Interventions to promote patient utilisation of cardiac rehabilitation

Background: International clinical practice guidelines routinely recommend that cardiac patients participate in rehabilitation programmes for comprehensive secondary prevention. However, data show that only a small proportion of these patients utilise rehabilitation. Objectives: First, to assess interventions provided to increase patient enrolment in, adherence to, and completion of cardiac rehabilitation. Second, to assess intervention costs and associated harms, as well as interventions intended to promote equitable CR utilisation in vulnerable patient subpopulations. Search methods: Review authors performed a search on 10 July 2018, to identify studies published since publication of the previous systematic review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); the National Health Service (NHS) Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)), in the Cochrane Library (Wiley); MEDLINE (Ovid); Embase (Elsevier); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); and Conference Proceedings Citation Index ‐ Science (CPCI‐S) on Web of Science (Clarivate Analytics). We checked the reference lists of relevant systematic reviews for additional studies and also searched two clinical trial registers. We applied no language restrictions. Selection criteria: We included randomised controlled trials (RCTs) in adults with myocardial infarction, with angina, undergoing coronary artery bypass graft surgery or percutaneous coronary intervention, or with heart failure who were eligible for cardiac rehabilitation. Interventions had to aim to increase utilisation of comprehensive phase II cardiac rehabilitation. We included only studies that measured one or more of our primary outcomes. Secondary outcomes were harms and costs, and we focused on equity. Data collection and analysis: Two review authors independently screened the titles and abstracts of all identified references for eligibility, and we obtained full papers of potentially relevant trials. Two review authors independently considered these trials for inclusion, assessed included studies for risk of bias, and extracted trial data independently. We resolved disagreements through consultation with a third review author. We performed random‐effects meta‐regression for each outcome and explored prespecified study characteristics. Main results: Overall, we included 26 studies with 5299 participants (29 comparisons). Participants were primarily male (64.2%). Ten (38.5%) studies included patients with heart failure. We assessed most studies as having low or unclear risk of bias. Sixteen studies (3164 participants) reported interventions to improve enrolment in cardiac rehabilitation, 11 studies (2319 participants) reported interventions to improve adherence to cardiac rehabilitation, and seven studies (1567 participants) reported interventions to increase programme completion. Researchers tested a variety of interventions to increase utilisation of cardiac rehabilitation. In many studies, this consisted of contacts made by a healthcare provider during or shortly after an acute care hospitalisation. Low‐quality evidence shows an effect of interventions on increasing programme enrolment (19 comparisons; risk ratio (RR) 1.27, 95% confidence interval (CI) 1.13 to 1.42). Meta‐regression revealed that the intervention deliverer (nurse or allied healthcare provider; P = 0.02) and the delivery format (face‐to‐face; P = 0.01) were influential in increasing enrolment. Low‐quality evidence shows interventions to increase adherence were effective (nine comparisons; standardised mean difference (SMD) 0.38, 95% CI 0.20 to 0.55), particularly when they were delivered remotely, such as in home‐based programs (SMD 0.56, 95% CI 0.37 to 0.76). Moderate‐quality evidence shows interventions to increase programme completion were also effective (eight comparisons; RR 1.13, 95% CI 1.02 to 1.25), but those applied in multi‐centre studies were less effective than those given in single‐centre studies, leading to questions regarding generalisability. A moderate level of statistical heterogeneity across intervention studies reflects heterogeneity in intervention approaches. There was no evidence of small‐study bias for enrolment (insufficient studies to test for this in the other outcomes). With regard to secondary outcomes, no studies reported on harms associated with the interventions. Only two studies reported costs. In terms of equity, trialists tested interventions designed to improve utilisation among women and older patients. Evidence is insufficient for quantitative assessment of whether women‐tailored programmes were associated with increased utilisation, and studies that assess motivating women are needed. For older participants, again while quantitative assessment could not be undertaken, peer navigation may improve enrolment. Authors' conclusions: Interventions may increase cardiac rehabilitation enrolment, adherence and completion; however the quality of evidence was low to moderate due to heterogeneity of the interventions used, among other factors. Effects on enrolment were larger in studies targeting healthcare providers, training nurses, or allied healthcare providers to intervene face‐to‐face; effects on adherence were larger in studies that tested remote interventions. More research is needed, particularly to discover the best ways to increase programme completion

Cochrane corner:increasing patient utilisation of cardiac rehabilitation

No abstract available

What empirical research has been undertaken on the ethics of clinical research in India?:A systematic scoping review and narrative synthesis

IntroductionThe post-2005 rise in clinical trials and clinical research conducted in India was accompanied by frequent reports of unethical practices, leading to a series of regulatory changes. We conducted a systematic scoping review to obtain an overview of empirical research pertaining to the ethics of clinical trials/research in India.MethodsOur search strategy combined terms related to ethics/bioethics, informed consent, clinical trials/research and India, across nine databases, up to November 2019. Peer-reviewed research exploring ethical aspects of clinical trials/research in India with any stakeholder groups was included. We developed an evidence map, undertook a narrative synthesis and identified research gaps. A consultation exercise with stakeholders in India helped contextualise the review and identify additional research priorities.ResultsTitles/Abstracts of 9699 articles were screened, full text of 282 obtained and 80 were included. Research on the ethics of clinical trials/research covered a wide range of topics, often conducted with little to no funding. Studies predominantly examined what lay (patients/public) and professional participants (eg, healthcare staff/students/faculty) know about topics such as research ethics or understand from the information given to obtain their consent for research participation. Easily accessible groups, namely ethics committee members and healthcare students were frequently researched. Research gaps included developing a better understanding of the recruitment-informed consent process, including the doctor-patient interaction, in multiple contexts and exploring issues of equity and justice in clinical trials/research.ConclusionThe review demonstrates that while a wide range of topics have been studied in India, the focus is largely on assessing knowledge levels across different population groups. This is a useful starting point, but fundamental questions remain unanswered about informed consent processes and broader issues of inequity that pervade the clinical trials/research landscape. A priority-setting exercise and appropriate funding mechanisms to support researchers in India would help improve the clinical trials/research ecosystem

Bimodal distribution and set point HBV DNA viral loads in chronic infection:retrospective analysis of cohorts from the UK and South Africa

CITATION: Downs, L. O. 2020. Bimodal distribution and set point HBV DNA viral loads in chronic infection : retrospective analysis of cohorts from the UK and South Africa. Wellcome Open Research, 14(5):113, doi: 10.12688/wellcomeopenres.15941.2.The original publication is available at: https://pubmed.ncbi.nlm.nih.govENGLISH ABSTRACT: Hepatitis B virus (HBV) viral load (VL) is used as a biomarker to assess risk of disease progression, and to determine eligibility for treatment. While there is a well recognised association between VL and the expression of the viral e-antigen protein, the distributions of VL at a population level are not well described. We here present cross-sectional, observational HBV VL data from two large population cohorts in the UK and in South Africa, demonstrating a consistent bimodal distribution. The right skewed distribution and low median viral loads are different from the left-skew and higher viraemia in seen in HIV and hepatitis C virus (HCV) cohorts in the same settings. Using longitudinal data, we present evidence for a stable 'set-point' VL in peripheral blood during chronic HBV infection. These results are important to underpin improved understanding of HBV biology, to inform approaches to viral sequencing, and to plan public health interventions.Publisher's versio

Bimodal distribution and set point HBV DNA viral loads in chronic infection:retrospective analysis of cohorts from the UK and South Africa

CITATION: Downs, L. O. 2020. Bimodal distribution and set point HBV DNA viral loads in chronic infection : retrospective analysis of cohorts from the UK and South Africa. Wellcome Open Research, 14(5):113, doi: 10.12688/wellcomeopenres.15941.2.The original publication is available at: https://pubmed.ncbi.nlm.nih.govENGLISH ABSTRACT: Hepatitis B virus (HBV) viral load (VL) is used as a biomarker to assess risk of disease progression, and to determine eligibility for treatment. While there is a well recognised association between VL and the expression of the viral e-antigen protein, the distributions of VL at a population level are not well described. We here present cross-sectional, observational HBV VL data from two large population cohorts in the UK and in South Africa, demonstrating a consistent bimodal distribution. The right skewed distribution and low median viral loads are different from the left-skew and higher viraemia in seen in HIV and hepatitis C virus (HCV) cohorts in the same settings. Using longitudinal data, we present evidence for a stable 'set-point' VL in peripheral blood during chronic HBV infection. These results are important to underpin improved understanding of HBV biology, to inform approaches to viral sequencing, and to plan public health interventions.Publisher's versio

Liver transplantation in ornithine transcarbamylase deficiency: A retrospective multicentre cohort study

Ornithine transcarbamylase deficiency (OTCD) is an X-linked defect of ureagenesis and the most common urea cycle disorder. Patients present with hyperammonemia causing neurological symptoms, which can lead to coma and death. Liver transplantation (LT) is the only curative therapy, but has several limitations including organ shortage, significant morbidity and requirement of lifelong immunosuppression. This study aims to identify the characteristics and outcomes of patients who underwent LT for OTCD. // We conducted a retrospective study for OTCD patients from 5 UK centres receiving LT in 3 transplantation centres between 2010 and 2022. Patients' demographics, family history, initial presentation, age at LT, graft type and pre- and post-LT clinical, metabolic, and neurocognitive profile were collected from medical records.// A total of 20 OTCD patients (11 males, 9 females) were enrolled in this study. 6/20 had neonatal and 14/20 late-onset presentation. 2/20 patients had positive family history for OTCD and one of them was diagnosed antenatally and received prospective treatment. All patients were managed with standard of care based on protein-restricted diet, ammonia scavengers and supplementation with arginine and/or citrulline before LT. 15/20 patients had neurodevelopmental problems before LT. The indication for LT was presence (or family history) of recurrent metabolic decompensations occurring despite standard medical therapy leading to neurodisability and quality of life impairment. Median age at LT was 10.5 months (6–24) and 66 months (35–156) in neonatal and late onset patients, respectively. 15/20 patients had deceased donor LT (DDLT) and 5/20 had living related donor LT (LDLT). Overall survival was 95% with one patient dying 6 h after LT. 13/20 had complications after LT and 2/20 patients required re-transplantation. All patients discontinued dietary restriction and ammonia scavengers after LT and remained metabolically stable. Patients who had neurodevelopmental problems before LT persisted to have difficulties after LT. 1/5 patients who was reported to have normal neurodevelopment before LT developed behavioural problems after LT, while the remaining 4 maintained their abilities without any reported issues. // LT was found to be effective in correcting the metabolic defect, eliminates the risk of hyperammonemia and prolongs patients' survival

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

A randomized controlled trial to assess the clinical and cost effectiveness of a nurse-led Antenatal Asthma Management Service in South Australia (AAMS study)

Background: Pregnancy presents a unique situation for the management of asthma as it can alter the course of asthma severity and its treatment, which in turn can affect pregnancy outcomes. Despite awareness of the substantial adverse effects associated with asthma during pregnancy, little has been done to improve its management and reduce associated perinatal morbidity and mortality. The aim of this randomized controlled trial is to evaluate the clinical and cost effectiveness of an Antenatal Asthma Management Service. Methods/design: Design: Multicentre, randomized controlled trial. Inclusion criteria: Women with physician diagnosed asthma, which is not currently in remission, who are less than 20 weeks gestation with a singleton pregnancy and do not have a chronic medical condition. Trial entry and randomization: Eligible women with asthma, stratified by treatment site, disease severity and parity, will be randomized into either the ‘Standard Care Group’ or the ‘Intervention Group’. Study groups: Both groups will be followed prospectively throughout pregnancy. Women in the ‘Standard Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive additional care through the nurse-led Antenatal Asthma Management Service, based in the antenatal outpatient clinic. Women will receive asthma education with a full assessment of their asthma at 18, 24, 30 and 36 weeks gestation. Each antenatal visit will include a 60 min session where asthma management skills are assessed including: medication adherence and knowledge, inhaler device technique, recognition of asthma deterioration and possession of a written asthma action plan. Furthermore, subjects will receive education about asthma control and management skills including trigger avoidance and smoking cessation counseling when appropriate. Primary study outcome: Asthma exacerbations during pregnancy. Sample size: A sample size of 378 women will be sufficient to show an absolute reduction in asthma exacerbations during pregnancy of 20% (alpha 0.05 two-tailed, 90% power, 5% loss to follow-up). Discussion: The integration of an asthma education program within the antenatal clinic setting has the significant potential to improve the participation of pregnant women in the self-management of their asthma, reduce asthma exacerbations and improve perinatal health outcomes.Luke E Grzeskowiak, Gustaaf Dekker, Karen Rivers, Kate Roberts-Thomson, Anil Roy, Brian Smith, Jeffery Bowden, Robert Bryce, Michael Davies, Justin Beilby, Anne Wilson, Philippa Middleton, Richard Ruffin, Jonathan Karnon, Vicki L Clifton and for the AAMS study grou

Deletion of Genes Implicated in Protecting the Integrity of Male Germ Cells Has Differential Effects on the Incidence of DNA Breaks and Germ Cell Loss

Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1), MSH2 (MutS homolog 2, involved in mismatch repair pathway), and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage).We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility