Evaluation of the Call for a Kit intervention to increase bowel cancer screening uptake in Lancashire, England

Objective: To evaluate the ‘Call for a Kit’ health promotion intervention that was initiated in Lancashire, England to improve bowel cancer screening uptake. Methods: Within the intervention, screening non-responders are called and invited to attend a consultation with a health promotion team member at their primary care practice. In this audit, we analysed the proportion of those contacted who attended the in-person clinic versus those who received a phone consultation, the number returning a test kit from in-person versus phone consultations, and the extent to which test kit return was moderated by sociodemographic characteristics. Results: In 2019, 68 practices participated in the intervention which led to 10,772 individuals being contacted; 2464 accepted the invitation to an in-person consultation, of whom 1943 attended. A further 1065 agreed to and attended a consultation over the phone. The 3008 consultations resulted in 2890 test kits being ordered, of which 1608 (55.6%) were returned. The intervention therefore yielded a 14.9% response rate in the total cohort; 71.5% of test kits came from individuals attending the in-person consultation. Women and those registered with a practice in socioeconomically deprived areas were less likely to return the test kit. Individuals with a black, mixed or a non-Indian/Pakistani Asian ethnic background were significantly more likely to accept the offer of an in-person consultation and return the test kit. Conclusion: Our analysis demonstrated the strong likelihood of people returning a test kit after an in-person appointment but also the usefulness of using phone consultations as a safety net for people unable or unwilling to attend in-person clinics

Evaluation of the Call for a Kit intervention to increase bowel cancer screening uptake in Lancashire, England

Objective To evaluate the ‘Call for a Kit’ health promotion intervention that was initiated in Lancashire, England to improve bowel cancer screening uptake. Methods Within the intervention, screening non-responders are called and invited to attend a consultation with a health promotion team member at their primary care practice. In this audit, we analysed the proportion of those contacted who attended the in-person clinic versus those who received a phone consultation, the number returning a test kit from in-person versus phone consultations, and the extent to which test kit return was moderated by sociodemographic characteristics. Results In 2019, 68 practices participated in the intervention which led to 10,772 individuals being contacted; 2464 accepted the invitation to an in-person consultation, of whom 1943 attended. A further 1065 agreed to and attended a consultation over the phone. The 3008 consultations resulted in 2890 test kits being ordered, of which 1608 (55.6%) were returned. The intervention therefore yielded a 14.9% response rate in the total cohort; 71.5% of test kits came from individuals attending the in-person consultation. Women and those registered with a practice in socioeconomically deprived areas were less likely to return the test kit. Individuals with a black, mixed or a non-Indian/Pakistani Asian ethnic background were significantly more likely to accept the offer of an in-person consultation and return the test kit. Conclusion Our analysis demonstrated the strong likelihood of people returning a test kit after an in-person appointment but also the usefulness of using phone consultations as a safety net for people unable or unwilling to attend in-person clinics.Output Status: Forthcoming/Available Onlin

Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.

BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .)

Special article : Quarterly Economic Commentary: Volume 10-18

The Fraser ofAllander Institute has, since its inception, sought to promote debate and research into the Scottish economy. One way in which we have done this is to publish, every quarter, a collection of views and results from those who conduct research in this area. In the current volume J McGilvray presents a review of the responses to the government's consultation paper on water and sewerage in Scotland. In previous volumes, a large number of articles appeared and addressed a wide variety of subjects. Articles which appeared in volumes 10 - 18 are documented on the following pages and those wishing to obtain backcopies can do so, through the Institute, by contacting the editor. Articles appear by volume & number and are labelled according to whether they were a Feature Article (FA), Briefing Paper (BP), Economic Perspective (EP) or a Special Article (SA

Improving early childhood care and development, HIV testing, treatment and support, and nutrition in Mokhotlong, Lesotho: study protocol for a cluster randomized controlled trial

Background Since 1990, the lives of 48 million children under the age of 5 have been saved because of increased investments in reducing child mortality. However, despite these unprecedented gains, more than 200 million children in low and middle income countries (LMIC) cannot meet their developmental potential due to poverty, poor health and nutrition, and lack of necessary stimulation and care. Lesotho has high levels of poverty, HIV and malnutrition, all of which affect child development outcomes. There is a unique opportunity to address these complex issues through the widespread network of informal preschools in rural villages in the country, which provide a setting for inclusive, integrated Early Childhood Care and Development (ECCD), HIV and nutrition interventions. Methods We are conducting a cluster randomised controlled trial in Mokhotlong district, Lesotho, to evaluate a newly developed community-based intervention programme to integrate HIV testing and treatment services, ECCD, and nutrition education for caregivers with children aged 1-5 years living in rural villages. Caregivers and their children are randomly assigned by village to intervention or control condition. We select, train, and supervise community health workers recruited to implement the intervention, which consists of nine group-based sessions with caregivers and children over 12 weeks (eight weekly sessions, and a ninth top up session one month later), followed by a locally hosted community health outreach day event. Group-based sessions focus on using early dialogic booksharing to promote cognitive development and caregiver-child interaction, health-related messages, including motivation for HIV-testing and treatment uptake for young children, and locally appropriate nutrition education. All children aged 1-5 years and their primary caregivers living in study villages are eligible for participation. Caregivers and their children will be interviewed and assessed at baseline, immediately after completion of the intervention, and 12 months post intervention. Discussion This study provides a unique opportunity to assess the potential of an integrated early childhood development intervention to prevent or mitigate developmental delays in children living in a context of extreme poverty and high HIV rates in rural Lesotho. This paper presents the intervention content and research protocol for the study

Preconception Care Between Pregnancies: The Content of Internatal Care

For more than two decades, prenatal care has been a cornerstone of our nation’s strategy for improving pregnancy outcomes. In recent years, however, a growing recognition of the limits of prenatal care and the importance of maternal health before pregnancy has drawn increasing attention to preconception and internatal care. Internatal care refers to a package of healthcare and ancillary services provided to a woman and her family from the birth of one child to the birth of her next child. For healthy mothers, internatal care offers an opportunity for wellness promotion between pregnancies. For high-risk mothers, internatal care provides strategies for risk reduction before their next pregnancy. In this paper we begin to define the contents of internatal care. The core components of internatal care consist of risk assessment, health promotion, clinical and psychosocial interventions. We identified several priority areas, such as FINDS (family violence, infections, nutrition, depression, and stress) for risk assessment or BBEEFF (breastfeeding, back-to-sleep, exercise, exposures, family planning and folate) for health promotion. Women with chronic health conditions such as hypertension, diabetes, or weight problems should receive on-going care per clinical guidelines for their evaluation, treatment, and follow-up during the internatal period. For women with prior adverse outcomes such as preterm delivery, we propose an internatal care model based on known etiologic pathways, with the goal of preventing recurrence by addressing these biobehavioral pathways prior to the next pregnancy. We suggest enhancing service integration for women and families, including possibly care coordination and home visitation for selected high-risk women. The primary aim of this paper is to start a dialogue on the content of internatal care

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden