Towards elimination of mother-to-child transmission of HIV: performance of different models of care for initiating lifelong antiretroviral therapy for pregnant women in Malawi (Option B+).

INTRODUCTION: Malawi introduced a new strategy to improve the effectiveness of prevention of mother-to-child HIV transmission (PMTCT), the Option B+ strategy. We aimed to (i) describe how Option B+ is provided in health facilities in the South East Zone in Malawi, identifying the diverse approaches to service organization (the "model of care") and (ii) explore associations between the "model of care" and health facility-level uptake and retention rates for pregnant women identified as HIV-positive at antenatal (ANC) clinics. METHODS: A health facility survey was conducted in all facilities providing PMTCT/antiretroviral therapy (ART) services in six of Malawi's 28 districts to describe and compare Option B+ service delivery models. Associations of identified models with program performance were explored using facility cohort reports. RESULTS: Among 141 health facilities, four "models of care" were identified: A) facilities where newly identified HIV-positive women are initiated and followed on ART at the ANC clinic until delivery; B) facilities where newly identified HIV-positive women receive only the first dose of ART at the ANC clinic, and are referred to the ART clinic for follow-up; C) facilities where newly identified HIV-positive women are referred from ANC to the ART clinic for initiation and follow-up of ART; and D) facilities serving as ART referral sites (not providing ANC). The proportion of women tested for HIV during ANC was highest in facilities applying Model A and lowest in facilities applying Model B. The highest retention rates were reported in Model C and D facilities and lowest in Model B facilities. In multivariable analyses, health facility factors independently associated with uptake of HIV testing and counselling (HTC) in ANC were number of women per HTC counsellor, HIV test kit availability, and the "model of care" applied; factors independently associated with ART retention were district location, patient volume and the "model of care" applied. CONCLUSIONS: A large variety exists in the way health facilities have integrated PMTCT Option B+ care into routine service delivery. This study showed that the "model of care" chosen is associated with uptake of HIV testing in ANC and retention in care on ART. Further patient-level research is needed to guide policy recommendations

Evaluation of the use of serum C-reactive protein concentration to predict outcome in puppies infected with canine parvovirus

OBJECTIVE—To evaluate associations of serum C-reactive protein (CRP) concentration with duration of hospitalization and with outcome in puppies with canine parvoviral enteritis. DESIGN—Prospective observational study. ANIMALS—79 client-owned puppies with naturally acquired canine parvovirus infection. PROCEDURES—All puppies received supportive care. Serum CRP concentration was measured at the time of admission, approximately every 10 to 12 hours for the first 48 hours, and then every 24 hours until discharge from the hospital or death. Associations between outcome and CRP concentration at various time points or changes in CRP concentration over time were assessed via multiple logistic regression. Associations of CRP concentration with survival time and duration of hospitalization among survivors were estimated with Cox proportional hazards regression. Use of CRP concentration to predict outcome was evaluated by means of receiver operating characteristic curve analysis. RESULTS—Serum CRP concentrations at admission and 12 and 24 hours later were positively associated with odds of death, and CRP concentrations at 12 and 24 hours after admission were negatively associated with survival time for puppies. Among survivors, duration of hospitalization was positively associated with CRP concentrations at 12, 24, and 36 hours after admission. Sensitivity and specificity of CRP concentration to differentiate between survivors and nonsurvivors at 24 hours after admission were 86.7% and 78.7%, respectively (considered moderately accurate). CONCLUSIONS AND CLINICAL RELEVANCE—Although serum CRP concentration was associated with outcome in puppies with canine parvovirus enteritis, it did not prove to be a good predictor of outcome when used alone.http://avmajournals.avma.org/loi/javmaam2014mn201

Building a knowledge translation platform in Malawi to support evidence-informed health policy

Abstract With the support of the World Health Organization’s Evidence-Informed Policy Network, knowledge translation platforms have been developed throughout Africa, the Americas, Eastern Europe, and Asia to further evidence-informed national health policy. In this commentary, we discuss the approaches, activities and early lessons learned from the development of a Knowledge Translation Platform in Malawi (KTPMalawi). Through ongoing leadership, as well as financial and administrative support, the Malawi Ministry of Health has strongly signalled its intention to utilize a knowledge translation platform methodology to support evidence-informed national health policy. A unique partnership between Dignitas International, a medical and research non-governmental organization, and the Malawi Ministry of Health, has established KTPMalawi to engage national-level policymakers, researchers and implementers in a coordinated approach to the generation and utilization of health-sector research. Utilizing a methodology developed and tested by knowledge translation platforms across Africa, a stakeholder mapping exercise and initial capacity building workshops were undertaken and a multidisciplinary Steering Committee was formed. This Steering Committee prioritized the development of two initial Communities of Practice to (1) improve data utilization in the pharmaceutical supply chain and (2) improve the screening and treatment of hypertension within HIV-infected populations. Each Community of Practice’s mandate is to gather and synthesize the best available global and local evidence and produce evidence briefs for policy that have been used as the primary input into structured deliberative dialogues. While a lack of sustained initial funding slowed its early development, KTPMalawi has greatly benefited from extensive technical support and mentorship by an existing network of global knowledge translation platforms. With the continued support of the Malawi Ministry of Health and the Evidence-Informed Policy Network, KTPMalawi can continue to build on its role in facilitating the use of evidence in the development and refinement of health policy in Malawi

The impact of a knowledge translation intervention employing educational outreach and a point-of-care reminder tool vs standard lay health worker training on tuberculosis treatment completion rates: study protocol for a cluster randomized controlled trial

Abstract Background Despite availability of effective treatment, tuberculosis (TB) remains an important cause of morbidity and mortality globally, with low- and middle-income countries most affected. In many such settings, including Malawi, the high burden of disease and severe shortage of skilled healthcare workers has led to task-shifting of outpatient TB care to lay health workers (LHWs). LHWs improve access to healthcare and some outcomes, including TB completion rates, but lack of training and supervision limit their impact. The goals of this study are to improve TB care provided by LHWs in Malawi by refining, implementing, and evaluating a knowledge translation strategy designed to address a recognized gap in LHWs’ TB and job-specific knowledge and, through this, to improve patient outcomes. Methods/design We are employing a mixed-methods design that includes a pragmatic cluster randomized controlled trial and a process evaluation using qualitative methods. Trial participants will include all health centers providing TB care in four districts in the South East Zone of Malawi. The intervention employs educational outreach, a point-of-care reminder tool, and a peer support network. The primary outcome is proportion of treatment successes, defined as the total of TB patients cured or completing treatment, with outcomes taken from Ministry of Health treatment records. With an alpha of 0.05, power of 0.80, a baseline treatment success of 0.80, intraclass correlation coefficient of 0.1 based on our pilot study, and an estimated 100 clusters (health centers providing TB care), a minimum of 6 patients per cluster is required to detect a clinically significant 0.10 increase in the proportion of treatment successes. Our process evaluation will include interviews with LHWs and patients, and a document analysis of LHW training logs, quarterly peer trainer meetings, and mentorship meeting notes. An estimated 10–15 LHWs and 10–15 patients will be required to reach saturation in each of 2 planned interview periods, for a total of 40–60 interview participants. Discussion This study will directly inform the efforts of knowledge users within TB care and, through extension of the approach, other areas of care provided by LHWs in Malawi and other low- and middle-income countries. Trial registration ClinicalTrials.gov NCT02533089 . Registered 20 August 2015. Protocol Date/Version 29 May 2016/Version 2

Impact of a tuberculosis treatment adherence intervention versus usual care on treatment completion rates: results of a pragmatic cluster randomized controlled trial

Abstract Background With the global shortage of skilled health workers estimated at 7.2 million, outpatient tuberculosis (TB) care is commonly task-shifted to lay health workers (LHWs) in many low- and middle-income countries where the shortages are greatest. While shown to improve access to care and some health outcomes including TB treatment outcomes, lack of training and supervision limit the effectiveness of LHW programs. Our objective was to refine and evaluate an intervention designed to address common causes of non-adherence to TB treatment and LHW knowledge and skills training needs. Methods We employed a pragmatic cluster randomized controlled trial. Participants included 103 health centres (HCs) providing TB care in four districts in Malawi, randomized 1:1 stratified by district and HC funding (Ministry of Health, non-Ministry funded). At intervention HCs, a TB treatment adherence intervention was implemented using educational outreach, a point-of-care reminder tool, and a peer support network. Clusters in the control arm provided usual care. The primary outcome was the proportion of patients with successful TB treatment (i.e., cure or treatment completion). We used a generalized linear mixed model, with district as a fixed effect and HC as a random effect, to compare proportions of patients with treatment success, among the trial arms, with adjustment for baseline differences. Results We randomized 51 HCs to the intervention group and 52 HCs to the control group. Four intervention and six control HCs accrued no eligible patients, and 371 of 1169 patients had missing outcome, HC, or demographic data, which left 74 HCs and 798 patients for analysis. Randomization group was not related to missing outcome, however, district, age, and TB type were significantly related and included in the primary analysis model. Among the 1153 patients with HC and demographic data, 297/605 (49%) and 348/548 (64%) in the intervention and control arms, respectively, had treatment success. The intervention had no significant effect on treatment success (adjusted odds ratio 1.35 [95% confidence interval 0.93–1.98]). Conclusion We found no significant effect of the intervention on TB treatment outcomes with high variability in implementation quality, highlighting important challenges to both scale-up and sustainability. Trial registration ClinicalTrials.gov NCT02533089 . Registered August 20, 2015

Additional file 2: of The impact of a knowledge translation intervention employing educational outreach and a point-of-care reminder tool vs standard lay health worker training on tuberculosis treatment completion rates: study protocol for a cluster randomized controlled trial

Letter of information and consent to participate in a research study - patient version (English version). (DOCX 28 kb

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease