The association between brain volume loss and disability in multiple sclerosis: A systematic review.

BACKGROUND: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, degenerative disease of the central nervous system that affects approximately 2.8 million people worldwide. Compelling evidence from observational studies and clinical trials indicates a strong association between brain volume loss (BVL) and the accumulation of disability in MS. However, the considerable heterogeneity in study designs and methods of assessment of BVL invites questions concerning the generalizability of the reported findings. Therefore, we conducted this systematic review to characterize the relationship between BVL and physical disability in patients with MS. METHODS: A systematic literature search of MEDLINE and EMBASE databases was performed supplemented by gray literature searches. The following study designs were included: prospective/retrospective cohort, cross-sectional and case-control. Only English language articles published from 2010 onwards were eligible for final inclusion. There were no restrictions on MS subtype, age, or ethnicity. Of the 1620 citations retrieved by the structured searches, 50 publications met our screening criteria and were included in the final data set. RESULTS: Across all BVL measures, there was considerable heterogeneity in studies regarding the underlying study population, the definitions of BVL and image analysis methodologies, the physical disability measure used, the measures of association reported and whether the analysis conducted was univariable or multivariable. A total of 36 primary studies providing data on the association between whole BVL and physical disability in MS collectively suggest that whole brain atrophy is associated with greater physical disability progression in MS patients. Similarly, a total of 15 primary studies providing data on the association between ventricular atrophy and physical disability in MS suggest that ventricular atrophy is associated with greater physical disability progression in MS patients. Along similar lines, the existing evidence based on a total of 13 primary studies suggests that gray matter atrophy is associated with greater physical disability progression in MS patients. Four primary studies suggest that corpus callosum atrophy is associated with greater physical disability progression in MS patients. The majority of the existing evidence (6 primary studies) suggests no association between white matter atrophy and physical disability in MS. It is difficult to assign a relationship between basal ganglia volume loss and physical disability as well as medulla oblongata width and physical disability in MS due to very limited data. CONCLUSION: The evidence gathered from this systematic review, although very heterogeneous, suggests that whole brain atrophy is associated with greater physical disability progression in MS patients. Our review can help define future imaging biomarkers for physical disability progression and treatment monitoring in MS.

Socioeconomic burden of schizophrenia: a targeted literature review of types of costs and associated drivers across 10 countries.

AIMS: Schizophrenia has the highest median societal cost per patient of all mental disorders. This review summarizes the different costs/cost drivers (cost components) associated with schizophrenia in 10 countries, including all cost types and stakeholder perspectives, and highlights aspects of disease associated with greatest costs. MATERIALS AND METHODS: Targeted literature review based on a search of published research from 2006 to 2021 in the United States (US), United Kingdom (UK), France, Germany, Italy, Spain, Canada, Japan, Brazil, and China. RESULTS: Sixty-four published articles (primary studies and literature reviews) were included. Comprehensive data were available on costs in schizophrenia overall, with very limited data for individual countries except the US. Most data is related to direct and not indirect costs, with extremely scarce data for several key cost components (adverse events, suicide, long-term care). Total schizophrenia-related per person per year (PPPY) costs were $2,004-94,229, with considerable variability among countries. Indirect costs were the main cost driver (50-90% of all costs), ranging from $1,852 to $62,431 PPPY. However, indirect costs are not collected systematically or incorporated in health technology assessments. Total schizophrenia-related PPPY direct costs were $4,394-31,798, with inpatient cost as the main cost driver (∼20-99% of direct costs). Intangible costs were not reported. Despite limited evidence, total schizophrenia-related costs were higher in patients with than without negative symptoms, largely due to increased costs of medication and medical visits. LIMITATIONS: As this was not a systematic review, prioritization of studies may have resulted in exclusion of potentially relevant data. All costs were converted to USD but not corrected for inflation or subjected to a gross domestic product deflator. CONCLUSIONS: Direct costs are most commonly reported in schizophrenia. The substantial underreporting of indirect and intangible costs undervalues the true economic burden of schizophrenia from a payer, patient, and societal perspective.

The true costs of diseases such as schizophrenia extend far beyond the obvious direct costs of hospital visits, outpatient appointments and medications to include indirect costs such as loss of productivity among patients and caregivers due to unemployment, early retirement and premature death. This review of literature published between 2006 and 2021 reveals that the indirect costs of schizophrenia actually account for between 50% and 90% of all costs, but are often not taken into account in healthcare planning. In addition, intangible costs, including the pain, suffering, stress, and anxiety experienced by patients and caregivers due to schizophrenia have not been reported in the literature. Costs were also higher for patients with negative symptoms of schizophrenia (where patients appear withdrawn and lacking in emotion, with few social relationships) compared with those with positive symptoms (including delusions or hallucinations). This is largely due to the greater costs for medications and medical visits among patients with negative symptoms. In summary, this review demonstrates that the true cost of schizophrenia, including direct, indirect, and intangible costs, is likely to be substantially higher than the values for the cost of disease currently reported.

Opportunistic infections associated with Janus kinase inhibitor treatment for rheumatoid arthritis: A structured literature review.

BACKGROUND: The availability of Janus kinase (JAK) inhibitors has transformed the management of rheumatoid arthritis (RA), helping patients achieve clinical remission. However, the emergence of opportunistic infections (OIs) associated with the use of JAK inhibitors has been reported. This structured literature review was conducted to summarize reports of OIs associated with JAK inhibitor treatment for RA in clinical trials. METHODS: Structured searches were performed in MEDLINE® and Embase® to identify relevant clinical trial data through March 2021. Bibliographic searches of recent reviews were also conducted, and gray literature searches were used to supplement key gap areas. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. RESULTS: Following screening, 105 publications describing 62 unique clinical trials reporting the rates of OIs in RA patients treated with JAK inhibitors were included. Overall, the highest exposure-adjusted incidence rate was reported for herpes zoster (HZ) infection (any form), followed by OI (any) and tuberculosis based on limited data from clinical trials with approved doses of JAK inhibitors. Lack of head-to-head trials and differences in trial design preclude direct comparison across JAK inhibitors. Higher rates of OIs were noted in the Asian and Australian populations compared with the global population. Higher rates of OIs were also noted with increasing dose of JAK inhibitors in most clinical trial data. CONCLUSIONS: HZ was the most common OI reported among RA patients using all currently approved JAK inhibitors in clinical trials, although tuberculosis and other OIs were also reported. More long-term safety studies in the real-world setting are needed to compare the risk of OIs between various JAK inhibitors.