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.

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.

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.

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.

Self-reported disability in relation to mortality in rural Malawi: a longitudinal study of over 16 000 adults.

OBJECTIVES: We investigated whether self-reported disability was associated with mortality in adults in rural Malawi. SETTING: Karonga Health and Demographic Surveillance Site (HDSS), Northern Malawi. PARTICIPANTS: All adults aged 18 and over residing in the HDSS were eligible to participate. During annual censuses in 2014 and 2015, participants were asked if they experienced difficulty in any of six functional domains and were classified as having disabilities if they reported 'a lot of difficulty' or 'can't do at all' in any domain. Mortality data were collected until 31 December 2017. 16 748 participants (10 153 women and 6595 men) were followed up for a median of 29 months. PRIMARY AND SECONDARY OUTCOME MEASURES: We used Poisson regression to examine the relationship between disability and all-cause mortality adjusting for confounders. We assessed whether this relationship altered in the context of obesity, hypertension, diabetes or HIV. We also evaluated whether mortality from non-communicable diseases (NCD) was higher among people who had reported disability, as determined by verbal autopsy. RESULTS: At baseline, 7.6% reported a disability and the overall adult mortality rate was 9.1/1000 person-years. Adults reporting disability had an all-cause mortality rate 2.70 times higher than those without, and mortality rate from NCDs 2.33 times higher than those without. CONCLUSIONS: Self-reported disability predicts mortality at all adult ages in rural Malawi. Interventions to improve access to healthcare and other services are needed.

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.

Direct maternal deaths attributable to HIV in the era of antiretroviral therapy: evidence from three population-based HIV cohorts with verbal autopsy.

OBJECTIVE: To assess whether HIV is associated with an increased risk of mortality from direct maternal complications. DESIGN: Population-based cohort study using data from three demographic surveillance sites in Eastern and Southern Africa. METHODS: We use verbal autopsy data, with cause of death assigned using the InSilicoVA algorithm, to describe the association between HIV and direct maternal deaths amongst women aged 20-49 years. We report direct maternal mortality rates by HIV status, and crude and adjusted rate ratios comparing HIV-infected and uninfected women, by study site and by ART availability. We pool the study-specific rate ratios using random-effects meta-analysis. RESULTS: There was strong evidence that HIV increased the rate of direct maternal mortality across all the study sites in the period ART was widely available, with the rate ratios varying from 4.5 in Karonga, Malawi [95% confidence interval (CI) 1.6-12.6] to 5.2 in Kisesa, Tanzania (95% CI 1.7-16.1) and 5.9 in uMkhanyakude, South Africa (95% CI 2.3-15.2) after adjusting for sociodemographic confounders. Combining these adjusted results across the study sites, we estimated that HIV-infected women have 5.2 times the rate of direct maternal mortality compared with HIV-uninfected women (95% CI 2.9-9.5). CONCLUSION: HIV-infected women face higher rates of mortality from direct maternal causes, which suggests that we need to improve access to quality maternity care for these women. These findings also have implications for the surveillance of HIV/AIDS-related mortality, as not all excess mortality attributable to HIV will be explicitly attributed to HIV/AIDS on the basis of a verbal autopsy interview.

The relationship of breast density in mammography and magnetic resonance imaging in women with triple negative breast cancer.

PURPOSE: To evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC). METHODS: The institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson's Chi Square, Wilcoxon Rank-Sum and logistic regression. RESULTS: Of 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23-96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts. CONCLUSIONS: The higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.

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.

Investigating associations between rural-to-urban migration and cardiometabolic disease in Malawi: a population-level study.

BACKGROUND: The extent to which rural-to-urban migration affects risk for cardiometabolic diseases (CMD) in Africa is not well understood. We investigated prevalence and risk for obesity, diabetes, hypertension and precursor conditions by migration status. METHODS: In a cross-sectional survey in Malawi (February 2013-March 2017), 13 903 rural, 9929 rural-to-urban migrant and 6741 urban residents (≥18 years old) participated. We interviewed participants, measured blood pressure and collected anthropometric data and fasting blood samples to estimate population prevalences and odds ratios, using negative binomial regression, for CMD, by migration status. In a sub-cohort of 131 rural-urban siblings-sets, migration-associated CMD risk was explored using conditional Poisson regression. RESULTS: In rural, rural-to-urban migrant and urban residents, prevalence estimates were; 8.9, 20.9 and 15.2% in men and 25.4, 43.9 and 39.3% in women for overweight/obesity; 1.4, 2.9 and 1.9% in men and 1.5, 2.8 and 1.7% in women for diabetes; and 13.4, 18.8 and 12.2% in men and 13.7, 15.8 and 10.2% in women for hypertension. Rural-to-urban migrants had the greatest risk for hypertension (adjusted relative risk for men 1.18; 95% confidence interval 1.04-1.34 and women 1.17: 95% confidence interval 1.05-1.29) and were the most screened, diagnosed and treated for CMD, compared with urban residents. Within sibling sets, rural-to-urban migrant siblings had a higher risk for overweight and pre-hypertension, with no evidence for differences by duration of stay. CONCLUSIONS: Rural-to-urban migration is associated with increased CMD risk in Malawi. In a poor country experiencing rapid urbanization, interventions for the prevention and management of CMD, which reach migrant populations, are needed.

Sex and area differences in the association between adiposity and lipid profile in Malawi.

BACKGROUND: Evidence from high-income countries shows that higher adiposity results in an adverse lipid profile, but it is unclear whether this association is similar in Sub-Saharan African (SSA) populations. This study aimed to assess the association between total and central adiposity measures and lipid profile in Malawi, exploring differences by sex and area of residence (rural/urban). METHODS: In this cross-sectional study, data from 12 096 rural and 12 847 urban Malawian residents were used. The associations of body mass index (BMI) and waist to hip ratio (WHR) with fasting lipids (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)) were assessed by area and sex. RESULTS: After adjusting for potential confounders, higher BMI and WHR were linearly associated with increased TC, LDL-C and TG and reduced HDL-C. BMI was more strongly related to fasting lipids than was WHR. The associations of adiposity with adverse lipid profile were stronger in rural compared with urban residents. For instance, one SD increase in BMI was associated with 0.23 mmol/L (95% CI 0.19 to 0.26) increase in TC in rural women and 0.13 mmol/L (95% CI 0.11 to 0.15) in urban women. Sex differences in the associations between adiposity and lipids were less evident. CONCLUSIONS: The consistent associations observed of higher adiposity with adverse lipid profiles in men and women living in rural and urban areas of Malawi highlight the emerging adverse cardio-metabolic epidemic in this poor population. Our findings underline the potential utility of BMI in estimating cardiovascular risk and highlight the need for greater investment to understand the long-term health outcomes of obesity and adverse lipid profiles and the extent to which lifestyle changes and treatments effectively prevent and modify adverse cardio-metabolic outcomes.

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.

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.

A comparison of all-cause and cause-specific mortality by household socioeconomic status across seven INDEPTH network health and demographic surveillance systems in sub-Saharan Africa.

BACKGROUND: Understanding socioeconomic disparities in all-cause and cause-specific mortality can help inform prevention and treatment strategies. OBJECTIVES: To quantify cause-specific mortality rates by socioeconomic status across seven health and demographic surveillance systems (HDSS) in five countries (Ethiopia, Kenya, Malawi, Mozambique, and Nigeria) in the INDEPTH Network in sub-Saharan Africa. METHODS: We linked demographic residence data with household survey data containing living standards and education information we used to create a poverty index. Person-years lived and deaths between 2003 and 2016 (periods varied by HDSS) were stratified in each HDSS by age, sex, year, and number of deprivations on the poverty index (0-8). Causes of death were assigned to each death using the InterVA-4 model based on responses to verbal autopsy questionnaires. We estimated rate ratios between socioeconomic groups (2-4 and 5-8 deprivations on our poverty index compared to 0-2 deprivations) for specific causes of death and calculated life expectancy for the deprivation groups. RESULTS: Our pooled data contained almost 3.5 million person-years of observation and 25,038 deaths. All-cause mortality rates were higher among people in households with 5-8 deprivations on our poverty index compared to 0-2 deprivations, controlling for age, sex, and year (rate ratios ranged 1.42 to 2.06 across HDSS sites). The poorest group had consistently higher death rates in communicable, maternal, neonatal, and nutritional conditions (rate ratios ranged 1.34-4.05) and for non-communicable diseases in several sites (1.14-1.93). The disparities in mortality between 5-8 deprivation groups and 0-2 deprivation groups led to lower life expectancy in the higher-deprivation groups by six years in all sites and more than 10 years in five sites. CONCLUSIONS: We show large disparities in mortality on the basis of socioeconomic status across seven HDSS in sub-Saharan Africa due to disparities in communicable disease mortality and from non-communicable diseases in some sites. Life expectancy gaps between socioeconomic groups within sites were similar to the gaps between high-income and lower-middle-income countries. Prevention and treatment efforts can benefit from understanding subpopulations facing higher mortality from specific conditions.

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.

Dietary sodium intake in urban and rural Malawi, and directions for future interventions.

Background: High dietary sodium intake is a major risk factor for hypertension. Data on population sodium intake are scanty in sub-Saharan Africa, despite a high hypertension prevalence in most countries. Objective: We aimed to determine daily sodium intake in urban and rural communities in Malawi. Design: In an observational cross-sectional survey, data were collected on estimated household-level per capita sodium intake, based on how long participants reported that a defined quantity of plain salt lasts in a household. In a subset of 2078 participants, 24-h urinary sodium was estimated from a morning spot urine sample. Results: Of 29,074 participants, 52.8% of rural and 50.1% of urban individuals lived in households with an estimated per capita plain salt consumption >5 g/d. Of participants with urinary sodium data, 90.8% of rural and 95.9% of urban participants had estimated 24-h urinary sodium >2 g/d; there was no correlation between household per capita salt intake and estimated 24-h urinary sodium excretion. Younger adults were more likely to have high urinary sodium and to eat food prepared outside the home than were those over the age of 60 y. Households with a member with previously diagnosed hypertension had reduced odds (OR: 0.59; 95% CI: 0.51, 0.68) of per capita household plain salt intake >5 g/d, compared with those where hypertension was undiagnosed. Conclusions: Sodium consumption exceeds the recommended amounts for most of the population in rural and urban Malawi. Population-level interventions for sodium intake reduction with a wide focus are needed, targeting both sources outside the home as well as home cooking. This trial was registered at clinicaltrials.gov as NCT03422185.