Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice

The design of caring environments and the quality of life of older people

There has been little systematic research into the design of care environments for older people. This article reviews empirical studies from both the architectural and the psychological literature. It outlines the instruments that are currently available for measuring both the environment and the quality of life of older people, and it summarises the evidence on the layout of buildings, the sensory environment and the privacy of residents. The conclusion is drawn that all evidence-based design must be a compromise or dynamic and, as demands on the caring environment change over time, this compromise must be re-visited in the form of post-occupancy evaluation

Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study.

BACKGROUND: Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. METHODS: The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. FINDINGS: We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27-1·77 for CD4 cell count <100 cells per μL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1·48, 95% CI 1·20-1·82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0·626]). INTERPRETATION: We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial. FUNDING: The Wellcome Trust

Improving the radical cure of vivax malaria (IMPROV): a study protocol for a multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens.

BACKGROUND: Plasmodium vivax malaria is a major cause of morbidity and recognised as an important contributor to mortality in some endemic areas. The current recommended treatment regimen for the radical cure of P. vivax includes a schizontocidal antimalarial, usually chloroquine, combined with a 14 day regimen of primaquine. The long treatment course frequently results in poor adherence and effectiveness. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising safety. The proposed multicentre randomised clinical trial aims to provide evidence across a variety of endemic settings on the safety and efficacy of high dose short course primaquine in glucose-6-phosphate-dehydrogenase (G6PD) normal patients. DESIGN: This study is designed as a placebo controlled, double blinded, randomized trial in four countries: Indonesia, Vietnam, Afghanistan and Ethiopia. G6PD normal patients diagnosed with vivax malaria are randomized to receive either 7 or 14 days high dose primaquine or placebo. G6PD deficient (G6PDd) patients are allocated to weekly primaquine doses for 8weeks. All treatment is directly observed and recurrent episodes are treated with the same treatment than allocated at the enrolment episode. Patients are followed daily until completion of treatment, weekly until 8 weeks and then monthly until 1 year after initiation of the treatment. The primary endpoint is the incidence rate (per person year) of symptomatic recurrent P. vivax parasitaemia over 12 months of follow-up, for all individuals, controlling for site, comparing the 7 versus 14-day primaquine treatment arms. Secondary endpoints are other efficacy measures such as incidence risk at different time points. Further endpoints are risks of haemolysis and severe adverse events. DISCUSSION: This study has been approved by relevant institutional ethics committees in the UK and Australia, and all participating countries. Results will be disseminated to inform P. vivax malaria treatment policy through peer-reviewed publications and academic presentations. Findings will contribute to a better understanding of the risks and benefits of primaquine which is crucial in persuading policy makers as well as clinicians of the importance of radical cure of vivax malaria, contributing to decreased transmission and a reduce parasite reservoir. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01814683 . Registered March 18, 2013

Timing of initiation, patterns of breastfeeding, and infant survival: prospective analysis of pooled data from three randomised trials

Background Although the benefi ts of exclusive breastfeeding for child health and survival, particularly in the post-neonatal period, are established, the independent benefi cial eff ect of early breastfeeding initiation remains unclear. We studied the association between timing of breastfeeding initiation and post-enrolment neonatal and postneonatal mortality up to 6 months of age, as well as the associations between breastfeeding pattern and mortality. Methods We examined associations between timing of breastfeeding initiation, post-enrolment neonatal mortality (enrolment 28 days), and post-neonatal mortality up to 6 months of age (29–180 days) in a large cohort from three neonatal vitamin A trials in Ghana, India, and Tanzania. Newborn babies were eligible for these trials if their mother reported that they were likely to stay in the study area for the next 6 months, they could feed orally, were aged less than 3 days, and the primary caregiver gave informed consent. We excluded infants who initiated breastfeeding after 96 h, did not initiate, or had missing initiation status. We pooled the data from both randomised groups of the three trials and then categorised time of breastfeeding initiation as: at ≤1 h, 2–23 h, and 24–96 h. We defi ned breastfeeding patterns as exclusive, predominant, or partial breastfeeding at 4 days, 1 month, and 3 months of age. We estimated relative risks using log binomial regression and Poisson regression with robust variances. Multivariate models controlled for site and potential confounders. Findings Of 99 938 enrolled infants, 99 632 babies initiated breastfeeding by 96 h of age and were included in our prospective cohort. 56 981 (57·2%) initiated breastfeeding at ≤1 h, 38 043 (38·2%) at 2–23 h, and 4608 (4·6%) at 24–96 h. Compared with infants initiating breastfeeding within the fi rst hour of life, neonatal mortality between enrolment and 28 days was higher in infants initiating at 2–23 h (adjusted relative risk 1·41 [95% CI 1·24–1·62], p<0·0001), and in those initiating at 24–96 h (1·79 [1·39–2·30], p<0·0001). These associations were similar when deaths in the fi rst 4 days of life were excluded (1·32 [1·10–1·58], p=0·003, for breastfeeding initiation at 2–23 h, and 1·90 [1·38–2·62], p=0·0001, for initiation at 24–96 h). When data were stratifi ed by exclusive breastfeeding status at 4 days of age (p value for interaction=0·690), these associations were also similar in magnitude but with wider confi dence intervals for initiation at 2–23 h (1·41 [1·12–1·77], p=0·003) and for initiation at 24–96 h (1·51 [0·63–3·65], p=0·357). Exclusive breastfeeding was also associated with the lower mortality during the fi rst 6 months of life (1–3 months mortality: exclusive vs partial breastfeeding at 1 month 1·83 [1·45–2·32], p<0·0001, and exclusive breastfeeding vs no breastfeeding at 1 month 10·88 [8·27–14·31], p<0·0001). Interpretation Our fi ndings suggest that early initiation of breastfeeding reduces neonatal and early infant mortality both through increasing rates of exclusive breastfeeding and by additional mechanisms. Both practices should be promoted by public health programmes and should be used in models to estimate lives saved

causation or confounding?

Background Despite an overall reduction in suicide, educational disparities in suicide have not decreased over the last decade. The mechanisms behind educational disparities in suicide, however, remain unclear: low educational status may increase the risk of suicide (“causation”) or low educational status and suicide may share confounders. This paper assesses whether educational disparities in suicide (EDS) are more likely to be due to causation. Method The DEMETRIQ study collected and harmonized register-based data on mortality follow-up from forty population censuses from twelve European populations. More than 102,000 suicides were registered over 392 million person-years. Three analyses were carried out. First, we applied an instrumental variable approach that exploits changes in the legislation on compulsory educational age to instrument educational status. Second, we analyzed EDS by age under the hypothesis that increasing EDS over the life cycle supports causation. Finally, we compared EDS in men and women under the assumption that greater EDS in women would support causation. Findings The instrumental variable analysis showed no evidence for causation between higher education and suicide, for men or women. The life-cycle analysis showed that the decrease of educational inequalities in suicide between the baseline 1991 period and the 2001 follow-up period was more pronounced and statistically significant in the first three younger age groups. The gender analysis indicated that EDS were systematic and greater in men than in women: the rate ratio of suicide for men with low level of education (RR = 2.51; 95% CI:2.44–2.58) was higher than the rate ratio in women (RR = 1.32; 95CI%:1.26–1.38). Interpretation Overall, there was little support for the causation hypothesis, suggesting that the association between education and suicide is confounded. Educational inequalities in suicide should be addressed in early life by early targeting of groups who struggle to complete their education and display higher risk of mental disorder or of mental health vulnerabilities.publishersversionpublishe

Determinants of successful lifestyle change during a 6-month preconception lifestyle intervention in women with obesity and infertility

Funding The LIFEstyle study was supported by a grant from ZonMw (Prevention program—Health Care Efficiency Research; Project number 50-50110-96-518). This work was funded by the Dutch Heart Foundation (2013T085) and the European Commission (Horizon2020 project 633595 DynaHealth). Neither ZonMw nor the Dutch Heart Foundation nor the European Commission had a role in data collection, analysis, interpretation of data, or writing the report. cknowledgements We would like to thank the women who participated in this study. We thank all participating hospitals and their staff for their contribution to this study, and the LIFEstyle coaches and research nurses, research midwives, and office members of the Dutch Consortium 2.0 (http://www.studies-obsgyn.nl) for their hard work and dedication. We would like to acknowledge Mrs. A. Bolster (University Medical Center Groningen) as senior trainer of the intervention coachesPeer reviewe

Incidence and severity of SARS-CoV-2 infection in children and young people with HIV in Europe

We assessed incidence of SARS-CoV-2 infection and disease severity among children and young people with HIV from cohorts across nine European countries. Of 1717 included, with median duration of follow-up 20.1 months, 134 (8%) had documented SARS-CoV-2 infection, a rate of 49 [95% confidence interval (CI) 42–58] per 1000 person-years. All symptomatic cases had mild coronavirus disease 2019 (COVID-19), three were hospitalized, and no deaths were reported, which may be reassuring for clinicians and families