (91.60)↓-£3.50 (−35.35 to 29.21)SECONDARY CARE: INPATIENTChiropody Unit£0.00£88.17 (431.93)£88.17£0.00£0.00£0.00↓-£88.17Other£0.00£88.17 (431.93)£88.17£0.00£0.00£0.00↓-£88.17Total£0.00£176.34 (597.42)£176.34 (597.42)£0.00£0.00£0.00↓-£176.34 (− 364.84 to 0)SERVICE TOTAL£50.68 (71.34)£254.06 (602.06)£304.74 (592.87)£48.55 (103.56)£62.06 (82.85)£110.61 (145.90)↓-£194.13 (− 393.52 to 0.35)a95% bootstrapped confidence interval, based on 5000 replications ↓ demarks a reduction in cost for Digital Supply Chain compared to Traditional Supply Chain
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
['CR31', 'CR33', 'CR4', 'CR4', 'CR9', 'CR10', 'CR34', 'CR27', 'CR3', 'CR8', 'CR9', 'CR35', 'CR4', 'CR35']
|
The two supply chains provided orthoses that were largely comparable in terms reductions in plantar pressure after a period of continued use despite significant differences at point of supply. Since HRQoL, capability and economic data also failed to reveal any difference between supply chains, any benefits of one process over the other must lie outside of the parameters we quantified. It follows that pressure relief is not an adequate basis for choosing one supply chain over the other. This outcome is sensitive to the assumptions in our research design. It has been noted that preference-based measures of HRQoL can be insensitive for patients with impaired mobility [31–33]. For instance, the EQ-5D-5 L offers five relatively narrow levels of mobility: no problems, slight, moderate, severe or extreme problems walking. For many orthoses users these options lack nuance, and therefore may be too blunt to fully capture changes in HRQoL related to orthotic interventions. Assumptions may also have an impact on the use of cost data. A recent survey identified that digital and traditional supply chains are in use internal and external to the NHS, which will distribute costs differently than our models [4]. Also, an unexpected outcome was that digital supply chain assessments took longer than in the traditional supply chain. This was likely because the digital processes were new to staff and could be streamlined with practice. This illustrates that possible savings might not be immediate as there would be a learning period and longer term cost analysis is required. Indeed financial modelling might need to cover several years in the case of purchasing capital equipment (for both supply chains). The difference between chains of £13.17 might also be impacted if other suppliers are used compared to those used in the study. The issue of cost and seeking economies in processes might drive supply chain innovation. Some parts of the processes, such as CNC manufacture, are naturally designed for large volume and potentially continuous operation. Capitalising on the potential this offers requires other parts of the supply process to be adapted, such as ensuring sufficient volumes of orthoses are required and facilities management outside of normal working hours. These issues could be addressed by distributing different parts of the supply chain across a network of contractors to seek economies associated with scale, or using a single supply chain to support multiple health organisations. The context for costs might also be very sensitive to local arrangements, such as availability of extra space without capital expenditure, and in situ staff capacity and skills. One of the motivations behind this trial was the potential to ‘future proof’ foot orthoses supply by moving to a digital context and later exploring innovations such as additive manufacturing. Moving to a digital context requires a much more thorough analysis of service, supply chain models, innovation opportunities and longer term economic planning than our trial allowed. The orthoses used were typical of those recently reported [4] and the levels of pressure relief were similar to those reported by Burns [9] (~ 18% using Pedar) but less than those reported by Paton [10] (~ 30% using Tekscan). These differences may be due to variability between different measurement systems used [34] and the use of a ‘no insole’ control instead of sham orthotic by Paton. Changes in efficacy were observed between point of supply and 6 months suggesting insole integrity or durability may have been affected, this is demonstrated by Paton 2014 who investigated effect of wear on insole performance [27]. Results confirm that foot orthoses made bespoke for each patient can move patients from a classification of “at risk of ulceration” (> 200 kPa) to lower risk category [3]. This suggests the orthoses tested were largely typical of those in the literature and fit for purpose. That orthoses produced by different supply chains and across different published studies both demonstrate pressure relief, might suggest that pressure reliving effects at the level of groups of patients are not sensitive to the nuances of different orthoses design. This is somewhat contrary to the within patient differences that we and others have reported when small orthoses design features are manipulated, such as changes in material and geometry [8,9]. This suggests that there is not consistent “best” approach overall, but that a number of approaches can deliver the intended pressure relief for an individual patient. Several limitations are important to note. Differences in plantar pressure when wearing the control insole at the point of supply and 6 months suggests a change to the pressure profile. This may relate to changes in the participants foot structure or tissues associated with disease progression and the risk status [35], though this was not recorded. The effect size used to power this study was a conservative estimate and was in line with the non-inferiority margin identified. However, the sample size calculations were powered by effect sizes for plantar pressure outcomes, as this was assumed a prerequisite for other outcomes being pertinent. There is therefore insufficient statistical power to make definitive assessments for cost effectiveness of the supply chains. If the digital supply chain were to be adopted as routine practice a number of additional economic factors would need to be considered, including the initial cost of software, equipment and space, and the ongoing need to train staff. More detailed process cost modelling is required to better understand the impact of these costs in specific service context. The non-inferiority margin used for this study was based on a limited number of studies; more robust studies to assess orthotic effect are required to ensure a more robust and clinically meaningful boundary can be established. The follow-up period was 6 months and practitioners replace orthoses at different intervals, so a longer term follow up is relevant [4]. We did not control footwear beyond it being suitable to accommodate orthoses. Control of footwear has been recommended for assessment of orthotic effect [35], however this was a pragmatic trial including an evaluation of the supply chains in their entirety requiring the use of real practice footwear selected by orthotists and patients.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC6325812']
|
['30636974']
|
[]
|
Custom made foot orthoses produced by both traditional and digital supply chains provide significant reduction in pressure compared to a flat 3 mm Poron insert and retain this functionality throughout 6 months of regular use. There is only a marginal difference in terms of cost and health status between supply chain processes used to design, produce and maintain foot orthoses. Custom made orthoses were also demonstrated to reduce the number of regions of the foot identified as at risk due to high pressures. Effectiveness was found to be higher in the digital supply chain however, there was no statistically significant difference between supply chains after 6 months of use. Further to this after 6 months, orthoses were found to be inferior to a pre-defined margin based on prior studies demonstrating effective pressure reduction. Further studies to assess the long-term effectiveness of foot orthoses are needed to ensure appropriate design, production and monitoring can be implemented for management of risk with foot orthoses in the diabetic foot.
|
PMC6325812
|
Research
| null | 30,636,974
|
A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
|
Parker DJ, Nuttall GH, Bray N, Hugill T, Martinez-Santos A, Edwards RT, Nester C.
|
J Foot Ankle Res. 2019 Jan 8;12:2. doi: 10.1186/s13047-018-0311-0. eCollection 2019.
|
Parker DJ
|
J Foot Ankle Res
| 2,019
|
2019/01/15
|
PMC6325812
| null |
10.1186/s13047-018-0311-0
|
oa_comm/txt/all/PMC6325812.txt
|
71a5bcf70ea528536eba3e8c36bc6702
|
J Foot Ankle Res. 2019 Jan 8; 12:2
|
2021-06-19 03:25:33
|
CC BY
|
no
|
['PMC8080700']
|
['33911100']
|
[]
|
Non-fatal stroke constitutes one of the major causes of disability in old age1,2. Forecasts indicate that the total cost resulting from this illness will triple between 2012 and 2030, with a major part of the projected increase in costs deriving from older adults3. Furthermore, recent data from the American Heart Association indicates that the oldest population have greatest disabilities, receive less evidenced-based care, and are less likely to be discharged to their residences3. A large number of stroke survivors, some 69 to 80%, initially present impairments in the upper limbs4. Upper extremity hemiparesis is considered to be one of the most frequent conditions underlying stroke-induced disability5, and between 55 and 75% of cases show significant residual deficits6. Among these deficits, those pertaining to the hand are those which persist the most. Thus, functions such as grasping, holding and manipulating objects are deficient in a high percentage of patients between 3 and 6 months after stroke, and full functional recovery of the hand has only been documented in between 5 and 20% of these subjects7. These impairments will impact functional motor ability and quality of life, and exert a great economic, social and personal toll. The available research emphasises the need for interdisciplinary and multimodal approaches in the rehabilitation of the paretic hand8. Neuromuscular electrical stimulation (NMES) is one of the techniques proposed for upper limb recovery following a stroke9–12. Based on the use of electrical current to produce repetitive contractions of muscles it helps in restoring or assisting movements that would not otherwise occur because of hemiparesis. This treatment has certain characteristics labeled as important components of an effective intervention to promote motor recovery after stroke8,13, such as: repetitive movement, intensive practice, proprioceptive and exteroceptive input, visual feedback, and subject’s attention. In addition, it is also a low-cost and safe technique, easy to apply, without significantly increasing demands on stretched therapist’s time, and allows intensive home applications. The specific mechanisms underlying this intervention are complex and unclear, but findings suggest that improvements could be mediated by local and central effects. At the local level, reference has been made to changes in muscular strength, modification of viscoelastic characteristics, and increase of blood flow14,15. Mechanisms also could involve increased presynaptic inhibition of muscle spindle reflex activity16. NMES could influence cortical plasticity17,18. It is hypothesised that either concurrent stimulation of afferent fibres, or antidromic discharge triggered by stimulation lead to enhanced synaptic remodelling, but evidence is still lacking. Concomitant physiologic changes in the brain including activation of primary sensory and motor areas, and the supplementary motor area, a reduction of intracortical inhibition, and an increased amplitude of motor-evoked potentials could be associated with NMES19. Regarding previous systematic reviews and meta-analysis, Eraifej et al.20found significant benefit from functional electrical estimulation applied within 2 months of stroke on activities of daily living. However, high quality large-scale randomised controlled trials are needed to obtain firm conclusions about its effectiveness or the optimum therapeutic window. They also stated the need of future research to identify the optimal parameters in order to standardise treatment for future studies. Nascimento et al.21concluded that cyclical electrical stimulation increases strength and improves activity after stroke but there are insufficient data to provide evidence regarding the effect of different doses or modalities of electrical stimulation. Concerning the stimulation parameters required, there are still discussions in the literature, as some previous studies pointed out11,17,18,22. Therefore, more evidence is required to establish the most efficient NMES protocols (current, dose, parameters, modality, muscle targeted, etc) and to define the characteristics of the candidates for this type of treatment. In this regard, the parameters of the electrical current used are currently subject of debate, and more data are needed to optimise the application of electrostimulation. Some reviews have pointed out that the comparison of stimulation parameters is complicated due to the disparity of variables, or the omission of data23,24. On one hand, it has been noted that one of the factors associated with a bad treatment result could relate to the use of inappropriate parameters25, the choice of which could result in different neurophysiological responses or, on the other hand, that the parameters might not be decisive in the effect of the intervention, but it has not yet been possible to confirm their clinical relevance17. A recent study published in 2020 was aimed to review the efficacy of the various parameters of application on the NMES in dysphagia generated after stroke. This concludes that the greatest efficacy of the technique was reached when applied at 60–80 Hz, 700 μs of pulse duration, at the motor intensity threshold, and in sessions of 20–30 min. The authors stated that there must be an adequate combination of between frequency and intensity to reach a quality muscular contraction, stimulating mainly type II fibres and adjusting to the needs of the target muscles in dysphagia26. Stimulation frequency is one of the basic parameters to be programmed in the NMES equipment. Regarding the recovery of the upper limb, the most commonly used parameters have been low frequency rectangular biphasic currents, with frequency values varying from 20 to 100 Hz. It is unknown which frequencies are the most effective within this wide range, although the most used in upper limb distal applications of clinical trials aimed at the motor recovery of adults after stroke range from 35 to 50 Hz23. Two studies have been found which examined the effectiveness of electrostimulation in relation to stimulation frequency, but they were limited to fine motor control and muscular fatigue in the hand27,28. Additionally, despite the enormous impact that stroke has on older adults, there is a complete paucity of literature directed expressly at old age with distinct physiological characteristics and the presence of comorbidity, which could entail the need for specific adaptations in their healthcare29. Therefore, considering the bibliographic background, it was decided to conduct a trial with the objective of assessing and comparing the effect of two NMES protocols with different stimulation frequencies (35 Hz versus 50 Hz) on hand motor impairment (range of motion, grip and pinch strength, muscle tone and muscle electrical activity) and upper limb function (manual dexterity and functional independence) in older adults with spastic hemiparesis after stroke.
|
PMC8080700
|
Article
| null | 33,911,100
|
A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke
|
Sentandreu-Mañó T, Tomás JM, Ricardo Salom Terrádez J.
|
Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8.
|
Sentandreu-Mañó T
|
Sci Rep
| 2,021
|
2021/04/29
|
PMC8080700
| null |
10.1038/s41598-021-88607-8
|
oa_comm/txt/all/PMC8080700.txt
|
1e815305846faefe057359df37b6b0ad
|
Sci Rep. 2021 Apr 28; 11:9131
|
2021-06-20 18:20:18
|
CC BY
|
no
|
['PMC8080700']
|
['33911100']
|
['Fig1', 'Tab1', 'Tab1']
|
Among the 262 eligible patients, the 69 participants selected were randomly placed into one of the three groups, resulting in the three balanced groups of 23 participants. There were eight dropouts during the study period: two patients died because of exacerbations of their chronic diseases, one patient had a hip fracture, two patients were excluded because of a change in the rehabilitation centre, two patients needed a rest because of a fall that happened at home, and finally, one patient was excluded because of a lack of adherence to treatment. Therefore, the final sample analysed was 61, 20 in the control group, 20 in the 50 Hz treatment group, and 21 in the 35 Hz treatment group (see Fig.1).Figure 1Participant flowchart according to CONSORT 2010. With respect to the descriptive characteristics of the sample, 60.7% of the sample were men. Mean age was 70.95 years (SD = 7.18 years), with a range from 60 to 86 years, and an average body mass index of 25.32 (SD = 2.62). The average time elapsed since the stroke to the beginning of the study was 5.77 months (SD = 3.16), with a minimum of 1 month and a maximum of 15 months. Mean score in the Mini-Mental State Examination (MMSE) was 27.43 (SD = 3.56), 72.1% of subjects had suffered ischemic strokes, 49.2% had the right side of the body affected, 11.5% presented mild aphasia, 96.7% reported the right hand as the dominant hand, 54.1% had shoulder motor control, 44.3% had hypertension, 31.1% had diabetes, and finally, 45.9% were ex-smokers. Baseline characteristics of the control and experimental groups are presented in Table1. There were no statistically significant differences in baseline variables among groups (p > 0.05) (Table1). There were no significant differences in the number of treatment sessions completed between the groups (p > 0.05). There were no adverse events related to the trial. One subject felt forearm pain during stimulation session, but it was resolved by decreasing the intensity of the current.Table 1Means and standard deviations or percentages at baseline of the control and experimental groups and their tests for statistical differences.Variable50 Hz NMES group (n = 20)35 Hz NMES group (n = 21)Control group (n = 20)P valueGender (% male)6551.7600.948Age (years)71.25 (6.99)70.14 (7.25)71.50 (7.56)0.816BMI (kg/m2)25.33 (2.35)24.49 (2.31)26.19 (2.99)0.114Time post-stroke (months)5.30 (2.13)6.19 (3.92)5.80 (3.24)0.673MMSE27.10 (3.89)27.81 (3.34)27.35 (3.59)0.816Stroke (% ischemic)7561.9800.45Hemiparesis (% right)5552.4400.648Aphasia (%)209.550.373Dominant hand (% right)10095.2951Shoulder control motor (%)6547.6500.523Hypertension (%)4047.6450.949Diabetes (%)3523.8350.735Ex-smokers (%)6033.3450.26Pain (%)7071.4550.501Wrist resting angle (º)− 10.50 (10.87)− 10.48 (9.74)− 5.50 (5.60)0.138Wrist active extension (º)13.10 (6.54)17.57 (11.89)19.25 (18.01)0.309Wrist passive extension (º)36.25 (14.77)46.43 (12.56)40.75 (16.65)0.094MCP resting angle (º)− 35.00 (15.64)− 37.14 (13.93)− 29.75 (17.28)0.308MCP active extension (º)6.00 (9.95)15.24 (13.83)12.75 (12.19)0.05Grip strength (kgf)3.81 (3.01)5.83 (4.70)4.80 (6.30)0.417Pinch strength (kgf)1.67 (1.55)2.44 (2.12)2.09 (2.39)0.485MAS score for wrist flexors2.05 (0.99)2.24 (0.77)1.85 (0.75)0.345MAS score for MCP flexors1.65 (1.23)1.81 (0.98)1.35 (1.04)0.396Peak EMG amplitude extensors (µV)62.75 (52.77)73.24 (42.40)89.95 (112.86)0.521ACR extensors (%)45.25 (12.52)39.70 (12.65)42.35 (12.05)0.366BBT5.55 (5.52)6.05 (7.71)8.55 (10.05)0.447Barthel Index59.50 (13.85)60.71 (14.26)58.25 (17.11)0.873NMESNeuromuscular electrical stimulation,BMIBody mass index,MMSEMini-Mental State Examination,MCPMetacarpophalangeal,MASModified Ashworth Scale,ACRco-activation ratio of the antagonist,BBTBox and Block Test.
|
PMC8080700
|
Article
| null | 33,911,100
|
A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke
|
Sentandreu-Mañó T, Tomás JM, Ricardo Salom Terrádez J.
|
Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8.
|
Sentandreu-Mañó T
|
Sci Rep
| 2,021
|
2021/04/29
|
PMC8080700
| null |
10.1038/s41598-021-88607-8
|
oa_comm/txt/all/PMC8080700.txt
|
1e815305846faefe057359df37b6b0ad
|
Sci Rep. 2021 Apr 28; 11:9131
|
2021-06-20 18:20:18
|
CC BY
|
no
|
['PMC8080700']
|
['33911100']
|
['Tab2', 'Tab2']
|
A Repeated Measures MANOVA (RM-MANOVA) was calculated for the five measures of range of motion for the three groups (control, 35 Hz NMES and 50 Hz NMES) in the four time points. The results of the multivariate effect of the interaction among these factors (range of motion, group and time) were statistically significant: Pillai’s trace = .754, F = 2.42, p = .001, η2= .377. Once the RM-MANOVA gave significant results follow-up repeated measures ANOVAs were performed for each dependent variable. There was a statistically significant group per time interaction on the resting angle (F = 7.18; p < .001; η2= .20), active extension (F = 17.31; p < .001; η2= .37), and passive extension (F = 9.96; p< .001; η2= .26) of the wrist, as well as in the resting angle (F = 5; p< .001; η2= .15), and active extension (F = 3.25; p = .026; η2= .10) of the metacarpophalangeal joints (MCP). Table2shows the means, standard deviations, mean differences of baseline measures against all other time points, as well as Cohen’s d for these differences for all these dependent variables, and their statistical significance. With all the detailed information in Table2, a general pattern of mean differences arises. Both 35 Hz and 50 Hz NMES had consistent effects in improving the range of motion for all dependent variables. Control group only presented a significant gain in the case of wrist passive extension, but was ineffective for all other measures of range of motion. Another clear result is that gains produced by the 35 Hz were larger than those in the 50 Hz group.Table 2Means, standard deviations, mean differences, confidence intervals and effect sizes of the variables related to the range of motion in all the time points.MeasureControl group (n = 20)35 Hz NMES (n = 21)50 Hz NMES (n = 20)Range of motion (º)Testing timeMean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Wrist resting angleBaseline− 5.50 (5.60)− 10.48 (9.74)− 10.50 (10.87)1-month− 4.75 (4.99)− 0.75 (− 2.92, 1.42)− 0.14− 5.24 (9.01)− 5.23 (− 7.35, − 3.12)*− 0.57− 6.00 (8.52)− 4.50 (− 6.67, − 2.32)*− 0.472-months− 5.50 (5.60)0.00 (− 2.24, 2.24)0.00− 3.90 (7.36)− 6.57 (− 8.75, − 4.38)*− 0.78− 5.25 (7.86)− 5.25 (− 7.49, − 3.00)*− 0.56Follow-up− 4.75 (5.73)− 0.75 (− 3.50, 2.00)− 0.13− 5.95 (10.5)− 4.52 (− 7.21, − 1.83)*− 0.45− 5.25 (8.35)− 5.25 (− 8.00, − 2.49)*− 0.55Wrist active extensionBaseline19.25 (18.0)17.57 (11.8)13.10 (6.54)1-month19.85 (18.8)− 0.60 (− 4.04, 2.84)− 0.0327.81 (15.2)− 10.23 (− 13.59, − 6.88)*− 0.7717.25 (8.96)− 4.15 (− 7.59, − 0.71)*− 0.542-months20.25 (19.3)− 1.00 (− 5.28, 3.28)− 0.0532.29 (17.1)− 14.71 (− 18.9, − 10.5)*− 1.0321.50 (11.0)− 8.40 (− 12.6, − 4.11)*− 0.95Follow-up22.00 (19.7)− 2.75 (− 7.47, 1.97)− 0.1536.90 (17.3)− 19.33 (− 23.9, − 14.72)*− 1.5421.00 (11.5)− 7.90 (− 12.6, − 3.17)*− 0.86Wrist passive extensionBaseline40.75 (16.6)46.43 (12.5)36.25 (14.7)1-month44.25 (13.8)− 3.50 (− 6.95, − 0.04)*− 0.2357.38 (10.9)− 10.95 (− 14.32, − 7.57)*− 0.9644.00 (13.6)− 7.75 (− 11.20, − 4.29)*− 0.562-months44.75 (13.7)− 4.00 (− 7.40, − 0.59)*− 0.2760.24 (14.3)− 13.81 (− 17.13, − 10.4)*− 1.0650.25 (11.9)− 14.00 (− 17.40, − 10.5)*− 1.07Follow-up48.25 (14.6)− 7.50 (− 10.42, − 4.5)*− 0.4960.95 (13.0)− 14.52 (− 17.37, − 11.6)*− 1.1649.75 (13.6)− 13.50 (− 16.42, − 10.6)*− 0.98MCP resting angleBaseline− 29.75 (17.2)− 37.14 (13.9)− 35.00 (15.6)1-month− 31.00 (16.3)1.25 (− 2.14, 4.64)0.07− 30.24 (12.6)− 6.90 (− 10.21, − 3.59)*− 0.53− 32.75 (13.1)− 2.25 (− 5.64, 1.14)− 0.162-months− 29.00 (15.4)− 0.75 (− 3.58, 2.08)− 0.04− 29.05 (14.8)− 8.09 (− 10.86, − 5.32)*− 0.57− 31.75 (13.7)− 3.25 (− 6.08, − 0.41)*− 0.22Follow-up− 27.75 (15.4)− 2.00 (− 6.12, 2.12)− 0.12− 29.05 (15.2)− 8.09 (− 12.11, − 4.07)*− 0.56− 30.50 (14.0)− 4.50 (− 8.62, − 0.38)*− 0.31MCP active extensionBaseline12.75 (12.1)15.24 (13.8)6.00 (9.95)1-month12.75 (12.1)0.00 (− 2.62, 2.62)0.0021.67 (11.5)− 6.42 (− 8.99, − 3.86)*− 0.529.25 (10.04)− 3.25 (− 5.87, − 0.62)*− 0.332-months13.75 (12.1)− 1.00 (− 4.67, 2.67)− 0.0822.14 (11.1)− 6.90 (− 10.49, − 3.31)*− 0.5610.50 (10.7)− 4.50 (− 8.17, − 0.82)*− 0.44Follow-up15.50 (11.3)− 2.75 (− 7.91, 2.41)− 0.2424.05 (10.0)− 8.81 (− 13.84, − 3.76)*− 0.7511.25 (11.9)− 5.25 (− 10.41, − 0.08)*− 0.49SDStandard deviation,MDMean difference (baseline minus each time),CI 95%Confidence interval 95%,ESEffect size,dCohen’s d.*The difference is statistically significant p < .05.
|
PMC8080700
|
Article
| null | 33,911,100
|
A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke
|
Sentandreu-Mañó T, Tomás JM, Ricardo Salom Terrádez J.
|
Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8.
|
Sentandreu-Mañó T
|
Sci Rep
| 2,021
|
2021/04/29
|
PMC8080700
| null |
10.1038/s41598-021-88607-8
|
oa_comm/txt/all/PMC8080700.txt
|
1e815305846faefe057359df37b6b0ad
|
Sci Rep. 2021 Apr 28; 11:9131
|
2021-06-20 18:20:18
|
CC BY
|
no
|
['PMC8080700']
|
['33911100']
|
['Tab3', 'Tab3']
|
A RM-MANOVA was calculated for the two measures of hand strength for the three groups in the four time points. The results of the multivariate effect of the interaction among these factors (hand strength, group and time) were statistically significant: Pillai’s trace = .252, F = 2.73, p = .016, η2= .126. Once the RM-MANOVA gave significant results follow-up repeated measures ANOVAs were performed for each dependent variable. There were significant interaction (group x time) effects on hand grip strength (F = 2.55; p = .031; η2= .08) as for the pinch strength (F = 3.29; p = .013; η2= .10). There were gains in both experimental groups for the two dynamometric strength measurements, as it can be seen in the means and mean differences of Table3. Additionally, post-hoc tests were performed via Bonferroni corrections. Regarding the 35 Hz group, there were statistically significant gains in both measures of strength among baseline and the three time moments (half treatment, end of treatment, and follow-up). In the case of 50 Hz group, there was no significant gain between 1 month and baseline in grip strength, but there were significant mean differences and large effects for the rest of comparisons. The largest difference was between baseline and follow-up for the 35 Hz NMES (Mean difference = 2.69 kgf, d = 0.56). Mean differences and Cohen’s d of all times against baseline are shown in Table3. Looking at these effect sizes, the 50 Hz NMES had slightly largest effects than the 35 Hz NMES.Table 3Means, standard deviations, mean differences, confidence intervals and effect sizes of the variables related to the hand strength and the EMG activity in all the time points.MeasureControl group (n = 20)35 Hz NMES (n = 21)50 Hz NMES (n = 20)Strength (kgf)Testing timeMean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Grip strengthBaseline4.80 (6.30)5.83 (4.70)3.81 (3.01)1-month5.35 (7.05)− 0.55 (− 1.66, 0.56)− 0.087.00 (4.92)− 1.16 (− 2.25, − 0.07)*− 0.254.71 (3.31)− 0.90 (− 2.01, 0.21)− 0.292-months5.34 (6.31)− 0.53 (− 1.67, 0.59)− 0.087.71 (5.08)− 1.88 (− 2.99, − 0.77)*− 0.406.09 (3.37)− 2.27 (− 3.41, − 1.13)*− 0.73Follow-up5.95 (7.15)− 1.15 (− 2.38, 0.08)− 0.178.52 (5.06)− 2.69 (− 3.89, − 1.48)*− 0.566.24 (3.68)− 2.42 (− 3.66, − 1.18)*− 0.74Pinch strengthBaseline2.09 (2.39)2.44 (2.12)1.67 (1.55)1-month2.31 (2.40)− 0.22 (− 0.64, 0.19)− 0.093.02 (2.04)− 0.58 (− 0.99, − 0.17)*− 0.282.36 (1.84)− 0.69 (− 1.11, − 0.27)*− 0.412-months2.69 (2.49)− 0.60 (− 1.16, − 0.03)*− 0.253.13 (1.97)− 0.69 (− 1.24, − 0.13)*− 0.342.71 (1.58)− 1.05 (− 1.61, − 0.48)*− 0.68Follow-up2.39 (2.07)− 0.30 (− 0.92, 0.32)− 0.133.37 (2.01)− 0.92 (− 1.53, − 0.32)*− 0.462.96 (1.98)− 1.29 (− 1.91, − 0.67)*− 0.74EMG activityTesting timeMean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Peak A extensors (µV)Baseline89.95 (112.86)73.24 (42.40)62.75 (52.77)1-month95.45 (105.88)− 5.50 (− 16.60, 5.60)− 0.05102.62 (40.22)− 29.38 (− 40.22, − 18.54)*− 0.7373.85 (55.49)− 11.10 (− 22.20, 0.00)− 0.212-months97.50 (104.31)− 7.55 (− 22.41, 7.31)− 0.07116.52 (55.81)− 43.28 (− 57.79, − 28.78)*− 0.8984.45 (51.09)− 21.70 (− 36.56, − 6.83)*− 0.43Follow-up92.25 (103.84)− 2.30 (− 20.60, 16.00)− 0.02130.48 (58.56)− 57.23 (− 75.10, − 39.37)*− 1.14101.60 (87.80)− 38.85 (− 57.15, − 20.54)*− 0.55ACR extensors (%)Baseline42.35 (12.05)39.70 (12.65)45.25 (12.52)1-month43.71 (8.67)− 1.36 (− 7.54, 4.80)− 0.1333.89 (10.84)5.80 (− 0.21, 11.82)0.5041.64 (9.49)3.60 (− 2.56, 9.77)0.332-months42.28 (9.54)0.06 (− 5.52, 5.65)0.0030.86 (10.69)8.83 (3.37, 14.29)*0.7735.07 (7.17)10.18 (4.59, 15.77)*1.02Follow-up40.90 (10.58)1.44 (− 4.27, 7.16)0.1331.12 (10.62)8.58 (2.99, 14.16)*0.7534.90 (8.63)10.34 (4.62, 16.06)*0.98SDStandard deviation,MDMean difference (baseline minus each time),CI 95%Confidence interval 95%,ESEffect size,dCohen’s d,AAmplitude,ACRCo− activation ratio of the antagonist; * The difference is statistically significant p < .05.
|
PMC8080700
|
Article
| null | 33,911,100
|
A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke
|
Sentandreu-Mañó T, Tomás JM, Ricardo Salom Terrádez J.
|
Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8.
|
Sentandreu-Mañó T
|
Sci Rep
| 2,021
|
2021/04/29
|
PMC8080700
| null |
10.1038/s41598-021-88607-8
|
oa_comm/txt/all/PMC8080700.txt
|
1e815305846faefe057359df37b6b0ad
|
Sci Rep. 2021 Apr 28; 11:9131
|
2021-06-20 18:20:18
|
CC BY
|
no
|
['PMC8080700']
|
['33911100']
|
['Tab4', 'Tab4']
|
A RM-MANOVA was calculated for the two indicators of muscle tone for the three groups in the four time points. The results of the multivariate effect of the interaction among these factors (muscle tone, group and time) were significant: Pillai’s trace = .474, F = 2.79, p = .002, η2= .237. Afterwards, repeated measures ANOVAs were performed for each dependent variable. There were also some statistically significant group per time interactions on the Modified Ashworth Scale (MAS) for the wrist flexors (F = 7.35; p< .001; η2= .20) and the flexors of the MCP of the fingers (F = 10.62; p< .001; η2= .27). Gains were present in both treatment groups. Table4summarises these means and standard deviations. Post-hoc tests were performed. For the control group no pairs of time points were significantly different (p> .05), with the exception of a small improvement in wrist flexors between baseline and the follow-up. Regarding the experimental groups, there were statistically significant improvements among baseline and the 2-months and follow-up testing times for all dependent variables (wrist flexors and MCP flexors), and with large effect sizes. Mean differences and Cohen’s d of all times against baseline are shown in Table4for the three groups. A careful look at the effect sizes for 35 Hz vs. 50 Hz group shows that 35 Hz NMES had larger effects on muscle tone.Table 4Means, standard deviations, mean differences, confidence intervals and effect sizes of the variables related to muscle tone in all the time points.MeasureControl group (n = 20)35 Hz NMES (n = 21)50 Hz NMES (n = 20)MASTesting timeMean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Wrist flexorsBaseline1.85 (0.75)2.24 (0.77)2.05 (0.99)1-month1.85 (0.75)0.00 (− 0.23, 0.23)0.001.71 (0.72)0.52 (0.29, 0.75)*0.731.85 (0.93)0.20 (− 0.03, 0.43)0.212-months1.75 (0.72)0.10 (− 0.23, 0.43)0.141.29 (0.85)0.95 (0.62, 1,27)*1.201.20 (0.70)0.85 (0.51, 1.18)*1.01Follow-up1.45 (0.61)0.40 (0.01, 0.78)*0.601.14 (0.91)1.09 (0.72, 1.46)*1.341.05 (0.61)1.00 (0.61, 1.38)*1.25MCP flexorsBaseline1.35 (1.04)1.81 (0.98)1.65 (1.23)1-month1.30 (1.03)0.05 (− 0.19, 0.29)0.051.62 (1.12)0.19 (− 0.04, 0.42)0.181.15 (0.88)0.50 (0.25, 0.74)*0.482-months1.30 (1.03)0.05 (− 0.23, 0.33)0.051.00 (0.89)0.81 (0.53, 1.08)*0.880.95 (0.76)0.70 (0.41, 0.98)*0.70Follow-up1.10 (0.85)0.25 (− 0.04, 0.54)0.270.90 (0.83)0.90 (0.61, 1.19)*1.100.95 (0.76)0.70 (0.40, 0.99)*0.70MASModified Ashworth Scale,MCPMetacarpophalangeal,SDStandard deviation,MDMean difference (baseline minus each time),CI 95%Confidence interval 95%,ESEffect size,dCohen’s d; * The difference is statistically significant p < .05.
|
PMC8080700
|
Article
| null | 33,911,100
|
A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke
|
Sentandreu-Mañó T, Tomás JM, Ricardo Salom Terrádez J.
|
Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8.
|
Sentandreu-Mañó T
|
Sci Rep
| 2,021
|
2021/04/29
|
PMC8080700
| null |
10.1038/s41598-021-88607-8
|
oa_comm/txt/all/PMC8080700.txt
|
1e815305846faefe057359df37b6b0ad
|
Sci Rep. 2021 Apr 28; 11:9131
|
2021-06-20 18:20:18
|
CC BY
|
no
|
['PMC8080700']
|
['33911100']
|
['Tab3']
|
A RM-MANOVA was calculated for the two indicators of electromyographic (EMG) activity for the three groups in the four time points. The results of the multivariate effect of the interaction among these factors, peak amplitude extensors and the antagonist co-activation ratio (ACR) for the extensors, were statistically significant: Pillai’s trace = .603, F = 8.19, p< .001, η2= .301. Repeated measures ANOVAs were performed for each dependent variable. Statistically significant changes were found for the values related to the peak EMG amplitude (F = 8.18; p< .001; η2= .22) and the ACR assessing the performance of the wrist extensors (F = 4.12; p = .002; η2= .12). Both experimental groups showed up improvements. Considering the post-hoc tests, the control group showed no significant gains in the three time points against baseline for the two EMG measures (p> .05). Regarding the experimental groups, there were statistically significant gains among baseline and the 2-months and follow-up testing times for the two dependent variables with large effect sizes. When we compared 35 Hz and 50 Hz effects, 35 Hz NMES had larger effects for peak EMG amplitude extensors while 50 Hz NMES had larger effects for ACR extensors. Mean differences and Cohen’s d of all times against baseline are shown in Table3for the three groups.
|
PMC8080700
|
Article
| null | 33,911,100
|
A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke
|
Sentandreu-Mañó T, Tomás JM, Ricardo Salom Terrádez J.
|
Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8.
|
Sentandreu-Mañó T
|
Sci Rep
| 2,021
|
2021/04/29
|
PMC8080700
| null |
10.1038/s41598-021-88607-8
|
oa_comm/txt/all/PMC8080700.txt
|
1e815305846faefe057359df37b6b0ad
|
Sci Rep. 2021 Apr 28; 11:9131
|
2021-06-20 18:20:18
|
CC BY
|
no
|
['PMC8080700']
|
['33911100']
|
['Tab5']
|
A RM-MANOVA was calculated for the two functional measures for the three groups in the four time points. The results of the multivariate effect of the interaction among these factors, Barthel Index and Box and Block Test (BBT), were statistically significant: Pillai’s trace = .403, F = 4.79, p< .001, η2= .201. Once the RM-MANOVA gave significant results follow-up repeated measures ANOVAs were performed for each dependent variable. There were no significant interaction (group x time) effects on BBT (F = 1.03; p = .38; η2= .03). The Barthel Index showed a statistically significant interaction in favour of the NMES group of 35 Hz (F = 7.97; p< .001; η2= .22). Mean differences and Cohen’s d of all times against baseline are shown in Table5for the three groups. The control and the 50 Hz groups did not significantly change compared to baseline. However, Barthel Index significantly improved with respect to baseline for the 35 Hz group and with large effects.Table 5Means, standard deviations, mean differences, confidence intervals and effect sizes of functional outcome measures in all the time points.Control group (n = 20)35 Hz NMES (n = 21)50 Hz NMES (n = 20)MeasureTesting timeMean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)Mean (SD)MD (CI 95%)ES (d)BBTBaseline8.55 (10.05)6.05 (7.71)5.55 (5.52)1-month11.05 (13.20)− 2.50 (− 4.97, − 0.02)*− 0.289.57 (8.86)− 3.52 (− 5.93, − 1.11)*− 0.428.70 (9.11)− 3.15 (− 5.62, − 0.67)*− 0.292-months12.20 (12.95)− 3.65 (− 7.11, − 0.18)*− 0.3111.62 (9.89)− 5.57 (− 8.95, − 2.19)*− 0.6310.75 (9.51)− 5.20 (− 8.66, − 1.73)*− 0.66Follow-up13.50 (14.04)− 4.95 (− 9.85, − 0.04)*− 0.4013.90 (11.64)− 7.85 (− 12.64, − 3.06)*− 0.8014.10 (13.63)− 8.55 (− 13.45, − 3.64)*− 0.82Barthel IndexBaseline58.25 (17.11)60.71 (14.26)59.50 (13.85)1-month60.75 (18.01)− 2.50 (− 6.89, 1.89)− 0.1469.29 (9.78)− 8.57 (− 12.86, − 4.28)*− 0.7062.25 (13.72)− 2.75 (− 7.14, 1.64)− 0.202-months63.00 (18.60)− 4.75 (− 10.82, 1.32)− 0.2774.76 (13.08)− 14.04 (− 19.97, − 8.12)*− 1.0263.50 (14.15)− 4.00 (− 10.07, 2.07)− 0.29Follow-up64.50 (19.66)− 6.25 (− 12.40, − 0.09)*− 0.3479.05 (13.10)− 18.33 (− 24.33, − 12.32)*− 1.3464.25 (14.98)− 4.75 (− 10.90, 1.40)− 0.33BBTBox and Block Test,SDStandard deviation,MDMean difference (baseline minus each time),CI 95%Confidence interval 95%,ESEffect size;dCohen’s d; * The difference is statistically significant p < .05.
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PMC8080700
|
Article
| null | 33,911,100
|
A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke
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Sentandreu-Mañó T, Tomás JM, Ricardo Salom Terrádez J.
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Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8.
|
Sentandreu-Mañó T
|
Sci Rep
| 2,021
|
2021/04/29
|
PMC8080700
| null |
10.1038/s41598-021-88607-8
|
oa_comm/txt/all/PMC8080700.txt
|
1e815305846faefe057359df37b6b0ad
|
Sci Rep. 2021 Apr 28; 11:9131
|
2021-06-20 18:20:18
|
CC BY
|
no
|
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