Effect of running therapy on depression (EFFORT-D). Design of a randomised controlled trial in adult patients [ISRCTN 1894]

<p>Abstract</p> <p>Background</p> <p>The societal and personal burden of depressive illness is considerable. Despite the developments in treatment strategies, the effectiveness of both medication and psychotherapy is not ideal. Physical activity, including exercise, is a relatively cheap and non-harmful lifestyle intervention which lacks the side-effects of medication and does not require the introspective ability necessary for most psychotherapies. Several cohort studies and randomised controlled trials (RCTs) have been performed to establish the effect of physical activity on prevention and remission of depressive illness. However, recent meta-analysis's of all RCTs in this area showed conflicting results. The objective of the present article is to describe the design of a RCT examining the effect of exercise on depressive patients.</p> <p>Methods/Design</p> <p>The EFFect Of Running Therapy on Depression in adults (EFFORT-D) is a RCT, studying the effectiveness of exercise therapy (running therapy (RT) or Nordic walking (NW)) on depression in adults, in addition to usual care. The study population consists of patients with depressive disorder, Hamilton Rating Scale for Depression (HRSD) ≥ 14, recruited from specialised mental health care. The experimental group receives the exercise intervention besides treatment as usual, the control group receives treatment as usual. The intervention program is a group-based, 1 h session, two times a week for 6 months and of increasing intensity. The control group only performs low intensive non-aerobic exercises. Measurements are performed at inclusion and at 3,6 and 12 months.</p> <p>Primary outcome measure is reduction in depressive symptoms measured by the HRSD. Cardio-respiratory fitness is measured using a sub maximal cycling test, biometric information is gathered and blood samples are collected for metabolic parameters. Also, co-morbidity with pain, anxiety and personality traits is studied, as well as quality of life and cost-effectiveness.</p> <p>Discussion</p> <p>Exercise in depression can be used as a standalone or as an add-on intervention. In specialised mental health care, chronic forms of depression, co-morbid anxiety or physical complaints and treatment resistance are common. An add-on strategy therefore seems the best choice. This is the first high quality large trial into the effectiveness of exercise as an add-on treatment for depression in adult patients in specialised mental health care.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1894">NTR1894</a></p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Personality traits as predictors of exercise treatment adherence in major depressive disorder: lessons from a randomised clinical trial

Objective: The objective of this study was to explore the determinants of adherence in the EFFORT-D (EFFect Of Running Therapy) study in a specialised mental health care hospital setting. Methods: Patients with major depressive disorder (MDD) were given treatment as usual and half were randomised to an exercise intervention. Adherence was measured at 3 months (T3) and 6 months (T6) and was defined as participation in the overall study protocol (total n = 42, adhered n = 28) or intervention (total n = 24, adhered n = 9). Potential determinants were age, BMI, tobacco and alcohol use, severity of depression, anxiety, fitness (VO2max kg−1 and Wmax kg−1) and personality traits at baseline. ANOVA, Chi-square tests and block-wise logistic regression were performed, and reliability of the scales was determined. Results: Numbers were found too low for analyses on smoking, drinking and anxiety. Higher agreeableness was significantly associated with better adherence to the overall study protocol (OR 1.2; p = 0.03; 95% CI: 1.01–1.4) and severity of depression was negatively associated with adherence in the intervention group (OR 0.70; p = 0.046;95% CI: 0.49–0.99). Conclusions: To adhere to a study protocol involving exercise or to a clinical exercise programme, MDD patients need substantial personal support. Measurement of personality traits and the severity of depression as potential predictors of adherence could be considered for this purpose.Keypoints Adherence to exercise and study protocols in a randomised controlled trial was low Patients with severe major depressive disorder need substantial personal support Measurement of personality traits could be considered

EFFORT-D study process evaluation: Challenges in conducting a trial into the effects of running therapy in patients with major depressive disorder

Background: Exercise is currently seen as an effective treatment for major depressive disorder (MDD). However, existing studies have focused mainly on mild-to-moderate depression. The moderate positive effect of exercise found in meta-analyses concerning these studies differs, however, from the harsh daily clinical practice, when trying to implement exercise as an adjunctive treatment. We aimed to evaluate the feasibility of aerobic exercise in MDD and identify future problems for implementation. Methods: The EFFect Of Running Therapy on Depression (EFFORT-D) study was a randomized clinical trial examining the effectiveness of running therapy or Nordic walking in inpatients and outpatients with MDD. We conducted a process evaluation based on the method of Linnan and Steckler. Participant inclusion, dropout and no show were registered qualitatively and quantitatively. Results: The inclusion and delivered dose of the exercise interventions were limited (60 and 75%, respectively), leading to 80% less inclusion than foreseen. Motivational doubts were the main reason not to participate in the study. The unexpected high dropout rates (40% after 3 months and 80% after 12 months) were frequently related to lack of motivation due to disease characteristics and severity. The duration of the intervention, longer than 3 months was another underlying factor for poor adherence. Conclusions: Depression severity appeared to be the key factor determining dropout, followed by the duration of exercise intervention, expressed by a pre- and post-inclusion lack of motivation. Both running therapy and Nordic walking were apparently unsuitable for most patients with MDD in the current format. Emphasis on motivational issues is necessary from the early start of the intervention in these patients with MDD. Also a tailored and stepped-care approach is advised for future implementation

Screening for Dystonia Genes DYT1, 11 and 16 in Patients with Writer's Cramp

Task-specific focal upper limb dystonia can be part of the phenotypic spectrum of different types of hereditary dystonia. We investigated whether writer's cramp as presenting symptom is associated with mutations in DYT11, DYT16, or with the DYT1 GAG deletion in 43 patients. No DYT11 and DYT16 mutations were identified. One patient carried the GAG deletion in the DYT1 gene. In our cohort, writer's cramp as presenting symptom is not associated with mutations in DYT11, DYT16, but it can be the sole manifestation of DYT1 GAG deletion mutation carriers. (C) 2009 Movement Disorder Societ

Accelerometer-measured sedentary behaviour and physical activity of inpatients with severe mental illness

Sedentary behaviour and lack of physical activity threatens health. Research concerning these behaviours of inpatients with severe mental illness is limited but urgently needed to reveal prevalence and magnitude. In total, 184 inpatients (men n =108, women n =76, mean age 57,4, 20% first generation antipsychotics, 40% second generation antipsychotics, 43% antidepressants, mean years hospitalisation 13 years), with severe mental illness of a Dutch psychiatric hospital wore an accelerometer for five days to objectively measure total activity counts per hour and percentages in sedentary behaviour, light intensity physical activity and moderate to vigorous physical activity. Accelerometer data were compared with data of 54 healthy ward employees. Patients showed significantly less activity counts per hour compared to employees (p=0.02), although the differences were small (d=0.32). Patients were sedentary during 84% of the wear time (50 min/h), spend 10% in light intensity physical activity and 6% in moderate to vigorous physical activity. Age was the only significant predictor, predicting less total activity counts/h in higher ages. Decreasing sedentary behaviour and improving physical activity in this population should be a high priority in clinical practice

Screening for Dystonia Genes DYT1, 11 and 16 in Patients with Writer's Cramp

Task-specific focal upper limb dystonia can be part of the phenotypic spectrum of different types of hereditary dystonia. We investigated whether writer's cramp as presenting symptom is associated with mutations in DYT11, DYT16, or with the DYT1 GAG deletion in 43 patients. No DYT11 and DYT16 mutations were identified. One patient carried the GAG deletion in the DYT1 gene. In our cohort, writer's cramp as presenting symptom is not associated with mutations in DYT11, DYT16, but it can be the sole manifestation of DYT1 GAG deletion mutation carriers. (C) 2009 Movement Disorder Societ

Physical activity and quality of life in longterm hospitalized patients with severe mental illness: a cross-sectional study

Background: Increasing physical activity in patients with severe mental illness is believed to have positive effects on physical health, psychiatric symptoms and as well quality of life. Till now, little is known about the relationship between physical activity and quality of life in long-term hospitalized patients with severe mental illness and knowledge of the determinants of behavioural change is lacking. The purpose of this study was to elucidate the relationship between objectively measured physical activity and quality of life, and explore modifiable psychological determinants of change in physical activity in long-term hospitalized patients with severe mental illness. Methods: In 184 inpatients, physical activity was measured using an accelerometer (ActiGraph GTX+). Quality of life was assessed by EuroQol-5D and WHOQol-Bref. Attitude and perceived self-efficacy towards physical activity were collected using the Physical Activity Enjoyment Scale and the Multidimensional Self Efficacy Questionnaire, respectively. Patient and disease characteristics were derived retrospectively from electronic patient records. Associations and potential predictors were analysed using hierarchical regression. Results: Physical activity was positively related with and a predictor of all quality of life outcomes except on the environmental domain, independent of patient and disease characteristics. However, non-linear relationships showed that most improvement in quality of life lies in the change from sedentary to light activity. Attitude and self-efficacy were not related to physical activity. Conclusions: Physical activity is positively associated with quality of life, especially for patients in the lower spectrum of physical activity. An association between attitude and self-efficacy and physical activity was absent. Therefore, results suggest the need of alternative, more integrated and (peer-)supported interventions to structurally improve physical activity in this inpatient population. Slight changes from sedentary behaviour to physical activity may be enough to improve quality of life