Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Contribution of mental and physical disorders to disability in military personnel.

Background: Combat operations in Southwest Asia have exposed millions of military personnel to risk of mental disorders and physical injuries, including traumatic brain injury (TBI). The contribution of specific disorders to disability is, however, uncertain. Aims: To estimate the contributions of mental and physical health conditions to disability in military personnel. Methods: The sample consisted of military personnel who participated in the cross-sectional 2013 Canadian Forces Mental Health Survey. Disability was measured using the World Health Organization Disability Assessment. The International Classification of Functioning, Disability, and Health was used to classify participants with moderate/severe disability. Chronic mental disorders and physical conditions were measured by self-reported health professional diagnoses, and their contribution to disability was assessed using logistic regression and resulting population attributable fractions. Results: Data were collected from 6696 military members. The prevalence of moderate/severe disability was 10%. Mental disorders accounted for 27% (95% confidence interval [CI] 23-31%) and physical conditions 62% (95% CI 56-67%) of the burden of disability. Chronic musculoskeletal problems 33% (95% CI 26-39%), back problems 29% (95% CI 23-35%), mood disorders 16% (95% CI 11-19%) and post-traumatic stress disorder (PTSD) 9% (95% CI 5-12%) were the leading contributors to disability. After-effects of TBI accounted for only 3% (95% CI 1-4%) of disability. Mental and physical health interacted broadly, such that those with mental disorders experienced disproportionate disability in the presence of physical conditions. Conclusions: Chronic musculoskeletal conditions, back problems, mood disorders and PTSD are primary areas of focus in prevention and control of disability in military personnel.

Predictive value of quick Sepsis-Related Organ Failure Scores following sepsis-related Medical Emergency Team calls: a retrospective cohort study.

We conducted a cohort study of adult ward patients who had a Medical Emergency Team (MET) call triggered by confirmed or suspected sepsis in an Australian tertiary centre to assess the predictive utility of systemic inflammatory response syndrome (SIRS) and quick Sepsis-Related Organ Failure Assessment (qSOFA) scores for 28-day mortality over a 12-month period. Sepsis was the causative aetiology in 970 MET calls for 646 patients with a mean age of 68 years and median Charlson Comorbidity score (CCS) of 3.0. Four hundred and seven (63%) patients had microbiological identification of a causative organism with 35 (9%) demonstrating multi-drug resistance. The 28-day mortality rate was 22%. Independent risk factors for 28-day mortality included age (incidence rate ratio [IRR] 1.038; P <0.001) and CCS (IRR 1.102; P <0.001). qSOFA positive patients had a three-fold risk of 28 day mortality compared to those who were negative (IRR 3.15; P=0.02). Both the SIRS and qSOFA score had poor sensitivity (86% versus 62%, respectively) for mortality as a sole diagnostic tool and should be investigated as part of a multiparameter panel within a large prospective study.

Validation of the Lupus Impact Tracker in an Australian patient cohort.

OBJECTIVES: The objective of this article is to validate the Lupus Impact Tracker (LIT), a disease-specific patient-reported outcome (PRO) tool, in systemic lupus erythematosus (SLE) patients in a multi-ethnic Australian cohort. METHODS: Patients attending the Monash Lupus Clinic were asked to complete the LIT, a 10-item PRO. Psychometric testing assessing criterion validity, construct validity, test-retest reliability (TRT) and internal consistency reliability (ICR) were performed. We compared the LIT scores across patient characteristics, and correlations between LIT scores and SLEDAI-2k, PGA, and SLICC-SDI were examined. RESULTS: LIT data were obtained from 73 patients. Patients were 84% female with a median age of 41 years, and 34% were Asian. The cohort had mild-moderate disease activity with a median (IQR) Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2k) of 4 (IQR 2-6). The median LIT score was 32.5 (IQR 17.5-50). LIT demonstrated criterion validity against SLEDAI-2k and SDI. Construct validity assessed by confirmatory factor analysis demonstrated an excellent fit (Goodness of fit index 0.95, Comparative Fit Index 1, Root Mean Square Error of Approximation <0.0001). The LIT demonstrated TRT with an overall intraclass correlation coefficient of 0.986 (95% CI 0.968-0.995). ICR was demonstrated with a Cronbach's alpha of 0.838. Patients with disability, low socioeconomic status, or higher disease activity had significantly worse LIT scores. CONCLUSION: The LIT demonstrated properties consistent with its being valid in this population. Lower socioeconomic status appears to have a significant impact on patient-reported health-related quality of life in SLE.