Community outreach programs and major adherence lapses with antiretroviral therapy in rural Kakamega, Kenya.

We investigated features of major adherence lapses in antiretroviral therapy (ART) at public Emusanda Health Centre in rural Kakamega County, Kenya using medical records from 2008 to 2015 for all 306 eligible patients receiving ART. Data were modelled using survival analysis. Patients were more likely to lapse if they received stavudine (hazard ratio (HR) 2.54, 95% confidence interval (95%CI):1.44-4.47) or zidovudine (HR 1.64, 95%CI:1.02-2.63) relative to tenofovir. Each day a patient slept hungry per month increased risk of major adherence lapse by 3% (95%CI:0-7%). Isolated home visits by community health workers (CHWs) were more effective to assist patients to return to the health centre than isolated phone calls (HR 2.52, 95%CI:1.02-6.20).

The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis.

OBJECTIVE: The type 1 interferon (IFN) pathway is up-regulated in dermatomyositis (DM). We sought to define how organ-specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic type I IFN activity in adult patients with DM. METHODS: RNA sequencing was performed on 355 whole blood samples collected from 202 well-phenotyped DM patients followed up during the course of their clinical care. A previously defined 13-gene type I IFN score was modeled as a function of demographic, serologic, and clinical variables using both cross-sectional and longitudinal data. RESULTS: The pattern of type I IFN-driven transcriptional response was stereotyped across samples with a sequential modular activation pattern strikingly similar to systemic lupus erythematosus. The median type I IFN score was higher or lower in patients with anti-melanoma differentiation-associated protein 5 (anti-MDA-5) or anti-Mi-2 antibodies, respectively, compared to patients without these antibodies. Absolute type I IFN score was independently associated with muscle and skin disease activity, interstitial lung disease, and anti-MDA-5 antibodies. Changes in the type I IFN score over time were significantly associated with changes in skin or muscle disease activity. Stratified analysis accounting for heterogeneity in organ involvement and antibody class revealed high correlation between changes in the type I IFN score and skin disease activity (Spearman's ρ = 0.84-0.95). CONCLUSION: The type I IFN score is independently associated with skin and muscle disease activity as well as certain clinical and serologic features in DM. Accounting for the effect of muscle disease and anti-MDA-5 status revealed that the type I IFN score is strongly correlated with skin disease activity, providing support for type I IFN blockade as a therapeutic strategy for DM.

Dermatomyositis autoantibodies: how can we maximize utility?

The past 15 years has seen significant advances in the characterization of myositis-specific autoantibodies (MSAs) and their associated phenotypes in patients with dermatomyositis (DM). As more careful studies are performed, it is clear that unique combinations of clinical and pathological phenotypes are associated with each MSA, despite the fact that there is considerable heterogeneity within antibody classes as well as overlap across the groups. Because risk for interstitial lung disease (ILD), internal malignancy, adverse disease trajectory, and, potentially response to therapy differ by DM MSA group, a deeper understanding of MSAs and validation and standardization of assays used for detection are critical for optimizing diagnosis and treatment. Like any test, the diagnostic sensitivity and specificity of assays for various MSAs is not perfect. Currently tests for MSAs are helpful at minimum for a clinician to assess relative risk or contribute to diagnosis and perhaps counsel the appropriate patient about what to expect. With international standardization and larger studies it is likely that more antibody tests will make their way into formal schemata for diagnosis and actionable risk assessment in DM. In this review, we summarize key considerations for interpreting the clinical and pathologic associations with MSA in DM and identify critical gaps in knowledge and practice that will maximize their clinical utility and utility for understanding disease pathogenesis.

Ten-year survival with analysis of gender difference, risk factors, and causes of death during 13 years of public antiretroviral therapy in rural Kenya.

Evidence for why antiretroviral therapy (ART) outcomes differ by gender in developing countries has been inconclusive. In this first study to assess 10-year survival on ART in Kenya, our objective was to compare gender differences in survival for those who began ART as adults and as children. Kakamega County Referral Hospital (KCRH) is a tertiary rural hospital that has provided public ART to Kenyans since 2004. All patients enrolled in ART at KCRH who died between July 2004 and March 2017 and a sample of living patients were included in a survival analysis that bootstrapped sampled data. Case-cohort regressions identified adjusted hazard ratios. In total, 1360 patients were included in the study. Ten-year survival was 77% (95% confidence band [CB] 73-81%), significantly different for men (65%; 95% CB: 45-74%) and women (83%; 95% CB: 78-86%) who began therapy as adults. Ten-year survival was intermediate with no significant gender difference (76%; 95% CB: 69-81%) for patients who began therapy as children. Hazard of death was increased for men (hazard ratio [HR] 1.56; 95% confidence interval [CI] 1.13-2.17), infants (HR 2.87; 95% CI 1.44-5.74), patients with consistently poor clinic attendance (HR 3.94; 95% CI 3.19-4.86), and divorced patients (HR 2.25; 95% CI 1.19-4.25). Tuberculosis, diarrheal illnesses, human immunodeficiency virus (HIV) wasting syndrome, and malaria were leading causes of death. Survival was significantly lower for men than for women in all time periods, but only for patients who began therapy as adults, indicating against biological etiologies for the gender mortality difference.