Accelerometer Measured Sedentary and Physical Activity Behaviors of Working Patients after Total Knee Arthroplasty, and their Compensation Between Occupational and Leisure Time

Purpose Objective measurements of sedentary and physical activity (PA) behavior are scarce among working-age patients who undergo total knee arthroplasty (TKA). Aim was to assess sedentary and PA behaviors using accelerometers and to identify compensation effects between occupational and leisure time of sedentary and PA behavior. Methods One year post-TKA, 51 patients wore an ActiGraph(GT3x) accelerometer for 7 days. Sedentary time, prolonged sedentary bouts (≥ 30 min) and PA (light-intensity and moderate-to-vigorous PA) were examined. Compliance with the guideline of > 150 min moderate-to-vigorous PA per week was calculated. Compensation effects were analyzed using multilevel models, splitting effects into routine and within-day compensation, stratifying by physical and non-physical jobs. The routine compensation effects are the ones of interest, representing habitual compensation during a week. Results Participants spent 60% of time in sedentary bouts and 17% in prolonged sedentary bouts, with 37% of PA spent in light-intensity and 3% in moderate-to-vigorous activity. About 70% of patients met the PA guideline. Routine compensation effects were found for workers in physical jobs, who compensated for their occupational light-intensity PA with less light-intensity PA during leisure time. Workers in non-physical jobs did not compensate for their occupational prolonged sedentary bouts, as these continued during leisure time. Conclusion This study showed that working TKA patients are highly sedentary 1 year after surgery, but most met the PA guideline. Especially those with non-physical jobs do not compensate for their occupational prolonged sedentary bouts. This stresses the need to stimulate PA among TKA patients not complying with the guidelines and those with non-physical jobs

Digital Interventions for People With Co-Occurring Depression and Problematic Alcohol Use: A Systematic Review and Meta-Analysis

Aims: This systematic review and meta-analysis assessed the effectiveness of digital interventions addressing depressive symptoms and alcohol use simultaneously among people with co-occurring depression and problematic alcohol use.Methods: Seven databases were searched for trials evaluating digital interventions aimed at depression and alcohol use. Random-effects meta-analyses were conducted to pool effects on depressive symptoms and alcohol use up to 3-month and 6-month follow-up. Overall quality for every outcome was assessed with GRADE (Grading of Recommendations Assessment, Development and Evaluation).Results: The pooled effect of digital interventions compared to their comparators was in favour of digital interventions. Small but significant effects on depressive symptoms at 3-month follow-up were found (g = 0.34, 95% confidence interval (CI): 0.06-0.62, P = 0.02, k = 6) and non-significant effects at 6-month follow-up (g = 0.29, 95% CI: -0.16 to 0.73, P = 0.15, k = 5). For alcohol use, the pooled effect of digital interventions was small and non-significant at 3-month follow-up (g = 0.14, 95% CI: -0.02 to 0.30, P = 0.07, k = 6) and significant at 6-month follow-up (g = 0.14, 95% CI: 0.07-0.20, P = 0.005, k = 5). Sensitivity analysis indicated the latter finding to be sensitive to statistical estimator choice. Quality of evidence was moderate, except for depressive symptoms at 6-month follow-up for which it was low.Conclusion: Based on the literature, digital interventions are effective in reducing depressive symptoms at 3-month follow-up and alcohol use at 6-month follow-up among people with comorbid depression and problematic alcohol use. More high-quality trials are needed to confirm the current findings.</p

Study protocol for a multicentre randomized controlled trial on effectiveness of an outpatient multimodal rehabilitation program for adolescents with chronic musculoskeletal pain (2B Active)

BACKGROUND: Chronic musculoskeletal pain (CMP) in adolescents can influence functioning and well-being, and has negative consequences for families and society as well. According to the Fear Avoidance Model, fear of movement and pain catastrophizing can influence the occurrence and maintenance of chronic pain complaints and functional disability. Primary objective is to evaluate the effectiveness of a multimodal rehabilitation program in reducing functional disability for adolescents with CMP compared with care as usual. METHODS/DESIGN: Pragmatic multicentre parallel group randomized controlled trial. Randomization by minimization (ratio 1:1) and treatment allocation will be concealed, computer-generated and performed by an independent organization. After randomization, data collection and researchers remain blinded. Inclusion of 124 adolescents and their parents is intended. This sample size is based on a 25 % difference in group mean on the primary outcome, with α = 5 %, β = 80 % and expected 15 % loss to follow up. Study population are adolescents (12-21 years) with CMP with an indication for outpatient rehabilitation treatment in the Netherlands. The intervention group receives a Multimodal Rehabilitation Program (MRP), a multidisciplinary outpatient individual rehabilitation program. MRP consists of 2 different treatment approaches: A graded exposure module or a combination module of graded exposure and physical training. Selection of a module depends on the needs of the patient. To both modules a parent module is added. The control group receives care as usual, which is the care currently provided in Dutch rehabilitation centres. Treatment duration varies between 7 and 16 weeks, depending on treatment allocation. Self-reported measurements are at baseline, and at 2, 4, 10 and 12 months after start of treatment. Intention to treat analysis for between group differences on all outcome variables will be performed. Primary outcome is functional disability (Functional Disability Inventory). Secondary outcome variables are fear of pain, catastrophizing, perceived harmfulness, pain intensity, depressive symptoms, and quality of life. Total direct and indirect costs and health related quality of life will be measured. Process evaluation focuses on protocol adherence, patient centeredness and treatment expectations. DISCUSSION: A pragmatic approach was chosen, to ensure that results obtained are most applicable to daily practice. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT02181725 (7 February 2014). Funded by Fonds Nuts Ohra, Stichting Vooruit, and Adelante

Sex Proportionality in Pre-clinical and Clinical Trials: An Evaluation of 22 Marketing Authorization Application Dossiers Submitted to the European Medicines Agency

This study assessed to what extent women were included in all phases of drug development; whether the clinical studies in the marketing authorization application dossiers include information per sex; and explored whether there are differences between women and men in the drugs' efficacy and safety. Data were extracted from dossiers submitted to the European Medicines Agency. Twenty-two dossiers of drugs approved between 2011 and 2015 for the treatment of various diseases were included. Female animals were included in only 9% of the pharmacodynamics studies, but female and male animals were included in all toxicology studies. Although fewer women than men were included in the clinical studies used to evaluate pharmacokinetics (PK) (29 to 40% women), all dossiers contained sex-specific PK parameter estimations. In the phase III trials, inclusion of women was proportional to disease prevalence for depression, epilepsy, thrombosis, and diabetes [participation to prevalence ratio (PPR) range: 0.91–1.04], but women were considered underrepresented for schizophrenia, hepatitis C, hypercholesterolemia, HIV, and heart failure (PPR range: 0.49-0.74). All dossiers contained sex-specific subgroup analyses of efficacy and safety. There seemed to be higher efficacy for women in one dossier and a trend toward lower efficacy in another dossier. More women had adverse events in both treatment (73.0 vs. 70.6%, p < 0.001) and placebo groups (69.5 vs. 65.5%, p < 0.001). In conclusion, women were included throughout all phases of clinical drug research, and sex-specific information was available in the evaluated dossiers. The included number of women was, however, not always proportional to disease prevalence rates

Effectiveness of an add-on guided internet-based emotion regulation training (E-TRAIN) in adolescents with depressive and/or anxiety disorders: study protocol for a multicenter randomized controlled trial

During adolescence, depressive and anxiety disorders are among the most common mental health disorders. Both disorders tend to persist, are predictive for other mental disorders, and are associated with severe impairment in diverse areas. Although Cognitive Behavioral Therapy (CBT) has proven to be an effective treatment, a considerable number of adolescents do not respond to CBT and residual symptoms often remain. Therefore, it is of great importance to improve treatment outcomes for depressed and/or anxious adolescents. Dysfunctional emotion regulation appears to be a transdiagnostic factor in the development and maintenance of aforementioned disorders. Enhancing emotion regulation skills may therefore reduce symptom severity. In light of this, we developed a guided internet-based emotion regulation training (E-TRAIN) that will be added to CBT. This study aims to evaluate the effectiveness of E-TRAIN + CBT compared to CBT alone on depressive and anxiety outcomes among adolescents with depressive and/or anxiety disorder. Methods: In this multicenter two-arm randomized controlled trial with parallel group design, we aim to include 138 adolescents, aged 13–19 years, referred for treatment and diagnosed with depressive and/or anxiety disorder. Participants will be allocated to either CBT or CBT + E-TRAIN. Assessments will take place at baseline, and at 3 (T1), 6 (T2) and 12 (T3) months after baseline. We will conduct multi-informant assessments: the adolescent, a parent/caregiver, and the CBT therapist will be asked to fill in questionnaires. The continuous primary outcome measure is self-reported depressive and anxiety symptoms at six months after baseline, measured with the RCADS25. Secondary outcome measures include anxiety or depression diagnosis based on a semi-structured clinical interview, emotion (dys) regulation, and parent-report measures of anxiety, depression and emotion (dys) regulation. Discussion: This study is the first randomized controlled trial to examine the additional value of a guided internet-based emotion regulation training to regular CBT in adolescents with depressive and/or anxiety disorders. If this intervention is effective, it can be implemented in mental health care and improve treatment for these young people. Trial registration: Registered on June 23, 2021 in The Netherlands Trial Register (NL9564). Retrospectively registered. Recruitment started in May 2021 and is ongoing

Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach

Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks

Renal function in familial longevity: the Leiden Longevity Study

a b s t r a c t a r t i c l e i n f o Studying renal function in subjects with a familial propensity for longevity may provide insight in (un)known mechanisms that determine the age-related decline in renal function of normal subjects. In the Leiden Longevity Study, middle-aged offspring of non-agenarian siblings and their partners as environmentally matched controls were included. Information was collected on lifestyle, medical history, medication use, and a non-fasting blood sample was drawn. Renal function (estimated glomerular filtration rate, eGFR) was assessed with the Chronic Kidney Disease epidemiology collaboration (CKD-EPI) formula. Linear mixed models were used to account for familial dependencies within the offspring and all analyses were stratified by sex. eGFR was similar between female offspring and female controls (0.44 ml/min/1.73 m 2 (SE 0.72) difference, p = 0.54, age-adjusted). Male offspring had a higher eGFR compared to male controls (1.78 ml/min/1.73 m 2 (SE 0.78) difference, p = 0.022, age-adjusted), and further adjustments for various characteristics did not materially change this difference. Among men with a history of hypertension, or myocardial infarction and/or stroke, offspring had a higher eGFR compared to controls (4.74 ml/min/1.73 m 2 (SE 1.53) difference, p = 0.002, age-adjusted, and 6.21 ml/min/1.73 m 2 (SE 2.85) difference, p = 0.033, age-adjusted, respectively). Middle-aged men, but not women, with a propensity for longevity have better renal function compared to environmentally matched controls, especially among those with a history of cardiovascular disease