UK Renal Registry 18th Annual Report: Chapter 11 2014 Multisite Dialysis Access Audit in England, Northern Ireland and Wales and 2013 PD One Year Follow-up: National and Centre-specific Analyses

Data are presented from the third combined vascular and peritoneal dialysis access audit. In 2014, 53 centres in England, Wales and Northern Ireland (out of 62) returned data on first access from 4,339 incident haemodialysis (HD) patients and 1,090 incident peritoneal dialysis (PD) patients. Of the 5,429 incident patients, 20.1% started dialysis on PD, 27.8% started with an arteriovenous fistula (AVF), 1.0% with an arteriovenous graft (AVG), 27.1% on a tunnelled line (TL) and 24.0% on a non-tunnelled line (NTL). Older patients (565 years) were more likely to start haemodialysis using AVF compared to their younger counterparts (36.2% vs. 32.8%). Thirteen of the nineteen centres (68%) using the physician led percutaneous insertion technique had over 20% of their incident patients starting on PD when compared to only seven out of fourteen centres (50%) which used single technique (open surgical or laparoscopic) for their PD catheter insertion. Wide variations were apparent between centres for use of AVF as the first haemodialysis access ranging from 10-54%. Eight of the 49 centres were achieving close to the 65% target for AV fistula in their incident patients. Length of time known to nephrology services and likelihood of commencing dialysis using either an AVF or a PD catheter are strongly associated. Patients who were known to a nephrologist for over one year were more likely to start dialysis with AVF, as compared to those who were referred between 90-365 days (39.2% vs. 24.6%). Similarly, patients who were known to a nephrologist between 90 days and one year were more likely to start on PD when compared to patients who were referred ,90 days prior to dialysis start (26.9% vs. 9.1%). By comparison, amongst the late presenters, only 3.5% had first access documented as an AVF and 87.3% started dialysis on either a tunnelled line or a nontunnelled line. Initial surgical assessment was a key determinant of the likelihood of AVF formation. Of the incident patients known to renal services for longer than three months and in those assessed by a surgeon at least three months prior to starting dialysis, 71.4% started dialysis with an AVF whereas of those who were not seen by a surgeon only 10.8% did. Thirty one of the 38 centres were 2 or 3 standard deviations below the 85% target for prevalent haemodialysis patients with an AV fistula. For centres returning data on one-year peritoneal dialysis outcomes, the majority of centres (28/32) maintained 550% of patients on PD at one year, having censored for transplantation. This report demonstrates wide variations in practice between centres across several domains in the provision of dialysis access and further work will be required to understand the underlying reasons

Reducing child undernutrition through dietary diversification, reduced aflatoxin exposure, and improved hygiene practices: the immediate impacts in central Tanzania

Open Access Article; Published online: 28 Nov 2019The study aimed to quantify the immediate effects of dietary diversification, food safety, and hygiene interventions on child undernutrition in four rural villages in Kongwa district of central Tanzania. One hundred mothers with their children of less than 24 months old were recruited for this study. The difference-in-difference (DID) method was used to assess the effects of intensive intervention through a learning-by-doing process on the topic of aflatoxin free diversified food utilization and improved hygiene practices. Periodic anthropometric measurements were conducted on the 0th, 7th, 14th, and 21st days, and DID estimator showed the significant and positive average marginal effects of the intervention on Z-Scores being 0.459, 0.252, and 0.493 for wasting, stunting, and underweight, respectively. Notably, at the end of the study, the mean aflatoxin M1 level in urine samples decreased by 64% in the intervention group, while it decreased by 11% in the control group. The study provides quantitative evidence on intensive 21-day training for mothers incorporating integrated technologies yielded positive impacts on their children’s nutritional outcomes

Case Report: HIV test misdiagnosis

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Informing targeted HIV self-testing: a protocol for discrete choice experiments in Malawi, Zambia and Zimbabwe

Introduction HIV self-testing (HIVST) is a new approach to HIV testing where a person collects his or her own specimen, performs an HIV test and interprets the result, either alone or with someone he or she trusts. It is becoming increasingly relevant as a complement to standard-of-care HIV testing and is now recommended by the World Health Organization. Few studies have explored user preferences around HIVST service delivery and optimal models for increasing uptake and linkage to care, particularly among hard-to-reach populations. This paper describes an ongoing study that uses discrete choice experiments (DCE) to identify key HIVST service characteristics that drive people’s willingness to self-test for HIV and link to care, measure the relative strength of user preferences, and explore preference heterogeneity in Southern Africa. Method and Analysis Two DCEs – one on HIVST delivery and one on linkage to care after a positive self-test – are being administered in Malawi, Zambia and Zimbabwe. The designs in each country were informed by a qualitative study, which identified key HIVST service characteristics that influence user decision-making and refined scenario presentations and illustrations. Following data collection, DCE data will be analysed using a multinomial logit model as well as latent class, nested logit and generalised mixed models to examine heterogeneity in preferences by sociodemographic background, HIV testing experience and sexual behaviour. Ethics and dissemination The study has been approved by the College of Medicine Research Ethics Committee in Malawi, the Biomedical Ethics Committee of the University of Zambia, the Medical Research Council of Zimbabwe and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings from the study will be presented at international conferences and in peer-reviewed journals. The results will help inform the HIVST implementation strategy in Southern Africa, particularly among populations underserved by standard-of-care services, such as men and young women

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

Factors affecting tuberculosis health message recall 2 years after active case finding in Blantyre, Malawi.

SETTING: Urban slums, Blantyre, Malawi. OBJECTIVE: To explore tuberculosis (TB) community-wide active case finding (cwACF) recall and accompanying messaging 2 years after the intervention. DESIGN: This mixed-methods study used population-weighted random cluster sampling to select three cwACF-receiving and three non-cwACF-receiving neighbourhoods in Blantyre. Qualitative data were collected using 12 focus group discussions (community peer-group members) and five in-depth interviews (TB officers) with script guides based on the concepts of the Health Belief Model (HBM). Thematic analysis was used to explore transcripts employing deductive coding. Questionnaires completed by focus group participants were used to collect quantitative data, providing a 'knowledge score' evaluated through univariate/multivariate analysis, analysis of variance and multiple linear regression. RESULTS: Community peer-group participants (n = 118) retained high awareness and positive opinions of cwACF and recognised the relationship between early diagnosis and reduced transmission, considering cwACF to have prompted subsequent health-seeking behaviour. TB-affected individuals (personal/family: 47.5%) had significantly higher knowledge scores than unaffected individuals (P = 0.039), but only if resident in cwACF-receiving neighbourhoods (P = 0.005 vs. P = 0.582), implying effect modification between exposures, albeit statistically under-powered (P = 0.229). CONCLUSION: Consistent with epidemiological evidence and HBM theory, cwACF may have a permanent impact on knowledge and behaviour, particularly in communities with a high prevalence of TB-affected individuals. Behaviour change strategies should be explicitly included in cwACF planning and evaluation

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background: Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. Methods and Findings: 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007). Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen

Structured medical electives:a concept whose time has come?

Background: Most international electives in which medical students from high-income countries travel abroad are largely unstructured, and can lead to problematic outcomes for students as well as sending and receiving institutions. We analyse the problems of unstructured medical electives and describe the benefits of an elective experience that includes more organisation and oversight from the sending medical school.Results: A number of structured elective programmes have been developed, including those at the Medical School for International Health, Israel and the University of Dundee, United Kingdom. These programmes provide significant pre-departure training in global health and the ethical dimensions of electives, support and monitoring during the elective, and post-elective debrief. Crucially, the programmes themselves are developed on the basis of long-term engagement between institutions, and have an element of reciprocity. We further identify two major problems in current medical electives: the different ethical contexts in which electives take place, and the problem of 'voluntourism', in which the primary beneficiary of the activity is the medical student, rather than the receiving institution or health system. These two issues should be seen in the light of unequal relations between sending and receiving institutions, which largely mirror unequal relations between the Global North and South.Conclusion: We argue that more structured elective programmes could form a useful corrective to some of the problems identified with medical electives. We recommend that medical schools in countries such as the UK strongly consider developing these types of programmes, and if this is not possible, they should seek to further develop their pre-departure training curricula.</p

A pilot study to determine the normal haematological indices for young Malawian adults in Blantyre, Malawi

Background Reference ranges for haematological and other laboratory tests in most African countries are based on populations in Europe and America and, because of environmental and genetic factors, these may not accurately reflect the normal reference ranges in African populations.Aim To determine the distribution of haematological parameters in healthy individuals residing in Blantyre, Malawi. We also examined the effect of sociodemographic and nutritional factors on the haematological variables.Methods We conducted a proof-of-concept cross-sectional study, involving 105 healthy blood donors at Malawi Blood Transfusion Service in Blantyre. Eligible participants were HIV-negative males and females, aged 19 to 35 years, who did not have any evidence of acute or chronic illness, or bloodborne infection. We performed the haematological tests at the Malawi- Liverpool Wellcome Trust laboratory in Blantyre, and the screening tests at Malawi Blood Transfusion Service laboratories.Results Out of 170 consenting healthy volunteers, haematological results were available for 105 participants. The proportions of results which were below the lower limit of the manufacturer’s reference ranges were 35.2% (37/105) for haemoglobin, 15.2% (16/105) for neutrophils, 23.8% (25/105) for eosinophils, and 88.6 % (93/105) for basophils. The proportions of results that were above the upper limit of the manufacturer’s reference ranges were 9.5% (10/105) for platelets and 12.4% (13/105) for monocytes. We also observed that the mean leucocyte and basophil counts were significantly higher in males than females (p = 0.042 and p = 0.015, respectively). There were no statistically significant differences in haematological results observed among different ethnic, age, and body mass index groups.Conclusions Over half of otherwise healthy study participants had at least one abnormal haematological result, using previously established foreign standards. More detailed studies are needed to establish locally relevant normal ranges for different age groups and other demographic characteristics of the Malawian population. This will lead to accurate interpretation of laboratory results

The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1

Serotype 1 is one of the most common causes of pneumococcal disease worldwide. Pneumococcal protein vaccines are currently being developed as an alternate intervention strategy to pneumococcal conjugate vaccines. Pre-requisites for an efficacious pneumococcal protein vaccine are universal presence and minimal variation of the target antigen in the pneumococcal population, and the capability to induce a robust human immune response. We used in silico analysis to assess the prevalence of seven protein vaccine candidates (CbpA, PcpA, PhtD, PspA, SP0148, SP1912, SP2108) among 445 serotype 1 pneumococci from 26 different countries, across four continents. CbpA (76%), PspA (68%), PhtD (28%), PcpA (11%) were not universally encoded in the study population, and would not provide full coverage against serotype 1. PcpA was widely present in the European (82%), but not in the African (2%) population. A multi-valent vaccine incorporating CbpA, PcpA, PhtD and PspA was predicted to provide coverage against 86% of the global population. SP0148, SP1912 and SP2108 were universally encoded and we further assessed their predicted amino acid, antigenic and structural variation. Multiple allelic variants of these proteins were identified, different allelic variants dominated in different continents; the observed variation was predicted to impact the antigenicity and structure of two SP0148 variants, one SP1912 variant and four SP2108 variants, however these variants were each only present in a small fraction of the global population (<2%). The vast majority of the observed variation was predicted to have no impact on the efficaciousness of a protein vaccine incorporating a single variant of SP0148, SP1912 and/or SP2108 from S. pneumoniae TIGR4. Our findings emphasise the importance of taking geographic differences into account when designing global vaccine interventions and support the continued development of SP0148, SP1912 and SP2108 as protein vaccine candidates against this important pneumococcal serotype