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Aims: Automated retinal image analysis using Artificial Intelligence (AI) can detect diabetic retinopathy as accurately as human graders, but it is not yet licensed in the NHS Diabetic Eye Screening Programme (DESP) in England. This study aims to assess perceptions of People Living with Diabetes (PLD) and Healthcare Practitioners (HCP) towards AI's introduction in DESP., Methods: Two online surveys were co-developed with PLD and HCP from a diverse DESP in North East London. Surveys were validated through interviews across three centres and distributed via DESP centres, charities, and the British Association of Retinal Screeners. A coding framework was used to analyse free-text responses., Results: 387 (24%) PLD and 98 (37%) HCP provided comments. Themes included trust, workforce impact, the patient-practitioner relationship, AI implementation challenges, and inequalities. Both groups agreed AI in DESP was inevitable, would improve efficiency, and save costs. Concerns included job losses, data security, and AI decision safety. A common misconception was that AI would directly affect patient interactions, though it only processes retinal images., Conclusions: Limited understanding of AI was a barrier to acceptance. Educating diverse PLD groups and HCP about AI's accuracy and reliability is crucial to building trust and facilitating its integration into screening practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: While people with type 2 diabetes (T2D) are more susceptible to infections, studies potentially underestimate the true burden of infection-related mortality since they rely on clinical coding systems primarily structured by body system, and by only focusing on underlying cause. This study examined cause-specific mortality in people with T2D compared to the general population during 2015-2019, focusing on infections., Methods: 509,403 people aged 41-90 years with T2D alive on 1/1/2015 in Clinical Practice Research Datalink were matched to 976,431 without diabetes on age, sex, and ethnicity. Recorded underlying cause of death was identified through national linked mortality data; infection-related deaths were counted across all ICD-10 (10th revision of the International Classification of Diseases) chapters, not just infection chapters A00-B99. All-cause and cause-specific hazard ratios (HR) for mortality during 2015-2019 compared people with T2D to people without diabetes and were estimated using Cox models adjusting for region. Additional analyses for sepsis related mortality considered the impact of including any mention of sepsis on the death certificate., Findings: 85,367/509,403 (16.8%) people with T2D died during 2015-2019 compared to 106,824/976,431 (10.9%) of people without diabetes of the same sex, age and ethnicity. All infections (11,128/85,367 = 13.0%) represented the third highest underlying cause of death among people with T2D after cardiovascular disease and cancer; a much higher contribution than counting only from specific infection chapters (1046/85,367 = 1.2%). The HR for people with T2D vs non-diabetes for all infection mortality (1.82, 95% CI 1.78-1.86) was higher than that estimated for all-cause (HR = 1.65, 95% CI 1.64-1.66). The estimated mortality rate associated with sepsis among people with T2D was highly dependent on whether any mention was included (2.2 per 1000 person-years) or only underlying cause (0.2 per 1000 person-years); but the HR for people with T2D vs non-diabetes was similar (any mention HR = 2.26, 95% CI 2.19-2.34 vs underlying cause only HR = 2.52, 95% CI 2.27-2.80)., Interpretation: People with T2D die from infections at a higher rate than similar people without diabetes, and the overall burden is greater than previously reported. Routine statistics concentrating on underlying cause of death may somewhat under-estimate the importance of infections as causes of death among people with T2D. These findings emphasise the potential importance of awareness, earlier diagnosis and treatment of infections to prevent premature deaths., Funding: National Institute for Health and Care Research., Competing Interests: NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work., (© 2024 The Author(s).)

Background: Limited evidence suggests elevated risks of cardiovascular disease (CVD) among people diagnosed with tuberculosis (TB) disease, though studies have not adjusted for pre-existing CVD risk. We carried out a cohort study using two separate datasets, estimating CVD incidence in people with TB versus those without., Methods: Using data from the United States (Veterans Health Administration) and the United Kingdom (Clinical Practice Research Datalink) for 2000-2020 we matched adults with incident TB disease and no CVD history 2-years before TB diagnosis (US n=2,121; UK n=15,820) with up to 10 people without TB on the basis of age, sex, race/ethnicity and healthcare practice. Participants were followed beginning 2-years before TB diagnosis and for 2-years subsequently. The acute period was defined as 3-months before/after TB diagnosis. TB, CVD and covariates were identified from electronic routinely collected data (primary and secondary care; mortality). Poisson models estimated incident rate ratios (IRR) for CVD events in people with TB compared to those without., Results: CVD incidence was consistently higher in people with TB, including during the baseline period (pre-TB) and particularly in the acute period: IRRs were US 3.5 (95% Confidence Interval 2.7-4.4), UK 2.7 (2.2-3.3). Rate Ratios remained high after adjusting for differences in pre-existing CVD risk: US 3.2 (2.2-4.4), UK 1.6 (1.2-2.1)., Conclusion: Increased CVD incidence was observed in people with TB versus those without, especially within months of TB diagnosis, persistent after adjustment for differences in pre-existing risk. Enhancing CVD screening and risk management may improve long-term outcomes in people with TB., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: People with type 1 diabetes (T1D) have raised infection rates compared to those without, but how these risks vary by age, sex and ethnicity, or by glycated haemoglobin (HbA1c), remain uncertain., Methods: 33,829 patients with T1D in Clinical Practice Research Datalink on 01/01/2015 were age-sex-ethnicity matched to two non-diabetes patients. Infections were collated from primary care and linked hospitalisation records during 2015-2019, and incidence rate ratios (IRRs) were estimated versus non-diabetes. For 26,096 people with T1D, with ≥3 HbA1c measurements in 2012-2014, mean and coefficient of variation were estimated, and compared across percentiles., Results: People with T1D had increased risk for infections presenting in primary care (IRR = 1.81, 95%CI 1.77-1.85) and hospitalisations (IRR = 3.37, 3.21-3.53) compared to non-diabetes, slightly attenuated after further adjustment. Younger ages and non-White ethnicities had greater relative risks, potentially explained by higher HbA1c mean and variability amongst people with T1D within these sub-groups. Both mean HbA1c and greater variability were strongly associated with infection risks, but the greatest associations were at the highest mean levels (hospitalisations IRR = 4.09, 3.64-4.59) for >97 versus ≤53 mmol/mol., Conclusions: Infections are a significant health burden in T1D. Improved glycaemic control may reduce infection risks, while prompter infection treatments may reduce hospital admissions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The English National Health Service (NHS) Diabetic Eye Screening Programme (DESP) performs around 2.3 million eye screening appointments annually, generating approximately 13 million retinal images that are graded by humans for the presence or severity of diabetic retinopathy. Previous research has shown that automated retinal image analysis systems, including artificial intelligence (AI), can identify images with no disease from those with diabetic retinopathy as safely and effectively as human graders, and could significantly reduce the workload for human graders. Some algorithms can also determine the level of severity of the retinopathy with similar performance to humans. There is a need to examine perceptions and concerns surrounding AI-assisted eye-screening among people living with diabetes and NHS staff, if AI was to be introduced into the DESP, to identify factors that may influence acceptance of this technology., Methods and Analysis: People living with diabetes and staff from the North East London (NEL) NHS DESP were invited to participate in two respective focus groups to codesign two online surveys exploring their perceptions and concerns around the potential introduction of AI-assisted screening.Focus group participants were representative of the local population in terms of ages and ethnicity. Participants' feedback was taken into consideration to update surveys which were circulated for further feedback. Surveys will be piloted at the NEL DESP and followed by semistructured interviews to assess accessibility, usability and to validate the surveys.Validated surveys will be distributed by other NHS DESP sites, and also via patient groups on social media, relevant charities and the British Association of Retinal Screeners. Post-survey evaluative interviews will be undertaken among those who consent to participate in further research., Ethics and Dissemination: Ethical approval has been obtained by the NHS Research Ethics Committee (IRAS ID: 316631). Survey results will be shared and discussed with focus groups to facilitate preparation of findings for publication and to inform codesign of outreach activities to address concerns and perceptions identified., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: People living with type 2 diabetes (T2D) are at higher infection risk, but it is unknown how this risk varies by ethnicity or whether the risk is similarly observed in people with nondiabetic hyperglycemia ("prediabetes")., Research Design and Methods: We included 527,151 patients in England with T2D and 273,216 with prediabetes, aged 18-90, and alive on 1 January 2015 on the Clinical Practice Research Datalink. Each was matched to two patients without diabetes or prediabetes on age, sex, and ethnic group. Infections during 2015-2019 were collated from primary care and linked hospitalization records. Infection incidence rate ratios (IRRs) for those with prediabetes or T2D were estimated, unadjusted and adjusted for confounders., Results: People with T2D had increased risk for infections presenting in primary care (IRR 1.51, 95% CI 1.51-1.52) and hospitalizations (IRR 1.91, 1.90-1.93). This was broadly consistent overall within each ethnic group, although younger White T2D patients (age <50) experienced a greater relative risk. Adjustment for socioeconomic deprivation, smoking, and comorbidity attenuated associations, but IRRs remained similar by ethnicity. For prediabetes, a significant but smaller risk was observed (primary care IRR 1.35, 95% CI 1.34-1.36; hospitalization IRR 1.33, 1.31-1.35). These were similar within each ethnicity for primary care infections, but less consistent for infection-related hospitalizations., Conclusions: The elevated infection risk for people with T2D appears similar for different ethnic groups and is also seen in people with prediabetes. Infections are a substantial cause of ill-health and health service use for people with prediabetes and T2D. This has public health implications with rising prediabetes and diabetes prevalence., (© 2023 by the American Diabetes Association.)

Background: People with neuromuscular disease (NMD) experience a broader range of chronic diseases and health symptoms compared to the general population. However, no comprehensive analysis has directly quantified this to our knowledge., Methods: We used a large UK primary care database (Clinical Practice Research Datalink) to compare the prevalence of chronic diseases and other health conditions, including recent infections between 23,876 patients with NMD ever recorded by 2019 compared to 95,295 age-sex-practice matched patients without NMD. Modified Poisson regression estimated Prevalence Ratios (PR) to summarise the presence of the disease/condition ever (or for infections in 2018) in NMD patients versus non-NMD patients., Results: Patients with NMD had significantly higher rates for 16 of the 18 conditions routinely recorded in the primary care Quality and Outcomes Framework (QOF). Approximately 1-in-10 adults with NMD had ≥4 conditions recorded (PR = 1.39, 95%CI 1.33-1.45). Disparities were more pronounced at younger ages (18-49). For other (non-QOF) health conditions, significantly higher recorded levels were observed for rarer events (pulmonary embolism PR = 1.96 95%CI 1.76-2.18, hip fractures PR = 1.65 95%CI 1.47-1.85) as well as for more common primary care conditions (constipation PR = 1.52 95%CI 1.46-1.57, incontinence PR = 1.52 95%CI 1.44-1.60). The greatest co-morbidity burden was in patients with a myotonic disorder. Approximately 1-in-6 (17.1%) NMD patients had an infection recorded in the preceding year, with the risk of being hospitalised with an infection nearly double (PR = 1.92, 95%CI 1.79-2.07) compared to non-NMD patients., Conclusion: The burden of chronic co-morbidity among patients with NMD is extremely high compared to the general population, and they are also more likely to present in primary and secondary care for acute events such as infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Carey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Adequate sleep duration is necessary for many aspects of child health, development, and well-being, yet sleep durations for children are declining, and effective strategies to increase sleep in healthy children remain to be elucidated., Objective: To determine whether nonpharmaceutical interventions to improve sleep duration in healthy children are effective and to identify the key components of these interventions., Data Sources: CENTRAL, MEDLINE, Embase, PsycINFO, Web of Science Core collection, ClinicalTrials.gov, and WHO trials databases were searched from inception to November 15, 2021., Study Selection: Randomized clinical trials of interventions to improve sleep duration in healthy children were independently screened by 2 researchers. A total of 28 478 studies were identified., Data Extraction and Synthesis: Data were processed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline. Random-effects meta-analytic models were used to estimate pooled effect sizes., Main Outcomes and Measures: Difference in sleep duration, measured in minutes., Results: A total of 13 539 child participants from 45 randomized clinical trials were included. Of these, 6897 (50.9%) were in the intervention group and 6642 (49.1%) in the control group, and the mean age ranged from 18 months to 19 years. Pooled results indicate that sleep interventions were associated with 10.5 minutes (95% CI, 5.6-15.4) longer nocturnal sleep duration. There was substantial variation between trials. Sources of variation that were not associated with the study effect size included age group, whether the population was identified as having a sleep problem or being at a socioeconomic disadvantage (eg, coming from a low-income family or area), method of assessment of sleep duration (objective vs subjective), location of intervention delivery (home vs school), whether interventions were delivered in person or used parental involvement, whether behavioral theory was used, environmental change, or had greater or lower intensity. Interventions that included earlier bedtimes were associated with a 47-minute sleep extension (95% CI, 18.9-75.0; 3 trials) compared with remaining studies (7.4 minutes; 95% CI, 2.9-11.8; 42 trials) (P = .006 for group difference). Trials of shorter duration (6 months or less) had larger effects., Conclusions and Relevance: Interventions focused on earlier bedtimes may offer a simple, pragmatic, effective way to meaningfully increase sleep duration that could have important benefits for child health.

Background: In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators., Objective: To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019., Methods: The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019)., Results: Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period., Conclusions: Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred., Competing Interests: The authors have declared that no competing interests exist.

Background: The COVID-19 pandemic's first wave in England during spring 2020 resulted in an approximate 50% increase in all-cause mortality. Previously, risk factors such as age and ethnicity, were identified by studying COVID-related deaths only, but these were under-recorded during this period., Objective: To use a large electronic primary care database to estimate the impact of risk factors (RFs) on excess mortality in England during the first wave, compared with the impact on total mortality during 2015-19., Methods: Medical history, ethnicity, area-based deprivation and vital status data were extracted for an average of 4.8 million patients aged 30-104 years, for each year between 18-March and 19-May over a 6-year period (2015-2020). We used Poisson regression to model total mortality adjusting for age and sex, with interactions between each RF and period (pandemic vs. 2015-19). Total mortality during the pandemic was partitioned into "usual" and "excess" components, assuming 2015-19 rates represented "usual" mortality. The association of each RF with the 2020 "excess" component was derived as the excess mortality ratio (EMR), and compared with the usual mortality ratio (UMR)., Results: RFs where excess mortality was greatest and notably higher than usual were age >80, non-white ethnicity (e.g., black vs. white EMR = 2.50, 95%CI 1.97-3.18; compared to UMR = 0.92, 95%CI 0.85-1.00), BMI>40, dementia, learning disability, severe mental illness, place of residence (London, care-home, most deprived). By contrast, EMRs were comparable to UMRs for sex. Although some co-morbidities such as cancer produced EMRs significantly below their UMRs, the EMRs were still >1. In contrast current smoking has an EMR below 1 (EMR = 0.80, 95%CI 0.65-0.98) compared to its UMR = 1.64., Conclusions: Studying risk factors for excess mortality during the pandemic highlighted differences from studying cause-specific mortality. Our approach illustrates a novel methodology for evaluating a pandemic's impact by individual risk factor without requiring cause-specific mortality data., Competing Interests: The authors have declared that no competing interests exist.

Background: Older adults from minority ethnic backgrounds are at increased risk of contracting COVID-19 and developing severe infection and have increased risk of mortality. Whilst an age-based vaccination approach prioritising older groups is being implemented worldwide, vaccine hesitancy is high amongst minority ethnic groups., Methods and Findings: We conducted a systematic review and convergent synthesis to systematically examine perceptions of vaccinations amongst older adults from minority ethnic backgrounds. We included studies that reported on perceptions, beliefs, and attitudes towards vaccinations in older adults aged ≥65 years from a minority ethnic background. We excluded studies of vaccinations in investigation or development, studies focused on specific medical conditions, studies where ethnic background or age group was unidentifiable, systematic reviews, editorials, and conference abstracts. We searched MEDLINE, Embase, Virtual Health Library, Web of Science, Cochrane Library, medRxiv, and PROSPERO databases from inception to 15 July 2021. Risk of bias for studies was assessed using the Mixed Methods Appraisal Tool. The quality of evidence of collective outcomes was estimated using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) framework. A total of 28 eligible studies conducted between 1997 and 2020 were included in the final analysis (17 quantitative surveys, 8 focus group or interview studies, 2 mixed methods studies, and 1 case-control study). The majority were US studies in English or Spanish, except for 6 studies set in Hong Kong, 2 studies in Japan, 1 study in Brazil, and 1 multi-centre study (including China, Indonesia, Turkey, South Korea, Greece, UK, Brazil, and Nigeria). In total, 28,262 individuals with an estimated mean age of 69.8 years were included, 63.2% of whom were female. We summarised the common concepts and themes across studies and populations using a convergent synthesis analysis. Thirteen themes categorised as barriers or facilitators were identified and grouped into structural factors-healthcare provider and system related, patient related, and policy and operational-and were analysed by minority ethnic group. The main limitation of the study was the predominance of studies from the US and East Asia., Conclusions: In this systematic review, we found that factors influencing vaccination uptake involve healthcare provider and system, patient-related, and governance-level factors that are specific to the older ethnic minority community being served. The evidence included in this review is supported by high or moderate certainty and can be translated to practice and policy. A tailored, multi-level approach combining increased education, access, and culturally competent discussions with trusted healthcare professionals to address health beliefs can maximise the potential impact of widespread vaccination policies., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: none declared. Further details of The BMJ policy on financial interests are here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

Background: Step-count monitors (pedometers, body-worn trackers and smartphone applications) can increase walking, helping to tackle physical inactivity. We aimed to assess the effect of step-count monitors on physical activity (PA) in randomised controlled trials (RCTs) amongst community-dwelling adults; including longer-term effects, differences between step-count monitors, and between intervention components., Methods: Systematic literature searches in seven databases identified RCTs in healthy adults, or those at risk of disease, published between January 2000-April 2020. Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcome was mean differences (MD) with 95% confidence intervals (CI) in steps at follow-up between treatment and control groups. Our preferred outcome measure was from studies with follow-up steps adjusted for baseline steps (change studies); but we also included studies reporting follow-up differences only (end-point studies). Multivariate-meta-analysis used random-effect estimates at different time-points for change studies only. Meta-regression compared effects of different step-count monitors and intervention components amongst all studies at ≤4 months., Results: Of 12,491 records identified, 70 RCTs (at generally low risk of bias) were included, with 57 trials (16,355 participants) included in meta-analyses: 32 provided change from baseline data; 25 provided end-point only. Multivariate meta-analysis of the 32 change studies demonstrated step-counts favoured intervention groups: MD of 1126 steps/day 95%CI [787, 1466] at ≤4 months, 1050 steps/day [602, 1498] at 6 months, 464 steps/day [301, 626] at 1 year, 121 steps/day [- 64, 306] at 2 years and 434 steps/day [191, 676] at 3-4 years. Meta-regression of the 57 trials at ≤4 months demonstrated in mutually-adjusted analyses that: end-point were similar to change studies (+ 257 steps/day [- 417, 931]); body-worn trackers/smartphone applications were less effective than pedometers (- 834 steps/day [- 1542, - 126]); and interventions providing additional counselling/incentives were not better than those without (- 812 steps/day [- 1503, - 122])., Conclusions: Step-count monitoring leads to short and long-term step-count increases, with no evidence that either body-worn trackers/smartphone applications, or additional counselling/incentives offer further benefit over simpler pedometer-based interventions. Simple step-count monitoring interventions should be prioritised to address the public health physical inactivity challenge., Systematic Review Registration: PROSPERO number CRD42017075810 .

Objective: To identify randomised controlled trials (RCTs) of physical activity (PA) interventions with objective PA outcomes in adults and to evaluate whether intervention effects were sustained beyond 12 months., Design: Systematic review and meta-analysis., Data Sources: Seven databases (Medline, Embase, PsycINFO, Web of Science, Cochrane library, CINAHL (Cumulative Index of Nursing and Allied Health Literature) and ASSIA (Applied Social Sciences Index and Abstracts)) were searched from January 2000 until December 2019., Eligibility Criteria: RCTs reporting objective PA outcomes beyond 12 months with community-based participants aged ≥18 years were included; those where controls received active interventions, including advice to increase PA levels, were excluded., Data Extraction and Synthesis: Two independent reviewers completed extraction of aggregate data and assessed risk of bias. Meta-analyses used random-effects models at different follow-up points. Primary outcomes were daily steps and weekly minutes of moderate-to-vigorous PA (MVPA)., Results: Of 33 282 records identified, nine studies (at generally low risk of bias) were included, five in meta-analyses with 12 months to 4 year follow-up. We observed 12 month increases for intervention vs control participants in steps/day (mean difference (MD)=554 (95% CIs: 384 to 724) p<0.0001, I 2 =0%; 2446 participants; four studies) and weekly MVPA minutes (MD=35 (95% CI: 27 to 43) p<0.0001, I 2 =0%; 2647 participants; four studies). Effects were sustained up to 4 years for steps/day (MD=494 (95% CI: 251 to 738) p<0.0001, I 2 =0%; 1944 participants; four studies) and weekly MVPA minutes (MD=25 (95% CI: 13 to 37) p<0.0001, I 2 =0%; 1458 participants; three studies)., Conclusions: There are few PA interventions with objective follow-up beyond 12 months, more studies are needed. However, this review provided evidence of PA intervention effects beyond 12 months and sustained up to 4 years for both steps/day and MVPA. These findings have important implications for potential long-term health benefits., Prospero Registration Number: CRD42017075753., Competing Interests: Competing interests: TH and DGC acknowledge conflicts of interest in terms of funding from the National Institute for Health Research for the PACE-Lift and PACE-UP trials., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The growing use of cardiac implantable electronic devices (CIED) has led to infections requiring intervention. These are traditionally managed using a percutaneous transvenous approach to fully extract the culpable leads. Indications for such strategies are well-established and range from simple traction to the use of powered extraction tools including laser sheaths. Where such attempts fail, or if there are further complications, then there may be need for a cardiothoracic surgical approach. Limited evidence is currently available on the merits of individual strategies, and these are mainly drawn from case reports or series. Most utilise cardiopulmonary bypass, cardioplegic arrest and entry within the right atrium to allow direct visualisation of any vegetation and safely explant all CIED components whilst avoiding perforation, valvular and paravalvular damage. In this review, we describe a number of these and the unique challenges faced by surgeons when attempting to extract CIED. It is clear that future work should concentrate on creating clear consensus and guidelines on indications, risks and measures of efficacy outcomes for various surgical techniques., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Beating-heart on-pump coronary artery bypass grafting (BH-ONCAB) offers a hybrid coronary revascularization technique that may confer the benefits of an "off-pump" operation while maintaining the hemodynamic stability and mechanical support of conventional on-pump CABG (C-ONCAB). This study aimed to identify whether BH-ONCAB confers a morbidity or mortality benefit over C-ONCAB in the immediate and midterm postoperative period., Methods: A systematic literature review identified 13 studies incorporating 3,930 patients (937 BH-ONCAB; 2,993 C-ONCAB) fulfilling our inclusion criteria. Outcomes were meta-analyzed using random-effects modelling. Between-study heterogeneity was investigated through quality assessment, subgroup, and risk of bias analysis., Results: No difference was seen in overall 30-day mortality (13 studies; odds ratio, 0.60; 95% confidence interval, 0.32 to 1.14; p = 0.12), or midterm survival (5 studies; hazard ratio, 0.65; 95% confidence interval, 0.22 to 1.88; p = 0.43) between BH-ONCAB and C-ONCAB. BH-ONCAB was associated with significantly fewer postoperative myocardial infarction events (odds ratio, 0.32; 95% confidence interval, 0.11 to 0.92; p = 0.03); however, no significant difference was observed in other postoperative morbidity outcomes. Intraoperatively, BH-ONCAB resulted in significantly less intraaortic balloon pump use, shorter cardiopulmonary bypass time, and less blood loss. The number of anastomoses and vessels grafted were not significantly different between BH-ONCAB and C-ONCAB., Conclusions: BH-ONCAB is a safe and comparable alternative to C-ONCAB in terms of early mortality and late survival. Furthermore, BH-ONCAB may confer a particular advantage in preventing perioperative myocardial infarction and reducing overall blood loss. Future work should focus on larger matched studies and multicenter randomized controlled trials that risk-stratify patients according to preoperative ventricular function and renal insufficiency to allow us to optimize our surgical revascularization strategy in these high-risk patients., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether beating-heart on-pump coronary artery bypass grafting (BH-ONCAB) offered superior mortality and morbidity outcomes when compared with conventional on-pump coronary artery bypass grafting (C-ONCAB). Morbidity outcomes consisted of renal failure, stroke (transient or permanent), myocardial infarction, angina, congestive cardiac failure, reintervention and arrhythmias. Best evidence papers investigating BH-ONCAB versus C-ONCAB were considered. Where data were duplicated, the more credible evidence-based and recently published study was included. Two hundred and thirty-one papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. Two were prospective randomized controlled trials and the remaining 10 observational studies, of which one was propensity-matched. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Five of these studies demonstrated significantly improved mortality following BH-ONCAB; however, one study exhibited better survival after C-ONCAB. Notably, this study incorporated BH-ONCAB patients with significantly more haemodynamic instability, thus possibly explaining the worse mortality outcomes. In terms of morbidity, a slightly more mixed picture is drawn. Five studies report morbidity in favour of BH-ONCAB, whereas three studies include individual outcomes favouring C-ONCAB. The remaining studies showed equivalent mortality and morbidity data. In summary, the results presented here suggest that BH-ONCAB may improve survival following coronary artery bypass surgery. A key observation is that the greatest benefits of BH-ONCAB appear to be in studies including patients with considerably higher risk characteristics at the time of surgery (haemodialysis, end-stage coronary artery disease, emergency surgery, low ejection fraction). There are limitations of the current evidence presented. Only two studies were randomized controlled trials. There was variability in sample size, selection criteria and preoperative risk profiles between the studies. The studies span many years, and the outcomes may have been affected by evolving technologies and differing patient profiles between these periods., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

A best evidence topic was written according to a structured protocol. The question addressed was whether on-pump beating heart coronary artery bypass (BH-ONCAB) surgery has a different outcome profile in comparison to off-pump coronary artery bypass (OPCAB). A total of 205 papers were found by systematic search of which 7 provided the largest and most recent outcome analysis comparing BH-ONCAB with OPCAB, and represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results were tabulated. Reported outcome measures included mortality, stroke, myocardial infarction, renal failure, myocardial damage, change in ejection fraction, number of bypass grafts and completeness of revascularization. With the exception of one study that favoured the off-pump technique, our review did not demonstrate a statistically significant difference in terms of mortality between the groups. We did not identify a statistically significant difference in any reported morbidity outcomes. However, there was a trend towards better outcomes for the on-pump beating heart technique, despite a higher risk profile in terms of age, ejection fraction and burden of coronary disease in this group. Consistent statistically significant differences between the groups were the mean number of grafts performed and the completeness of revascularization, both of which were higher with the on-pump beating heart technique. Limitations to the current evidence include the finding that most of the current data arise from specialist off-pump surgeons or centres that would usually only carry out BH-ONCAB in the higher risk patients where the added safety of cardiopulmonary bypass is desired., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Early outcomes for off-pump coronary artery bypass grafting (OPCAB) have been extensively compared with on-pump coronary revascularization (ONCAB); however, the long-term effects of OPCAB continue to be debated. This study aims to compare the mid-term (>1year; ≤5 years) and long-term (>5 years) survival and major adverse cardiovascular and cerebrovascular events of OPCAB versus ONCAB., Methods: A systematic search identified 32 studies meeting our inclusion criteria. These were analyzed using random effects modeling, with subgroup evaluation according to study type. Primary outcomes were mid- and long-term survival over a follow-up period greater than 1 year. Secondary outcomes were mid- and long-term events including repeat revascularization, myocardial infarction, angina, heart failure, and cerebrovascular accidents., Results: Off-pump coronary artery bypass grafting confers similar overall mid-term survival when compared with ONCAB (hazard ratio, 1.06; 95% confidence interval, 0.95 to 1.19; p=0.31). On-pump coronary artery bypass grafting was associated with a significant trend towards a long-term survival advantage (hazard ratio, 1.06; 95% confidence interval, 1.00 to 1.13; p=0.05); however, this was no longer present when subgroup analysis of only randomized controlled trials, registry-based studies, and propensity-matched studies was performed. There was an increase in angina recurrence among two studies after OPCAB, but no difference was seen in 11 other studies reporting data as odds ratio. No significant differences were observed in other secondary outcomes., Conclusions: This analysis demonstrates comparable mid-term mortality and mid- to long-term morbidity between OPCAB and ONCAB. On-pump coronary artery bypass grafting may be associated with improved long-term survival when all study types are analyzed; however, analysis of only randomized controlled trials and propensity-matched studies demonstrates comparable long-term mortality between OPCAB and ONCAB., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether off-pump coronary artery bypass grafting (CABG) surgery offered superior long-term outcomes compared with on-pump CABG surgery. Best evidence papers were considered to be those that had a follow-up period of ≥5 years, had >50 patients in either cohort, did not utilize concomitant interventions nor comprised low-risk, high-risk or sub-population groups. Where potential duplicate data sets from the same institution were likely, the more credible and recently published study was included. Two hundred and fifty-six papers were found as a result of the reported search, of which 16 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The 16 studies comprised 4 prospective randomized controlled trials (RCTs), with the remaining 12 retrospective, of which 8 were propensity-score matched. All 4 RCTs contained fewer than 450 participants. Two studies concluded with a survival advantage towards on-pump CABG: one, a large registry-based study, the Veterans Affairs, with >25 000 patients, and another, a propensity-matched retrospective study involving almost 8000 patients. The remaining 14 studies all provided evidence to suggest comparable long-term survival. In addition, all other long-term outcomes mentioned within these studies including angina recurrence, myocardial infarction heart failure, need for revascularization, stroke, graft patency, cognitive and quality of life showed similar results between the two groups. We conclude that off-pump CABG surgery may have similar or slightly reduced long-term survival compared with on-pump CABG surgery. Other long-term indicators such as cardiovascular or cerebrovascular events or neuro-psychological outcomes were similar between the two groups. Despite these conclusions, the evidence is limited by substantial variability in patient selection and study methods. The CORONARY (coronary artery bypass surgery off- or on-pump revascularization study) trial recently presented results, which showed no significant differences in composite outcomes at 1 year; it will be interesting to observe whether these comparable outcomes are maintained for a much longer time frame., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Superior vena cava (SVC) syndrome is a known but rare complication of pacemaker lead implantation, accounting for approximately less than 0.5% of cases. Its pathophysiology is due to either infection or endothelial mechanical stress, causing inflammation and fibrosis leading to thrombosis, and therefore stenosis of the SVC. Due to the various risks including thrombo-embolic complications and the need to provide symptomatic relief, medical and surgical interventions are sought early. We present the case of a 48-year Caucasian male who presented with localised swelling and pain at the site of pacemaker implantation. Inflammatory markers were normal, but diagnostic imaging revealed three masses along the pacemaker lead passage. A surgical approach using cardiopulmonary bypass and circulatory arrest was used to remove the vegetations. Culture from the vegetations showed Staphylococcus epidermidis. The technique presented here allowed for safe and effective removal of both the thrombus and infected pacing leads, with excellent exposure and minimal post-procedure complications.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have been widely proposed as in vitro models of myocardial physiology and disease. A significant obstacle, however, is their immature phenotype. We hypothesised that Ca(2+) cycling of iPSC-CM is influenced by culture conditions and can be manipulated to obtain a more mature cellular behaviour. To test this hypothesis we seeded iPSC-CM onto fibronectin coated microgrooved polydimethylsiloxane (PDMS) scaffolds fabricated using photolithography, or onto unstructured PDMS membrane. After two weeks in culture, the structure and function of iPSC-CM were studied. PDMS microgrooved culture substrates brought about cellular alignment (p < 0.0001) and more organised sarcomere. The Ca(2+) cycling properties of iPSC-CM cultured on these substrates were significantly altered with a shorter time to peak amplitude (p = 0.0002 at 1 Hz), and more organised sarcoplasmic reticulum (SR) Ca(2+) release in response to caffeine (p < 0.0001), suggesting improved SR Ca(2+) cycling. These changes were not associated with modifications in gene expression. Whilst structured tissue culture may make iPSC-CM more representative of adult myocardium, further construct development and characterisation is required to optimise iPSC-CM as a model of adult myocardium., (Copyright © 2012 Elsevier Ltd. All rights reserved.)