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Despite increasing levels of adult hypertension in sub-Saharan Africa (SSA), there is limited information on elevated blood pressure among children in SSA. We described the distribution of blood pressure among children in rural Uganda and estimated hypertension prevalence. We conducted a cross-sectional study in south-western Uganda, collecting demographic, anthropometric and blood pressure measurements from children aged 6-12 years. Children with elevated blood pressure (systolic and/or diastolic blood pressure greater or equal to the 95th percentile for age, height and sex) were invited for two further assessments 6-18 months later. We described blood pressure distribution at first assessment, assessed associations with demographic and anthropometric characteristics and estimated prevalence of hypertension as defined by having elevated blood pressure on three separate occasions months apart. Blood pressure (BP) was measured in 1913 children (50% male, 3% overweight or obese, 22% stunted) at the first assessment. Mean (SD) systolic and diastolic BP at first assessment was 113.4 mmHg (±10.8) and 69.5 mmHg (±8.3), respectively, and 44.2% had elevated BP. Older age, higher BMI, and being female were associated with higher BP, and stunted height was associated with lower BP. An estimated 7.8% [95% CI:(6.6-9.1)], (males: 6.8%, females: 9.0%), had elevated BP on three separate occasions, and were considered hypertensive. High blood pressure levels among adults in SSA may be set early in life. In this study, obesity (a common lifestyle modifiable risk factor in other settings) was largely irrelevant. More research is needed to understand the main drivers for elevated blood pressure in SSA further.

Seroprevalence studies have proven an important tool to monitor the progression of the coronavirus disease 2019 (COVID-19) pandemic. We present results of consecutive population-based seroprevalence surveys performed in Denmark in 2020. In spring, late summer and autumn/winter of 2020, invitation letters including a questionnaire covering symptoms were sent to representative samples of the population above 12 years and to parents of children below 18 years in the sample. Blood samples were analysed for total Ig and seroprevalence estimates per population segment were calculated and compared to other surveillance parameters. Based on 34 081 participants (participation rate 33%), seroprevalence estimates increased from 1.2% (95%CI: 0.3–1.9%) in May to 4.1% (95%CI: 3.1–4.9%) in December 2020. Seroprevalence estimates were roughly three times higher in those aged 12–29 years compared to 65 + and higher in metropolitan municipalities. By December 2020, 1.5% of the population had tested positive by RT-PCR. Infected individuals in older age groups were hospitalised several fold more often than in younger. Amongst seropositives, loss of taste/smell were the more specific symptoms, 32–56% did not report any symptoms. In more than half of seroconverted families, we did not see evidence of transmission between generations. Seroprevalence increased during 2020; adolescents were primarily infected in the autumn/winter. Denmark has a high per capita test rate; roughly one undiagnosed infection of SARS-CoV-2 were estimated to occur for each diagnosed case. Approximately half were asymptomatically infected. The epidemic appears to have progressed relatively modestly during 2020 in Denmark.

Summary Background The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2. Methods In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 – RR. Findings During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51–0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22–3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155–0·246]). Protection against repeat infection was 80·5% (95% CI 75·4–84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179–0·251], estimated protection 78·8% [74·9–82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7–62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1–83·2] vs female 79·1% [73·9–83·3]) or evidence of waning protection over time (3–6 months of follow-up 79·3% [74·4–83·3] vs ≥7 months of follow-up 77·7% [70·9–82·9]). Interpretation Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on. Funding None.

IntroductionViolence against women is a global public health concern; around a quarter of women will experience intimate partner physical or sexual violence during their lifetime. We assessed the impact of a gender transformative intervention for women designed to prevent intimate partner violence (IPV).MethodsWe conducted a cluster randomised controlled trial in Mwanza city, Tanzania, among women in newly formed neighbourhood groups to evaluate a 10-session participatory intervention that aims to empower women, prevent IPV and promote healthy relationships. Following a baseline interview, groups were randomly assigned (1:1 ratio) to the intervention or control arm. An intention-to-treat analysis was conducted to assess the impact of the intervention on the main outcomes, assessed 24 months postintervention. These included past-year physical IPV and sexual IPV (primary); past-year emotional abuse; and acceptability and tolerance of IPV.ResultsBetween September 2015 and February 2017, 1265 women were recruited in 66 neighbourhoods and randomly allocated to intervention (n=627 women in 33 neighbourhoods) or control (n=638 women in 33 neighbourhoods). Assessment of outcomes was completed for 551 (88%) intervention and 575 (90%) control women. Among intervention women, 113 (21%) reported physical IPV compared with 117 (20%) control women (adjusted OR (aOR) 0.98, 95% CI 0.72 to 1.33, p=0.892), and 109 (20%) intervention women reported sexual IPV compared with 121 (21%) control women (aOR 0.98, 95% CI 0.72 to 1.32, p=0.881). Intervention women reported less emotional abuse (aOR 0.74, 95% CI 0.56 to 0.98, p=0.035), and were less likely to express attitudes accepting of IPV (aOR 0.49, 95% CI 0.36 to 0.66, pConclusionThese results indicate that the intervention was effective in reducing emotional abuse and positively impacting attitudes and beliefs condoning IPV, but was not sufficient to reduce physical or sexual IPV.Trial registration numberNCT02592252.

Background Soil-transmitted helminth (STH) infections are highly prevalent in resource-limited countries. We assessed the effect of a combination intervention aiming to enhance handwashing with soap on STH reinfection following mass drug administration among primary school children in Kagera region, Northwestern Tanzania. Methods We conducted a cluster randomised trial in sixteen primary schools with known high STH prevalence. Schools were randomly assigned in a 1:1 ratio to either receive the intervention or continue with routine health education. The intervention included teacher-led classroom teaching, parental engagement sessions, environmental modifications and improved handwashing stations. The evaluation involved two cross-sectional surveys in a representative sample of students, with the end-line survey conducted 12 months after the baseline survey. The primary outcome was the combined prevalence of Ascaris lumbricoides and Trichuris trichiura infections at the end-line survey. Secondary outcomes included reported handwashing behaviour, the prevalence and intensity of individual STHs, and hand contamination with STH ova and coliform bacteria. End-line STH prevalence and intensity were adjusted for baseline differences of potential confounders. Results At the end-line survey, 3081 school children (1566 from intervention schools and 1515 from control schools) provided interview data and stool specimens. More school children in the intervention group reported the use of water and soap during handwashing compared to school children in the control group (58% vs. 35%; aOR=1.76, 95%CI 1.28–2.43, p=0.001). The combined prevalence of A. lumbricoides and T. trichiura infections was 39% in both trial arms (aOR = 1.19; 95%CI 0.74–1.91). The prevalence of A. lumbricoides was 15% in the intervention and 17% in the control arm (aOR =1.24, 95%CI 0.59–2.59) and that of T. trichiura was 31% in both arms (aOR=1.17, 95%CI 0.73–1.88). No significant differences were found for STH infection intensity in both the main study and the hand contamination sub-study. Conclusions The intervention was effective in increasing reported handwashing behaviour at school, but failed to show a similar effect in the home. The intervention had no effect on STH infection, possibly due to infection in the home environment, other transmission routes such as contaminated water or food or limited changes in school children’s handwashing behaviour. Trial registration The trial was registered on June 21, 2017, by the International Standard Randomised Controlled Trial Number (ISRCTN45013173).

Objective To compare self-reported outcomes, clinical trajectory and utility of baseline questionnaire responses in predicting prognosis in functional and recognised pathophysiological neurological disorders. Methods Baseline data on 2581 patients included health-related quality of life, psychological and physical symptoms, illness perceptions, consultation satisfaction and demographics. The prospective cohort included neurology outpatients classified with a functional (reporting symptoms ‘not at all’ or ‘somewhat explained’ by ‘organic disease’; n = 716) or recognised pathophysiological disorder (‘largely’ or ‘completely explained’; n = 1865). Logistic regression and deep neural network models were used to predict self-reported global clinical improvement (CGI) at 12-months. Results Patients with functional and recognised pathophysiological disorders reported near identical outcomes at 12-months with 67% and 66% respectively reporting unchanged or worse CGI. In multivariable modelling ‘negative expectation of recovery’ and ‘disagreement with psychological attribution’ predicted same or worse outcome in both groups. Receipt of disability-related state benefit predicted same or worse CGI outcome in the functional disorder group only (OR = 2.28 (95%-CI: 1.36–3.84) in a group-stratified model) and was not related to a measure of economic deprivation. Deep neural network models trained on all 92 baseline features predicted poor outcome with area under the receiver-operator curve of 0.67 in both groups. Conclusions Those with functional and recognised pathophysiological neurological disorder share similar outcomes, clinical trajectories, and poor prognostic markers in multivariable models. Prediction of outcome at a patient level was not possible using the baseline data in this study.

Introduction: The burden of kidney disease in sub-Saharan Africa is currently poorly understood. Very limited monitoring and treatment is available for people affected. The association with other diseases and with mortality is unknown in this setting. We sought to determine the association between kidney function and subsequent all-cause mortality. Methods: In a general population cohort with detailed measurement of health-related parameters in rural Uganda, we estimated the baseline glomerular filtration rate (GFR) between 2011-2014 in 5,678 participants. We followed participants up to March 2019 with regular ascertainment of mortality and migration. Using multivariable cox regression, we determined associations between baseline eGFR and mortality. Results: The median age of the participants at baseline was 36 years (IQR 24-50), 60.7% were female, 14.6% hypertensive, 9.7% HIV-positive and 1.8% diabetic. We registered 140 deaths with a median follow-up of 5.0 years. Adjusting for age and sex, HIV, hypertension, diabetes, BMI, marital status, and alcohol and tobacco use participants with eGFR ≤45 mls/min/1.73m2 had six-fold higher mortality compared to those with eGFR ≥90mls/min/1.73m2 (HR 6.12 (95% CI 2.27-16.45)) with strong evidence of a linear trend for risk of mortality as renal function declined (P

ObjectivesCervical cancer is the leading cause of cancer-related mortality among women in sub-Saharan Africa (SSA). Data on human papillomavirus (HPV) epidemiology in adolescent girls in SSA are essential to inform HPV vaccine policy recommendations for cervical cancer prevention. We assessed the burden of HPV infection, and risk factors for infection, among adolescent girls around the time of sexual debut.MethodsCross-sectional study of secondary school girls aged 17–18 years in Tanzania. Consenting participants provided samples for HPV and STI testing. Vaginal swabs were tested for 37 HPV genotypes by Roche Linear Array. Logistic regression was used to identify factors associated with HPV infection. Y chromosome was tested as a marker of recent condomless sex.Results163/385 girls (42.3%) reported previous penetrative sex. HPV was detected in 125/385 (32.5%) girls, including 84/163 (51.5%) girls reporting previous sex and 41/222 (18.5%) reporting no previous sex. High-risk (HR) genotypes were detected in 70/125 (56.0%) girls with HPV infection. The most common HR genotype was HPV-16 (15/385; 3.9%). The prevalence of other HR HPV vaccine genotypes was between 0.8% and 3.1%. Among 186 girls who reported no previous sex, were negative for Y chromosome, and had no STI, 32 (17%) had detectable HPV. Lactobacillus sp and bacterial vaginosis-associated bacteria were negatively and positively associated, respectively, with HPV.ConclusionsHPV prevalence among adolescent girls around the time of sexual debut was high. However, prevalence of most vaccine genotypes was low, indicating that extending the age range of HPV vaccination in this region may be cost-effective.

We conducted a cross‐sectional study among school/college students in Tanzania and Uganda to determine the prevalence of high blood pressure (BP) and associated factors. Participants were classified to have high BP if they had pre‐hypertension or hypertension. Interviews were done using the WHO STEPS instrument. Using data from both countries (n = 1596), the overall prevalence of high BP was 40% (95% CI: 37‐42). The prevalence of pre‐hypertension was 29% (95% CI: 26‐31) and that of hypertension was 11% (95% CI: 10‐13). High BP was independently associated with obesity (aOR = 6.7, 95% CI: 2.2‐20.0), male sex (aOR = 3.2, 95% CI: 2.4‐4.4), and among males aged above 20 years (aOR = 5.5, 95% CI: 2.9−10.5). Consumption of fruits/vegetables was associated with decreased odds for high BP (aOR = 0.7, 95% CI: 0.50‐0.98). The increasing burden of pre‐hypertension across age groups could explain the early onset of hypertension and cardiovascular diseases (CVDs) among young African adults. There is a need for longitudinal studies to explore the drivers of pre‐hypertension in East African adolescents.

ObjectivesBacterial vaginosis (BV) increases women’s susceptibility to sexually transmitted infections (STIs) and HIV and may partly explain the high incidence of STI/HIV among girls and young women in East and southern Africa. The objectives of this study were to investigate the association between BV and sexual debut, to investigate other potential risk factors of BV and to estimate associations between BV and STIs.MethodsSecondary school girls in Mwanza, aged 17 and 18 years, were invited to join a cross-sectional study. Consenting participants were interviewed and samples were obtained for STI and BV testing. Factors associated with prevalent BV were analysed using multivariable logistic regression. Y-chromosome was tested as a biomarker for unprotected penile-vaginal sex.ResultsOf the 386 girls who were enrolled, 163 (42%) reported having ever had penile-vaginal sex. Ninety-five (25%) girls had BV. The prevalence of BV was 33% and 19% among girls who reported or did not report having ever had penile-vaginal sex, respectively. BV was weakly associated with having ever had one sex partner (adjusted odds ratio (aOR) 1.59;95% CI 0.93 to 2.71) and strongly associated with two or more partners (aOR = 3.67; 95% CI 1.75 to 7.72), receptive oral sex (aOR 6.38; 95% CI 1.22 to 33.4) and having prevalent human papillomavirus infection (aOR = 1.73; 95% CI 1.02 to 2.95). Of the 223 girls who reported no penile-vaginal sex, 12 (5%) tested positive for an STI and 7 (3%) tested positive for Y-chromosome. Reclassifying these positive participants as having ever had sex did not change the key results.ConclusionsTanzanian girls attending school had a high prevalence of BV. Increasing number of sex partner was associated with BV; however, 19% of girls who reported no penile-vaginal sex had BV. This suggests that penile-vaginal sexual exposure may not be a prerequisite for BV. There was evidence of under-reporting of sexual debut.

Background: The degree to which infection with SARS-CoV-2 confers immunity towards subsequent infection is not yet known. In 2020, as part of Denmark’s extensive, free-of-charge PCR-testing strategy, 4 million individuals (69% of the population) underwent 10.6 million tests. Using these national PCR-test data from 2020, we estimated the natural immunity towards SARS-CoV-2 after infection and investigated differences by age, sex and time since infection. Methods: Analysing the second surge of the epidemic (September–December, 2020) we compared infection rates between those with and without a previous positive test from the first surge (March–May). In an alternative time-to-event analysis, we compared infection rates throughout the year between those with and without a previous confirmed infection three or more months earlier. Rate ratios were adjusted for potential cofounders and natural immunity was estimated as one minus the rate ratio. Findings: Among PCR positive individuals from the first surge, 0·65% tested positive again during the second surge compared with 3·3% without a previous infection. The natural immunity was 80·5% (95% CI 75·4–84·5). The time-to-event analysis gave a similar estimate, as did the use of two and four months’ separation between repeat positive tests, and limiting the cohort to frequently tested health staff only. Among those aged 65+ years, observed immunity was 47% (95% CI 24·7–62·8). There was no difference in immunity by sex or evidence of waning immunity over time. Interpretation: Person-identifiable test results from large scale national PCR-testing in Denmark suggest that the within-season immunity following symptomatic or non-symptomatic infection is around 80%, although significantly lower in the elderly. These findings may inform decisions of which groups to vaccinate and advocate for vaccination of previously infected individuals as natural protection among elderly citizens cannot be relied upon. Funding: No designated funding was received for this study. DM was funded by the European Centers for Disease Control and Prevention programme EUPHEM. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The present study was based on existing administrative data and did not require ethical approval.

Background: Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral haemorrhagic zoonosis associated with severe morbidity, mortality and expanding geographical scope. Human symptoms have poor specificity and case definitions vary. We determined the clinical manifestations of RVF in humans. Methods: In this systematic review and meta-analysis we searched Medline, Embase, Global Health, and Web of Science databases from indexing inception to 15th October 2019. Studies published in English, reporting frequency of symptoms in humans, and laboratory confirmed RVF were included. Animals studies, those among asymptomatic volunteers and single case reports for which a proportion could not be estimated were excluded. Quality assessment was done, data extracted, and pooled frequency estimates calculated using random effects meta-analysis. Results: Of the 3765 articles retrieved, 32 were included in the systematic review and meta-analysis. Nine RVF clinical syndromes were reported including general febrile, gastrointestinal, hepatic, renal, neurological, haemorrhagic, obstetric, visual, and cardio-pulmonary syndromes. The most common clinical manifestations included fever (81%; 95% Confidence Interval (CI) 69-91), nausea (38%; 12-67), jaundice (26%; 16-36), renal failure (41%; 23-59), encephalitis (21%; 11-33), haemorrhagic disease (26%; 17-36), miscarriage (54%), partial blindness (24%; 7-45), and cough (4%; 0-17), respectively. Death occurred in 21% (95% CI 14-29) of cases. Interpretation: This study delineates the complex symptomatology of human RVF disease into syndromes. This approach is likely to improve case definitions and detection rates, impact outbreaks control, increase public awareness about RVF, and subsequently inform ‘one-health’ policies. Study protocol registration number: CRD42019128928. Funding: (UK Department of Health and Social care) The work was conducted at the MRC/UVRI and LSHTM Uganda Research Unit which is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordant agreement and is also part of the EDCTP2 programme supported by the European Union. This project was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC)/Department of Health, through the UK Vaccines Network which is a Government Funding Stream (Grant no: 16/107/02). SL was supported by the PANDORA-ID-NET Consortium (EDCTP Reg/Grant RIA2016E-1609) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2) programme under the Horizon 2020, the European Union’s Framework Programme for Research and Innovation. GMW is supported by an Oak foundation fellowship and a Wellcome Trust grant (grant number 203077_Z_16_Z). Declaration of Interests: All authors declare no potential conflicts of interest.

To quantify the burden of HIV, syphilis and schistosome infection and associated risk factors among adults living in seven fishing communities of Lake Victoria in northwest Tanzania.Cross-sectional study conducted between 2015 and 2016 in the selected communities. In each community, we randomly selected a sample of adults from the general population and from three putative risk groups including the following: (i) fishermen, (ii) fish processors and traders, and (iii) women working in the recreational facilities. Participants were interviewed to obtain information about potential risk factors, and venous blood was collected for detection of HIV, syphilis and schistosome infections. We used logistic regression models to quantify the associations between potential risk factors and HIV, and also between schistosome infection and HIV.We enrolled 1128 people from selected fishing communities. The overall prevalence of HIV, syphilis and schistosome infection was 14.2%, 15.6% and 83.1%, respectively. Female recreational facility workers had the highest prevalence of HIV (30.4%) and syphilis (24%). The odds of being HIV infected were generally higher in all age categories. Transactional sex was commonly reported and especially receiving gifts for sex was found to be strongly associated with HIV (adjusted OR = 2.50; 95% CI: 1.44-4.34, P = 0.008). Confirmed serological syphilis was associated with increased odds of having HIV infection. HIV was not associated with schistosome infection in a combined dataset and when we examined this separately for men and women alone.We observed a high burden of HIV, syphilis and schistosome infections in the fishing communities. Targeted efforts to treat and control infections have the potential to improve health among their residents.Quantifier la charge du VIH, de la syphilis et de l’infection à schistosomes et les facteurs de risque associés chez les adultes vivant dans sept communautés de pêcheurs du lac Victoria dans le nord-ouest de la Tanzanie. MÉTHODES: Etude transversale menée entre 2015-2016 dans les communautés sélectionnées. Dans chaque communauté, nous avons sélectionné aléatoirement un échantillon d'adultes de la population générale et de trois groupes à risque présumés, notamment: 1) les pêcheurs, 2) les transformateurs et commerçants de poisson et 3) les femmes travaillant dans les établissements de loisirs. Les participants ont été interrogés pour obtenir des informations sur les facteurs de risque potentiels, et du sang veineux a été collecté pour la détection du VIH, de la syphilis et des infections à schistosome. Nous avons utilisé des modèles de régression logistique pour quantifier les associations entre les facteurs de risque potentiels et le VIH, ainsi qu'entre l'infection à schistosome et le VIH. RÉSULTATS: Nous avons recruté 1.128 personnes dans une sélection de communautés de pêcheurs. La prévalence globale de l'infection par le VIH, la syphilis et les schistosomes était de 14,2%, 15,6% et 83,1% respectivement. Les travailleuses des établissements de loisirs avaient la prévalence la plus élevée du VIH (30,4%) et de la syphilis (24%). Les chances d'être infecté par le VIH étaient généralement plus élevées dans toutes les catégories d'âge. Les rapports sexuels transactionnels étaient fréquemment rapportés et surtout le fait de recevoir des cadeaux pour le sexe était fortement associé au VIH (OR ajusté = 2,50; IC95%: 1,44-4,34 ; P = 0,008). La syphilis sérologique confirmée était associée à une probabilité accrue d'être infecté par le VIH. Le VIH n'était pas associé à une infection à schistosome dans un ensemble de données combinées et lorsque nous avons examiné cela séparément pour les hommes et les femmes.Nous avons observé une charge élevée d'infections par le VIH, la syphilis et les schistosomes dans les communautés de pêcheurs. Des efforts ciblés pour traiter et contrôler les infections ont le potentiel d'améliorer la santé des résidents.

Introduction Soil transmitted helminths (STH) can affect over 50% of children in some parts of Tanzania. Control measures involve annual deworming campaigns in schools, but re-infection is rapid. This paper presents the design and baseline survey results of an ongoing school-based cluster-randomised controlled trial in Kagera region, NW Tanzania. The trial aims to determine whether the effect of routine deworming on the prevalence of Ascaris lumbricoides and Trichuris trichiura infections among school aged children can be sustained when combined with a behaviour change intervention promoting handwashing with water and soap. Methods As part of the trial, a total of 16 schools were randomised to receive the intervention (N = 8) or as controls (N = 8). Randomisation was stratified per district and restricted to ensure pre-trial STH prevalence was balanced between study arms. The combination intervention to be tested comprises class-room based teacher-led health education, improvement of handwash stations, coloured nudges to facilitate handwashing and parental engagement sessions. The impact evaluation involves two cross-sectional surveys conducted at baseline and endline. The objectives of the baseline survey were: (i) to confirm whether the deworming campaign was successful, and identify and treat students still infected about 2 weeks after deworming, (ii) to document any baseline differences in STH prevalence between trial arms, and (iii) to assess handwashing behaviours, and access to water and sanitation at school and home. We randomly sampled 35 students per class in Grades 1–6 (an average of 200 children per school), stratified to ensure equal representation between genders. Assenting students were interviewed using a structured questionnaire and asked to provide a stool specimen. Results Results of the baseline survey conducted about 2 weeks after deworming shows balanced demographic and STH prevalence data across trial arms. We observed a low prevalence of ascariasis (< 5%) as expected; however, the prevalence of trichuriasis was still about 35% in both arms. Conclusion The randomisation procedure was successful in achieving a balanced distribution of demographic characteristics and helminth infections between trial arms. The intervention is being rolled out. The current deworming treatment regimen may need to be revised with regards to the treatment of trichuriasis.

Background Chronic kidney disease (CKD) is a substantial cause of morbidity and mortality worldwide with disproportionate effects in sub-Saharan Africa (SSA). The optimal methods to estimate glomerular filtration rate (GFR) and therefore to determine the presence of CKD in SSA are uncertain. We plan to measure iohexol excretion to accurately determine GFR in Malawi, South Africa and Uganda. We will then assess the performance of existing equations to estimate GFR and determine whether a modified equation can better improve estimation of GFR in sub-Saharan Africa. Methods The African Research on Kidney Disease (ARK) study is a three-country study embedded within existing cohorts. We seek to enrol 3000 adults > 18 years based on baseline serum creatinine. Study procedures include questionnaires on socio-demographics and established risk factors for kidney disease along with anthropometry, body composition, blood pressure, blood chemistry and urine microscopy and albuminuria. We will measure GFR (mGFR) by plasma clearance of iohexol at 120, 180 and 240 min. We will compare eGFR determined by established equations with mGFR using Bland-Altman plots. We will use regression methods to estimate GFR and compare the newly derived model with existing equations. Discussion Through the ARK study, we aim to establish the optimal approach to estimate GFR in SSA. The study has the advantage of drawing participants from three countries, which will increase the applicability of the findings across the region. It is also embedded within established cohorts that have longitudinal information and serial measures that can be used to characterize kidney disease over a period of time. This will help to overcome the limitations of previous research, including small numbers, selected population sub-groups, and lack of data on proteinuria. The ARK collaboration provides an opportunity for close working partnerships across different centres, using standardized protocols and measurements, and shared bio-repositories. We plan to build on the collaboration for this study for future work on kidney disease in sub-Saharan Africa, and welcome additional partners from across the continent.

Background There are 2.5 million neonatal deaths each year; the majority occur within 48 h of birth, before stabilisation. Evidence from 11 trials shows that kangaroo mother care (KMC) significantly reduces mortality in stabilised neonates; however, data on its effect among neonates before stabilisation are lacking. The OMWaNA trial aims to determine the effect of initiating KMC before stabilisation on mortality within seven days relative to standard care. Secondary objectives include exploring pathways for the intervention’s effects and assessing incremental costs and cost-effectiveness between arms. Methods We will conduct a four-centre, open-label, individually randomised, superiority trial in Uganda with two parallel groups: an intervention arm allocated to receive KMC and a control arm receiving standard care. We will enrol 2188 neonates (1094 per arm) for whom the indication for KMC is ‘uncertain’, defined as receiving ≥ 1 therapy (e.g. oxygen). Admitted singleton, twin and triplet neonates (triplet if demise before admission of ≥ 1 baby) weighing ≥ 700–≤ 2000 g and aged ≥ 1– Discussion The OMWaNA trial aims to assess the effectiveness of KMC in reducing mortality among neonates before stabilisation, a vulnerable population for whom its benefits are uncertain. The trial will improve understanding of pathways underlying the intervention’s effects and will be among the first to rigorously compare the incremental cost and cost-effectiveness of KMC relative to standard care. The findings are expected to have broad applicability to hospitals in sub-Saharan Africa and southern Asia, where three-quarters of global newborn deaths occur, as well as important policy and programme implications. Trial registration ClinicalTrials.gov, NCT02811432. Registered on 23 June 2016.

Background: The burden of kidney disease in sub-Saharan Africa is currently poorly understood. Very limited monitoring and treatment is available for people affected. The association with other diseases and with mortality is unknown in this setting. We sought to determine the association between kidney function and subsequent all-cause mortality. Methods: In a general population cohort with detailed measurement of health-related parameters in rural Uganda, we estimated the baseline glomerular filtration rate (GFR) between 2011-2014 in 5,678 participants. We followed participants up to March 2019 with regular ascertainment of mortality and migration. Using multivariable cox regression, we determined associations between baseline eGFR and mortality. Findings: The median age of the participants at baseline was 36 years (IQR 24-50), 60·7% were female, 14·6% hypertensive, 9·7% HIV-positive and 1·8% diabetic. We registered 140 deaths with a median follow-up of 5·0 years. Adjusting for age and sex, HIV, hypertension, diabetes, BMI, marital status, and alcohol and tobacco use participants with eGFR ≤45 mls/min/1·73m2 had six-fold higher mortality compared to those with eGFR ≥90mls/min/1·73m2(HR 6·12 (95% CI 2·27-16·45)) with strong evidence of a linear trend for risk of mortality as renal function declined (P

ObjectivesTo estimate the incidence of unintentional fatal drowning and describe associated risk factors among Lake Victoria fishing communities, and to assess perceived social, financial and other impacts among families and colleagues of persons who drowned.DesignA retrospective, observational mixed-methods study, conducted between September 2017 and February 2018.SettingEight Tanzanian fishing communities on Lake Victoria.ParticipantsPersons who drowned in the preceding 24 months were identified using an extensive community networking approach. Adult family members, colleagues or community members familiar with the habits and behaviours of people who drowned and/or circumstances of drowning incidents participated in surveys (n=44) and in-depth interviews (n=22).Main outcome measuresPooled drowning incidence, with sensitivity analyses allowing for uncertainties in population estimates. Risk factors were identified through the evaluation of behavioural characteristics of persons who drowned and circumstances of drowning incidents. Perceived socioeconomic impacts were assessed through semi-structured interviews with their family members and colleagues.ResultsThe estimated drowning incidence was 217/100 000 person-years (95% CI 118 to 425/100 000). Of 86 victims identified, 70 (81%) were fishermen (79% aged 18–40 years; all men) and 9 were children (all ≤10 years). All deaths occurred in the lake. Most adults (65/77; 84%) were fishing from a boat when they drowned; 57/77 (74%) died in the evening (from ~5 pm) or at night. Six children (67%) drowned while swimming/playing at the lakeshore unsupervised. Few victims (2/86; 2%) were wearing a life jacket at the time of death. Reported socioeconomic impacts of these deaths ranged from income loss to family break-up.ConclusionsDrowning is a significant risk in Tanzanian lakeside fishing communities, with estimated mortality exceeding national incidence rates of fatal malaria, tuberculosis or HIV, but preventative strategies appear uncommon. Socioeconomic impact at the family level may be substantial. Intervention strategies are required to reduce the drowning burden among this neglected at-risk population.

Background Immediate uptake of antiretroviral therapy (ART) after an HIV-positive diagnosis (Test and Treat) is now being implemented in Uganda. Data are limited on lost to follow-up (LTFU) in high-risk cohorts that have initiated ‘Test and Treat’. We describe LTFU in a cohort of women of high-risk sexual behaviour who initiated ART under “Test and Treat”. Methods We performed a retrospective cohort study of participant records at the Good Health for Women Project (GHWP) clinic, a clinic in Kampala for women at high-risk of HIV-infection. We included HIV positive women ≥18 years who initiated ART at GHWP between August 2014 and March 2018. We defined LTFU as not taking an ART refill for ≥3 months from the last clinic appointment among those not registered as dead or transferred to another clinic. We used the Kaplan-Meier technique to estimate time to LTFU after ART initiation. Predictors of LTFU were assessed using a multivariable Cox proportional hazards model. Results The mean (±SD) age of the 293 study participants was 30.3 (± 6.5) years, with 274 (94%) reporting paid sex while 38 (13%) had never tested for HIV before enrolment into GHWP. LTFU within the first year of ART initiation was 16% and the incidence of LTFU was estimated at 12.7 per 100 person-years (95%CI 9.90–16.3). In multivariable analysis, participants who reported sex work as their main job at ART initiation (Adjusted Hazards Ratio [aHR] =1.95, 95%CI 1.10–3.45), having baseline WHO clinical stage III or IV (aHR = 2.75, 95% CI 1.30–5.79) were more likely to be LTFU. Conclusion LTFU in this cohort is high. Follow up strategies are required to support women on Test and Treat to remain on treatment, especially those who engage in sex work and those who initiate ART at a later stage of disease.

Background Huntington’s disease (HD) is an autosomal dominantly inherited neurodegenerative disorder, caused by an expansion of a trinucleotide (CAG) repeat in the huntingtin gene. There is no cure and only sparse symptomatic treatment. Structural brain imaging is the most applied and well documented technique to demonstrate longitudinal structural changes in premanifest and manifest HD gene-expansion carriers. Changes in the striatum are registered as far as 15 years before symptom onset with MRI. PET studies have found hypometabolism in the Caudate nucleus, Putamen and the temporal and frontal cortex years before clinical diagnosis along with hypermetabolism in Thalamus prior to symptom onset. Aims By a hybrid brain PET-MRI using FDG, we wished to simultaneously characterize the structural and metabolic brain changes in premanifest HD gene-expansion carriers and address the question whether changes in the metabolism precede the structural changes. Methods We recruited 21 premanifest HD gene-expansion carriers and 17 controls from the Neurogenetics Clinic, Danish Dementia Research Centre, Rigshospitalet, Denmark. We included individuals with CAG repeat ≥39 and a Unified HD Rating scale total motor score ≤5. Results We found a significantly lower (p=0.028) striatal metabolism in the HD gene expansion carrier group compared to gene-negative controls, while there was no significant striatal volume difference. We found a significant correlation between both striatal metabolism and CAP score and striatal volume and CAP score. The higher the CAP score, the lower the metabolism and striatal volume. We also found a significant positive association between striatal metabolism and MRI volume. Conclusions Our results suggest that striatal hypometabolism precedes atrophy; however longitudinal studies on larger cohorts using hybrid FDG-PET/MRI are needed to precisely assess the changes and evolution in time.

Background: Globally, about 30% of women have experienced physical and/or sexual violence from an intimate partner during their lifetime. We assessed the impact of a violence prevention intervention delivered to women participating in a group-based microfinance scheme. Methods: We conducted an unblinded, cluster randomized controlled trial among women in 66 microfinance groups, in Tanzania, to evaluate a 10-session participatory intervention that aims to empower women, prevent IPV and promote healthy relationships. If at least 70% of members consented, microfinance groups were randomly assigned to receive the intervention or be wait-listed for the intervention post-trial (control). Main outcomes, assessed 24 months post-intervention, were: a composite of reported past-year physical and/or sexual IPV (primary); past-year physical, sexual and emotional IPV; and acceptability and tolerance of IPV. An intention-to-treat analysis was conducted adjusting for age, education and baseline measure of the respective outcome. The trial is registered at ClinicalTrials.gov, NCT02592252. Findings: Between September 2014 and June 2015, 33 groups (n=544 women) were allocated to intervention and 33 (n=505 women) to control. Overall, 485 (89%) intervention and 434 (86%) control women completed outcomes assessment. Among intervention women, 112 (23%) reported past-year physical and/or sexual IPV compared with 119 (27%) among control women (adjusted odds ratio [aOR] 0·69, 95%CI 0·47-1·01, p=0·056). Intervention women reported significantly less physical IPV (aOR 0·64, 95%CI 0·41-0·99, p=0·043). They were also less likely to be accepting of IPV (aOR 0·45, 95%CI 0·34-0·61, p

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. This article describes the preparatory simulation study for a Bayesian response-adaptive dose-finding trial design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of Dexamethasone in reducing excessive menstrual bleeding and to determine the best dose for further study. To maximise learning about the dose response, patients receive placebo or an active dose with randomisation probabilities adapting based on evidence from patients already recruited. The dose-response relationship is estimated using a flexible Bayesian Normal Dynamic Linear Model. Several competing design options were considered including: number of doses, proportion assigned to placebo, adaptation criterion, and number and timing of adaptations. We performed a fractional factorial study using SAS software to simulate virtual trial data for candidate adaptive designs under a variety of scenarios and to invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial results using Normal linear models to estimate the effects of each design feature on empirical type I error and statistical power. Our readily-implemented approach using widely available statistical software identified a final design which performed robustly across a range of potential trial scenarios.

Background Intimate partner violence (IPV) is recognised as an important public health and social problem, with far reaching consequences for women’s physical and emotional health and social well-being. Furthermore, controlling behaviour by a partner has a similar impact on women’s well-being, yet little is known about the prevalence of this type of behaviour and other related abuses in Tanzania and in other sub-Saharan African countries. Methods We conducted a cross-sectional study to determine the lifetime and past 12-month prevalence of physical and sexual IPV, economic abuse, emotional abuse and controlling behaviour among ever-partnered women in Mwanza, Tanzania. Women (N = 1049) were enrolled in an ongoing trial (Maisha study) to assess the impact of microfinance combined with gender training on participants’ experience IPV, and other related outcomes. Interviews were conducted by same sex interviewers to collect information about socio-demographic characteristics, experiences of specific acts of IPV and abuse, and symptoms of poor mental health status. Results Overall, about 61% of women reported ever experiencing physical and/or sexual IPV (95% CI: 58–64%) and 27% (95% CI: 24–29%) experienced it in the past 12 months. Partner controlling behaviour was the most prevalent type of abuse with 82% experiencing it in their lifetime and 63% during the past 12 months. Other types of abuses were also common, with 34% of women reporting economic abuse and 39% reporting emotional abuse during the past 12 months. The prevalence of IPV and abuses varied by socio-demographic characteristics, showing much higher prevalence rates among younger women, women with young partners and less educated women. After we adjusted for age and socio-economic status, physical violence (OR = 1.8; 95% CI: 1.3–2.7) and sexual violence (OR = 2.8; 95% CI: 1.9–4.1) were associated with increased reporting of symptoms of poor mental health. Similarly, experience of abuse during the past 12 months was associated with increased reporting of symptoms of poor mental health. Conclusions The high prevalence of IPV and abuses and its strong links with symptoms of poor mental health underline the urgent need for developing and testing appropriate interventions in settings like Tanzania to tackle both violence and abusive behaviours among intimate partners. Trial registration ClinicalTrials.gov – ID NCT02592252 , registered retrospectively on 13 August 2015.

Background Worldwide, almost one third (30%) of women who have been in a relationship have experienced physical and/or sexual violence from an intimate partner. Given the considerable negative impacts of intimate partner violence (IPV) on women’s physical health and well-being, there is an urgent need for rigorous evidence on violence prevention interventions. Methods The study, comprising a cluster randomized controlled trial (RCT) and in-depth qualitative study, will assess the impact on women’s past year experience of physical and/or sexual IPV of a participatory gender training curriculum (MAISHA curriculum) delivered to women participating in group-based microfinance in Tanzania. More broadly, the study aims to learn more about the factors that contribute to women’s vulnerability to violence and understand how the intervention impacts on the lives of women and their families. Sixty-six eligible microfinance loan groups are enrolled and randomly allocated to: the 10-session MAISHA curriculum, delivered over 20 weeks (n = 33); or, to no intervention (n = 33). Study participants are interviewed at baseline and at 24 months post-intervention about their: household; partner; income; health; attitudes and social norms; relationship (including experiences of different forms of violence); childhood; and community. For the qualitative study and process evaluation, focus group discussions are being conducted with study participants and MAISHA curriculum facilitators. In-depth interviews are being conducted with a purposive sample of 18 participants. The primary outcome, assessed at 24 months post-intervention, is a composite of women’s reported experience of physical and/or sexual IPV during the past 12 months. Secondary outcomes include: reported experience of physical, sexual and emotional/psychological IPV during the past 12 months, attitudes towards IPV and reported disclosure of IPV to others. Discussion The study forms part of a wider programme of research (MAISHA) that includes: a complementary cluster RCT evaluating the impact of delivering the MAISHA curriculum to women not receiving formal group-based microfinance; an economic evaluation; and a cross-sectional survey of men to explore male risk factors associated with IPV. MAISHA will generate rigorous evidence on violence prevention interventions, as well as further insights into the different forms and consequences of violence and drivers of violence perpetration. Trial registration ClinicalTrials.gov ID: NCT02592252, registered retrospectively on 13 August 2015. Electronic supplementary material The online version of this article (10.1186/s12905-018-0546-8) contains supplementary material, which is available to authorized users.

BackgroundThere remains an urgent need for a prophylactic HIV vaccine to control generalised epidemics. PrEP has demonstrated effectiveness of 86% and is recommended by WHO; uptake is generally high, but retention is disappointing in some settings. The EDCTP2 project PrEPVacc will assess the efficacy of two combination prophylactic vaccine regimens (DNA, MVA and Env protein/adjuvant) each compared to placebo and the proportion of infections averted by F/TAF in comparison to TDF/FTC. A Registration Cohort, recruiting HIV negative volunteers at risk of HIV will precede the trial.MethodsThe PrEPVacc partnership agreed that 70% vaccine efficacy had public health relevance. The trial uses nstage software for multi-arm, multi-stage designs (MAMS) and the averted infections ratio (AIR) methodology with participants randomised (i) 1:1:1 to active product or placebo (ii) 1:1 to TDF/FTC : F/TAF until week 26 (presumed peak immunogenicity). Access to PrEP in the Registration Cohort and after week 26 will be standard of care. HIV seroconversions occurring between weeks 0–26 will inform the PrEP analysis, incorporating HIV incidence amongst those who do not take up PrEP locally in the Registration Cohort. Seroconversions after week 26 will inform vaccine analyses.ResultsUp to 556 participants per group affords 92% power to detect vaccine efficacy of 70% at the final analysis, assuming incidence of 4/100-person years and 10% loss with 81% and 97% power to conclude that F/TAF can avert half or more of the infections prevented by TDF/FTC if effectiveness of TDF/FTC is 70% and 80%, respectively.ConclusionPrEPVacc adopts a pragmatic approach to uncertainties around HIV incidence in settings where PrEP is increasingly available. This innovative adaptive trial design uses validated software to determine vaccine efficacy and a novel methodology to evaluate a new PrEP agent, overcoming the challenge of demonstrating non-inferiority when adherence to TDF/FTC is high and the number of outcome events very low.

BackgroundMedical patients are often screened for distress in the clinic using a questionnaire such as the Hospital Anxiety and Depression Scale (HADS) while awaiting their consultation. However, might the context of the clinic artificially inflate the distress score? To address this question we aimed to determine whether those who scored high on the HADS in the clinic remained high scorers when reassessed later at home.MethodWe analysed data collected by a distress and depression screening service for cancer out-patients. All patients had completed the HADS in the clinic (on computer or on paper) prior to their consultation. For a period, patients with a high score (total of ⩾15) also completed the HADS again at home (over the telephone) 1 week later. We used these data to determine what proportion remained high scorers and the mean change in their scores. We estimated the effect of ‘regression to the mean’ on the observed change.ResultsOf the 218 high scorers in the clinic, most [158 (72.5%), 95% confidence interval (CI) 66.6–78.4] scored high at reassessment. The mean fall in the HADS total score was 1.74 (95% CI 1.09–2.39), much of which could be attributed to the estimated change over time (regression to the mean) rather than the context.ConclusionsPre-consultation distress screening in clinic is widely used. Reassuringly, it only modestly overestimates distress measured later at home and consequently would result in a small proportion of unnecessary further assessments. We conclude it is a reasonable and convenient strategy.

Objective To determine whether a higher score on Item 9 of the Patient Health Questionnaire-9 (range zero to three) was more likely to indicate suicidality as determined at subsequent clinical interview in cancer outpatients. Method Analysis of anonymized data (with ethical approval) obtained from the routine clinical administration of self-report questionnaires and telephone interviews to patients attending a cancer centre in the UK. Results Complete data were available on 330 patients. Those with higher scores on the item were more likely to be suicidal at interview. However, a substantial number of those (54/235; 23%) who scored only one on the item were also found to be suicidal. Conclusions A higher score on Item 9 of the PHQ-9 indicates a greater likelihood that the patient is suicidal. However, even patients who score only 1 may be suicidal and consequently also require further assessment.

Background Patients with serious medical illnesses, such as cancer, are at increased risk of suicide but are also often facing death. The Patient Health Questionnaire-9 (PHQ-9) is widely used to screen patients for depression. It includes an item that asks about thoughts of death and hurting yourself (Item-9). Objective To describe the nature of thoughts of death and suicide reported in clinical interviews carried out to further assess suicidal ideation of cancer outpatients who had endorsed the "suicidal thoughts item" (Item-9) of the PHQ-9 during routine depression screening. Method Secondary analysis of anonymized service data (with ethical approval) derived from the routine clinical administration of self-report questionnaires and telephone interviews to outpatients attending a Cancer Centre in the UK. Results Complete data were available on 330/463 (71%) of patients who had endorsed Item-9. In a subsequent structured telephone interview, approximately one-third of these patients denied any thoughts that they would be better off dead, another third acknowledged having thoughts that they would be better off dead, but not of suicide, and the remaining third reported clear thoughts of committing suicide. Conclusion Only one-third of cancer outpatients who endorse the "suicidal thoughts item" of the PHQ-9 report suicidal thoughts at a subsequent interview. Services planning to set up depression screening with the PHQ-9 need to carefully consider the relative benefits and burden to their service and patients of including Item-9 and interviewing all those who endorse it.

Summary Background Millennium Development Goal (MDG) 5 calls for a reduction of 75% in the maternal mortality ratio (MMR) between 1990 and 2015. We estimated levels and trends in maternal mortality for 183 countries to assess progress made. Based on MMR estimates for 2015, we constructed scenario-based projections to highlight the accelerations needed to accomplish the Sustainable Development Goal (SDG) global target of less than 70 maternal deaths per 100,000 live births globally by 2030. Methods We updated the open access UN Maternal Mortality Estimation Inter-agency Group (MMEIG) database. Based upon nationally-representative data for 171 countries, we generated estimates of maternal mortality and related indicators with uncertainty intervals using a Bayesian model, which extends and refines the previous UN MMEIG estimation approach. The model combines the rate of change implied by a multilevel regression model with a time series model to capture data-driven changes in country-specific MMRs, and includes a data model to adjust for systematic and random errors associated with different data sources. Results The global MMR declined from 385 deaths per 100,000 live births (80% uncertainty interval ranges from 359 to 427) in 1990 to 216 (207 to 249) in 2015, corresponding to a relative decline of 43.9% (34.0 to 48.7) during the 25-year period, with 303,000 (291,000 to 349,000) maternal deaths globally in 2015. Regional progress in reducing the MMR since 1990 ranged from an annual rate of reduction of 1.8% (0 to 3.1) in the Caribbean to 5.0% (4.0 to 6.0) for Eastern Asia. Regional MMRs for 2015 range from 12 (11 to 14) for developed regions to 546 (511 to 652) for sub-Saharan Africa. Accelerated progress will be needed to achieve the SDG goal; countries will need to reduce their MMRs at an annual rate of reduction of at least 7.5%. Interpretation Despite global progress in reducing maternal mortality, immediate action is required to begin making progress towards the ambitious SDG 2030 target, and ultimately eliminating preventable maternal mortality. While the rates of reduction that are required to achieve country-specific SDG targets are ambitious for the great majority of high mortality countries, the experience and rates of change between 2000 and 2010 in selected countries–those with concerted efforts to reduce the MMR- provide inspiration as well as guidance on how to accomplish the acceleration necessary to substantially reduce preventable maternal deaths. Funding Funding from grant R-155-000-146-112 from the National University of Singapore supported the research by LA and SZ. AG is the recipient of a National Institute of Child Health and Human Development, grant # T32-HD007275. Funding also provided by USAID and HRP (the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction).

Background Although it is increasingly recognized that cancer patients often have sleep problems, we lack data on their prevalence and associations in representative clinical populations. We aimed to determine (i) the prevalence of sleep problems amongst outpatients of a cancer centre and (ii) the association with medical variables, emotional distress and pain. Methods Secondary analysis of self-report and medical data on 2862 cancer centre outpatients. Sleep problems were identified using the sleep item from the Patient Health Questionnaire-9: ‘Over the last two weeks, how often have you been bothered by trouble falling or staying asleep or sleeping too much?’ scored on a four-point frequency scale. Emotional distress was measured using the Hospital Anxiety and Depression Scale and pain using the subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Core 30 questionnaire. Medical data were obtained from the cancer centre clinical database. Results Sleep problems (bothered more than half the days during the previous 2 weeks) were reported by 30.2% (865/2862, 95% CI = 28.5 to 31.9) of the patients. They were common in both patients with active cancer (34.5%) and in cancer survivors (28.0%). There was only a modest association with cancer site and treatment status, but there was a strong association with pain (odds ratio = 2.7, 95% CI = 2.2 to 3.4) and emotional distress (odds ratio = 4.5, 95% CI = 3.7 to 5.6). Conclusions Sleep problems are common in cancer outpatients and are strongly associated with pain and emotional distress. A combined approach to the management of sleep, pain and emotional distress is indicated. Copyright © 2011 John Wiley & Sons, Ltd.

Purpose: This study aimed to determine which methods of remote symptom assessment cancer outpatients would be comfortable using, including those involving information technology, and whether this varied with age and gender. Methods: A questionnaire survey of 477 outpatients attending the Edinburgh Cancer Centre in Edinburgh, UK. Results: Most patients reported that they would not feel comfortable using methods involving technology such as a secure website, email, mobile phone text message, or a computer voice on the telephone but that they would be more comfortable using more traditional methods such as a paper questionnaire, speaking to a nurse on the telephone, or giving information in person. Conclusions: The uptake of new, potentially cost-effective technology-based methods of monitoring patients' symptoms at home might be limited by patients' initial discomfort with the idea of using them. It will be important to develop methods of addressing this potential barrier (such as detailed explanation and supervised practice) if these methods are to be successfully implemented.

Hypertension control rates are low in sub-Saharan Africa. Population-specific determinants of blood pressure (BP) control have not been adequately described. The authors measured BP and conducted interviews to determine factors associated with BP control among adults attending a hypertension clinic in Tanzania. Three hundred adults were enrolled. BP was controlled in 47.7% of patients at the study visit but only 28.3% over three consecutive visits. Demographic and socioeconomic factors were not associated with control. Obesity and higher medication cost were associated with decreased control. Their effect was mediated through adherence. Good knowledge of (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.0-6.1; P=.047), attitudes towards (OR, 2.7; 95% CI, 1.0-7.1; P=.04), and practices concerning (OR, 5.4; 95% CI, 2.3-13.0; P

Summary Background Major depression is an important complication of cancer. However, reliable data are lacking for the prevalence of depression in patients with cancer in different primary sites, the association of depression with demographic and clinical variables within cancer groupings, and the proportion of depressed patients with cancer receiving potentially effective treatment for depression. We investigated these questions with data from a large representative clinical sample. Methods We analysed data from patients with breast, lung, colorectal, genitourinary, or gynaecological cancer who had participated in routine screening for depression in cancer clinics in Scotland, UK between May 12, 2008, and Aug 24, 2011. Depression screening was done in two stages (first, Hospital Anxiety and Depression Scale; then, major depression section of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition). Data for depression status were linked with demographic and clinical data obtained from the Scottish National Cancer Registry. Findings We analysed data for 21 151 patients. The prevalence of major depression was highest in patients with lung cancer (13·1%, 95% CI 11·9–14·2%), followed by gynaecological cancer (10·9%, 9·8–12·1), breast cancer (9·3%, 8·7–10·0), colorectal cancer (7·0%, 6·1–8·0), and genitourinary cancer (5·6%, 4·5–6·7). Within these cancer groupings, a diagnosis of major depression was more likely in patients who were younger, had worse social deprivation scores, and, for lung cancer and colorectal cancer, female patients. 1130 (73%) of 1538 patients with depression and complete patient-reported treatment data were not receiving potentially effective treatment. Interpretation Major depression is common in patients attending cancer clinics and most goes untreated. A pressing need exists to improve the management of major depression for patients attending specialist cancer services. Funding Cancer Research UK and Chief Scientist Office of the Scottish Government.

BACKGROUND: Medical conditions are often complicated by major depression, with consequent additional impairment of quality of life. We aimed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer (depression care for people with cancer) with usual care. METHODS: SMaRT Oncology-2 is a parallel-group, multicentre, randomised controlled effectiveness trial. We enrolled outpatients with major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. Depression care for people with cancer is a manualised, multicomponent collaborative care treatment that is delivered systematically by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. Outcome data were collected up until 48 weeks. The primary outcome was treatment response (≥50% reduction in Symptom Checklist Depression Scale [SCL-20] score, range 0-4) at 24 weeks. Trial statisticians and data collection staff were masked to treatment allocation, but participants could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN40568538. FINDINGS: 500 participants were enrolled between May 12, 2008, and May 13, 2011; 253 were randomly allocated to depression care for people with cancer and 247 to usual care. 143 (62%) of 231 participants in the depression care for people with cancer group and 40 (17%) of 231 in the usual care group responded to treatment: absolute difference 45% (95% CI 37-53), adjusted odds ratio 8·5 (95% CI 5·5-13·4), p

OBJECTIVE: Somatic symptoms unexplained by disease are common in all medical settings. The process of identifying such patients requires a clinical assessment often supported by clinical tests. Such assessments are time-consuming and expensive. Consequently the observation that such patients tend to report a greater number of symptom has led to the use of self-rated somatic symptom counts as a simpler and cheaper diagnostic aid and proxy measure for epidemiological surveys. However, despite their increasing popularity there is little evidence to support their validity. METHODS: We tested the score on a commonly used self-rated symptom questionnaire- the Patient Health Questionnaire (PHQ 15) (plus enhanced iterations including an additional 10 items on specific neurological symptoms and an additional 5 items on mental state) for diagnostic sensitivity and specificity against a medical assessment (with 18 months follow-up) in a prospective cohort study of 3781 newly attending patients at neurology clinics in Scotland, UK. RESULTS: We found 1144/3781 new outpatients had symptoms that were unexplained by disease. The patients with symptoms unexplained by disease reported higher symptoms count scores (PHQ 15: 5.6 (95% CI 5.4 to 5.8) vs 4.2 (4.1 to 4.4) p

Objective To determine the validity of a 50% drop in the 20-item Symptom Checklist Depression Scale (SCL-20) score against the “gold standard” of no longer meeting criteria for major depression as assessed using a diagnostic interview in an outpatient cancer population and also to examine the validity of other potential cut-offs (i.e., percentage drops). Materials and Methods Secondary analysis of data from a randomized trial which compared collaborative care with usual care for cancer patients with major depression. A total of 194 trial participants who had both SCL-20 scores and depression diagnoses on the Structured Clinical Interview for DSM-IV at both baseline and at 12-week outcome formed the analyzed sample. Results A 50% reduction in the SCL-20 score from baseline to 12 weeks correctly identified the patients who no longer met criteria for major depression in 153 (78.9%) of 194 (95% CI 73.1% to 84.6%) cases. Most of those misclassified had not achieved a 50% reduction in SCL-20 score despite no longer meeting criteria for major depression. Examination of the performance of percentage drops other than 50% on the SCL-20 using a receiver operating characteristics (ROC) curve and histogram of misclassification suggested that the 50% drop was best if both a low overall misclassification rate and the minimizing of false positives of improvement were required. Conclusions A 50% reduction in the SCL-20 score performs well as a conservative measure of change in depression status in cancer patients.

Heavy Menstrual Bleeding (HMB) is common and existing treatments often ineffective. The MRC funded DexFEM trial aims to investigate whether oral dexamethasone (Dex; a glucocorticoid) reduces HMB. Our integrated approach to the development of a Bayesian response-adaptive dose-finding study uses SAS for data handling, generating scripts and executing analysis in WinBUGS. The clinical aims are twofold: (i) to determine if Dex is efficacious in reducing HMB compared with placebo and, if so, (ii) to identify the optimal dose for further phase III study. Patients are randomised to placebo or one of several active Dex doses. Randomisation probabilities change as outcome data accumulate from patients already recruited. This design ensures that maximum information is gathered on the dose-response curve, and also that fewer women are randomised to inferior doses. Development of an adaptive design cannot invoke standard frequentist concepts of power. We estimate the dose-response curve in a Bayesian Normal Dynamic Linear Model. Several competing design options are considered including: the number of doses; the criterion for adapting the randomisation; the length of the run-in before adaptation commences; the frequency with which randomisation probabilities are adapted. Through extensive simulation work we assess the performance of candidate designs under a variety of plausible scenarios for dose-response curve shape and outcome measure variance, and decide on a final design. Adaptive designs offer flexibility and efficiency and are likely to be used more in the future. Our integrated approach is a practical, powerful tool for the development of such designs.

Lung cancer commonly occurs in older adults who live in deprived areas and have multiple medical comorbidities. As well as suffering severe physical deterioration they are aware of their poor prognosis. It is therefore unsurprising that people with lung cancer have a high rate of depression. Whilst there are effective treatments for depression in people who do not have cancer, it is uncertain which treatments, if any, are effective in depressed cancer patients; the special characteristics of the condition only increase that uncertainty for people with lung cancer.We therefore conducted a systematic review of relevant randomised controlled trials to determine which, if any, treatments have been found to be effective for depression in patients with lung cancer. Surprisingly, we found no completed trials of treatments in patients selected for having depression and no trials that had evaluated treatments known to be effective for depression in the general population. We did, however, find six trials of interventions intended to improve quality of life in unselected patients with lung cancer. These suggested that enhanced care is more effective in reducing depressive symptoms than standard care.Whilst it may be reasonable to treat depression in individuals with lung cancer with standard treatments until more specific evidence is available, clinicians should be aware that the effectiveness and potential adverse effects of these treatments remain unknown in this patient group. Evidence from randomised trials is urgently required. © 2012 Elsevier Ireland Ltd.

International audience; Objectives: To determine disability, distress and employment status in new neurology patients with physical symptoms unexplained by organic disease and to compare this with that of patients with symptoms explained by organic disease. Methods: As part of a cohort study ( the Scottish Neurological Symptoms Study) neurologists rated the extent to which each new patient's symptoms were explained by organic disease. In this paper patients whose symptoms were rated as "not at all", or only "somewhat" explained by disease were considered cases and those whose symptoms were "largely" or "completely" explained by disease were designated as controls. All patients completed self-ratings of disability and health status (SF-12) and emotional distress (HADS) and also reported their employment and state financial benefit status. Cases and controls were compared. Results: 3,781 patients were recruited; 1,144 (30%) were cases and 2,637 (70%) controls. Cases had slightly worse physical health status (SF12 score 42 vs 44; difference in means= -1.7 (95% CI -2.5 to -0.9)) and worse mental health status (SF12 score 43 vs 47; difference in means= -3.5 (95% CI -4.3 to -2.7). Unemployment was similar in cases and controls (50% v 50%) but cases were more likely to not to be working because of their health (54% v 37% (of the 50% not working) ; OR 2.0 (95% CI 1.6 to 2.4) and also more likely to be receiving disability related state financial benefits (27% v 22%; OR 1.3 (95% CI 1.1 to 1.6)). Conclusions: New neurology patients with symptoms unexplained by organic disease had greater disability, distress and more disability related state financial benefits than those whose symptoms were explained by disease.

Introduction Prevalence and incidence of HIV infection and other sexually transmitted infections (STIs) are particularly high among adolescent girls in sub-Saharan Africa. The role played by the vaginal microbiota in susceptibility to HIV and other STIs in adolescent girls is unclear. The aim of this study was to characterise the vaginal microbiota of adolescent girls in Tanzania around the time of their sexual debut. Methods Girls aged 17–18 years old attending secondary schools in Mwanza City were invited to join a cross-sectional study. After informed consent/assent, girls were interviewed and vaginal swabs were obtained and tested for the following species by in-house quantitative PCR: Lactobacillus crispatus, L. iners , L. gasseri, L. jensenii, L. vaginalis, Atopobium vaginae, and Gardnerella vaginalis . Differences in the prevalence of bacterial species were analysed using logistic regression. Results Of the 403 girls enrolled, 385 provided samples for this analysis. Of these, 163 reported having had sexual intercourse. Prevalences of bacterial species were as follows (overall; sexually active/sexually naive): L. crispatus (69%; 60%/75%), L. iners (83%; 85%/80%), L. gasseri (22%; 21%/23%), L. jensenii (49%; 40%/55%), L. vaginalis (66%; 55%/74%), A. vaginae (44%; 56%/34%), and G. vaginalis (62%; 75%/52%). Prevalences of A. vaginae and G. vaginalis were higher among girls who reported sexual intercourse (OR: 2.5; 95% CI: 1.7–3.8 and OR: 2.8; 95% CI: 1.8–4.4, respectively), while prevalences of L. crispatus, L. jensenii, and L. vaginalis were lower in sexually active girls (OR: 0.5; 95% CI: 0.3–0.8, OR: 0.5; 95% CI: 0.4–0.8, and OR: 0.4; 95% CI: 0.3–0.6, respectively). Conclusion Among girls attending secondary school in Tanzania, sexual debut was associated with quantifiable changes in vaginal microbiota. BV-associated bacteria were present in many girls before reported sexual debut. Additionally, the prevalence of L. crispatus was higher than expected; a recent study showed the prevalence among African women to be relatively low (17–38%). This challenges the view that women in sub-Saharan Africa have less L. crispatus colonisation. Disclosure of interest statement The authors do not have a conflict of interest. No pharmaceutical grants were received in the development of this study.

Introduction Prevalence and incidence of HIV infection and other sexually transmitted infections (STI) are particularly high among adolescent girls in sub-Saharan Africa. One area in need of further research is the role played by the vaginal microbiota in the susceptibility to HIV and other STI in adolescent girls. The aim of this study was to characterise the vaginal microbiota of adolescent girls in Tanzania around the time of their sexual debut. Methods Girls attending secondary schools in Mwanza City, ages 17 and 18 years old, were invited to join a cross-sectional study. After informed consent/assent, girls were interviewed and nurse-assisted, self-collected swabs were obtained for STI and BV testing. BV was considered as a binary outcome: Nugent scores 7–10 were considered BV positive. Factors associated with prevalent BV were analysed using multivariable logistic regression. Results Of the 403 girls who enrolled in the study, 176 (44%) reported having had sexual intercourse and 8 (2%) reported receiving cunnilungus. Ninety-five (25%) girls had BV, 9 (2%) were infected with Chlamydia trachomatis , 8 (2%) had Neisseria gonorrhoea, 18 (5%) had Trichomonas vaginalis , 85 (21%) had Human papilloma virus and 6 (2%) Mycoplasma genitalium . Six (2%) girls were infected with HSV-2. Among girls who were sexually naive, 19% had BV compared to 32% in sexually active girls. BV was independently associated with sexual debut (aOR = 2.11; 95% CI: 1.32,3.39); oral sex (aOR = 7.94; 95% 1.53,40.3); >1 sex partner (aOR = 2.55; 95% CI: 1.21,5.39); and HPV (aOR = 1.73; 95% CI: 1.02,2.94). Conclusion In this study among girls attending secondary school in Mwanza, Tanzania, sexual debut was associated with BV; however, 19% of girls who were sexually naive had BV. This suggests that sexual intercourse may not be a prerequisite for BV. Oral sex was also associated with BV although the reported prevalence of this sexual behaviour was low. Disclosure of interest statement The authors do not have a conflict of interest. No pharmaceutical grants were received in the development of this study.

Clinical trials are expensive. Understanding where a trial is needed and what questions to address is therefore important. We ask if pilot work using observational healthcare data can be used to inform a trial. Symptoms of significant psychological distress are common in cancer patients but are often left untreated. It is unknown to what extent such distress symptoms persist over time and require treatment. Should a clinical trial be devised to determine if patients would benefit from treatment? How many and what patients are likely to suffer from persistent distress and to require treatment? On what criteria should patients be included in a trial, and when should trial outcomes be evaluated? We address these questions using repeated, psychological symptom data that were routinely collected from over 20,000 outpatients who attended selected oncology clinics in Scotland. However, the limitations to routinely collected observational healthcare data are many. We approach the analysis within a missing data context and develop a Bayesian model in WinBUGS to estimate the posterior predictive distribution for the incomplete longitudinal responses and covariates under both MAR and MNAR mechanisms and use this model to generate multiply imputed datasets for analysis in SAS. The findings are compared with those from a purpose-designed, prospective, clinical study in the same population. Meaningful analysis of observational healthcare data requires subject-matter knowledge, good quality data and appropriate statistical methods. With flexible modelling techniques now more practicable, we believe pilot work with such data could help inform future trial designs.