A comparison of the associations between adiposity and lipids in Malawi and the United Kingdom.

BACKGROUND: The prevalence of excess adiposity, as measured by elevated body mass index (BMI) and waist-hip ratio (WHR), is increasing in sub-Saharan African (SSA) populations. This could add a considerable burden of cardiovascular and metabolic diseases for which these populations are currently ill-prepared. Evidence from white, European origin populations shows that higher adiposity leads to an adverse lipid profile; whether these associations are similar in all SSA populations requires further exploration. This study compared the association of BMI and WHR with lipid profile in urban Malawi with a contemporary cohort with contrasting socioeconomic, demographic, and ethnic characteristics in the United Kingdom (UK). METHODS: We used data from 1248 adolescents (mean 18.7 years) and 2277 Malawian adults (mean 49.8 years), all urban-dwelling, and from 3201 adolescents (mean 17.8 years) and 6323 adults (mean 49.7 years) resident in the UK. Adiposity measures and fasting lipids were assessed in both settings, and the associations of BMI and WHR with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed by sex and age groups in both studies. RESULTS: Malawian female adults were more adipose and had more adverse lipid profiles than their UK counterparts. In contrast, Malawian adolescent and adult males were leaner and had more favourable lipid profiles than in the UK. Higher BMI and WHR were associated with increased TC, LDL-C and TG and reduced HDL-C in both settings. The magnitude of the associations of BMI and WHR with lipids was mostly similar or slightly weaker in the Malawian compared with the UK cohort in both adolescents and adults. One exception was the stronger association between increasing adiposity and elevated TC and LDL-C in Malawian compared to UK men. CONCLUSIONS: Malawian adult women have greater adiposity and more adverse lipid profiles compared with their UK counterparts. Similar associations of adiposity with adverse lipid profiles were observed for Malawian and UK adults in most age and sex groups studied. Sustained efforts are urgently needed to address the excess adiposity and adverse lipid profiles in Malawi to mitigate a future epidemic of cardio-metabolic disease among the poorest populations.

Sentinel lymph node positivity in patients undergoing mastectomies for ductal carcinoma in situ (DCIS).

Current guidelines recommend sentinel lymph node biopsy (SLNB) for patients undergoing mastectomy for a preoperative diagnosis of ductal carcinoma in situ (DCIS). We examined the factors associated with sentinel lymph node positivity for patients undergoing mastectomy for a diagnosis of DCIS on preoperative core biopsy (PCB). The Institutional Breast Cancer Database was queried for patients with PCB demonstrating pure DCIS followed by mastectomy and SLNB from 2010 to 2018. Patients were divided according to final pathology (DCIS or invasive cancer). Clinico-pathologic variables were analyzed using Pearson's chi-squared, Wilcoxon Rank-Sum and logistic regression. Of 3145 patients, 168(5%) had pure DCIS on PCB and underwent mastectomy with SLNB. On final mastectomy pathology, 120(71%) patients had DCIS with 0 positive sentinel lymph nodes (PSLNs) and 48(29%) patients had invasive carcinoma with 5(10%) cases of ≥1 PSLNs. Factors positively associated with upstaging to invasive cancer in univariate analysis included age (P = .0289), palpability (P < .0001), extent of disease on imaging (P = .0121), mass on preoperative imaging (P = .0003), multifocality (P = .0231) and multicentricity (P = .0395). In multivariate analysis, palpability (P = .0080), extent of disease on imaging (P = .0074) and mass on preoperative imaging (P = .0245) remained significant (Table 2). In a subset of patients undergoing mastectomy for DCIS with limited disease on preoperative evaluation, SLNB may be omitted as the risk of upstaging is low. However, patients who present with clinical findings of palpability, large extent of disease on imaging and mass on preoperative imaging have a meaningful risk of upstaging to invasive cancer, and SLNB remains important for management.

Community-Level Knowledge and Perceptions of Stroke in Rural Malawi.

Background and Purpose- The incidence of stroke in Malawi is unknown but major risk factors, including hypertension, obesity, and diabetes mellitus, are highly prevalent. We sought to understand community-level knowledge about stroke. Methods- A population-based cross-sectional study was conducted in rural Malawi (2016-2017). Adults aged ≥15 years were randomly selected and interviewed about their knowledge and perceptions of stroke symptoms, risk factors, and prevention. Logistic regression was used to investigate sociodemographic factors associated with stroke knowledge. Results- Of 812 selected, 739 (91% response rate) were seen and consented; 57% were female, and the median age was 52.0 years. Knowledge of stroke was poor: 71% knew no (correct) risk factors. Witchcraft (20.6%) was mentioned as frequently as hypertension (19.8%) as a cause. Knowledge of stroke was greatest in the most educated and wealthy and lowest in men, the never married, and the youngest age group. HIV-positive individuals had higher knowledge of prevention (odds ratio, 2.91; 95% CI, 1.21-7.03) than HIV negative individuals. Conclusions- Knowledge about stroke is very low in this community, particularly among the least educated and poor. Programs to support prevention, early recognition, and timely hospital presentation after a stroke are needed.

Tumor-Infiltrating Lymphocytes in a Contemporary Cohort of Women with Ductal Carcinoma In Situ (DCIS).

BACKGROUND: Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) are less understood. METHODS: Our institutional database of 668 patients with pure DCIS from 2010 to 2018 was queried. TILs were evaluated by International TILs Working Group guidelines. Percentage of TILs was assessed from the densest focus (hotspot) in one high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses (to define sparse versus dense TILs), logistic, and Cox regression models. RESULTS: Sixty-nine patients with DCIS and TILs were evaluated, of whom 54 (78%) were treated by breast-conserving surgery. Thirteen (19%) patients had ipsilateral recurrence. Each recurrence (n = 13) was matched to four controls (n = 56) based on date of surgery. Median follow-up was 6.7 years. TILs were defined as sparse (< 45%) or dense (≥ 45%). Dense TILs were associated with younger age (p = 0.045), larger tumor size (p < 0.001), high nuclear grade (p = 0.010), comedo histology (p = 0.033), necrosis (p = 0.027), estrogen receptor (ER) negativity (p = 0.037), and ipsilateral recurrence (p = 0.001). Nine patients with dense TILs had mean time to recurrence of 73.5 months compared with four patients with sparse TILs with mean time to recurrence of 97.9 months (p = 0.003). CONCLUSIONS: Dense TILs were significantly associated with age, tumor size, nuclear grade, comedo histology, necrosis, and ER status and was a significant predictor of recurrence in patients with pure DCIS.

Lusting, learning and lasting in school: sexual debut, school performance and dropout among adolescents in primary schools in Karonga district, northern Malawi.

Age at sexual debut is known to have implications for future sexual behaviours and health outcomes, including HIV infection, early pregnancy and maternal mortality, but may also influence educational outcomes. Longitudinal data on schooling and sexual behaviour from a demographic surveillance site in Karonga district, northern Malawi, were analysed for 3153 respondents between the ages of 12 and 25 years to examine the association between sexual debut and primary school dropout, and the role of prior school performance. Time to dropout was modelled using the Fine and Gray survival model to account for the competing event of primary school completion. To deal with the time-varying nature of age at sexual debut and school performance, models were fitted using landmark analyses. Sexual debut was found to be associated with a five-fold increase in rate of subsequent dropout for girls and a two-fold increase in dropout rate for boys (adjusted hazard ratio [aHR] of 5.27, CI 4.22-6.57, and 2.19, CI 1.77-2.7, respectively). For girls who were sexually active by age 16, only 16% ultimately completed primary schooling, compared with 70% aged 18 or older at sexual debut. Prior to sexual debut, girls had primary completion levels similar to those of boys. The association between sexual debut and school dropout could not be explained by prior poor school performance: the effect of sexual debut on dropout was as strong among those who were not behind in school as among those who were overage for their school grade. Girls who were sexually active were more likely to repeat a grade, with no effect being seen for boys. Pathways to dropout are complex and may differ for boys and girls. Interventions are needed to improve school progression so children complete primary school before sexual debut, and to improve sex education and contraception provision.

The Incidence Patterns Model to Estimate the Distribution of New HIV Infections in Sub-Saharan Africa: Development and Validation of a Mathematical Model.

BACKGROUND: Programmatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates. METHODS AND FINDINGS: We developed a predictive model, the Incidence Patterns Model (IPM), representing populations according to factors that have been demonstrated to be strongly associated with HIV acquisition risk: gender, marital/sexual activity status, geographic location, "key populations" based on risk behaviours (sex work, injecting drug use, and male-to-male sex), HIV and ART status within married or cohabiting unions, and circumcision status. The IPM estimates the distribution of new infections acquired by group based on these factors within a Bayesian framework accounting for regional prior information on demographic and epidemiological characteristics from trials or observational studies. We validated and trained the model against direct observations of HIV incidence by group in seven rounds of cohort data from four studies ("sites") conducted in Manicaland, Zimbabwe; Rakai, Uganda; Karonga, Malawi; and Kisesa, Tanzania. The IPM performed well, with the projections' credible intervals for the proportion of new infections per group overlapping the data's confidence intervals for all groups in all rounds of data. In terms of geographical distribution, the projections' credible intervals overlapped the confidence intervals for four out of seven rounds, which were used as proxies for administrative divisions in a country. We assessed model performance after internal training (within one site) and external training (between sites) by comparing mean posterior log-likelihoods and used the best model to estimate the distribution of HIV incidence in six countries (Gabon, Kenya, Malawi, Rwanda, Swaziland, and Zambia) in the region. We subsequently inferred the potential contribution of each group to transmission using a simple model that builds on the results from the IPM and makes further assumptions about sexual mixing patterns and transmission rates. In all countries except Swaziland, individuals in unions were the single group contributing to the largest proportion of new infections acquired (39%-77%), followed by never married women and men. Female sex workers accounted for a large proportion of new infections (5%-16%) compared to their population size. Individuals in unions were also the single largest contributor to the proportion of infections transmitted (35%-62%), followed by key populations and previously married men and women. Swaziland exhibited different incidence patterns, with never married men and women accounting for over 65% of new infections acquired and also contributing to a large proportion of infections transmitted (up to 56%). Between- and within-country variations indicated different incidence patterns in specific settings. CONCLUSIONS: It is possible to reliably predict the distribution of new HIV infections acquired using data routinely available in many countries in the sub-Saharan African region with a single relatively simple mathematical model. This tool would complement more specific analyses to guide resource allocation, data collection, and programme planning.

Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi.

BACKGROUND: The emerging burden of cardiovascular disease and diabetes in sub-Saharan Africa threatens the gains made in health by the major international effort to combat infectious diseases. There are few data on distribution of risk factors and outcomes in the region to inform an effective public health response. A comprehensive research programme is being developed aimed at accurately documenting the burden and drivers of NCDs in urban and rural Malawi; to design and test intervention strategies. The programme includes population surveys of all people aged 18 years and above, linking individuals with newly diagnosed hypertension and diabetes to healthcare and supporting clinical services. The successes, challenges and lessons learnt from the programme to date are discussed. RESULTS: Over 20,000 adults have been recruited in rural Karonga and urban Lilongwe. The urban population is significantly younger and wealthier than the rural population. Employed urban individuals, particularly males, give particular recruitment challenges; male participation rates were 80.3 % in the rural population and 43.6 % in urban, whilst female rates were 93.6 and 75.6 %, respectively. The study is generating high quality data on hypertension, diabetes, lipid abnormalities and risk factors. CONCLUSIONS: It is feasible to develop large scale studies that can reliably inform the public health approach to diabetes, cardiovascular disease and other NCDs in Sub-Saharan Africa. It is essential for studies to capture both rural and urban populations to address disparities in risk factors, including age structure. Innovative approaches are needed to address the specific challenge of recruiting employed urban males.

Psychosocial and Sexual Well-Being Following Nipple-Sparing Mastectomy and Reconstruction.

Nipple-sparing mastectomy (NSM) is considered an oncologically safe option for select patients. As many patients are candidates for nipple-sparing or skin-sparing mastectomy (SSM), reliable patient-reported outcome data are crucial for decision-making. The objective of this study was to determine whether patient satisfaction and/or health-related quality of life (HRQOL) were improved by preservation of the nipple with NSM compared to SSM and nipple reconstruction. Subjects were identified from a prospectively maintained database of patients who completed the BREAST-Q following mastectomy and breast reconstruction between March and October 2011 at Memorial Sloan Kettering Cancer Center. Fifty-two patients underwent NSM followed by immediate expander-implant reconstruction. A comparison group consisted of 202 patients who underwent SSM followed by immediate expander-implant reconstruction and later nipple reconstruction. HRQOL and satisfaction domains as measured by BREAST-Q scores were compared in multivariate linear regression analyzes that controlled for potential confounding factors. NSM patients reported significantly higher scores in the psychosocial (p = 0.01) and sexual well-being (p = 0.02) domains compared to SSM patients. There was no significant difference in the BREAST-Q physical well-being, satisfaction with breast, or satisfaction with outcome domains between the NSM and SSM groups. NSM is associated with higher psychosocial and sexual well-being compared to SSM and nipple reconstruction. Preoperative discussion of such HRQOL outcomes with patients may facilitate informed decision-making and realistic postoperative expectations.

Uptake of prevention of mother-to-child-transmission using Option B+ in northern rural Malawi: a retrospective cohort study.

To identify points of dropout on the pathway from offering HIV testing to maintenance on antiretroviral therapy (ART), following the introduction of the Option B+ policy for pregnant women in Malawi (lifelong ART for HIV-positive mothers and 6 weeks nevirapine for the infants), a retrospective cohort study within a demographic surveillance system in northern Malawi. Women living in the demographic surveillance system who initiated antenatal care (ANC) between July 2011 (date of policy change) and January 2013, were eligible for inclusion. Women who consented were interviewed at home about their health facility attendance and care since pregnancy, including antenatal clinic (ANC) visits, delivery and postpartum care. Women's reports, patient-held health records and clinic health records were manually linked to ascertain service use. Among 395 women, 86% had tested for HIV before the pregnancy, 90% tested or re-tested at the ANC visit, and <1% had never tested. Among 53 mothers known to be HIV-positive before attending ANC, 15 (28%) were already on ART prior to pregnancy. Ten women tested HIV-positive for the first time during pregnancy. Of the 47 HIV-positive mothers not already on ART, 26/47 (55%) started treatment during pregnancy. All but five women who started ART were still on treatment at the time of study interview. HIV testing was almost universal and most women who initiated ART were retained in care. However, nearly half of eligible pregnant women not on ART at the start of ANC had not taken up the invitation to initiate (lifelong) ART by the time of delivery, leaving their infants potentially HIV-exposed.

Factors associated with self-reported diagnosed asthma in urban and rural Malawi: Observations from a population-based study of non-communicable diseases.

The growing burden of asthma in low- and middle-income countries has been linked to urbanisation and lifestyle changes. However, this burden has not been well characterised in adults. Therefore, we investigated the prevalence of self-reported diagnosed asthma and associated factors in urban and rural adults in Malawi, Southern Africa. Within a cross-sectional population-based survey to determine the burden and risk factors for non-communicable diseases (NCDs) in the city of Lilongwe and rural Karonga district, we collected information on self-reported previously diagnosed asthma and asthma-related symptoms using an interviewer-led questionnaire. Other data collected included: demographic characteristics, socioeconomic status indicators, NCD comorbidities, environmental exposures, and anthropometric measurements. We used multivariable logistic regression models to explore factors associated with self-reported asthma adjusting for variables associated with the outcome in univariable analysis. Findings were corrected for multiple comparisons using the Bonferroni method. We analysed data from 30,483 adult participants (54.6% urban,45.4% rural and 61.9% female). A prior asthma diagnosis was reported in 5.1% of urban and 4.5% of rural participants. In urban females, being obese (>30 kg/m2) compared to normal weight (18.5-24.9 kg/m2) was associated with greater odds of asthma (OR = 1.59, 95% CI [1.26-2.01], p<0.001), after adjusting for confounders. We observed associations between previously diagnosed heart disease and asthma in female participants which remained significant in rural females after Bonferroni correction (OR = 2.30,95%CI [1.32-4.02], p = 0.003). Among rural males, current smokers had reduced odds of diagnosed asthma (OR = 0.46,95%CI [0.27-0.79], p = 0.004) compared to those who had never smoked. In Malawi the prevalence of self-reported diagnosed asthma was greatest in females and urban dwellers. Notably, our findings indicate relationships between excess body weight as well as comorbidities and diagnosed asthma in females. Future investigations using longitudinally collected data and clinical measurements of asthma are needed to better understand these associations.

Association between physical multimorbidity and common mental health disorders in rural and urban Malawian settings: Preliminary findings from Healthy Lives Malawi long-term conditions survey.

In low-income Africa, the epidemiology of physical multimorbidity and associated mental health conditions is not well described. We investigated the multimorbidity burden, disease combinations, and relationship between physical multimorbidity and common mental health disorders in rural and urban Malawi using early data from 9,849 adults recruited to an on-going large cross-sectional study on long-term conditions, initiated in 2021. Multimorbidity was defined as having two or more measured (diabetes, hypertension) or self-reported (diabetes, hypertension, disability, chronic pain, HIV, asthma, stroke, heart disease, and epilepsy) conditions. Depression and anxiety symptoms were measured using the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item General Anxiety Disorder scale (GAD-7) and defined by the total score (range 0-27 and 0-21, respectively). We determined age-standardized multimorbidity prevalence and condition combinations. Additionally, we used multiple linear regression models to examine the association between physical multimorbidity and depression and anxiety symptom scores. Of participants, 81% were rural dwelling, 56% were female, and the median age was 30 years (Inter Quartile Range 21-43). The age-standardized urban and rural prevalence of multimorbidity was 14.1% (95% CI, 12.5-15.8%) and 12.2% (95% CI, 11.6-12.9%), respectively. In adults with two conditions, hypertension, and disability co-occurred most frequently (18%), and in those with three conditions, hypertension, disability, and chronic pain were the most common combination (23%). Compared to adults without physical conditions, having one (B-Coefficient (B) 0.79; 95% C1 0.63-0.94%), two- (B 1.36; 95% CI 1.14-1.58%), and three- or more- physical conditions (B 2.23; 95% CI 1.86-2.59%) were associated with increasing depression score, p-trend <0.001. A comparable 'dose-response' relationship was observed between physical multimorbidity and anxiety symptom scores. While the direction of observed associations cannot be determined with these cross-sectional data, our findings highlight the burden of multimorbidity and the need to integrate mental and physical health service delivery in Malawi.

Assessing the international use of health technology assessments: exploring the merits of different methods when applied to the National Institute of Health Research Health Technology Assessment (NIHR HTA) programme.

OBJECTIVES: This study presents findings from a study that explores the merits of different methods for assessing the international use of UK funded research by the National Institute of Health Research Health Technology Assessment (NIHR HTA) Programme. METHODS: The study adopted an exploratory approach and used three core methods: (i) Academic use was explored through bibliometric and citation analysis of the top ten most cited health technology assessment (HTA) reports. (ii) Internet use was assessed using Webtrends software to identify the proportion of international visits of the top ten most downloaded HTA reports from January 1, 2004 to June 30, 2010. (iii) International HTA use was assessed by searching the Center for Reviews and Dissemination (CRD) HTA database to explore the citation of NIHR HTA reports in reports by non-UK HTA agencies. RESULTS: Bibliometric analysis identified published output and international citations with 41 percent of the 549 journals citing NIHR HTA reports being based in the United States. Nine of ten most downloaded reports from the NIHR HTA Web site (www.hta.ac.uk) had in excess of 50 percent of visits outside the United Kingdom. Four of five selected NIHR HTA reports were cited in twenty-eight other HTA reports, eighteen of these outside the United Kingdom. CONCLUSIONS: Assessing international use is important when exploring the uptake of research evidence. Methods used in identifying research impact, such as bibliometrics and Webtrends, are helpful in generating evidence of international use. HTA agencies should consider these techniques and international use when assessing the uptake of findings from research they undertake and/or commission.

Epidemiology of multimorbidity in low-income countries of sub-Saharan Africa: Findings from four population cohorts.

We investigated prevalence and demographic characteristics of adults living with multimorbidity (≥2 long-term conditions) in three low-income countries of sub-Saharan Africa, using secondary population-level data from four cohorts; Malawi (urban & rural), The Gambia (rural) and Uganda (rural). Information on; measured hypertension, diabetes and obesity was available in all cohorts; measured hypercholesterolaemia and HIV and self-reported asthma was available in two cohorts and clinically diagnosed epilepsy in one cohort. Analyses included calculation of age standardised multimorbidity prevalence and the cross-sectional associations of multimorbidity and demographic/lifestyle factors using regression modelling. Median participant age was 29 (Inter quartile range-IQR 22-38), 34 (IQR25-48), 32 (IQR 22-53) and 37 (IQR 26-51) in urban Malawi, rural Malawi, The Gambia, and Uganda, respectively. Age standardised multimorbidity prevalence was higher in urban and rural Malawi (22.5%;95% Confidence intervals-CI 21.6-23.4%) and 11.7%; 95%CI 11.1-12.3, respectively) than in The Gambia (2.9%; 95%CI 2.5-3.4%) and Uganda (8.2%; 95%CI 7.5-9%) cohorts. In multivariate models, females were at greater risk of multimorbidity than males in Malawi (Incidence rate ratio-IRR 1.97, 95% CI 1.79-2.16 urban and IRR 2.10; 95%CI 1.86-2.37 rural) and Uganda (IRR- 1.60, 95% CI 1.32-1.95), with no evidence of difference between the sexes in The Gambia (IRR 1.16, 95% CI 0.86-1.55). There was strong evidence of greater multimorbidity risk with increasing age in all populations (p-value <0.001). Higher educational attainment was associated with increased multimorbidity risk in Malawi (IRR 1.78; 95% CI 1.60-1.98 urban and IRR 2.37; 95% CI 1.74-3.23 rural) and Uganda (IRR 2.40, 95% CI 1.76-3.26), but not in The Gambia (IRR 1.48; 95% CI 0.56-3.87). Further research is needed to study multimorbidity epidemiology in sub-Saharan Africa with an emphasis on robust population-level data collection for a wide variety of long-term conditions and ensuring proportionate representation from men and women, and urban and rural areas.

Characterizing the evolving SARS-CoV-2 seroprevalence in urban and rural Malawi between February 2021 and April 2022: A population-based cohort study.

OBJECTIVES: This study aimed to investigate the changing SARS-CoV-2 seroprevalence and associated health and sociodemographic factors in Malawi between February 2021 and April 2022. METHODS: In total, four 3-monthly serosurveys were conducted within a longitudinal population-based cohort in rural Karonga District and urban Lilongwe, testing for SARS-CoV-2 S1 immunoglobulin (Ig)G antibodies using an enzyme-linked immunosorbent assay. Population seroprevalence was estimated in all and unvaccinated participants. Bayesian mixed-effects logistic models estimated the odds of seropositivity in the first survey, and of seroconversion between surveys, adjusting for age, sex, occupation, location, and assay sensitivity/specificity. RESULTS: Of the 2005 participants (Karonga, n = 1005; Lilongwe, n = 1000), 55.8% were female and median age was 22.7 years. Between Surveys (SVY) 1 and 4, population-weighted SARS-CoV-2 seroprevalence increased from 26.3% to 89.2% and 46.4% to 93.9% in Karonga and Lilongwe, respectively. At SVY4, seroprevalence did not differ by COVID-19 vaccination status in adults, except for those aged 30+ years in Karonga (unvaccinated: 87.4%, 95% credible interval 79.3-93.0%; two doses: 98.1%, 94.8-99.5%). Location and age were associated with seroconversion risk. Individuals with hybrid immunity had higher SARS-CoV-2 seropositivity and antibody titers, than those infected. CONCLUSION: High SARS-CoV-2 seroprevalence combined with low morbidity and mortality indicate that universal vaccination is unnecessary at this stage of the pandemic, supporting change in national policy to target at-risk groups.

Prediagnostic concentrations of plasma genistein and prostate cancer risk in 1,605 men with prostate cancer and 1,697 matched control participants in EPIC.

PURPOSE: Data from prospective epidemiological studies in Asian populations and from experimental studies in animals and cell lines suggest a possible protective association between dietary isoflavones and the development of prostate cancer. We examined the association between circulating concentrations of genistein and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of genistein were estimated by conditional logistic regression. RESULTS: Plasma genistein concentrations were not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of genistein compared with men in the lowest fifth was 1.00 (95 % confidence interval: 0.79, 1.27; p linear trend = 0.82). There was no evidence of heterogeneity in this association by age at blood collection, country of recruitment, or cancer stage or histological grade. CONCLUSION: Plasma genistein concentration was not associated with prostate cancer risk in this large cohort of European men.

Adult mortality and probable cause of death in rural northern Malawi in the era of HIV treatment.

OBJECTIVES: Developing countries are undergoing demographic transition with a shift from high mortality caused by communicable diseases (CD) to lower mortality rates caused by non-communicable diseases (NCD). HIV/AIDS has disrupted this trend in sub-Saharan Africa. However, in recent years, HIV-associated mortality has been reduced with the introduction of widely available antiretroviral therapy (ART). Side effects of ART may lead to increased risk of cardiovascular diseases, raising the prospects of an accelerated transition towards NCD as the primary cause of death. We report population-based data to investigate changes in cause of death owing to NCD during the first 4 years after introduction of HIV treatment. METHODS: We analysed data from a demographic surveillance system in Karonga district, Malawi, from September 2004 to August 2009. ART was introduced in mid-2005. Clinician review of verbal autopsies conducted 2-6 weeks after a death was used to establish a single principal cause of death. RESULTS: Over the entire period, there were 905 deaths, AIDS death rate fell from 505 to 160/100,000 person-years, and there was no evidence of an increase in NCD rates. The proportion of total deaths attributable to AIDS fell from 42% to 17% and from NCD increased from 37% to 49%. DISCUSSION: Our findings show that 4 years after the introduction of ART into HIV care in Karonga district, all-cause mortality has fallen dramatically, with no evidence of an increase in deaths owing to NCD.

An economic model of school-based behavioral interventions to prevent sexually transmitted infections.

OBJECTIVES: Reducing sexually transmitted infections (STI) and teenage pregnancy through effective health education is a high priority for health policy. Behavioral interventions which teach skills to practice safer sex may reduce the incidence of STIs. We evaluated the cost-effectiveness of school-based behavioral interventions in young people. METHODS: We developed an economic model to estimate the total number of STI cases averted, consequent gain in health related quality of life (HRQoL) and savings in medical costs, based on changes in sexual behavior. The parameters for the model were derived from a systematic literature search on the intervention effectiveness, epidemiology of STIs, sexual behavior and lifestyles, HRQoL and health service costs. RESULTS: The costs of providing teacher-led and peer-led behavioral interventions were €5.16 and €18 per pupil, respectively. For a cohort of 1000 boys and 1000 girls aged 15 years, the model estimated that the behavioral interventions would avert two STI cases and save 0.35 Quality Adjusted Life Years (QALYs). Compared to standard education, the incremental cost-effectiveness of the teacher-led and peer-led interventions was €24,268 and €96,938 per QALY gained, respectively. CONCLUSIONS: School-based behavioral interventions which provide information and teach young people sexual health skills can bring about improvements in knowledge and increased self-efficacy, though these may be limited in terms of impact on sexual behavior. There was uncertainty around the results due to the limited effect of the intervention on behavioral outcomes and paucity of data for other input parameters.

Developing a matrix to identify and prioritise research recommendations in HIV prevention.

BACKGROUND: HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research. METHODS: Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention. RESULTS: 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention. CONCLUSIONS: This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.

Trends and risk factors for non-communicable diseases mortality in Nairobi slums (2008-2017).

INTRODUCTION: Tracking progress in reaching global targets for reducing premature mortality from non-communicable diseases (NCDs) requires accurately collected population based longitudinal data. However, most African countries lack such data because of weak or non-existent civil registration systems. We used data from the Nairobi Urban Health and Demographic Surveillance System (NUDSS) to estimate NCD mortality trends over time and to explore the determinants of NCD mortality. METHODS: Deaths identified in the NUHDSS were followed up with a verbal autopsy to determine the signs and symptoms preceding the death. Causes of death were then assigned using InSilicoVA algorithm. We calculated the rates of NCD mortality in the whole NUHDSS population between 2008 and 2017, looking at how these changed over time. We then merged NCD survey data collected in 2008, which contains information on potential determinants of NCD mortality in a sub-sample of the NUHDSS population, with follow up information from the full NUHDSS including whether any of the participants died of an NCD or non-NCD cause. Poisson regression models were used to identify independent risk factors (broadly categorized as socio-demographic, behavioural and physiological) for NCD mortality, as well as non-NCD mortality. RESULTS: In the total NUHDSS population of adults age 18 and over, 23% were assigned an NCD as the most likely cause of death. There was evidence that NCD mortality decreased over the study period, with rates of NCD mortality dropping from 1.32 per 1000 person years in 2008-10 (95% CI: 1.13-1.54) to 0.93 per 1000 person years in 2014-17 (95% CI: 0.80-1.08). Of 5115 individuals who participated in the NCD survey in 2008, 421 died during the follow-up period of which 43% were attributed to NCDs. Increasing age, lower education levels, ever smoking and having high blood pressure were identified as independent determinants of NCD mortality in multivariate analyses. CONCLUSION: We found that NCDs account for one-quarter of mortality in Nairobi slums, although we document a reduction in the rate of NCD mortality over time. This may be attributed to increased surveillance and introduction of population-wide NCD interventions and health system improvements from research activities in the slums. To achieve further decline there is a need to strengthen health systems to respond to NCD care and prevention along with addressing social factors such as education.

Age patterns of HIV incidence in eastern and southern Africa: a modelling analysis of observational population-based cohort studies.

BACKGROUND: As the HIV epidemic in sub-Saharan Africa matures, evidence about the age distribution of new HIV infections and how this distribution has changed over the epidemic is needed to guide HIV prevention. We aimed to assess trends in age-specific HIV incidence in six population-based cohort studies in eastern and southern Africa, reporting changes in mean age at infection, age distribution of new infections, and birth cohort cumulative incidence. METHODS: We used a Bayesian model to reconstruct age-specific HIV incidence from repeated observations of individuals' HIV serostatus and survival collected among population HIV cohorts in rural Malawi, South Africa, Tanzania, Uganda, and Zimbabwe, in a collaborative analysis of the ALPHA network. We modelled HIV incidence rates by age, time, and sex using smoothing splines functions. We estimated incidence trends separately by sex and study. We used estimated incidence and prevalence results for 2000-17, standardised to study population distribution, to estimate mean age at infection and proportion of new infections by age. We also estimated cumulative incidence (lifetime risk of infection) by birth cohort. FINDINGS: Age-specific incidence declined at all ages, although the timing and pattern of decline varied by study. The mean age at infection was higher in men (cohort mean 27·8-34·6 years) than in women (24·8-29·6 years). Between 2000 and 2017, the mean age at infection per cohort increased slightly: 0·5 to 2·8 years among men and -0·2 to 2·5 years among women. Across studies, between 38% and 63% (cohort medians) of the infections in women were among those aged 15-24 years and between 30% and 63% of infections in men were in those aged 20-29 years. Lifetime risk of HIV declined for successive birth cohorts. INTERPRETATION: HIV incidence declined in all age groups and shifted slightly to older ages. Disproportionate new HIV infections occur among women aged 15-24 years and men aged 20-29 years, supporting focused prevention in these groups. However, 40-60% of infections were outside these ages, emphasising the importance of providing appropriate HIV prevention to adults of all ages. FUNDING: Bill & Melinda Gates Foundation.