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Context The relationship between dehydroepiandrosterone sulfate (DHEAS) and mortality is of scientific and public health interest, yet it remains poorly understood. Objective We examined the association between DHEAS and mortality from cancer, cardiovascular disease, and all causes in middle-aged and older men and women. Methods DHEAS was measured in stored serum samples collected from 1994 to 1998 from a case-cohort nested within EPIC-Heidelberg, that included 7370 men (mean age = 55.0) and women (mean age = 52.4 years). Median follow-up for incident mortality events was 17.7 years. All deaths due to cancer (n = 1040), cardiovascular diseases (n = 598), and all causes (n = 2407) that occurred in EPIC-Heidelberg until end of 2014 were included. Results The association between DHEAS and mortality was nonlinear such that both participants in the lowest (Q1) and highest (Q5) sex- and 5-year age-group specific quintiles of DHEAS were at increased hazard ratios (HR) of mortality from cardiovascular [Q1: HR = 1.83 (95% CI: 1.33-2.51), Q5: 1.39 (1.00-1.94)], cancer [Q1: 1.27 (1.01-1.60), Q5: 1.27 (1.02-1.60)] and all causes [Q1: 1.51 (1.25-1.82), Q5: 1.31 (1.08-1.58)], compared with participants in Q3. In men and women with below-median DHEAS levels, doubling of DHEAS was associated with lower hazards of cardiovascular [0.87, (0.78-0.96)], cancer [0.90, (0.83-0.97)], and total mortality [0.89, (0.83-0.95)]. In contrast, a doubling in DHEAS among participants with above-median levels was associated with 1.20, (1.01-1.42), 1.28, (1.01-1.62), and 1.19 (1.03-1.37) higher hazards of mortality from cancer, cardiovascular, and all causes, respectively. Conclusion In this large population-based study, DHEAS showed a J-shaped association with mortality. Both participants with lowest and highest levels experienced higher hazards of mortality from cancer, cardiovascular disease, and all causes.

Context The functional status of organs, such as the liver, involved in IGF-1 signaling pathways influences circulating levels of IGF-1 and hence its relationship to risk of chronic disease and mortality, yet this has received limited attention. Objective To examine the relationship between IGF-1 and risk of morbidity and mortality from cancer, cardiovascular diseases (CVD), and all causes, accounting for liver function. Methods This study was a case-cohort design nested within EPIC-Heidelberg. IGF-1 was measured in 7461 stored serum samples collected from 1994 to 1998. Median follow-up for incident mortality events was 17.5 years. The case-cohort included a subcohort of 1810 men and 1890 women, in addition to 1668 incident cases of cancer (623 breast, 577 prostate, 202 lung, and 268 colorectal), and 1428 cases of CVD (707 myocardial infarctions and 723 strokes) and 2441 cases of death. Results Higher IGF-1 levels showed direct associations with risks of breast (1.25; 95% CI [1.06-1.47]) and prostate (1.31; [1.09-1.57]) cancers. Restricted cubic splines plots and models including IGF-1 as quintiles revealed a U-shaped relationship between the biomarker and mortality. Participants with the lowest and the highest levels of IGF-1 experienced higher hazards of mortality from cancer, CVD, and all causes. The U-shaped form of the relationship persisted but was attenuated in analyses including only participants without any indications of liver dysfunction. Conclusion This large population-based prospective study showed that both individuals with lowest and highest levels of circulating IGF-1 were at increased risk of deaths from cancer, CVD, and all causes. For individuals with low IGF-1, the excess risks of death were more pronounced among individuals with liver cancer and cirrhosis but were also present among individuals without elevated liver enzymes.

BackgroundNT-proBNP has been hypothesized as a possible explanation for the paradoxical association between adiponectin and cardiovascular and all-cause mortality. We examined the heterogeneities by NT-proBNP, sex, BMI, smoking status, hypertension and diabetes status in the association between adiponectin and cardiovascular disease risk and mortality. MethodsWe used a case-cohort design nested within the EPIC-Heidelberg cohort, including 1,387 incident cases of myocardial infarction or stroke, 582 deaths from cardiovascular causes and 2,352 total deaths. We estimated hazard ratios for the association between 1SD increase in log-transformed adiponectin levels and cardiovascular disease risk, cardiovascular mortality and total mortality using Prentice-weighted Cox-proportional hazard models and assessed heterogeneity of the associations across strata of covariates. ResultsOverall, adiponectin was significantly associated with all-cause mortality [HR = 1.09, 95%CI: 1.03-1.16, p = 0.004], the association with cardiovascular mortality did not reach statistical significance [1.10 (0.99-1.37), p = 0.073] whereas there was no association with cardiovascular disease risk. There was significant heterogeneity by NT-proBNP in the association between adiponectin and all-cause mortality (phet = 0.019) such that significant increase in hazards of mortality were restricted to participants in the highest tertile of NT-proBNP. Among participants in the highest tertile NT-proBNP, adiponectin showed a dose-response relationship with total mortality such that; compared to participants in the lowest quintile, those in the third, fourth and fifth were at 1.22 (0.87-1.70), 1.50 (1.07-2.11), and 1.59 (1.15-2.21) higher hazards of mortality respectively. ConclusionsSignificant association between adiponectin and mortality was only observed in the context of high NT-proBNP. Our findings provide further support for hypothesis that NT-proBNP may explain the adiponectin paradox.

Background There is a lack of evidence-based recommendations for the age at which women with a family history of cancers other than breast cancer should start breast cancer screening. Methods Using Swedish family cancer data sets, the authors conducted a nationwide cohort study including 5,099,172 Swedish women born after 1931 (follow-up, 1958-2015). Accounting for calendar time, they calculated the relative risk of breast cancer for women with a family history of a discordant cancer in 1 first-degree relative. Furthermore, the authors used 10-year cumulative risk to determine the ages at which women with a family history of discordant cancer reached risk thresholds at which women in the general population were recommended to start breast cancer screening. Results A family history of cancer at 15 sites was associated with an increased risk of breast cancer. Among women younger than 50 years, the highest risk of breast cancer was observed for those with a family history of ovarian cancer (standardized incidence ratio, 1.44; 95% confidence interval, 1.26-1.64). In these women, the risk of breast cancer associated with a family history at other cancer sites ranged from 1.08-fold for prostate cancer to 1.18-fold for liver cancer. When breast cancer screening was recommended to be started at the age of 50 years for the general population, women with 1 first-degree relative with ovarian cancer attained the threshold risk for screening at the age of 46 years. Women with a family history of other discordant cancers did not reach the risk thresholds for screening at younger ages. Conclusions Many cancers showed familial associations with breast cancer, but women with a family history of these cancers (except for ovarian cancer) did not reach risk thresholds for screening at younger ages.

Summary Background Improving hypertension control is an important global health priority, yet, to our knowledge, there is no direct evidence on the relationship between blood pressure and mortality in sub-Saharan Africa. We aimed to investigate the relationship between systolic blood pressure and mortality in South Africa and to assess the comparative effectiveness of different systolic blood pressure targets for clinical care and population-wide hypertension management efforts. Methods In this country-wide, population-based cohort study, we used longitudinal data on adults aged 30 years and older from five waves (2008, 2010–11, 2012, 2014–15, and 2017) of the South African National Income Dynamics Study. We estimated the relationship between systolic blood pressure and 6-year all-cause mortality and compared the mortality reductions associated with lowering systolic blood pressure to different targets (120 mm Hg, 130 mm Hg, 140 mm Hg, 150 mm Hg). We also estimated the mean blood pressure reduction required to achieve each target, the share of the population in need of management, and the number needed to treat (NNT) to avert one death under different hypothetical population-wide scale-up scenarios. Findings Of the 8338 age-eligible respondents in the 2010–11 survey, 4993 had all required data and were included in our study. We found a weak, non-linear relationship between systolic blood pressure and 6-year mortality, with larger incremental mortality benefits at higher systolic blood pressure values: reducing systolic blood pressure from 160 mm Hg to 150 mm Hg was associated with a relative risk of mortality of 0·95 (95% CI 0·90 to 0·99; p=0·033), reducing systolic blood pressure from 150 mm Hg to 140 mm Hg had a relative risk of 0·96 (0·91 to 1·01; p=0·12), with no evidence of incremental benefits of reducing systolic blood pressure below 140 mm Hg. At the population level, reducing systolic blood pressure to 150 mm Hg among all those with a starting systolic blood pressure of more than 150 mm Hg was associated with the lowest NNT (n=50), 3·3 deaths averted (95% CI −0·6 to 0·3) per 1000 population, blood pressure management for 16% (95% CI 15·2 to 17·3) of individuals, and a −2·7 mm Hg mean change in systolic blood pressure required to achieve the 150 mm Hg scale-up target (−3·0 to −2·5; p Interpretation The relationship between systolic blood pressure and mortality is weaker in South Africa than in high-income and many low-income and middle-income countries. As such, we do not find compelling evidence in support of targets below 140 mm Hg and find that scaling up management based on a 150 mm Hg target is more efficient in terms of the NNT compared with strategies to reduce systolic blood pressure to lower values. Funding None

The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London-, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra,-and the Catalan Institute of OncologyICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1, MC-UU 12015/1 and MC UU_00006/1to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). Open Access funding enabled and organized by Projekt DEAL., BACKGROUND: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. RESULTS: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancerfree. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. CONCLUSION: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125., World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of OncologyICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) MR/N003284/1 MC-UU 12015/1 MC UU_00006/1 MR/M012190/1, Projekt DEAL

Objective The objective of the project was to strengthen the community health worker (CHW) programme in Ssisa sub-county, Wakiso district, Uganda by providing a coherent, structured and standardized training, supervision and motivation package so as to enhance their performance. Results The project trained all 301 CHWs who received non-financial incentives of t-shirts, gumboots and umbrellas, and 75 of them received solar equipment to support lighting their houses and charging phones. Twenty-four of the CHWs who had coordination roles received additional training. Three motorcycles were also provided to enhance transportation of CHW coordinators during their work including supervision. By end of the project, the CHWs had conducted 40,213 household visits, carried out health education sessions with 127,011 community members, and treated 19,387 children under 5 years of age. From the project evaluation, which used both quantitative and qualitative methods, 98% of the CHWs reported having improved competence in performance of their roles. In addition, the CHWs were highly motivated to do their work. The motorcycles were instrumental in supporting the work of CHW coordinators including monthly collection of reports and distribution of medicines. The project demonstrated that by improving training, supervision and motivation, performance of CHW programmes can be enhanced.

The comet assay is widely used for quantification of genomic damage in humans. Peripheral blood derived mononuclear cells (PBMCs) are the most often used cell type for this purpose. Since the comet assay can be performed in an enhanced throughput format, it can be applied to large sample collections such as biobanks. The European Prospective Investigation into Cancer and Nutrition (EPIC) study is one of the largest existing prospective cohort studies, and the German Cancer Research Institute (DKFZ) in Heidelberg is a participating center with 25.000 frozen blood samples stored from around 25 years ago, enabling retrospective assessment of disease risk factors. However, experience with decades long frozen samples in the comet assay is so far missing. In Heidelberg, 800 study participants were re-invited twice between 2010 and 2012 to donate further blood samples. Here, we analyzed 299 Heidelberg-EPIC samples, compiled from frozen PBMC and buffy coat preparations selected from the different sampling time points. In addition, 47 frozen PBMC samples from morbidly obese individuals were included. For buffy coat samples, we observed a poor correlation between DNA damage in the same donors assessed at two sampling time points. Additionally, no correlation between DNA damage in buffy coat samples and PBMCs was found. For PBMCs, a good correlation was observed between samples of the same donors at the two time points. DNA damage was not affected by age and smoking status, but high BMI (>30; obesity) was associated with increased DNA damage in PBMCs. There was no indication for a threshold of a certain BMI for increased DNA damage. In conclusion, while 25 year-long stored buffy coat preparations may require adaptation of certain experimental parameters such as cell density and electrophoresis conditions, frozen PBMC biobank samples can be analyzed in the comet assay even after a decade of storage.

Background Evidence-based guidance for starting ages of screening for first-degree relatives (FDRs) of patients with prostate cancer (PCa) to prevent stage III/IV or fatal PCa is lacking in current PCa screening guidelines. We aimed to provide evidence for risk-adapted starting age of screening for relatives of patients with PCa. Methods and findings In this register-based nationwide cohort study, all men (aged 0 to 96 years at baseline) residing in Sweden who were born after 1931 along with their fathers were included. During the follow-up (1958 to 2015) of 6,343,727 men, 88,999 were diagnosed with stage III/IV PCa or died of PCa. The outcomes were defined as the diagnosis of stage III/IV PCa or death due to PCa, stratified by age at diagnosis. Using 10-year cumulative risk curves, we calculated risk-adapted starting ages of screening for men with different constellations of family history of PCa. The 10-year cumulative risk of stage III/IV or fatal PCa in men at age 50 in the general population (a common recommended starting age of screening) was 0.2%. Men with ≥2 FDRs diagnosed with PCa reached this screening level at age 41 (95% confidence interval (CI): 39 to 44), i.e., 9 years earlier, when the youngest one was diagnosed before age 60; at age 43 (41 to 47), i.e., 7 years earlier, when ≥2 FDRs were diagnosed after age 59, which was similar to that of men with 1 FDR diagnosed before age 60 (41 to 45); and at age 45 (44 to 46), when 1 FDR was diagnosed at age 60 to 69 and 47 (46 to 47), when 1 FDR was diagnosed after age 69. We also calculated risk-adapted starting ages for other benchmark screening ages, such as 45, 55, and 60 years, and compared our findings with those in the guidelines. Study limitations include the lack of genetic data, information on lifestyle, and external validation. Conclusions Our study provides practical information for risk-tailored starting ages of PCa screening based on nationwide cancer data with valid genealogical information. Our clinically relevant findings could be used for evidence-based personalized PCa screening guidance and supplement current PCa screening guidelines for relatives of patients with PCa., Xing Xu and co-workers assess prostate cancer risk in relatives of men with prostate cancer., Author summary Why was this study done? Family history is the strongest known risk factor for prostate cancer (PCa), and current guidelines concur that an earlier screening for men with a family history of PCa is necessary. However, limited evidence-based guidance is available on at what age actually this early screening should start. This study was conducted to provide precise recommendations about at what age should relatives of PCa patients start screening based on the number of affected relatives and the age at onset of PCa in the family. What did the researchers do and find? In this nationwide study on 6,343,727 men, the risk of stage III/IV or fatal PCa in close family members of patients with PCa was estimated. It was observed that men with family history of PCa reach the screening risk threshold up to 12 years earlier than the general population. This study found that age, age at diagnosis of PCa in relative/s, and number of affected first-degree relatives (FDRs) are important elements in increased risk of stage III/IV or fatal PCa, and these factors accordingly resulted in different risk-adapted starting ages of PCa screening. Comparison between our evidence-based risk-adapted starting age of screening and recommended age of PCa screening by different guidelines showed a difference ranging from −2 to 11 years. What do these findings mean? This study made use of the largest dataset available, to our knowledge, to identify the optimal age for starting PCa screening in relatives of patients with PCa. This study took into account not only the number of relatives but also age at onset of PCa in the family members, which is an additional important piece of information for the guidelines. The results may contribute to a more evidence-based personalized PCa screening guidance in real-world settings, and clinicians could inform patients with PCa about this possibility and encourage individualized counseling for their relatives.

Background: Community health workers (CHWs) continue to play a crucial role in supporting health service delivery globally. Several CHW programmes around the world face vast challenges which affect their performance. Objectives: This study assessed the performance of CHWs and associated factors in a rural community in Wakiso district, Uganda. Methods: This was a cross-sectional study that employed a structured questionnaire to collect quantitative data from 201 CHWs in Wakiso district. The main study variable was CHW performance based on various roles carried out by CHWs. Multivariable logistic regression in STATA was used to establish the predictors of CHW performance. Results: Only 40 (19.9%) of the CHWs had a high performance which was associated with having attended additional / refresher trainings [AOR=12.79 (95% CI: 1.02-159.26)], and having attained secondary level education and above [AOR=3.93 (95% CI: 1.17-13.24)]. CHWs who were married [AOR=0.29 (95% CI: 0.09-0.94)] were less likely to perform highly. Among CHWs who had received essential medicines for treatment of childhood illnesses, the majority 90.3% (112/124) had experienced stock-outs in the 6 months preceding the study. Despite the majority of CHWs, 198 (98.5%), stating that being motivated was very important in their work, only 91 (45%) said that they were motivated. Conclusion: Additional / refresher trainings are necessary to enhance performance of CHWs. In addition, level of education should be considered while selecting CHWs. The health system challenges of low motivation of CHWs as well as stock-out of medicines need to be addressed to support their work. Keywords: Community health workers, performance, motivation, satisfaction, stock-outs, village health teams, Uganda.

Men are more likely than women to die due to coronavirus disease 2019 (COVID-19). An open question is whether these sex differences reflect men's generally poorer health and lower life expectancy compared to women of similar ages or if men face a unique COVID-19 disadvantage. Using age-specific data on COVID-19 mortality as well as cause-specific and all-cause mortality for 63 countries, we compared the sex difference in COVID-19 mortality to sex differences in all-cause mortality and mortality from other common causes of death to determine the magnitude of the excess male mortality disadvantage for COVID-19. We found that sex differences in the age-standardized COVID-19 mortality rate were substantially larger than for the age-standardized all-cause mortality rate and mortality rate for most other common causes of death. The excess male mortality disadvantage for COVID-19 was especially large in the oldest age groups. Our findings suggest that the causal pathways that link male sex to a higher mortality from a SARS-CoV-2 infection may be specific to SARS-CoV-2, rather than shared with the pathways responsible for the shorter life expectancy among men or sex differences for other common causes of death. Understanding these causal chains could assist in the development of therapeutics and preventive measures for COVID-19 and, possibly, other coronavirus diseases.

Background Wide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer. Methods We analyzed the occurrence of cancer in a nationwide cohort including all 5,099,172 Swedish women born after 1931 with at least one known first-degree relative. This was a record linkage study of Swedish family cancer datasets, including cancer registry data collected from January 1, 1958, to December 31, 2015. We calculated standardized incidence ratios (SIRs) and 10-year cumulative risk of breast cancer diagnosis for women with a family history of in situ and invasive breast cancer. Results Having one first-degree relative with breast carcinoma in situ was associated with 50% increased risk of invasive breast cancer (SIR = 1.5, 95% CI 1.4–1.7) when compared to those who had no family history of invasive breast cancer or breast carcinoma in situ in either first- or second-degree relatives. Similarly, having one first-degree relative with invasive breast cancer was associated with 70% (1.7, 1.7–1.8) increased risk. The 10-year cumulative risk for women at age 50 with a relative with breast carcinoma in situ was 3.5% (2.9–3.9%) and was not significantly different from 3.7% (3.6–3.8%) risk for 50-year-old women with a relative with invasive breast cancer (95% confidence intervals overlapped). Conclusions The risk of invasive breast cancer for women with a family history of breast carcinoma in situ was comparable to that for women with a family history of invasive breast cancer. Therefore, family history of breast carcinoma in situ should not be overlooked in recommendations for breast cancer prevention for women with a family history of breast cancer.

BackgroundScreening and vaccination against Hepatitis B virus (HBV) infection remains the most effective intervention in curbing the disease. However, there is limited evidence on the factors associated with the uptake of these services in Uganda. This study determined the uptake of HBV screening and vaccination status, and associated factors among Healthcare Providers (HCPs) in Wakiso district, Uganda.Materials and methodsThis cross-sectional study was conducted among 306 HCPs, randomly selected from 55 healthcare facilities. Prevalence ratios (PR) were used to determine the factors associated with HBV screening and vaccination status of HCPs.ResultsOf the 306 HCPs, 230 (75.2%) had ever screened for HBV infection while 177 (57.8%) were fully vaccinated. Being male was positively associated with 'ever been screened' for HBV infection (Adjusted PR = 1.27, 95%CI 1.13-1.41). Working in a public healthcare facility (Adjusted PR = 0.78, 95%CI 0.68-0.90) was negatively associated with ever been screened. Male sex (Adjusted PR = 1.21, 95%CI 1.01-1.46), the belief that the HBV vaccine was safe (Adjusted PR = 1.72, 95%CI 1.03-2.89) and ever been screened (Adjusted PR = 2.28, 95%CI 1.56-3.34) were positively associated with being fully vaccinated. However, working in a public healthcare facility (Adjusted PR = 0.79, 95%CI 0.64-0.98), self-perceived risk of HBV infection (Adjusted PR = 0.72, 95% CI:0.62-0.84), and working in a healthcare facility with infection control guidelines (Adjusted PR = 0.79, 95%CI 0.66-0.95) were negatively associated with being fully vaccinated.ConclusionThree quarters of HCPs had ever been screened for HBV while slightly more than half were fully vaccinated. HBV screening and vaccination interventions need to consider the HCP sex, risk perception, attitude towards safety and efficacy of the hepatitis B vaccine, and healthcare facility characteristics such as ownership and availability of infection control guidelines, in order to be successful.

BACKGROUND: The question of whether having a family history of prostatic borderline or in situ neoplasia (PBISN) is associated with an increased risk of invasive prostate cancer (PCa) or death from PCa remains unanswered. The objective of the current study was to provide an evidence-based risk estimation for the relatives of patients with PBISN.METHODS: Nationwide Swedish family cancer data sets were used for the current study, including data regarding all residents of Sweden who were born after 1931 and their parents. Standardized incidence ratios (SIRs), standardized mortality ratios (SMRs), and lifetime cumulative risks of PCa were calculated for men with different constellations of family history. Family history was defined as a dynamic (time-dependent) variable considering changes during follow-up (1958-2015).RESULTS: Of the 6,343,727 men in the current study, a total of 238,961 developed invasive PCa and 5756 were diagnosed with PBISN during the follow-up. Men with 1 first-degree relative who was diagnosed with PBISN had a 70% increased risk of invasive PCa (SIR, 1.7; 95% confidence interval, 1.5-1.9) and PCa death (SMR, 1.7; 95% confidence interval, 1.3-2.2) compared with men with no family history of PBISN or invasive PCa. These were rather close to estimates in men with 1 first-degree relative diagnosed with invasive PCa (SIR, 2.1 and SMR, 1.8). A higher risk of PCa in family members was found among patients with a family history of PBISN and/or PCa diagnosed before age 60 years. The results in terms of cumulative risk resembled this trend.CONCLUSIONS: A family history of PBISN appears to be as important as a family history of invasive PCa with regard to an increased risk of invasive PCa or PCa mortality. Such a history should not be overlooked in PCa screening recommendations or in future research regarding familial PCa. (Less)

Additional file 1 : Table S1. Relative risk of breast carcinoma in situ in women with family history of invasive breast cancer or breast carcinoma in situ.

Given that little is known about the epidemiology of unintentional injuries in children in low-income countries, this study sought to determine the incidence and characteristics of unintentional injuries among children aged ≤18 years in a slum community in Uganda. From a household survey, the incidence and odds ratios for factors associated with unintentional injury characteristics were calculated. Of 1583 children, 706 had suffered 787 unintentional injuries yielding an annual incidence rate of 497 injuries per 1000 children. Commonest injuries were cuts, bites or open wounds (30.6%) and bruises or superficial injuries (28.6%) with majority (75.5%) occurring at home. Boys were more likely to be injured at school (AOR 4.34; 95% CI 1.22-15.54) and to be injured from falls (AOR 1.41; 95% CI 1.01-1.96). Older children (12-18 years) were more likely to suffer from fractures (AOR 2.37; 95% CI 1.26-4.43), concussions and organ system injuries (AOR 3.58; 95% CI 1.03-12.39) and cuts, bites or open wounds (AOR 2.05; 95% CI 1.21-3.48). Older children were less likely to suffer burns or scalds as compared to the young children (AOR: 0.23; 95% CI 0.11-0.50). Unintentional injury incidence rate was high among children with most occurring in the homes.

Background: Familial breast cancer risk studies usually overlook the dynamic nature of family history. Methods: The authors assessed the effect of incorporating the timing of cancer diagnosis events into the assessment of familial risks of breast cancer in first-degree and second-degree relatives in a nationwide cohort study of 5,099,172 women (follow-up was between 1958-2015). Family history was assessed using 3 approaches: 1) as a static variable (ever having a relative with breast cancer); 2) as accumulative history; and 3) as a dynamic variable (time-dependent variable). Results: For women aged

Background Although reproductive history is recognised to affect the risk of breast cancer, current breast cancer screening guidelines do not consider risk differences by this important factor. As there is a need for an earlier screening in women at increased risk of breast cancer, we provided evidence-based risk-adapted starting age of screening based on different reproductive profiles. Material and methods We conducted a nationwide cohort study including 5,099,172 Swedish women born after 1931. Records of study participants in Swedish Cancer Registry, Multi-generation Register, Cause of Death Register, and national censuses (follow-up, 1958–2015) have been linked. We used 10-year cumulative risk of breast cancer curves to determine the age at which women with different reproductive factors attained the risk level at which breast screening is usually recommended. Results The 10-year cumulative risk of breast cancer at age 40, 45 and 50 years in the general population, at which current screening guidelines recommend screening was calculated. We found that women with various reproductive factors (defined by parity and age at first birth) obtained this level of risk at different ages. The difference was between nine years later and three years earlier. Conclusions This study provides the age at which women with particular reproductive profile could start risk-adapted breast cancer screening. This supplies novel information for clinicians and women about when to start breast cancer screening and is an important step towards a personalised screening.

Importance Breast cancer screening guidelines acknowledge the need for earlier screening for women at increased risk but provide limited guidance for women with a family history of breast cancer. A risk-adapted starting age of screening for relatives of patients with breast cancer may help supplement current screening guidelines. Objective To identify the risk-adapted starting age of breast cancer screening on the basis of a woman’s detailed family history. Design, Setting, and Participants This nationwide cohort study analyzed data recorded in the Swedish family-cancer data sets. All women born from 1932 onward and with at least 1 known first-degree relative (FDR) were included (N = 5 099 172). Data from January 1, 1958, to December 31, 2015, were collected. Data were analyzed from October 1, 2017, to March 31, 2019. Exposures Family history of breast cancer in FDRs and second-degree relatives (SDRs). Main Outcomes and Measures Primary invasive breast cancer diagnosis and the age at which women with different constellations of family history attained the risk level at which breast screening is usually recommended. Results Of the 5 099 172 women included in the study, 118 953 (2.3%) received a diagnosis of primary invasive breast cancer. A total of 102 751 women (86.4%; mean [SD] age at diagnosis, 55.9 [11.1] years) did not have family history of breast cancer in FDRs and SDRs at the time of their diagnosis. Risk-adapted starting age of breast cancer screening varied by number of FDRs and SDRs with breast cancer diagnosis and the age at diagnosis of the FDRs. For example, for screening recommendation at age 50 years for the general population (2.2% 10-year cumulative risk), women with multiple affected FDRs, with the youngest affected relative receiving a diagnosis before age 50 years, reached the benchmark risk level at age 27 years. When the youngest relative received a diagnosis after age 50 years, however, this risk level was attained at age 36 years. Conclusions and Relevance This study identifies possible risk-based starting ages for breast cancer screening based on population-based registers. These results may serve as high-quality evidence to supplement current screening guidelines for relatives of patients with breast cancer.

Unintentional injuries cause deaths, disabilities, productivity and financial losses and disproportionately affect children in low-income settings yet their cost remains under studied. This study determined the household out-of-pocket expenditure and missed school attendance due to unintentional childhood injuries in a Ugandan slum. We used a cross-sectional household survey design. Data were collected on occurrence and associated costs of unintentional injuries during a one-year period from July 2014 to June 2015. A total of 706 (44.7%) children who had suffered from injuries were reported in the one year period. More male children (N = 415, 58.7%) suffered injuries than females (N = 291, 41.2%). The average out-of-pocket expenditure on treating an injury was US $24.1 [standard deviation (SD) = ±$62.8] and mean school days lost were 25 days (SD = ±51.8). Road traffic injuries (RTIs) resulted in higher costs [mean difference was US $51.1 (95% CI: $11.4-$90.8)] compared to injuries that, for example, occurred at school. In a Ugandan slum community, unintentional childhood injuries resulted in high out-of-pocket expenditures and missed school attendance. The costs varied widely depending on external causes of the injury. These findings highlight the need to invest in population level injury prevention interventions to reduce injury costs by households.

Introduction Unintentional injuries burden communities’ worldwide causing deaths, disability, productivity and financial losses and disproportionately affect children in low-income settings but their cost on communities remains under studied. This study aimed to determine direct and indirect costs of unintentional childhood injuries in a resource deprived community. Methods We used a cross-sectional household survey design in Kasubi, a Kampala city slum. We collected data on occurrence and associated costs for a one-year period from July 2014 to June 2015. Data was entered in Epidata 3.02 and analyzed in Stata 13.0 statistical software. Descriptive and bivariate analysis were conducted to identify risk factors for injury, cost-estimates of injuries by severity, cause and nature. Results A total of 706 (44.7%) children who had suffered from injuries were reported in the one year period. More male children, (n=415, 58.7%) suffered injuries than females (n=291, 41.2%). The average out-of-pocket expenditure on treating an injury was US $24.1 (standard deviation [SD]=±$62.8) and mean school days lost was 25.1 days (SD=±51.8). Road traffic injuries (RTIs) resulted in higher costs (mean difference was US $51.1 (95% CI: $11.4 to $90.8) compared to injuries that occurred at school. Also, road traffic related injuries (mean difference=39.4; 95% CI: 13.1 to 65.7) resulted in significantly more school days lost compared to falls. Conclusion In a slum community within Uganda, unintentional childhood injuries resulted in high out-of-pocket expenditures and missed school attendance and the cost varied widely amongst the cases. These findings highlight the need to invest in population level injury prevention interventions to reduce household expenditure by poor households on injury treatment.

Introduction Childhood unintentional injuries remain understudied. This assessed the incidence and characteristics of all unintentional injuries among children aged 18 years and below in a slum community in Uganda. Methods A cross-sectional survey was conducted among households in a slum community using a semi-structured interviewer-administered questionnaire. Incidence of unintentional injuries in children Results Out of 1583 children in the 422 surveyed households, 44.6% (706/1583) had suffered from at least one unintentional injury yielding an annual incidence rate of 446 per 1000 children. Cuts, animal bites or open wounds 30.6% (185/608), and bruises or superficial injuries 28.6% (174/608) were the commonest injuries. Majority of injuries occurred at home, 75.5% (459/608). Falls 56.7% (345/608) and playing or recreation 83.6% (508/608) were the leading cause and activity at time of injury respectively. Boys were significantly more likely to be injured at school (AOR 4.34; 95% CI 1.22–15.54) and to be injured from falls (AOR 1.41; 95% CI 1.01–1.96), as compared to girls. Older children (12–18 years) were more likely to suffer from fractures (AOR 2.37; 95% CI 1.26–4.43) concussions and organ system injuries (AOR 3.58; 95% CI 1.–3 – 12.39) and cuts, bites or open wounds (AOR 2.05; 95% CI 1.21–3.48) as compared to younger children. Older children were less likely to have burns or scalds as compared to the youngest children (AOR: 0.23; 95% CI 0.11 to 0.50). Conclusions Unintentional injury incidence rate was high among children with most occurring in the homes. Injury prevention interventions should aim at creating safe playing spaces for children and developing awareness programs about injury prevention.

Introduction: Medical male circumcision is currently recognized as an additional important HIV preventive intervention to reduce the risk of heterosexually acquired HIV infection in men. However, sexual behaviours after medical circumcision can potentially reduce the expected benefits of the practice. This study explored the perceptions about medical male circumcision and sexual behaviours of adults in Kayunga district, Uganda.Methods: A cross-sectional study was carried out among 393 respondents using a semi structured questionnaire. In addition, four focus group discussions were conducted. Quantitative data was analysed using STATA 12. Univariate, bivariate and multivariate analyses were carried out. Qualitative data was analysed thematically.Results: The study established various perceptions about medical male circumcision and sexual behaviours. Majority 247 (64.5%) did not perceive circumcision as a practice that can lead men to have multiple sexual partners. Males were 3 times more likely to think that circumcision would lead to having multiple sexual partners than females (AOR=2.99, CI: 1.93-4.61). Only 89 (23.2%) believed that circumcision would lead to complacency and compromise the use of condoms to prevent against infection with HIV. Respondents who had education above primary were less likely to think that circumcision would compromise the use of condoms (AOR=0.49, CI: 0.31- 0.79). The perception that circumcised youths were less likely to abstain from sexual intercourse was less held among those with education above primary (AOR=0.58, CI: 0.37-0.91) and those older than 30 years (AOR=0.59, CI: 0.38-0.92).Conclusion: There were gaps in knowledge and negative perceptions about MMC in the study community. Measures are needed to avert the negative perceptions by equipping communities with sufficient, accurate and consistent information about medical male circumcision and sexual behaviour.Keywords: Perceptions, circumcision, sexual behaviours, HIV/AIDS, prevention

Poor solid waste management is among the major challenges facing urban slums in developing countries including Uganda. Understanding community concerns and willingness towards involvement in solid waste management improvement initiatives is critical for informing interventions in slums.Methods. We used a cross-sectional study to collect quantitative data from 435 residents in two urban slums in central Uganda. A semistructured questionnaire was used which assessed waste collection practices, separation and disposal methods, concerns regarding solid wastes, and willingness to participate in waste separation and composting. Data was analysed using STATA 12.Results. Food remains (38%) and plastics (37%) formed the biggest proportion of wastes generated in households. Most households (35.9%) disposed of general wastes by open dumping while 27% disposed of plastics by burning. Only 8.8% of households conducted composting while 55% carried out separation for some decomposable wastes. Separation was carried out for only banana peelings and leftover foods for feeding animals. Respondents expressed high willingness to separate (76.6%) and compost (54.9%) solid wastes.Conclusion. Practices in waste disposal and separation were poor despite high willingness to participate in initiatives to improve waste management, highlighting a need for authorities to engage residents of slums to improve their practices.

Background Cervical cancer is a leading cause of morbidity and mortality among women in Uganda, often due to late disease diagnosis. Early screening for the cancer has been shown to be the most effective measure against the disease. Studies conducted elsewhere have reported the lack of awareness and negative attitudes towards cervical cancer as barriers to early screening. This study assessed the knowledge and attitudes of Ugandan women about cervical cancer prevention with the aim of informing prevention and control interventions. Methods This study was conducted in Bugiri and Mayuge districts in eastern Uganda. It was a cross-sectional community based survey and collected data by means of a questionnaire. A total of 900 women aged 25–49 years participated in the study. Women’s knowledge and attitudes towards cervical cancer prevention were assessed and scored. Data were analysed using STATA 12.0 software. Bivariate and multivariate analyses were carried out to establish the relationship between knowledge levels and demographic characteristics. Results Most (794; 88.2%) of the respondents had heard about cervical cancer, the majority (557; 70.2%) having received information from radio and 120 (15.1%) from health facilities. Most women (562; 62.4%) knew at least one preventive measure and (743; 82.6%) at least one symptom or sign of the disease. The majority (684; 76.0%) of respondents perceived themselves to be at risk of cervical cancer, a disease most (852; 94.6%) thought to be very severe. Living in peri-urban areas (AOR = 1.62, 95% CI: 1.15 – 2.28), urban areas (AOR = 3.64, 95% CI: 2.14 – 6.19), having a higher monthly income (AOR = 0.50, 95% CI: 0.37 – 0.68) and having had an HIV test (AOR = 1.99, 95% CI: 1.34–2.96) were associated with level of knowledge about cervical cancer prevention. Conclusion Although general knowledge about cervical cancer prevention was relatively high among women, and attitudes mostly encouraging, specific knowledge about screening was low. There were also undesirable perceptions and beliefs regarding cervical cancer among respondents. There is therefore need for more education campaigns to bridge identified knowledge gaps, and scale up of cervical cancer screening services to all women to increase service uptake. Electronic supplementary material The online version of this article (doi:10.1186/s12905-017-0365-3) contains supplementary material, which is available to authorized users.

Objectives To explore community knowledge, facilitators and barriers to cervical cancer screening among women in rural Uganda so as to generate data to inform interventions. Design A qualitative study using focus group discussions and key informant interviews. Setting Discussions and interviews carried out in the community within two districts in Eastern Uganda. Participants Ten ( 10) focus group discussions with 119 screening-eligible women aged between 25 and 49 years and 11 key informant interviews with healthcare providers and administrators. Results Study participants’ knowledge about cervical cancer causes, signs and symptoms, testing methods and prevention was poor. Many participants attributed the cause of cervical cancer to use of contraception while key informants said that some believed it was due to witchcraft. Perceptions towards cervical cancer and screening were majorly positive with many participants stating that they were at risk of getting cervical cancer. The facilitators to accessing cervical cancer screening were: experiencing signs and symptoms of cervical cancer, family history of the disease and awareness of the disease/screening service. Lack of knowledge about cervical cancer and screening, health system challenges, fear of test outcome and consequences and financial constraints were barriers to cervical cancer screening. Conclusion Whereas perceptions towards cervical cancer and screening were positive, knowledge of study participants on cervical cancer was poor. To improve cervical cancer screening, effort should be focused on reducing identified barriers and enhancing facilitators.

Background In developing countries, inadequate access to effective screening for cervical cancer often contributes to the high morbidity and mortality caused by the disease. The largest burden of this falls mostly on underserved populations in rural areas, where health care access is characterized by transport challenges, ill equipped health facilities, and lack of information access. This study assessed uptake of cervical cancer screening and associated factors among women in rural Uganda. Methods This descriptive cross sectional study was carried out in Bugiri and Mayuge districts in eastern Uganda and utilised quantitative data collection methods. Data were collected using a semi-structured questionnaire on cervical cancer screening among females aged between 25 and 49 years who had spent six or more months in the area. Data were entered in Epidata 3.02 and analysed in STATA 12.0 statistical software. Univariate, bivariate and multivariate analyses were performed. Results Of the 900 women, only 43 (4.8%) had ever been screened for cervical cancer. Among respondents who were screened, 21 (48.8%) did so because they had been requested by a health worker, 17 (39.5%) had certain signs and symptoms they associated with cervical cancer while 16 (37.2%) did it voluntarily to know their status. Barriers to cervical cancer screening were negative individual perceptions 553 (64.5%) and health facility related challenges 142 (16.6%). Other respondents said they were not aware of the screening service 416 (48.5%). The independent predictors of cervical cancer screening were: being recommended by a health worker [AOR = 87.85, p

Womenâ s knowledge and attitudes towards cervical cancer prevention. Description of file: Study questionnaire. (PDF 456Â kb)

Womenâ s knowledge and attitudes towards cervical cancer prevention. Description of file: Study questionnaire. (PDF 456Â kb)

Background The World Health Organization recommends cervical cancer screening and vaccination programmes as measures to combat cervical cancer. The uptake of these measures remains low in Uganda, most especially in rural areas. An understanding of the factors that influence women’s decision to attend screening, and willingness to have their daughters vaccinated against cervical cancer is essential for any attempts to increase uptake of these services. This study assessed the factors associated with intention to screen for cervical cancer among women in eastern Uganda, and willingness to have their daughters vaccinated against the disease. Methods This cross sectional study involved 900 females aged 25 to 49 years in Bugiri and Mayuge districts in eastern Uganda. Data were collected using a pretested semi-structured questionnaire, entered in Epidata version 3.02 and analysed in STATA version 12.0. Unadjusted and adjusted prevalence ratios (PR) were computed using a generalized linear model with Poisson family, and a log link with robust standard errors. Results Majority 819 (91.0%) of respondents stated that they intended to go for cervical cancer screening in the subsequent six months. Among them, 603 (73.6%) wanted to know their status, 256 (31.3%) thought it was important, 202 (24.7%) wanted to reduce their chances of getting the disease, and 20 (2.4%) had been told to do so by a health worker. Majority 813 (90.4%) of respondents were willing to vaccinate their daughters against cervical cancer. Higher income (adjusted PR = 1.11, 95% CI: 1.03–1.20), cervical cancer screening status (adjusted PR = 0.81, 95% CI: 0.67–0.99) and knowledge of at least one test for cervical cancer (adjusted PR = 0.92, 95% CI: 0.85–0.98) were significantly associated with intention to screen for cervical cancer. No socio-demographic characteristic was associated with willingness to vaccinate daughters among women. Conclusion There is a very high intention to screen and willingness to vaccinate daughters against cervical cancer among women in eastern Uganda. To take advantage of this, there is need to avail opportunities for women to access cervical cancer screening and vaccinations particularly among rural communities.