Breast Cancer Risk Assessment and Primary Prevention Advice in Primary Care: A Systematic Review of Provider Attitudes and Routine Behaviours

Implementing risk-stratified breast cancer screening is being considered internationally. It has been suggested that primary care will need to take a role in delivering this service, including risk assessment and provision of primary prevention advice. This systematic review aimed to assess the acceptability of these tasks to primary care providers. Five databases were searched up to July–August 2020, yielding 29 eligible studies, of which 27 were narratively synthesised. The review was pre-registered (PROSPERO: CRD42020197676). Primary care providers report frequently collecting breast cancer family history information, but rarely using quantitative tools integrating additional risk factors. Primary care providers reported high levels of discomfort and low confidence with respect to risk-reducing medications although very few reported doubts about the evidence base underpinning their use. Insufficient education/training and perceived discomfort conducting both tasks were notable barriers. Primary care providers are more likely to accept an increased role in breast cancer risk assessment than advising on risk-reducing medications. To realise the benefits of risk-based screening and prevention at a population level, primary care will need to proactively assess breast cancer risk and advise on risk-reducing medications. To facilitate this, adaptations to infrastructure such as integrated tools are necessary in addition to provision of education

A Road Map for the Global Elimination of Congenital Syphilis

Congenital syphilis is the oldest recognized congenital infection, and continues to account for extensive global perinatal morbidity and mortality today. Serious adverse pregnancy outcomes caused by maternal syphilis infection are prevented with screening early in pregnancy and prompt treatment of women testing positive. Intramuscular penicillin, an inexpensive antibiotic on the essential medicine list of nations all over the world, effectively cures infection and prevents congenital syphilis. In fact, at a cost of $11–15 per disability adjusted life year (DALY) averted, maternal syphilis screening and treatment is among the most cost-effective public health interventions in existence. Yet implementation of this basic public health intervention is sporadic in countries with highest congenital syphilis burden. We discuss the global burden of this devastating disease, current progress and ongoing challenges for its elimination in countries with highest prevalence, and next steps in ensuring a world free of preventable perinatal deaths caused by syphilis

Dynamics of Neisseria gonorrhoeae transmission among female sex workers and clients: A mathematical modeling study.

BACKGROUND This study aimed to examine the transmission dynamics of Neisseria gonorrhoeae (NG) in heterosexual sex work networks (HSWNs) and the impact of variation in sexual behavior and interventions on NG epidemiology. METHODS The study employed an individual-based mathematical model to simulate NG transmission dynamics in sexual networks involving female sex workers (FSWs) and their clients, primarily focusing on the Middle East and North Africa region. A deterministic model was also used to describe NG transmission from clients to their spouses. RESULTS NG epidemiology in HSWNs displays two distinct patterns. In the common low-partner-number HSWNs, a significant proportion of NG incidence occurs among FSWs, with NG prevalence 13 times higher among FSWs than clients, and three times higher among clients than their spouses. Interventions substantially reduce incidence. Increasing condom use from 10 % to 50 % lowers NG prevalence among FSWs, clients, and their spouses from 12.2 % to 6.4 %, 1.2 % to 0.5 %, and 0.4 % to 0.2 %, respectively. Increasing symptomatic treatment coverage among FSWs from 0 % to 100 % decreases prevalence from 10.6 % to 4.5 %, 0.8 % to 0.4 %, and 0.3 % to 0.1 %, respectively. Increasing asymptomatic treatment coverage among FSWs from 0 % to 50 % decreases prevalence from 8.2 % to 0.4 %, 0.6 % to 0.1 %, and 0.2 % to 0.0 %, respectively, with very low prevalence when coverage exceeds 50 %. In high-partner-number HSWNs, prevalence among FSWs saturates at a high level, and the vast majority of incidence occurs among clients and their spouses, with a limited impact of incremental increases in interventions. CONCLUSION NG epidemiology in HSWNs is typically a "fragile epidemiology" that is responsive to a range of interventions even if the interventions are incremental, partially efficacious, and only applied to FSWs

Are DNA repair factors promising biomarkers for personalized therapy in gastric cancer?

Chronic inflammation is a driving force for gastric carcinogenesis. Reactive oxygen species (ROS) generated during the inflammatory process generates DNA damage that is processed through the DNA repair pathways. In this study, we profiled key DNA repair proteins (single-strand-selective monofunctional uracil-DNA glycosylase 1 [SMUG1], Flap endonuclease 1 [FEN1], X-ray repair cross-complementing gene 1 [XRCC1], and Ataxia telangiectasia mutated [ATM]) involved in ROS-induced oxidative DNA damage repair in gastric cancer and correlated to clinicopathological outcomes. High expression of SMUG1, FEN1, and XRCC1 correlated to high T-stage (T3/T4) (p-values: 0.001, 0.005, and 0.02, respectively). High expression of XRCC1 and FEN1 also correlated to lymph node-positive disease (p-values: 0.009 and 0.02, respectively). High expression of XRCC1, FEN1, and SMUG1 correlated with poor disease-specific survival (DSS) (p-values: 0.001, 0.006, and 0.05, respectively) and poor disease-free survival (DFS) (p-values: 0.001, 0.001, and 0.02, respectively). Low expression of ATM correlated to lymph node positivity (p=0.03), vascular invasion (p=0.05), and perineural invasion (p=0.005) and poor DFS (p=0.001) and poor DSS (p=0.003). In the multivariate Cox model, high XRCC1 and low ATM were independently associated with poor survival (p=0.008 and 0.011, respectively). Our observation supports the hypothesis that DNA repair factors are promising biomarkers for personalized therapy in gastric cancer. Antioxid. Redox Signal. 18, 2392–2398

Breast Cancer Risk Assessment and Primary Prevention Advice in Primary Care: A Systematic Review of Provider Attitudes and Routine Behaviours

From MDPI via Jisc Publications RouterHistory: accepted 2021-08-17, pub-electronic 2021-08-18Publication status: PublishedFunder: Manchester Cancer Research Centre; Grant(s): P122568 F07Implementing risk-stratified breast cancer screening is being considered internationally. It has been suggested that primary care will need to take a role in delivering this service, including risk assessment and provision of primary prevention advice. This systematic review aimed to assess the acceptability of these tasks to primary care providers. Five databases were searched up to July–August 2020, yielding 29 eligible studies, of which 27 were narratively synthesised. The review was pre-registered (PROSPERO: CRD42020197676). Primary care providers report frequently collecting breast cancer family history information, but rarely using quantitative tools integrating additional risk factors. Primary care providers reported high levels of discomfort and low confidence with respect to risk-reducing medications although very few reported doubts about the evidence base underpinning their use. Insufficient education/training and perceived discomfort conducting both tasks were notable barriers. Primary care providers are more likely to accept an increased role in breast cancer risk assessment than advising on risk-reducing medications. To realise the benefits of risk-based screening and prevention at a population level, primary care will need to proactively assess breast cancer risk and advise on risk-reducing medications. To facilitate this, adaptations to infrastructure such as integrated tools are necessary in addition to provision of education

Data quality and 30-day survival for out-of-hospital cardiac arrest in the UK out-of-hospital cardiac arrest registry: A data linkage study

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objectives The Out-of-Hospital Cardiac Arrest Outcomes (OHCAO) project aims to understand the epidemiology and outcomes of out-of-hospital cardiac arrest (OHCA) across the UK. This data linkage study is a subproject of OHCAO. The aim was to establish the feasibility of linking OHCAO data to National Health Service (NHS) patient demographic data and Office for National Statistics (ONS) date of death data held on the NHS Personal Demographics Service (PDS) database to improve OHCAO demographic data quality and enable analysis of 30-day survival from OHCA. Design and setting Data were collected from 1 January 2014 to 31 December 2014 as part of a prospective, observational study of OHCA attended by 10 English NHS Ambulance Services. 28 729 OHCA cases had resuscitation attempted by Emergency Medical Services and were included in the study. Data linkage was carried out using a data linkage service provided by NHS Digital, a national provider of health-related data. To assess data linkage feasibility a random sample of 3120 cases was selected. The sample was securely transferred to NHS Digital to be matched using OHCAO patient demographic data to return previously missing demographic data and provide ONS date of death data. Results A total of 2513 (80.5%) OHCAO cases were matched to patients in the NHS PDS database. Using the linkage process, missing demographic data were retrieved for 1636 (72.7%) out of 2249 OHCAO cases that had previously incomplete demographic data. Returned ONS date of death data allowed analysis of 30-day survival status. The results showed a 30-day survival rate of 9.3%, reducing unknown survival status from 46.1% to 8.5%. Conclusions In this sample, data linkage between the OHCAO registry and NHS PDS database was shown to be feasible, improving demographic data quality and allowing analysis of 30-day survival status

Host Biomarkers Are Associated With Response to Therapy and Long-Term Mortality in Pediatric Severe Malaria.

Background. Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions.Methods. This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria. One hundred eighty children aged 1–10 years were enrolled at Jinja Regional Referral Hospital in Uganda and followed for up to 6 months.Results. There were no differences between the 2 study arms in the rate of biomarker recovery. Median levels of Ang-2, CXCL10, and sFlt-1 were higher at admission in children who died in-hospital (n = 15 of 180; P < .001, P = .027, and P = .004, respectively). Elevated levels of Ang-2, sTREM-1, CXCL10, and sICAM-1 were associated with prolonged clinical recovery times in survivors. The Ang-2 levels were also associated with postdischarge mortality (P < .0001). No biomarkers were associated with neurodisability.Conclusions. Persistent endothelial activation and dysfunction predict survival in children admitted with severe malaria

Prospects for progress on health inequalities in England in the post-primary care trust era : professional views on challenges, risks and opportunities

Background - Addressing health inequalities remains a prominent policy objective of the current UK government, but current NHS reforms involve a significant shift in roles and responsibilities. Clinicians are now placed at the heart of healthcare commissioning through which significant inequalities in access, uptake and impact of healthcare services must be addressed. Questions arise as to whether these new arrangements will help or hinder progress on health inequalities. This paper explores the perspectives of experienced healthcare professionals working within the commissioning arena; many of whom are likely to remain key actors in this unfolding scenario. Methods - Semi-structured interviews were conducted with 42 professionals involved with health and social care commissioning at national and local levels. These included representatives from the Department of Health, Primary Care Trusts, Strategic Health Authorities, Local Authorities, and third sector organisations. Results - In general, respondents lamented the lack of progress on health inequalities during the PCT commissioning era, where strong policy had not resulted in measurable improvements. However, there was concern that GP-led commissioning will fare little better, particularly in a time of reduced spending. Specific concerns centred on: reduced commitment to a health inequalities agenda; inadequate skills and loss of expertise; and weakened partnership working and engagement. There were more mixed opinions as to whether GP commissioners would be better able than their predecessors to challenge large provider trusts and shift spend towards prevention and early intervention, and whether GPs’ clinical experience would support commissioning action on inequalities. Though largely pessimistic, respondents highlighted some opportunities, including the potential for greater accountability of healthcare commissioners to the public and more influential needs assessments via emergent Health & Wellbeing Boards. Conclusions - There is doubt about the ability of GP commissioners to take clearer action on health inequalities than PCTs have historically achieved. Key actors expect the contribution from commissioning to address health inequalities to become even more piecemeal in the new arrangements, as it will be dependent upon the interest and agency of particular individuals within the new commissioning groups to engage and influence a wider range of stakeholders.</p

Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele

Failure of elimination of amyloid-β (Aβ) from the brain and vasculature appears to be a key factor in the etiology of sporadic Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). In addition to age, possession of an apolipoprotein E (APOE) ε4 allele is a strong risk factor for the development of sporadic AD. The present study tested the hypothesis that possession of the APOE ε4 allele is associated with disruption of perivascular drainage of Aβ from the brain and with changes in cerebrovascular basement membrane protein levels. Targeted replacement (TR) mice expressing the human APOE3 (TRE3) or APOE4 (TRE4) genes and wildtype mice received intracerebral injections of human Aβ40. Aβ40 aggregated in peri-arterial drainage pathways in TRE4 mice, but not in TRE3 or wildtype mice. The number of Aβ deposits was significantly higher in the hippocampi of TRE4 mice than in the TRE3 mice, at both 3- and 16-months of age, suggesting that clearance of Aβ was disrupted in the brains of TRE4 mice. Immunocytochemical and Western blot analysis of vascular basement membrane proteins demonstrated significantly raised levels of collagen IV in 3-month-old TRE4 mice compared with TRE3 and wild type mice. In 16-month-old mice, collagen IV and laminin levels were unchanged between wild type and TRE3 mice, but were lower in TRE4 mice. The results of this study suggest that APOE4 may increase the risk for AD through disruption and impedance of perivascular drainage of soluble Aβ from the brain. This effect may be mediated, in part, by changes in age-related expression of basement membrane proteins in the cerebral vasculature