Summary Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124·1 million DALYs [95% UI 111·2 million to 137·0 million]), high systolic blood pressure (122·2 million DALYs [110·3 million to 133·3 million], and low birthweight and short gestation (83·0 million DALYs [78·3 million to 87·7 million]), and for women, were high systolic blood pressure (89·9 million DALYs [80·9 million to 98·2 million]), high body-mass index (64·8 million DALYs [44·4 million to 87·6 million]), and high fasting plasma glucose (63·8 million DALYs [53·2 million to 76·3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9·3% (6·9–11·6) decline in deaths and a 10·8% (8·3–13·1) decre...

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Aims: The NADPH oxidase (NOX) family of enzymes catalyzes the formation of reactive oxygen species (ROS). NOX enzymes not only have a key role in a variety of physiological processes but also contribute to oxidative stress in certain disease states. To date, while numerous small molecule inhibitors have been reported (in particular for NOX2), none have demonstrated inhibitory activity in vivo. As such, there is a need for the identification of improved NOX inhibitors to enable further evaluation of the biological functions of NOX enzymes in vivo as well as the therapeutic potential of NOX inhibition. In this study, both the in vitro and in vivo pharmacological profiles of GSK2795039, a novel NOX2 inhibitor, were characterized in comparison with other published NOX inhibitors. Results: GSK2795039 inhibited both the formation of ROS and the utilization of the enzyme substrates, NADPH and oxygen, in a variety of semirecombinant cell-free and cellbased NOX2 assays. It inhibited NOX2 in an NADPH competitive manner and was selective over other NOX isoforms, xanthine oxidase, and endothelial nitric oxide synthase enzymes. Following systemic administration in mice, GSK2795039 abolished the production of ROS by activated NOX2 enzyme in a paw inflammation model. Furthermore, GSK2795039 showed activity in a murine model of acute pancreatitis, reducing the levels of serum amylase triggered by systemic injection of cerulein. Innovation and Conclusions: GSK2795039 is a novel NOX2 inhibitor that is the first small molecule to demonstrate inhibition of the NOX2 enzyme in vivo. Antioxid. Redox Signal. 23, 358-374.

BackgroundWhile bacterial sexually transmitted infections (STIs) are important cofactors for HIV transmission, STI control has received little attention in recent years. The aim of this study was to assess STI treatment and HIV testing referral practices among health providers in Kenya.MethodsIn 2011 we assessed quality of case management for male urethritis at pharmacies, private clinics and government health facilities in coastal Kenya using simulated visits at pharmacies and interviews at pharmacies and health facilities. Quality was assessed using Ministry of Health guidelines.ResultsTwenty (77%) of 26 pharmacies, 20 (91%) of 22 private clinics and all four government facilities in the study area took part. The median (IQR) number of adult urethritis cases per week was 5 (2–10) at pharmacies, 3 (1–3) at private clinics and 5 (2–17) at government facilities. During simulated visits, 10% of pharmacies prescribed recommended antibiotics at recommended dosages and durations and, during interviews, 28% of pharmacies and 27% of health facilities prescribed recommended antibiotics at recommended dosages and durations. Most regimens were quinolone-based. HIV testing was recommended during 10% of simulated visits, 20% of pharmacy interviews and 25% of health facility interviews.ConclusionsIn an area of high STI burden, most men with urethritis seek care at pharmacies and private clinics. Most providers do not comply with national guidelines and very few recommend HIV testing. In order to reduce the STI burden and mitigate HIV transmission, there is an urgent need for innovative dissemination of up-to-date guidelines and inclusion of all health providers in HIV/STI programmes.

ObjectivesThe WHO recommends that men who have sex with men (MSM) reporting unprotected receptive anal intercourse (RAI) and either multiple partners or a partner with a sexually transmitted infection (STI) in the past 6 months should be presumptively treated for asymptomatic rectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. We evaluated this recommendation in a cohort of ‘high-risk’ MSM in Coastal Kenya.MethodsWe assessed presence of genitourinary and rectal symptoms, and determined prevalence and 3-month incidence of rectal NG and CT infections. We performed nucleic acid amplification testing of urine and rectal swab samples collected from MSM followed prospectively, and assessed predictive values of the WHO algorithm at baseline screening.ResultsOf 244 MSM screened, 240 (98.4%) were asymptomatic, and 147 (61.3%) reported any RAI in the past 6 months. Among 85 (35.4%) asymptomatic MSM meeting criteria for the WHO presumptive treatment (PT) recommendation, we identified 20 with rectal infections (six NG, 12 CT and two NG–CT co-infections). Among 62 asymptomatic MSM who did not meet criteria, we identified seven who were infected. The sensitivity and specificity of the WHO algorithm were 74.1% (95% CI 53.7% to 88.9%) and 45.8% (95% CI 36.7% to 55.2%), respectively. The 3-month incidence of any rectal NG or CT infection in asymptomatic men reporting any RAI was 39.7 (95% CI 24.3 to 64.8) per 100 person-years.ConclusionsAbout one-third of asymptomatic MSM were eligible to receive PT for NG and CT infections. Among MSM who would qualify for PT of rectal STIs, the number needed to treat in order to treat one infection was four. Our results support the value of the WHO screening algorithm and recommended PT strategy in this population.

Our evaluation demonstrates that in a large sexual health clinic, SMS reminders increased HIV/STI re-testing rates and if adopted more widely have great potential to reduce HIV/ STI infections in the MSM community. More randomised trials in other sexual health clinics and primary care settings are needed to assess if there is a similar effect to that seen at SSHC.Competing interests None declared.Ethics approval This study was conducted with the approval of the South Eastern Sydney Area Health Service research ethics committee.Contributors VK was responsible for overall management of the SMS programme. HL designed the SMS programme in the clinic medical record system and extracted the data for the analysis. HW in consultation with RG carried out the statistical analysis. CB and RG devised the original idea for the study. RG provided methodological advice on the evaluation design and analysis of the study. AM, CB and VK advised on clinical practice and interpretation of results. All authors read and approved the final manuscript.Provenance and peer review Not commissioned; externally peer reviewed.

We have recently reported high levels of fluoroquinolone resistance in a single region of Kenya. In this manuscript, we report high prevalence of fluoroquinolone resistance (53.2%) in Neisseria gonorrhoeae isolates from four clinics in three additional regions of Kenya. These findings highlight the need to change first-line treatment in these settings and the need to evaluate empiric management guidelines for treatment of gonococcal infection in Kenya.