Similar mortality and reduced loss to follow-up in integrated compared with vertical programs providing antiretroviral treatment in sub-saharan Africa.

BACKGROUND: Vertical HIV programs have achieved good results but may not be feasible or appropriate in many resource-limited settings. Médecins sans Frontières has treated HIV in vertical programs since 2000 and over time integrated HIV treatment into general health care services using simplified protocols. We analyzed the survival probability among patients receiving antiretroviral therapy (ART) from 2003 to 2010 in integrated versus vertical programs in 9 countries in sub-Saharan Africa. METHODS AND FINDINGS: Cox regression assessed mortality and program design association, adjusting for baseline age, body mass index, clinical WHO stage, tuberculosis, program age and setting. The analysis included 15,403 HIV-positive adults on ART in 7 vertical (14,124 patients) and 10 integrated (1279 patients) programs. Cox regression including 14,523 patients followed for up to 30 months ART showed similar outcomes for mortality (adjusted hazard ratio (aHR) 1.02; 95% confidence interval (CI): 0.83 to 1.24) and lower risk of loss to follow-up (aHR: 0.71; 95% CI: 0.61 to 0.83) in integrated compared with vertical programs. The greatest risk of death was from initiating ART at WHO stage 4 (aHR 1.99, 95% CI: 1.74 to 2.29), although greater program experience was protective (aHR: 0.77, 95% CI: 0.66 to 0.89). Risk of loss to follow-up was greater in experienced programs (aHR: 3.33; 95% CI: 2.92 to 3.79) and rural settings (aHR: 3.82; 95% CI: 3.49 to 4.20). CONCLUSIONS: ART delivery in integrated general health care programs results in good outcomes. Compared with vertical HIV programs, patients initiated ART in integrated programs at more advanced stages of clinical immunosuppression yet had similar risk of death and lower risk of loss to follow-up

The Epidemiology of Staphylococcus aureus and Panton-Valentine Leucocidin (pvl) in Central Australia, 2006-2010

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: The Central Australian Indigenous population has a high incidence of Staphylococcus aureus bacteremia (SAB) but little is known about the local molecular epidemiology. Methods: Prospective observational study of bacteremic and nasal colonizing S.aureus isolates between June 2006 to June 2010. All isolates underwent single nucleotide polymorphism (SNP) genotyping and testing for the presence of the Panton-Valentine Leucocidin (pvl) gene. Results: Invasive isolates (n = 97) were predominantly ST93 (26.6 %) and pvl positive (54.3 %), which was associated with skin and soft tissue infections (OR 4.35, 95 % CI 1.16, 16.31). Non-multiresistant MRSA accounted for 31.9 % of bacteremic samples and showed a trend to being healthcare associated (OR 2.16, 95 % CI 0.86, 5.40). Non-invasive isolates (n = 54) were rarely ST93 (1.9 %) or pvl positive (7.4 %). Conclusions: In Central Australia, ST93 was the dominant S.aureus clone, and was frequently pvl positive and associated with an aggressive clinical phenotype. Whether non-nasal carriage is more important with invasive clones or whether colonization occurs only transiently remains to be elucidated

The Australian multiple sclerosis (MS) immunotherapy study: A prospective, multicentre study of drug utilisation using the MSBase platform

To prospectively characterise treatment persistence and predictors of treatment discontinuation in an Australian relapsing-remitting multiple sclerosis (RRMS) population. Tertiary MS treatment centres participating in the MSBase registry prospectively assessed treatment utilisation, persistence, predictors of treatment discontinuation and switch rates. Multivariable survival analyses were used to compare treatment persistence between drugs and to identify predictors of treatment discontinuation. 1113 RRMS patients were studied. Patients persisted on their first disease-modifying therapy (DMT) for a median of 2.5 years. Treatment persistence on GA was shorter than on all IFNβ products (p<0.03). Younger age at treatment initiation and higher EDSS were predictive of DMT discontinuation. Patients persisted on subsequent DMTs, for 2.3 years. Patients receiving natalizumab (NAT) as a subsequent DMT persisted longer on treatment than those on IFNβ or GA (p<0.000). The primary reason for treatment discontinuation for any drug class was poor tolerability. Annualised switch or cessation rates were 9.5–12.5% for individual IFNβ products, 11.6% for GA and 4.4% for NAT. This multicentre MS cohort study is the first to directly compare treatment persistence on IFNβ and GA to NAT. We report that treatment persistence in our Australian RRMS population is short, although patients receiving IFNβ as a first DMT persisted longer on treatment than those on GA. Additionally, patients receiving NAT as a subsequent DMT were more likely to persist on treatment than those switched to IFNβ or GA. EDSS and age at DMT initiation were predictive of DMT discontinuation. Treatment intolerance was the principal reason for treatment cessation

Impact of HIV-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010

Association between early treatment of multiple sclerosis and patient-reported outcomes: a nationwide observational cohort study

Background Timing of disease-modifying therapy affects clinical disability in multiple sclerosis, but it is not known whether patient reported outcomes are also affected. This study investigates the relationship between treatment timing and patient-reported symptoms and health-related quality of life. Methods This was a nationwide observational cohort study of adults with relapsing multiple sclerosis, with disease onset between 2001 and 2016, and commenced on disease-modifying treatment within 4 years from disease onset. Patients commencing treatment within 0–2 years were compared with patients commencing treatment at 2–4 years. Indication bias was mitigated by propensity matching. Outcomes were patient-reported symptoms and health-related quality of life as measured by the Multiple Sclerosis Impact Scale (MSIS-29) and EuroQol-5 Dimensions-3 Level (EQ-5D). The follow-up period was 4–10 years from disease onset. Results There were 2648 patients (69% female, median age 32.8) eligible for matching. Mean follow-up time was 3.7 years. Based on 780 matched patients, each year of treatment delay was associated with a worse MSIS physical score by 2.75 points (95% CI 1.29 to 4.20), and worse MSIS psychological score by 2.02 points (95% CI 0.03 to 3.78), in the adjusted models. Among 690 matched patients, earlier treatment start was not associated with EQ-5D score during the follow-up. Conclusions Earlier commencement of disease-modifying treatment was associated with better patient-reported physical symptoms when measured using a disease-specific metric; however, general quality of life was not affected. This indicates that other factors may inform patients’ overall quality of life

Incidence of WHO stage 3 and 4 conditions following initiation of Anti-Retroviral Therapy in resource limited settings

To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS)

Women With Chronic Hypoparathyroidism Have Low Risk of Adverse Pregnancy Outcomes

Context: There are scarce data on the management of chronic hypoparathyroidism (hypoPT) in pregnant women. Objective: The aim of this study was to evaluate pregnancy outcome and total number of births in maternal chronic hypoPT. Methods: The Swedish National Patient Register, The Swedish Prescribed Drug Register, Swedish Medical Birth Register, and the Total Population Register were used to identify 97 women with chronic hypoPT and 1030 age-matched controls who delivered 139 and 1577 singleton infants, respectively, following diagnosis between 1997 and 2017. Results: Women in the chronic hypoPT group had more frequent diabetes (DM) and chronic kidney disease (CKD) compared with the control group (P = 0.043 and P < 0.001, respectively). After adjusting for DM, CKD, maternal age at delivery, and calendar year of delivery, chronic hypoPT cases were associated with increased risk of induction of labor (OR, 1.82; 95% CI, 1.13-2.94) and birth of infants with lower birth weight (beta-coefficient -188 g; 95% CI, -312.2 to -63.8) compared with controls. No difference was found in infant length, small for gestational age, or head circumference after adjustments. Mean gestational age at delivery after controlling for DM, CKD, and pre-eclampsia was not significantly younger (P = 0.119). There was no difference in congenital malformations or perinatal death and no difference in the total number of infants born between groups (P = 0.518). Conclusion: The majority of women with chronic hypoPT had normal pregnancy outcomes, and the overall risks appear low. Maternal chronic hypoPT is, however, associated with higher risk of induction of labor and slightly lower infant birth weight.Peer reviewe

Early Adherence to Antiretroviral Medication as a Predictor of Long-Term HIV Virological Suppression: Five-Year Follow Up of an Observational Cohort

OBJECTIVE: Previous studies have demonstrated a cross-sectional relationship between antiretroviral adherence and HIV virological suppression. We assessed the predictive value of baseline adherence in determining long-term virological failure. DESIGN: We assessed baseline adherence via an adherence questionnaire between administered to all consenting patients attending antiretroviral clinics in Khayelitsha township, South Africa, between May 2002 and March 2004. Virological status was ascertained after five years of follow up and multivariate analysis used to model associations of baseline variables and medication adherence with time to viral suppression or failure. RESULTS: Our adherence cohort comprised 207 patients, among whom 72% were female. Median age was 30 years and median CD4 count at initiation was 55 cells/mm(3). We found no statistically significant differences between baseline characteristics and early adherence groups. Multivariate analysis adjusting for baseline CD4 and age found that patients with suboptimal baseline adherence had a hazard ratio of 2.82 (95% CI 1.19-6.66, p = 0.018) for progression to virological failure compared to those whose baseline adherence was considered optimal. CONCLUSIONS: Our longitudinal study provides further confirmation of adherence as a primary determinant of subsequent confirmed virological failure, and serves as a reminder of the importance of initial early investments in adherence counseling and support as an effective way to maximize long-term treatment success