Patients with multiple sclerosis acquire disability either through: (1) Relapse-associated worsening (RAW), or (2) progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins, and the extent to which multiple sclerosis therapies delay disability accumulation. Using the Novartis-Oxford MS (NO.MS) data pool spanning all multiple sclerosis phenotypes and pediatric multiple sclerosis, we evaluated ∼200,000 EDSS transitions from >27,000 patients with ≤15 years follow-up. We analyzed three datasets: (A) A full analysis dataset containing all observational and randomized controlled clinical trials in which disability and relapses were assessed (N = 27,328); (B) All phase 3 clinical trials (N = 8364); and (C) All placebo-controlled phase 3 clinical trials (N = 4970). We determined the relative importance of RAW and PIRA, investigated the role of relapses on all-cause disability worsening using Andersen-Gill models, and observed the impact of the mechanism of worsening and disease modifying therapies (DMTs) on the time to reach milestone disability levels using time continuous Markov models. PIRA started early in multiple sclerosis, occurred in all phenotypes, and became the principal driver of disability accumulation in the progressive phase of the disease. Relapses significantly increased the hazard of all-cause disability worsening events: Following a year in which relapses occurred (vs a year without relapses), the hazard increased by 31–48%; all p < 0.001. Pre-existing disability and older age were the principal risk factors for incomplete relapse recovery. For placebo-treated patients with minimal disability (EDSS 1) it took 8.95 years until increased limitation in walking ability (EDSS 4) and 18.48 years to require walking assistance (EDSS 6). Treating patients with DMTs delayed these times significantly by 3.51 years (95% confidence limit: 3.19, 3.96) and by 3.09 years (2.60, 3.72), respectively. In relapsing-remitting multiple sclerosis (RRMS), patients who worsened exclusively due to RAW events took a similar time to reach milestone EDSS values compared with those with PIRA events; the fastest transitions were observed in patients with PIRA and superimposed relapses. Our data confirm relapses contribute to the accumulation of disability, primarily early in multiple sclerosis. PIRA starts already in RRMS and becomes the dominant driver of disability accumulation as the disease evolves. Pre-existing disability and older age are the principal risk factors for further disability accumulation. Using DMTs delays disability accrual by years, with the potential to gain time being highest in the earliest stages of multiple sclerosis.

BackgroundInternet search query trends have been shown to correlate with incidence trends for select infectious diseases and countries. Herein, the first use of Google search queries for malaria surveillance is investigated. The research focuses on Thailand where real-time malaria surveillance is crucial as malaria is re-emerging and developing resistance to pharmaceuticals in the region.MethodsOfficial Thai malaria case data was acquired from the World Health Organization (WHO) from 2005 to 2009. Using Google correlate, an openly available online tool, and by surveying Thai physicians, search queries potentially related to malaria prevalence were identified. Four linear regression models were built from different sub-sets of malaria-related queries to be used in future predictions. The models’ accuracies were evaluated by their ability to predict the malaria outbreak in 2009, their correlation with the entire available malaria case data, and by Akaike information criterion (AIC).ResultsEach model captured the bulk of the variability in officially reported malaria incidence. Correlation in the validation set ranged from 0.75 to 0.92 and AIC values ranged from 808 to 586 for the models. While models using malaria-related and general health terms were successful, one model using only microscopy-related terms obtained equally high correlations to malaria case data trends. The model built strictly of queries provided by Thai physicians was the only one that consistently captured the well-documented second seasonal malaria peak in Thailand.ConclusionsModels built from Google search queries were able to adequately estimate malaria activity trends in Thailand, from 2005–2010, according to official malaria case counts reported by WHO. While presenting their own limitations, these search queries may be valid real-time indicators of malaria incidence in the population, as correlations were on par with those of related studies for other infectious diseases. Additionally, this methodology provides a cost-effective description of malaria prevalence that can act as a complement to traditional public health surveillance. This and future studies will continue to identify ways to leverage web-based data to improve public health.

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Discrimination is associated with poorer mental and physical health outcomes. Taxi drivers have a higher risk of exposure to discrimination and higher rates of chronic conditions. A cross-sectional needs assessment was conducted with a multilingual group of 535 male taxi drivers in New York City. Drivers reporting higher discrimination were more likely to have higher perceived stress and were more likely to have anxiety/depression and chronic pain, adjusting for confounders. Workplace-based interventions designed to help drivers cope with discrimination, stress, and chronic health conditions, interventions to educate the taxi-riding public, and greater attention to these issues from administrative agencies are warranted.

Patients often discontinue from a clinical trial because their health condition is not improving or they cannot tolerate the assigned treatment. Consequently, the observed clinical outcomes in the trial are likely better on average than if every patient had completed the trial. If these differences between trial completers and non-completers cannot be explained by the observed data, then the study outcomes are missing not at random (MNAR). One way to overcome this problem-

Immigrant taxi drivers in metropolitan cities are exposed to experiences of discrimination and occupation-based health risks. Given the structural differences in health care systems in the United States and Canada, we investigated the differences in reports of discrimination, health conditions and concern about health conditions between taxi drivers in New York City and Toronto, Ontario. Participants were recruited for a taxi driver Needs Assessment Survey as part of a Taxi Network needs assessment project using a street side convenience sampling technique in New York City and Toronto. The matched sample contained 33 drivers from Toronto and 33 drivers from NYC. All Toronto drivers in our sample reported having health insurance while over a quarter of NYC drivers did not have health insurance. Toronto drivers reported greater everyday and workplace discrimination. Drivers in both cities experienced higher rates than average, and reported concern about, major health conditions. We also found preliminary evidence suggesting a relationship between experiencing discrimination and reporting chronic pain. Our findings suggest the need for future research to more closely examine the associations between discrimination and health among the taxi driver population.

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Investigators have proposed a “transdiagnostic vulnerability framework” that examines the relationship between smoking and broader emotional factors, including anhedonia, anxiety sensitivity, and distress tolerance. Because smoking and depression are more common in persons living with HIV and AIDS (PLWHA) than in the general population, understanding the relationship between smoking and mental health is critical. The following study aims to characterize levels of clinically significant depressive symptoms and these broader emotional factors as well as the relationship between these factors and smoking-related variables in a sample of PLWHA. This cross-sectional study employed convenience sampling to survey adult clients who attended one of three AIDS service organizations in New York City. The questionnaires assessed sociodemographic and HIV health care variables, tobacco use, and anxiety- and depression-related constructs. 150 PLWHA completed surveys. Among the 118 smokers, the prevalence of clinically depressive symptoms was 53%. Participants with clinically significant depressive symptoms had significantly higher mean anhedonia scores and anxiety sensitivity scores and lower mean distress tolerance total scores compared to participants without clinically significant depressive symptoms (p<0.001). Smoking cessation treatment for persons with co-morbid psychiatric disorders has been suboptimal and treatment for co-morbid mental health conditions tends to align with disorder-specific treatment. Given that PLWHA are a priority population, further research should address how to best tailor interventions to a group with multiple obstacles to successful tobacco cessation.