Triggering necroptosis in cisplatin and IAP antagonist-resistant ovarian carcinoma.

Ovarian cancer patients are typically treated with carboplatin and paclitaxel, but suffer a high rate of relapse with recalcitrant disease. This challenge has fostered the development of novel approaches to treatment, including antagonists of the 'inhibitor of apoptosis proteins' (IAPs), also called SMAC mimetics, as apoptosis-inducing agents whose action is opposed by caspase inhibitors. Surprisingly, IAP antagonist plus caspase inhibitor (IZ) treatment selectively induced a tumor necrosis factor-α (TNFα)-dependent death among several apoptosis-resistant cell lines and patient xenografts. The induction of necroptosis was common in ovarian cancer, with expression of catalytically active receptor-interacting protein kinase-3 (RIPK3) necessary for death, and in fact sufficient to compromise survival of RIPK3-negative, necroptosis-resistant ovarian cancer cells. The formation of a necrosome-like complex with a second critical effector, receptor-interacting serine-threonine kinase-1 (RIPK1), was observed. RIPK1, RIPK3 and TNFα were required for the induction of death, as agents that inhibit the function of any of these targets prevented cell death. Abundant RIPK3 transcript is common in serous ovarian cancers, suggesting that further evaluation and targeting of this RIPK3-dependent pathway may be of clinical benefit

The impact of armed conflict on cancer among civilian populations in low- and middle-income countries: a systematic review

Commitee On Publication Ethics ecancermedicalscience Submit article Articles Editorials Special issues Author interviews Category Sub-category Article type Volume Keyword Bookmark and Share Article metrics: 204 views https://doi.org/10.3332/ecancer.2020.1039 Abstract | Full Article | PDF Review The impact of armed conflict on cancer among civilian populations in low- and middle-income countries: a systematic review Mohammed Jawad1, Christopher Millett1, Richard Sullivan2, Fadel Alturki3, Bayard Roberts4 and Eszter P Vamos1 1Public Health Policy Evaluation Unit, Imperial College London, Hammersmith, London W6 8RP, UK 2Institute of Cancer Policy, Cancer Epidemiology, Population and Global Health, King's College London and Guy's & St Thomas' NHS Trust, London, UK 3Faculty of Medicine, American University of Beirut, Lebanon 4Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London WC1H 9SH, UK Abstract Background: Armed conflicts are increasingly impacting countries with a high burden of cancer. The aim of this study is to systematically review the literature on the impact of armed conflict on cancer in low- and middle-income countries (LMICs). Methods: In November 2019, we searched five medical databases (Embase, Medline, Global Health, PsychINFO and the Web of Science) without date, language or study design restrictions. We included studies assessing the association between armed conflict and any cancer among civilian populations in LMICs. We systematically re-analysed the data from original studies and assessed quality using the Newcastle-Ottawa Scale. Data were analysed descriptively by cancer site. Results: Of 1,543 citations screened, we included 20 studies assessing 8 armed conflicts and 13 site-specific cancers (total study population: 70,172). Two-thirds of the studies were of low methodological quality (score <5) and their findings were often conflicting. However, among outcomes assessed by three or more studies, we found some evidence that armed conflict was associated with increases in the incidence and mortality of non-specific cancers, breast cancer and cervical cancer. Single studies reported a positive association between armed conflict and the incidence of stomach and testicular cancers, some as early as 3 years after the onset of conflict. Some studies reported a post-conflict impact on time to diagnosis. Conclusion: Our findings support the need for more rigorous longitudinal and cohort studies of populations in and immediately post-conflict to inform the development of basic packages of cancer services, and post-conflict cancer control planning and development

Nationwide study on trends in hospital admissions for major cardiovascular events and procedures among people with and without diabetes in England, 2004 to 2009

OBJECTIVE It is unclear whether people with and without diabetes equally benefitted from reductions in cardiovascular disease (CVD). We aimed to compare recent trends in hospital admission rates for angina, acute myocardial infarction (AMI), stroke, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) among people with and without diabetes in England. RESEARCH DESIGN AND METHODS We identified all patients aged >16 years with cardiovascular events in England between 2004–2005 and 2009–2010 using national hospital activity data. Diabetes- and nondiabetes-specific rates were calculated for each year. To test for time trend, we fitted Poisson regression models. RESULTS In people with diabetes, admission rates for angina, AMI, and CABG decreased significantly by 5% (rate ratio 0.95 [95% CI 0.94–0.96]), 5% (0.95 [0.93–0.97]), and 3% (0.97 [0.95–0.98]) per year, respectively. Admission rates for stroke did not significantly change (0.99 [0.98–1.004]) but increased for PCI (1.01 [1.005–1.03]) in people with diabetes. People with and without diabetes experienced similar proportional changes for all outcomes, with no significant differences in trends between these groups. However, diabetes was associated with an ~3.5- to 5-fold risk of CVD events. In-hospital mortality rates declined for AMI and stroke, remained unchanged for CABG, and increased for PCI admissions in both groups. CONCLUSIONS This national study suggests similar changes in admissions for CVD in people with and without diabetes. Aggressive risk reduction is needed to further reduce the high absolute and relative risk of CVD still present in people with diabetes

Sociodemographic factors and patient perceptions are associated with attitudes to kidney transplantation among haemodialysis patients

Background. Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude. Methods. In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript. Results. Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to incre- asing age, with unwillingness to consider transplantation. Conclusions. Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions

Sexual risk reduction among Zambian couples

Zambia has over 1 million HIV infections nationwide and an urban prevalence rate of 23%. This study compared the impact of maleinvolvement in multiple and single session risk reduction interventions among inconsistent condom users in Zambia and the role ofserostatus among HIV-seropositive and serodiscordant couples. Couples (N=392) were randomised into intervention arms. Amonginconsistent condom users at baseline (N=83), condom use increased in both conditions and this increase was maintained over a 12-month period. At 12 months, seronegative men in the multiple session condition increased sexual barrier (male and female condoms)use in comparison with those in the single session condition (F=16.13, p=0.001) while seropositive individuals increased sexualbarrier use regardless of condition. Results illustrate the importance of both single and multiple session risk reduction counsellingamong seronegative men in serodiscordant couples in Zambia, and highlight the differing perception of risk between seropositiveand serodiscordant persons.Keywords: HIV, men, women, Africa, high-risk behaviour, behavioural intervention

Quantifying the impact of the Public Health Responsibility Deal on salt intake, cardiovascular disease and gastric cancer burdens: Interrupted time series and microsimulation study

Background In 2011, England introduced the Public Health Responsibility Deal (RD), a public-private partnership (PPP) which gave greater freedom to the food industry to set and monitor targets for salt intakes. We estimated the impact of the RD on trends in salt intake and associated changes in cardiovascular disease (CVD) and gastric cancer (GCa) incidence, mortality and economic costs in England from 2011–2025. Methods We used interrupted time series models with 24 hours' urine sample data and the IMPACTNCD microsimulation model to estimate impacts of changes in salt consumption on CVD and GCa incidence, mortality and economic impacts, as well as equity impacts. Results Between 2003 and 2010 mean salt intake was falling annually by 0.20 grams/day among men and 0.12 g/d among women (P-value for trend both < 0.001). After RD implementation in 2011, annual declines in salt intake slowed statistically significantly to 0.11 g/d among men and 0.07 g/d among women (P-values for differences in trend both P < 0.001). We estimated that the RD has been responsible for approximately 9900 (interquartile quartile range (IQR): 6700 to 13,000) additional cases of CVD and 1500 (IQR: 510 to 2300) additional cases of GCa between 2011 and 2018. If the RD continues unchanged between 2019 and 2025, approximately 26 000 (IQR: 20 000 to 31,000) additional cases of CVD and 3800 (IQR: 2200 to 5300) cases of GCa may occur. Interpretation Public-private partnerships such as the RD which lack robust and independent target setting, monitoring and enforcement are unlikely to produce optimal health gains

The hypertension cascade of care in the midst of conflict: the case of the Gaza Strip

Although hypertension constitutes a substantial burden in conflict-affected areas, little is known about its prevalence, control, and management in Gaza. This study aims to estimate the prevalence and correlates of hypertension, its diagnosis and control among adults in Gaza. We conducted a representative, cross-sectional, anonymous, household survey of 4576 persons older than 40 years in Gaza in mid-2020. Data were collected through face-to-face interviews, anthropometric, and blood pressure measurements. Hypertension was defined in anyone with an average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg from two consecutive readings or a hypertension diagnosis. The mean age of participants was 56.9 ± 10.5 years, 54.0% were female and 68.5% were Palestinian refugees. The prevalence of hypertension was 56.5%, of whom 71.5% had been diagnosed. Hypertension was significantly higher among older participants, refugees, ex-smokers, those who were overweight or obese, and had other co-morbidities including mental illnesses. Two-thirds (68.3%) of those with hypertension were on treatment with one in three (35.6%) having their hypertension controlled. Having controlled hypertension was significantly higher in females, those receiving all medications for high blood pressure and those who never or rarely added salt to food. Investing in comprehensive but cost-effective initiatives that strengthen the prevention, early detection and timely treatment of hypertension in conflict settings is critical. It is essential to better understand the underlying barriers behind the lack of control and develop multi-sectoral programs to address these barriers

Associations between attainment of incentivised primary care indicators and incident diabetic retinopathy in England: a population-based historical cohort study

Background The associations between England’s incentivised primary care-based diabetes prevention activities and hard clinical endpoints remain unclear. We aimed to examine the associations between attainment of primary care indicators and incident diabetic retinopathy (DR) among people with type 2 diabetes. Methods A historical cohort (n = 60,094) of people aged ≥ 18 years with type 2 diabetes and no DR at baseline was obtained from the UK Clinical Practice Research Datalink (CPRD). Exposures included attainment of the Quality and Outcomes Framework (QOF) HbA1c (≤ 7.5% or 59 mmol/mol), blood pressure (≤ 140/80 mmHg), and cholesterol (≤ 5 mmol/L) indicators, and number of National Diabetes Audit (NDA) care processes completed (categorised as 0–3, 4–6, or 7–9), in 2010–2011. Outcomes were time to development of DR and sight-threatening diabetic retinopathy (STDR). Nearest neighbour propensity score matching was undertaken and Cox proportional hazards models then fitted using the matched samples. Concordance statistics were calculated for each model. Results 8263 DR and 832 STDR diagnoses were observed over mean follow-up periods of 3.5 (SD 2.1) and 3.8 (SD 2.0) years, respectively. HbA1c and blood pressure (BP) indicator attainment were associated with lower rates of DR (adjusted hazard ratios (aHRs) 0.94 (95% CI 0.89–0.99) and 0.87 (0.83–0.92), respectively), whereas cholesterol indicator attainment was not (aHR 1.03 (0.97–1.10)). All QOF indicators were associated with lower rates of STDR (aHRs 0.74 (0.62–0.87) for HbA1c, 0.78 (0.67–0.91) for BP, and 0.82 (0.67–0.99) for cholesterol). Completion of 7–9 vs. 0–3 NDA processes was associated with fewer STDR diagnoses (aHR 0.72 (0.55–0.94)). Conclusions Attainment of key primary care indicators is associated with lower incidence of DR and STDR among patients with type 2 diabetes in England