Dealing with confounding in observational studies: A scoping review of methods evaluated in simulation studies with single-point exposure.

The aim of this article was to perform a scoping review of methods available for dealing with confounding when analyzing the effect of health care treatments with single-point exposure in observational data. We aim to provide an overview of methods and their performance assessed by simulation studies indexed in PubMed. We searched PubMed for simulation studies published until January 2021. Our search was restricted to studies evaluating binary treatments and binary and/or continuous outcomes. Information was extracted on the methods' assumptions, performance, and technical properties. Of 28,548 identified references, 127 studies were eligible for inclusion. Of them, 84 assessed 14 different methods (ie, groups of estimators that share assumptions and implementation) for dealing with measured confounding, and 43 assessed 10 different methods for dealing with unmeasured confounding. Results suggest that there are large differences in performance between methods and that the performance of a specific method is highly dependent on the estimator. Furthermore, the methods' assumptions regarding the specific data features also substantially influence the methods' performance. Finally, the methods result in different estimands (ie, target of inference), which can even vary within methods. In conclusion, when choosing a method to adjust for measured or unmeasured confounding it is important to choose the most appropriate estimand, while considering the population of interest, data structure, and whether the plausibility of the methods' required assumptions hold.

Sick Leave Due to Stress, What are the Costs for Dutch Employers?

Purpose Stress-related illnesses are prevalent in Western society, causing sick leave and putting a heavy economic burden on employers and society. For Dutch employers it is particularly relevant to have insight into the costs of absenteeism due to stress-related illness, as they are legally obligated to continue payment of wages. Therefore, this study assessed the duration and costs of an episode of sick leave due to stress-related illness for Dutch employers. Methods Data on sick leave due to various stress-related illnesses were obtained from a nationwide occupational health service database. Stress-related illnesses included tension complaints, burn-out, overexertion, and other reactions to stress. The duration per sick leave episode was estimated in working days, after which the average cost per sick leave period was estimated using age- and gender-specific price weights. Results During the study period, 16,676 employees took 17,338 episodes of sick leave due to stress-related illness. On average, one episode of sick leave lasted 101 working days, for which the costs for the employer were on average €19,151 per worker. Women were responsible for most episodes of sick leave and were on average 37 days more absent per episode compared to men. Moreover, of all kinds of stress-related illnesses, burn-out had the longest duration of sick leave with 313 calendar days and 163 working days, resulting in an average cost of €30,770. Conclusions Sick leave due to stress-related illness places a heavy burden on employers and thus society. Further research should be conducted on how to reduce this burden.

PRIORITIES FOR HEALTH ECONOMIC METHODOLOGICAL RESEARCH: RESULTS OF AN EXPERT CONSULTATION.

BACKGROUND: The importance of economic evaluation in decision making is growing with increasing budgetary pressures on health systems. Diverse economic evidence is available for a range of interventions across national contexts within Europe, but little attention has been given to identifying evidence gaps that, if filled, could contribute to more efficient allocation of resources. One objective of the Research Agenda for Health Economic Evaluation project is to determine the most important methodological evidence gaps for the ten highest burden conditions in the European Union (EU), and to suggest ways of filling these gaps. METHODS: The highest burden conditions in the EU by Disability Adjusted Life Years were determined using the Global Burden of Disease study. Clinical interventions were identified for each condition based on published guidelines, and economic evaluations indexed in MEDLINE were mapped to each intervention. A panel of public health and health economics experts discussed the evidence during a workshop and identified evidence gaps. RESULTS: The literature analysis contributed to identifying cross-cutting methodological and technical issues, which were considered by the expert panel to derive methodological research priorities. CONCLUSIONS: The panel suggests a research agenda for health economics which incorporates the use of real-world evidence in the assessment of new and existing interventions; increased understanding of cost-effectiveness according to patient characteristics beyond the "-omics" approach to inform both investment and disinvestment decisions; methods for assessment of complex interventions; improved cross-talk between economic evaluations from health and other sectors; early health technology assessment; and standardized, transferable approaches to economic modeling.

Prognostic factors for high societal costs: a register-based study on 561,665 patients with shoulder disorders.

ABSTRACT: Shoulder disorders are common and associated with high societal costs, especially for a small group of patients. Prognostic factors can help identify high-cost patients, which is crucial to optimize early identification and develop tailored interventions. We aimed to identify prognostic factors for high societal costs, to examine whether the prognostic factors were similar for high healthcare costs and high costs of sick leave, and to investigate the model's robustness across 4 diagnostic categories. Using national Danish registers, potential prognostic factors (age, sex, educational level, long-term sick leave, admission, visits to general practitioner and physiotherapist, comorbidity, diabetes, low back pain, and neck pain) were included in a logistic regression model with high societal costs, defined by the top 10th percentile, as the main outcome. The model's prognostic accuracy was assessed using the Nagelkerke R2 and its discriminative ability using area under the receiver operating curve (AUC). Data on 80% of the patients (n = 449,302) were used to develop the model and 20% (n = 112,363) to validate the model. By far the strongest prognostic factor for high societal costs and high costs of sick leave was sick leave at the time of diagnosis (OR: 20.2, 95% CI: 19.5-20.9). Prognostic factors for high healthcare costs were high age, comorbidity, and hospital admission the year before diagnosis. The model was robust across diagnostic categories and sensitivity analyses. In the validation sample, the primary model's discriminative ability was good (AUC = 0.80) and the model explained 28% of the variation in the outcome (Nagelkerke R2 ).

Interpretation of trial-based economic evaluations of musculoskeletal physical therapy interventions.

BACKGROUND: As resources for healthcare are scarce, decision-makers increasingly rely on economic evaluations when making reimbursement decisions about new health technologies, such as drugs, procedures, devices, and equipment. Economic evaluations compare the costs and effects of two or more interventions. Musculoskeletal disorders have a high prevalence and result in high levels of disability and high costs worldwide. Because physical therapy interventions are usually the first line of treatment for musculoskeletal disorders, economic evaluations of such interventions are becoming increasingly important for stakeholders in the field of physical therapy, including physical therapists, decision-makers, and reseachers. However, economic evaluations are relatively difficult to interpret for the majority of stakeholders. OBJECTIVE: To support physical therapists, decision-makers, and researchers in the field of physical therapy interpreting trial-based economic evaluations and translating the results of such studies to clinical practice. METHODS: The design, analysis, and interpretation of economic evaluations performed alongside randomized controlled trials are discussed. To further illustrate and explain these concepts, we use a case study assessing the cost-effectiveness of exercise therapy compared to standard advice in patients with musculoskeletal disorders. CONCLUSIONS: Economic evaluations are increasingly being used in healthcare decision-making. Therefore, it is of utmost importance that their design, conduct, and analysis are state-of-the-art and that their interpretation is adequate. This masterclass will help physical therapists, decision-makers, and researchers in the field of physical therapy to critically appraise the quality and results of trial-based economic evaluations and to apply the results of such studies to their own clinical practice and setting.

The effect of a multidisciplinary lifestyle program for patients with rheumatoid arthritis, an increased risk for rheumatoid arthritis or with metabolic syndrome-associated osteoarthritis: the "Plants for Joints" randomized controlled trial protocol.

Low-grade inflammation and metabolic syndrome are seen in many chronic diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Lifestyle interventions which combine different non-pharmacological therapies have shown synergizing effects in improving outcomes in patients with other chronic diseases or increased risk thereof, especially cardiovascular disease. For RA and metabolic syndrome-associated OA (MSOA), whole food plant-based diets (WFPDs) have shown promising results. A WFPD, however, had not yet been combined with other lifestyle interventions for RA and OA patients. In this protocol paper, we therefore present Plants for Joints, a multidisciplinary lifestyle program, based on a WFPD, exercise, and stress management. The objective is to study the effect of this program on disease activity in patients with RA (randomized controlled trial [RCT] 1), on a risk score for developing RA in patients with anti-citrullinated protein antibody (ACPA) positive arthralgia (RCT 2) and on pain, stiffness, and function in patients with MSOA (RCT 3), all in comparison with usual care.We designed three 16-week observer-blind RCTs with a waiting-list control group for patients with RA with low to moderate disease activity (2.6 ≤ Disease Activity Score [DAS28] ≤ 5.1, RCT 1, n = 80), for patients at risk for RA, defined by ACPA-positive arthralgia (RCT 2, n = 16) and for patients with metabolic syndrome and OA in the knee and/or hip (RCT 3, n = 80). After personal counseling on diet and exercise, participants join 10 group meetings with 6-12 other patients to receive theoretical and practical training on a WFPD, exercise, and stress management, while medication remains unchanged. The waiting-list control group receives usual care, while entering the program after the RCT. Primary outcomes are: difference in mean change between intervention and control groups within 16 weeks for the DAS28 in RA patients (RCT 1), the RA-risk score for ACPA positive arthralgia patients (RCT 2), and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for MSOA patients (RCT 3). Continued adherence to the lifestyle program is measured in a two-year observational extension study.

Specialised orthotic care to improve functioning in adults with neuromuscular disorders: protocol of a prospective randomised open-label blinded end-point study.

INTRODUCTION: People suffering from leg muscle weakness caused by neuromuscular disorders (NMDs) are often provided with leg orthoses to reduce walking problems such as increased walking effort, diminished walking speed, reduced balance and falls. However, evidence for the effectiveness of leg orthoses to improve walking in this patient group is limited and there is an absence of standardised practice in orthotic prescription. In 2012 a Dutch multidisciplinary guideline was developed aimed to standardise the orthotic treatment process in NMD. Although application of the guideline in expert centres (specialised orthotic care) seems beneficial regarding clinical effectiveness, larger studies are necessary to confirm results and investigate cost-effectiveness. Therefore, this study aims to examine the effectiveness and cost-effectiveness of specialised orthotic care compared with usual orthotic care in adults with slowly progressive NMD. METHODS AND ANALYSIS: A prospective randomised open-label blinded end-point study will be performed, in which 70 adults with slowly progressive NMD are randomly assigned to specialised orthotic care (intervention) or usual orthotic care (control). Outcome measures are assessed at baseline and at 3 and 6 months follow-up. The primary endpoints are gross walking energy cost (J/kg/m) assessed during a 6 min walk test and achievement of personal goals, measured with the Goal Attainment Scale. Secondary endpoints include walking speed, gait biomechanics, stability, physical functioning, falls and fear of falling, perceived fatigue and satisfaction. For the economic evaluation, societal costs and health-related quality of life will be assessed using cost questionnaires and the 5-Level version of EuroQol 5 Dimension, retrospectively. ETHICS AND DISSEMINATION: The study is registered in the Dutch trial register (NL 7511) and the protocol has been approved by the Medical Ethics Committee of the Academic Medical Center in Amsterdam. Results will be presented at national and international scientific conferences and disseminated through peer-reviewed journals and media aimed at a broad audience including patients.