RHR and changes in RHR over a decade are associated with mortality risk, including from causes other than CVD such as breast, colorectal or lung cancer. Monitoring of RHR may have utility in identifying individuals at higher mortality risk.

Background: Hepatitis B Virus (HBV) infection is an important occupational health risk among primary healthcare providers (PHCPs). However, there is limited evidence on whether PHCPs’ level of knowledge and attitude can predict better HBV infection prevention practices. This study established the relationship between knowledge, attitude, and HBV infection prevention practices among PHCPs in Wakiso district, Central Uganda. Methods: A cross-sectional study design was used. Data were collected from 306 PHCPs, using a structured questionnaire. PHCPs were randomly selected from 55 healthcare facilities. STATA version 14.0 was used to analyse data. A ‘modified Poisson’ regression model was used for inferential statistics. Results: About 42.2% of PHCPs exhibited poor knowledge of HBV infection transmission and prevention, 41.8% had a negative attitude, and 41.5% exhibited poor prevention practices. Age (PR 1.82, 95% CI: 1.24–2.66) was positively associated with the level of knowledge. Healthcare facility level (PR 0.53, 95% CI: 0.34–0.84), main department of work (PR 0.69, 95% CI: 0.51–0.95), years in service (PR 0.66, 95% CI: 0.44–0.99), working in private not-for-profit healthcare facilities (PR 0.59, 95% CI: 0.34–0.99), and public healthcare facilities (PR 0.58, 95% CI: 0.42–0.80) were negatively associated with the level of knowledge. There was a negative association between the location of healthcare facility (PR 0.76, 95% CI: 0.62–0.93) and attitude, and a positive association between level of knowledge (PR 1.36, 95% 1.12–1.65) and attitude. Working in a public healthcare facility (PR 0.80, 95% CI: 0.64–0.99) was negatively associated with practices while having a positive attitude (PR 1.60, 95% CI: 1.28–1.99) predicted better HBV infection prevention practices. Conclusion: PHCPs who were more knowledgeable about HBV infection were more likely to have a positive attitude. In turn, having a positive attitude was associated with better HBV infection prevention practices. There is a need to sensitise PHCPs on HBV infection, and provision of screening and vaccination services in order to address the KAP gaps.

Organ-transplant recipients have an elevated risk of keratinocyte cancers: basal cell carcinoma (BCC) and squamous cell carcinoma. We assessed whether polygenic risk scores (PRSs) generated in nontransplantees from the UK Biobank and 23andMe (13,981 squamous cell carcinoma, 33,736 BCC, and >560,000 controls) can predict keratinocyte cancer risk in an independent organ-transplant recipient cohort. After adjusting for traditional risk factors, compared with the bottom 20%, organ-transplant recipients in the top 20% PRS had an increased risk of BCC (OR ¼ 3.25, 95% confidence interval ¼ 1.44e7.31, P ¼ 4.4 Â 10-3) and squamous cell carcinoma (OR ¼ 2.11, 95% confidence interval ¼ 0.98e4.53, P ¼ 0.055). For BCC, the top 20% PRS individuals had an absolute risk of 23%, whereas the risk in the bottom 20% was similar to that in the general nontransplantee population. Adding PRS to a model containing traditional skin cancer risk factors yielded a 3% increase in the area under the curve for receiver operating characteristic curve for BCC (0.73 vs. 0.70); adding the PRS did not significantly increase the area under the curve for receiver operating characteristic curve for squamous cell carcinoma. Organ-transplant recipients in the highest genetic risk quintile could benefit from more intense keratinocyte cancer screening and preventive strategies compared with their counterparts. The BCC PRS improves prediction over and above the traditional skin cancer risk factors by 3%.

Background In much of sub-Saharan Africa, health facilities serve as the primary source of routine vital statistics. These passive surveillance systems, however, are plagued by infrequent and unreliable reporting and do not capture events that occur outside of the formal health sector. Verbal autopsies (VA) have been utilized to estimate the burden and causes of mortality where civil registration and vital statistics systems are weak, but VAs have not been widely employed in national surveillance systems. In response, we trained lay community health workers (CHW) in a rural sub-county of western Uganda to conduct VA interviews in order to assess the feasibility of leveraging CHW to measure the burden of disease in resource limited settings. Methods and findings Trained CHWs conducted a cross-sectional survey of the 36 villages comprising the Bugoye sub-county to identify all deaths occurring in the prior year. The sub county has an estimated population of 50,249, approximately one-quarter of whom are children under 5 years of age (25.3%). When an eligible death was reported, CHWs administered a WHO 2014 VA questionnaire, the results of which were analyzed using the InterVA-4 tool. To compare the findings of the CHW survey to existing surveillance systems, study staff reviewed inpatient registers from neighboring referral health facilities in an attempt to match recorded deaths to those identified by the survey. Overall, CHWs conducted high quality VA interviews on direct observation, identifying 230 deaths that occurred within the sub-county, including 77 (33.5%) among children under five years of age. More than half of the deaths (123 of 230, 53.5%) were reported to have occurred outside a health facility and thus would not be captured by passive surveillance. More than two-thirds (73 of 107, 68.2%) of facility deaths took place in one of three nearby hospitals, yet only 35 (47.9%) were identified on our review of inpatient registers. Consistent with previous VA studies, the leading causes of death among children under five years of age were malaria (19.5%), prematurity (19.5%), and neonatal pneumonia (15.6%). while among adults, HIV/AIDS-related deaths illness (13.6%), pulmonary tuberculosis (11.4%) and malaria (8.6%) were the leading causes of death. No child deaths identified from inpatient registers listed HIV/AIDS as a cause of death despite 8 deaths (10.4%) attributed to HIV/AIDS as determined by VA. Conclusions Lay CHWs are able to conduct high quality VA interviews to capture critical information that can be analyzed using standard methodologies to provide a more complete estimate of the burden and causes of mortality. Similar approaches can be scaled to improve the measurement of vital statistics in order to facilitate appropriate public health interventions in rural areas of sub-Saharan Africa.

Background The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. Objective To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. Methods We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10–8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Results Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61–2.71, P = 2.08 × 10–8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77–3.21, P = 1.07 × 10–8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83–0.94, P = 6.93 × 10–5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78–0.90). Conclusion We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting.

Background: Keratinocyte cancer (KC) is the commonest cancer, imposing a high economic burden on the healthcare system. Observational studies have shown mixed associations between polyunsaturated fatty acids (PUFAs) and KC; basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We explored if genetically predicted PUFA levels are associated with BCC and SCC risks. Methods:We conducted a two sample Mendelian Randomisation study using PUFA level GWASs from the CHARGE consortium (n > 8,000), and the meta-analysis GWASs from UKB, 23andMe and Qskin for BCC (n=651,138) and SCC (n= 635,331) risk.Results: One standard deviation increase in genetically predicted levels of linoleic acid (OR = 0.94, 95% CI = 0.91-0.97, P = 1.4 × 10 -4 ) and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, P = 5.1 × 10 -4 ) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, P = 3.2 × 10 -4 ) and eicosapentaenoic acid (OR=1.10, 95% CI = 1.04-1.16, P = 1.5 × 10 -3 ) were associated with an increased BCC risk. Conclusion:Higher genetically predicted levels of linoleic acid and alpha-linolenic acid were associated with a reduced BCC risk, but arachidonic acid and eicosapentaenoic acid were associated with a higher BCC risk.

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.

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