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ObjectivesTo obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).MethodsWe searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as ‘all-cause mortality (ACM) or myocardial infarction (MI)’ at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.ResultsFive studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), pConclusionsThe 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

Objectives: To estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA. Methods: We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. Results: A total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. Conclusions: Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure. Methods We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. Results A total of 3169 TNFi treatment courses (RA/ PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. Conclusions Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.

ObjectivesTo examine age at diagnosis, prognostic factors and survival of prostate cancer (PCa) in Norwegian firefighters and three other occupations undergoing occupational health check-ups, and comparing with PCa cases in the general population.MethodsAll PCa cases diagnosed in 1960–2017 were extracted from the Cancer Registry of Norway. Firefighters, military employees, pilots and police officers were identified through occupational data from Statistics Norway. Age at diagnosis, clinical stage, prostate-specific antigen (PSA), Gleason score, performance status and overall survival and PCa-specific survival in cases in these occupations were compared with cases in the general population.ResultsFirefighters were significantly younger at PCa diagnosis than cases in the general population in 1960–1993 (mean difference: 2.1 years) and 2007–2017 (mean difference: 4.3 years). At diagnosis, firefighters had significantly lower PSA values, Gleason scores and performance status scores than the general population. Firefighters diagnosed in 2007–2017 had lower risk of all-cause death than the general population (crude HR 0.71 (0.53–0.95)). No difference remained after adjusting for age at diagnosis (HR 1.03 (0.77–1.37)). Firefighters were older at diagnosis in 1994–2006 (mean difference: 3.0 years), but showed no other significant differences in age at diagnosis, PSA values, Gleason scores or performance status compared with military employees, pilots and police officers.ConclusionsYounger age and better prognostic factors at PCa diagnosis among firefighters and other occupations with requirements for health check-ups than cases in the general population may indicate an increased diagnostic intensity, likely contributing to elevated PCa incidence in such occupations.

BackgroundThe outcomes of elective surgery in public versus Independent Sector Healthcare Providers (ISHPs) are a matter of policy relevance and theoretical interest.MethodsRetrospective study of all National Health Service (NHS) hospitals and ISHPs in England that provided NHS-funded elective surgery. We used data from the England-wide Hospital Episode Statistics to study 18 common surgical procedures performed between 2006 and 2019. In-hospital outcomes included length of stay, emergency transfers to another hospital or death. Posthospital outcomes included readmission or death within 28 days. Outcomes were compared for each operation type by propensity score matching and survival analysis.ResultsThe data set included 3 203 331 operations in 734 NHS hospitals and 468 259 operations in 274 ISHPs.In-hospital outcomes: Across all 18 included operation types, length of stay was significantly longer for patients treated in NHS hospitals compared with ISHPs. Effect sizes ranged from a hazard ratio (HR) of 2.15 (95% CI 1.72 to 2.68) for total hip replacement to 1.07 (95% CI 1.05 to 1.09) for wisdom tooth removal; a mean difference of 2.49 and 0.02 days, respectively.Postdischarge outcomes: Treatment at an ISHP was associated with a lower risk of emergency readmission compared with NHS treatment. HRs ranged from 0.36 (95% CI 0.28 to 0.46) for lumbar decompression to 0.75 (95% CI 0.67 to 0.85) for cholecystectomy; absolute risk differences of 1.5 and 1.3 percentage points. There was no difference in mortality.ConclusionElective surgery in an ISHP is associated with shorter lengths of stay and lower readmission rates than treatment in NHS hospitals across 18 operation types. The data were matched on observable covariates, but we cannot exclude selection bias due to unobserved confounders.

ObjectiveTo investigate the risk of hospitalisation for major chronic diseases across representative transport, rescue and security industries.MethodsWe performed a register-based study of 624 571 workers from six industries in Denmark between 2000 and 2005, followed up hospitalisation for chronic diseases up to 17 years, and compared with a 20% random sample of the economically active population.ResultsHR from the Cox regression models showed that seafarers had higher risk of lung cancer (men: 1.54, 95% CI 1.31 to 1.81; women: 1.63, 95% CI 1.13 to 2.36), and male seafarers had higher risk of diabetes (1.32, 95% CI 1.21 to 1.43) and oral cancer (1.51, 95% CI 1.21 to 1.88). Men and women in land transport had increased risk of diabetes (men: 1.68, 95% CI 1.63 to 1.73; women 1.55, 95% CI 1.40 to 1.71) and chronic respiratory disease (men: 1.21, 95% CI 1.16 to 1.25; women 1.42, 95% CI 1.32 to 1.53). Among women, a higher risk of gastrointestinal cancer was observed in aviation (1.53, 95% CI 1.23 to 1.89) and police force (1.29, 95% CI 1.01 to 1.65), oral cancer in defence forces (1.83, 95% CI 1.20 to 2.79), and chronic respiratory disease in rescue service (1.47, 95% CI 1.21 to 1.77), while men in defence forces, police force and rescue service had mainly lower risk of these chronic diseases.ConclusionsWe observed considerable health disparities from chronic diseases across transport, rescue and security industries, with workers in seafaring and land transport generally bearing the greatest relative burden.

ObjectiveEvidence on sex differences in outcomes after developing coronary heart disease (CHD) has focused on recurrent CHD, all-cause mortality or revascularisation. We assessed sex disparities in subsequent major adverse cardiovascular events (MACE) in adults surviving their first-time CHD.MethodsUsing a population-based cohort obtained from the Clinical Practice Research Datalink (CPRD GOLD) linked to hospitalisation and death records in the UK, we identified 143 702 adults (aged ≥18 years) between 1 January 1998 and 31 December 2017 with no prior history of MACE. MACE outcome was a composite of recurrent CHD, stroke, peripheral vascular disease, heart failure and cardiovascular-related mortality. Multivariable models (Cox and competing risks regressions) were used to assess differences between sexes.ResultsThere were 143 702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63 078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91 706 (63.8%). Women had a significantly lower risk of MACE (hazard ratio (HR), 0.68 (95% CI 0.67 to 0.69); sub-hazard ratio (HRsd), 0.71 (0.70 to 0.72), respectively) and recurrent CHD (n=66 543, 46.3%) (HR, 0.60 (0.59 to 0.61); HRsd, 0.62 (0.61 to 0.63)) when compared with men after incident CHD. However, women had a significantly higher risk of stroke (n=5740, 4.0%) (HR, 1.26 (1.19 to 1.33); HRsd, 1.32 (1.25 to 1.39)), heart failure (n=7905, 5.5%) (HR, 1.09 (1.04 to 1.15); HRsd, 1.13 (1.07 to 1.18)) and all-cause mortality (n=29 503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).ConclusionsAfter incident CHD, women have lower risk of composite MACE and recurrent CHD outcomes but higher risk of stroke, heart failure, and all-cause mortality compared with men.

ObjectiveIn this review and meta-analysis we sought to compare the efficacy and safety of direct endovascular thrombectomy (EVT) and bridging therapy for intravenous thrombolysis (IVT)-eligible patients with acute ischemic stroke caused by large vessel occlusions (AIS-LVO).MethodsWe searched Medline, Embase, and the Cochrane Library for published randomized clinical trials (RCTs) and observational studies providing outcomes of patients with IVT-eligible AIS-LVO who have undergone EVT with or without IVT. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0–2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as an mRS score of 0 or 1 at 90 days, (2) mortality at 90 days, (3) symptomatic intracranial hemorrhage (sICH), (4) any type of intracranial hemorrhage (ICH), (5) successful recanalization, and (6) clot migration.ResultsWe included three RCTs and six observational studies (4 of which were propensity score-adjusted studies) with a total of 3133 patients. In unadjusted and adjusted analyses, no differences in the rates of mRS scores 0–2, mRS scores 0–1, mortality at 90 days, sICH or successful recanalization were detected between patients with AIS-LVO who underwent direct EVT or bridging therapy. The patients treated with direct EVT had a lower risk ratio for any type of ICH and clot migration than did the patients treated with bridging therapy.ConclusionCompared with bridging therapy, direct EVT may be equally effective and yield a lower rate of ICH and clot migration in patients with AIS.Trail registration numberPROSPERO: CRD42021236691.

ObjectiveTo estimate the incidence of psoriatic arthritis (PsA) in patients with psoriasis who had received a continuous treatment with biological disease-modifying antirheumatic drugs (bDMARDs) compared with phototherapy.MethodsA retrospective non-randomised study involving patients with moderate-to-severe plaque psoriasis, who were prescribed at least 5 years of bDMARDs or at least three narrow-band ultraviolet light B (nb-UVB) phototherapy courses, and did not have a diagnosis of PsA at enrolment. Development of PsA in each patient was assessed by a rheumatologist according to the Classification for Psoriatic Arthritis criteria. The annual and cumulative incidence rate of PsA was estimated by using an event per person-years analysis. Cox proportional hazards models were undertaken to assess the hazard risk (HR) of PsA after adjustment for confounders.ResultsA total of 464 psoriatic patients (bDMARDs, n=234 and nb-UVB, n=230) were followed between January 2012 and September 2020 (corresponding to 1584 and 1478 person year of follow-up for the two groups, respectively). The annual incidence rate of PsA was 1.20 cases (95% CI 0.77 to 1.89) versus 2.17 cases (95% CI 1.53 to 3.06) per 100 patients/year in the bDMARDs versus phototherapy group, respectively (HR 0.29, 0.12–0.70; p=0.006). The variables independently associated with higher risk of PsA were older age (adjusted HR 1.04, 1.02–1.07), nail psoriasis (adjusted HR 3.15, 1.63–6.06) and psoriasis duration >10 years (adjusted HR 2.02, 1.09–3.76); notably, bDMARDs treatment was associated with a lower risk of incident PsA (adjusted HR 0.27, 0.11–0.66).ConclusionsbDMARDs treatment may delay or reduce the risk of incident PsA in patients with moderate-to-severe chronic plaque psoriasis.

ObjectiveTo evaluate whether baseline and changes in cardiovascular health (CVH) were related to incident atrial fibrillation (AF) risk in the elderly population.MethodsFrom the Korea National Health Insurance Service-Senior cohort, we included 208 598 participants without prior AF (median age: 70 (IQR 66–74) years; 90 916 (43.6%) men) who underwent national health check-ups between 1 January 2005 and 31 December 2012. Using the six metrics of the American Heart Association, participants were categorised as having low, moderate and high CVH.ResultsOver a median follow-up of 7.2 years, 7818 cases of incident AF occurred. In multivariable analysis, moderate (HR: 0.90; 95% CI: 0.86 to 0.94) and high (HR: 0.81; 95% CI: 0.73 to 0.91) CVH status at baseline were associated with a lower risk of incident AF. However, in 109 695 participants with changes in CVH between the first and second check-ups, the direction of change in CVH scores showed no consistent association with future AF incidence. In newly diagnosed participants with AF, the incidence of the composite outcome (stroke, major bleeding and all-cause death) decreased with every 1-point increase in the baseline CVH score (HR: 0.94; 95% CI: 0.89 to 0.99).ConclusionsIn the general elderly population, better baseline CVH metrics were associated with lower incident AF risk. In participants with newly diagnosed AF, better CVH was also associated with lower incidence of future composite outcomes. However, the direction of change in CVH status within 2 years showed an inconsistent influence on incident AF risk.

Patients with atrial fibrillation (AF) have a higher risk of dementia and mild cognitive impairment, in addition to a fivefold higher risk of stroke, compared with patients in normal sinus rhythm. Potential mechanisms of cognitive impairment or dementia related to AF include recurrent micro emboli versus cerebral hypoperfusion in association with increased oxidative stress, inflammation and disruption of the blood-brain barrier. Using linked electronic health records from the Clinical Practice Research Datalink in the UK, Cadogan and colleagues1 compared the incidence of dementia or mild cognitive impairment in 39 200 patients (median age 76 years, 45% women) with AF treated with either a vitamin-K antagonist (VKA) or a direct oral anticoagulant (DOAC). Incident dementia was diagnosed in 3.2% with a 16% lower risk of dementia in patients treated with a DOAC versus VKA (adjusted HR 0.84, 95% CI: 0.73 to 0.98) . Mild cognitive impairment was diagnosed in 4.0% with a 26% lower risk in those treated with a DOAC versus VKA (adjusted HR 0.74, 95% CI: 0.65 to 0.84) (figure 1). For patients taking a VKA, greater time with anticoagulation in therapeutic range was associated with a lower risk of dementia. Figure 1 Association between oral anticoagulant use and incident dementia and mild cognitive impairment, defined using clinical codes. ∧Adjusted for age, calendar year, time-on-treatment and sex. *Adjusted for age, calendar year, time-on-treatment, sex, body mass index, smoking status, hazardous alcohol consumption, socioeconomic status (practice level Index of Multiple Deprivation), primary care consultation frequency, diabetes, hypertension, myocardial infarction, statins, heart failure, stroke, vascular disease, renal disease, liver disease, antiplatelet drugs, ACE/ARB inhibitors, beta-blockers, antiarrhythmics, digoxin, diuretics, antipsychotics, antidepressants and proton …

BackgroundThere were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.MethodsWe performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.ResultsApixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, pFor thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, pConclusionsApixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.

Background and purposeDiabetes mellitus (DM) is a common metabolic disorder with increased risk of cardiovascular and cerebrovascular complications. However, its relationship with risk of subarachnoid haemorrhage (SAH), the most devastating form of stroke, remains controversial.MethodsTo evaluate the relationship between DM and risk of SAH, we performed a retrospective cohort study using a nationwide, population‐based, health screening database in Korea. We included participants without history of stroke who underwent a nationwide health screening programme between 2003 and 2004. Primary outcome was occurrence of SAH. Participants were followed up until development of SAH or December 2015. Multivariate Cox proportional hazards regression analysis was performed with adjustments for age, sex, systolic blood pressure, total cholesterol, body mass index, physical activity, smoking status, alcohol habit, household income and treatment with antihypertensive agents and statins.ResultsAmong 421 768 study participants, prevalence of DM was 9.6%. During a mean follow-up period of 11.6±1.9 years, 1039 patients developed SAH. Presence of DM was significantly associated with decreased risk of SAH (adjusted HR 0.68; 95% CI 0.53 to 0.86; pConclusionDM and elevated level of fasting blood glucose were inversely associated with risk of SAH. Further studies may elucidate the possibly protective, pathophysiological role played by hyperglycaemia in patients at risk of SAH.

Objectives To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.Methods We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region.Results In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use.Conclusions We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.http://dx.doi.org/10.1136/annrheumdis-2020-219517

BackgroundMore than half a million refugees have arrived to Sweden during the last decade. The aim was to investigate differences between refugees and Swedish-born individuals regarding different specific somatic and mental disorders, and subsequent disability pension and mortality.MethodsAll refugees (n=239 742) and Swedish-born individuals (n=4 133 898), aged 19–60 years, resident in Sweden on 31st of December in 2009 were included in this population-based prospective cohort study. Data from six nationwide Swedish registers were linked by the unique anonymised identification number. HRs with 95% CIs were computed for disability pension and mortality 2010–2013 by Cox regression models.ResultsCompared with their Swedish-born counterparts with mental or somatic diagnoses, refugees with these diagnoses had a higher risk of subsequent disability pension and a lower risk of mortality. Highest estimates for disability pension were seen for refugees with neoplasm (HR: 1.72; 95% CI: 1.56 to 1.91), musculoskeletal disorders (HR: 1.57; 95% CI: 1.47 to 1.67), diseases of the circulatory system (HR: 1.33; 95% CI: 1.22 to 1.45), depressive disorders (HR: 1.31; 95% CI: 1.21 to 1.41) and diabetes mellitus (HR: 1.30; 95% CI: 1.15 to 1.47). The risk of mortality was lowest for refugees with regard to bipolar disorders (HR: 0.37; 95% CI: 0.16 to 0.82), post-traumatic stress disorder (HR: 0.37; 95% CI: 0.25 to 0.54) and least pronounced in regard to neoplasm (HR: 0.69; 95% CI: 0.61 to 0.77) compared with Swedish-born with similar disorders.ConclusionRefugees have a generally higher risk of disability pension compared with Swedish-born with specific somatic and mental disorders. Despite this, refugees with all specific disorders have lower risk estimates of mortality, probably due to a healthy selection. The higher risk of disability pension might therefore be due to other causes besides poor health.

PurposeWe described the 6-year incidence and changes of retinopathy, and their associated risk factors in a multi-ethnic Asian population without diabetes.MethodsWe included 4374 participants with non-diabetes from a population-based cohort, the Singapore Epidemiology of Eye Disease Study, with gradable retinal photographs at baseline and 6-year follow-up visit. Retinopathy was assessed according to the modified Airlie House classification system.ResultsOver the 6-year period, the cumulative rates were 2.5% (106/4279) for retinopathy incidence, 1.0% (1/95) for retinopathy progression and 68.4% (65/95) for retinopathy regression. In multivariable analysis, higher diastolic blood pressure (DBP) (risk ratio (RR)=1.02; 95% CI: 1.00 to 1.04; per 10 mm Hg increase in DBP) and wider retinal arteriolar calibre (RR=1.36; 95% CI: 1.13 to 1.63; per SD increase in central retinal artery equivalent) were associated with higher risk of incident retinopathy, while higher level of high-density lipoprotein (HDL) was associated with lower risk of incident retinopathy (RR=0.56; 95% CI: 0.32 to 0.99; per mmol/L increase in HDL). Compared with Chinese, Malays were more likely to have retinopathy regression (RR=1.63; 95% CI: 1.20 to 2.22), while overweight (RR=0.47; 95% CI: 0.26 to 0.84) and higher glycosylated haemoglobin (HbA1c) level (RR=0.58; 95% CI: 0.37 to 0.93; per per cent increase in HbA1c) were associated with lower likelihood of retinopathy regression.ConclusionRisk of developing retinopathy in Asians without diabetes is generally low. However, regression of retinopathy over time is common, suggesting that these retinopathy signs may reflect subclinical reversible microvascular dysfunction. Several metabolic risk factors are associated with incidence or regression of retinopathy, suggesting that good metabolic control may still be important in the management of non-diabetic retinopathy.

BackgroundChronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB.MethodsIn smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0–4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit.Measurements and main resultsOf 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all pConclusionsHigher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.

PurposeRheumatoid arthritis (RA) is associated with a higher risk of diabetes mellitus (DM). Our aim was to determine associations between inflammatory disease activity (including evaluation of specific cytokines and chemokines) and incident DM.MethodsParticipants were adults with physician-confirmed RA from Veteran’s Affairs Rheumatoid Arthritis Registry. Disease activity and clinical assessments occur longitudinally as part of clinical care. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment. Cytokine/chemokine values were log-adjusted and standardised (per SD). Incident DM was defined based on validated algorithms using diagnostic codes and medications. Multivariable Cox proportional hazard models evaluated associations between clinical factors and incident DM. Independent associations between cytokines/chemokines and incident DM were assessed adjusting for age, sex, race, smoking, body mass index (BMI) and medication use at baseline.ResultsAmong 1866 patients with RA without prevalent DM at enrolment, there were 130 incident cases over 9223 person-years of follow-up. High Disease Activity Score (DAS28)-C reactive protein (CRP), obese BMI, older age and male sex were associated with greater risk for incident DM while current smoking and methotrexate use were protective. Patients using methotrexate were at lower risk. Several cytokines/chemokines evaluated were independently associated (per 1 SD) with DM incidence including interleukin(IL)-1, IL-6 and select macrophage-derived cytokines/chemokines (HR range 1.11–1.26). These associations were independent of the DAS28-CRP.ConclusionsHigher disease activity and elevated levels of cytokines/chemokines are associated with a higher risk of incident DM in patients with RA. Future study may help to determine if targeted treatments in at-risk individuals could prevent the development of DM.

BackgroundEmergency Medical Services (EMS) have experienced surges in demand as the COVID-19 pandemic has progressed with ambulances services in the UK declaring major incidents due to the risk of care being compromised. COVID-19 specific EMS telephone triage tools have been introduced to help manage demand. There has been no previous evaluation of the accuracy of EMS telephone triage in identifying patients with suspected COVID-19 at risk of serious adverse outcome.We aimed to assess accuracy of EMS telephone triage in identifying patients who need an EMS response and identify factors which affect triage accuracy.MethodPatients who made an emergency call to Yorkshire Ambulance Service between 2nd April and 29th June 2020 and were assessed using an AMPDS pandemic pathway for suspected COVID-19 were linked to Office for National Statistics death registration data, hospital and general practice electronic health care data collected by NHS Digital.Accuracy of decision to dispatch an ambulance was assessed in terms of death or need for organ support at 30 days from the first 999 call. Multivariable logistic regression was used to identify factors associated with false negative and false positive triage.ResultsOf 12, 653 callers included in the study population, 11.1% experienced the primary composite adverse outcome. Using the triage pathway, 16% of callers did not receive an emergency response and they had a lower risk (3.5%) of the primary outcome. Ambulances were dispatched to 4, 230 callers (33.4%) who were not subsequently conveyed to hospital and did not experience the primary outcome (false positive triage). Multivariable modelling found older age and presence of pre-existing respiratory disease were significant predictors of false positive triage.ConclusionEMS telephone triage avoided 16% of calls receiving an emergency ambulance, of whom 3.5% died or needed organ support by 30 days. Telephone triage can therefore reduce the burden of EMS responses but with the cost of a small proportion of patients who do not receive an initial emergency response deteriorating. Research is needed to identify the appropriate balance between over- and under-triage

ObjectiveTo determine the risk of death due to prominent mental disorders, substance abuse, and self-harm among US Olympians compared with the general population.MethodsAll female (n=2301) and male (n=5823) US Olympians who participated in the summer or winter Games between 1912 and 2012 were followed until 2016. The National Death Index certified their vital statuses and causes of death. We performed a Standard Mortality Ratio (SMR) analysis for all causes studied and applied the years-saved (YS) method to quantify differences in the risk of death for (1) anxiety, depression and self-harm and (2) substance abuse and eating disorders. Additionally, we examined the YS across sports with greater than 100 total deaths and between medalists and non-medalists.ResultsUS Olympians had a 32% (SMR=0.68, 95% CI 0.49 to 0.91) lower risk of death compared with the general population, resulting in a longevity advantage of 0.21 YS (95% CI 0.14 to 0.29) for deaths by depression, anxiety and self-harm and 0.12 years (95% CI 0.08 to 0.15) for substance abuse and eating disorders. There were no significant differences between medalists and non-medalists, but findings varied by sports. Most sports (eg, athletics, swimming, rowing) had significantly lower risks of deaths than the general population with the exceptions of fencing and shooting. Shooting showed a trend towards a higher risk through suicide by firearm.ConclusionOlympians have a lower risk of death, favouring an increased longevity compared with the general population for mental disorders, substance abuse and suicides.

ObjectivesTo investigate SARS-CoV-2 (the virus causing COVID-19) infection and exposure risks among grocery retail workers, and to investigate their mental health state during the pandemic.MethodsThis cross-sectional study was conducted in May 2020 in a single grocery retail store in Massachusetts, USA. We assessed workers’ personal/occupational history and perception of COVID-19 by questionnaire. The health outcomes were measured by nasopharyngeal SARS-CoV-2 reverse transcriptase PCR (RT-PCR) results, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9).ResultsAmong 104 workers tested, 21 (20%) had positive viral assays. Seventy-six per cent positive cases were asymptomatic. Employees with direct customer exposure had an odds of 5.1 (95% CI 1.1 to 24.8) being tested positive for SARS-CoV-2 after adjustments. As to mental health, the prevalence of anxiety and depression (ie, GAD-7 score >4 or PHQ-9 score >4) was 24% and 8%, respectively. After adjusting for potential confounders, those able to practice social distancing consistently at work had odds of 0.3 (95% CI 0.1 to 0.9) and 0.2 (95% CI 0.03 to 0.99) screening positive for anxiety and depression, respectively. Workers commuting by foot, bike or private cars were less likely to screen positive for depression (OR 0.1, 95% CI 0.02 to 0.7).ConclusionsIn this single store sample, we found a considerable asymptomatic SARS-CoV-2 infection rate among grocery workers. Employees with direct customer exposure were five times more likely to test positive for SARS-CoV-2. Those able to practice social distancing consistently at work had significantly lower risk of anxiety or depression.

ObjectivesSusceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker’s pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies.MethodsTo systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study.ResultsInterestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10−4) and lung function (rs4651005, OR=1.39, p=1.62×10−3; rs985256, OR=0.73, p=8.24×10−4 and rs6539952, OR=1.28, p=4.32×10−4) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of FAM13A (rs2609255, p=7.4 ×10−4), ANGPTL1 (rs4651005, p=5.4 ×10−7), SPATS2L (rs985256, p=1.1 ×10−5) and RP11-463O9.9 (rs6539952, p=7.1 ×10−6) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis.ConclusionsThese results provided a deeper understanding of the genetic predisposition basis of CWP.

ObjectivesOccupational asbestos exposure is causally linked to mesothelioma. However, whether exposure to only chrysotile asbestos is associated with mesothelioma risk, and the heterogeneity in risk by different fibre types/lengths remains unclear. We investigated whether mesothelioma risk differs among workers exposed to only chrysotile asbestos compared with chrysotile and ≥1 amphibole (ie, amosite, tremolite, anthophyllite and crocidolite) over the working lifetime.MethodsWe analysed next-of-kin interview data including occupational histories for 580 white men (176 cases and 404 controls) from a case–control study of mesothelioma conducted in the USA in 1975–1980. Asbestos exposure was determined by an occupational hygienist using a job-exposure matrix and exposure categories included chrysotile only and nine chrysotile–amphibole mixtures. Logistic regression models were used to estimate the ORs and 95% CIs of mesothelioma, comparing each asbestos category to the unexposed group, adjusted for age at death and data source. Analysis of contrasts was used to assess overall heterogeneity and pair-wise differences in risk.ResultsExposure to long and short chrysotile only was associated with increased mesothelioma risk compared with the unexposed (OR=3.8 (95% CI 1.3 to 11.2)). The complex mixture of extra-long amosite, short and long chrysotile, tremolite and anthophyllite was associated with the highest risk (OR=12.8 (95% CI 4.1 to 40.2)). There was evidence for overall heterogeneity among the asbestos exposure categories (p heterogeneity=0.02). However, the lower risk observed for exposure to chrysotile only compared with the complex mixture was not significant (p difference=0.10).ConclusionsOur findings suggest that policies aimed at regulating asbestos should target both pure chrysotile and mixtures that include amphibole.

ObjectiveEthnic differences in cardiovascular disease incidence, but not cardiovascular disease recurrence, are reported. We characterised long-term risk of major adverse cardiovascular event (MACE) and mortality following a non-fatal cardiovascular event in a British cohort of South Asians, African Caribbeans and Europeans.MethodsWe identified index and recurrent cardiovascular events and mortality between 1988 and 2017 using hospital records and death registry. Using multivariable hazards models, we separately calculated the adjusted HR of MACE and death following index event, adjusting for demographics, vascular and lifestyle risk factors. Using interaction terms, we evaluated if decade of index event modified the association between ethnicity and outcomes.ResultsSouth Asians were younger at the index event (median age 66 years, n=396) than Europeans (69 years, n=335) and African Caribbeans (70 years, n=70). During 4228 person-years, of the 801 patients, 537 developed MACE and 338 died, with the highest crude rate of MACE in South Asians. On adjustment of baseline factors, compared with the Europeans, the higher risk of MACE (HR 0.97, 95% CI 0.77 to 1.21) and the lower risk of mortality (HR 0.95, 95% CI 0.72 to 1.26) in South Asians was eliminated. African Caribbeans had similar outcomes to Europeans (HR MACE 1.04, 95% CI 0.74 to 1.47; and HR death 1.07, 95% CI 0.70 to 1.64). Long-term survival following an index event improved in South Asians (ptrend 0.02) and African Caribbeans (ptrend 0.07) compared with Europeans.ConclusionsBaseline vascular risk factors explained the observed ethnic variation in cardiovascular disease recurrence and long-term mortality, with a relative improvement in survival of minority ethnic groups over time.

ObjectivesThe prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases who are frequently treated with disease modifying therapies remains poorly understood. This meta-analysis aims to assess the prevalence and clinical outcomes of COVID-19 in autoimmune diseases.MethodsElectronic databases were searched for observational and case–controlled studies. We sorted medications into glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic or targeted synthetic DMARDs (b/tsDMARDs), which was also divided into monotherapy and b/tsDMARDs–csDMARDs combination therapy.ResultsWe analysed 62 observational studies with a total of 319 025 patients with autoimmune diseases. The prevalence of COVID-19 was 0.011 (95% CI: 0.005 to 0.025). Meta-analysis of seven case–controlled studies demonstrated that the risk of COVID-19 in autoimmune diseases was significantly higher than in control patients (OR: 2.19, 95% CI: 1.05 to 4.58, p=0.038). Meta-regression analysis showed glucocorticoids were significantly associated with the risk of COVID-19. For clinical outcomes, we assessed 65 studies with 2766 patients with autoimmune diseases diagnosed with COVID-19. The rates of hospitalisation and mortality were 0.35 (95% CI: 0.23 to 0.50) and 0.066 (95% CI: 0.036 to 0.12), respectively. Glucocorticoids, csDMARDs and b/tsDMARDs–csDMARDs combination therapy increased the risk of these outcomes, whereas b/tsDMARDs monotherapy, particularly antitumour necrosis factor agents, were associated with a lower risk of hospitalisation and death.ConclusionsOur meta-analysis demonstrated that patients with autoimmune diseases had an increased risk of COVID-19, primarily attributed to glucocorticoid use. b/tsDMARDs monotherapy was associated with a lower risk of severe COVID-19 suggesting its safety in the COVID-19 pandemic.

ObjectiveTo evaluate long-term risk of first cardiovascular (CV) events, CV deaths and all-cause deaths in community-dwelling participants of a cardiovascular disease (CVD) prevention programme delivered in a primary care setting.MethodsIndividuals who visited a primary healthcare service in Sollentuna (Sweden) and agreed to participate in the programme between 1988 and 1993 were followed. They had at least one CV risk factor but no prior myocardial infarction and received support to increase physical activity using the programme Physical Activity on Prescription and to adopt health-promoting behaviours including cooking classes, weight reduction, smoking cessation and stress management. Participants (n=5761) were compared with a randomly selected, propensity score-matched reference group from the general population in Stockholm County (n=34 556). All individuals were followed in Swedish registers until December 2011.ResultsIn the intervention group and the reference group there were 698 (12.1%) and 4647 (13.4%) first CV events, 308 (5.3%) and 2261 (6.5%) CV deaths, and 919 (16.5%) and 6405 (18.5%) all-cause deaths, respectively, during a mean follow-up of 22 years. The HR (95% CI) in the intervention group compared with the reference group was 0.88 (0.81 to 0.95) for first CV events, 0.79 (0.70 to 0.89) for CV deaths and 0.83 (0.78 to 0.89) for all-cause deaths.ConclusionsParticipation in a CVD prevention programme in primary healthcare focusing on promotion of physical activity and healthy lifestyle was associated with lower risk of CV events (12%), CV deaths (21%) and all-cause deaths (17%) after two decades. Promoting physical activity and healthy living in the primary healthcare setting may prevent CVD.

Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) registry was a large Japanese multicentre retrospective registry of consecutive patients with severe aortic stenosis (AS) before introduction of transcatheter aortic valve implantation. We sought to overview the data from the CURRENT AS registry to discuss the three major contemporary issues related to clinical practice in patients with severe AS: (1) under-referral/underuse of surgical aortic valve replacement (SAVR) in symptomatic patients with severe AS, (2) management of asymptomatic patients with severe AS and (3) management of patients with low-gradient severe aortic stenosis (LG-AS). First, despite the dismal prognosis of symptomatic patients with severe AS, SAVR, including those performed during follow-up, was reported to be underused. In the CURRENT AS registry, overall 53% of symptomatic patients underwent aortic valve replacement (AVR) during follow-up. Second, we reported that compared with conservative strategy, initial AVR strategy was associated with lower risk of all-cause death and heart failure hospitalisation in asymptomatic patients with severe AS. Although current recommendations for AVR are mainly dependent on the patient symptoms, some patients may not complain of any symptom because of their sedentary lifestyle. We also reported several important objective factors associated with worse clinical outcomes in asymptomatic patients with severe AS for risk stratification. Finally, initial AVR strategy was associated with better long-term clinical outcomes than conservative strategy in both patients with high-gradient AS and patients with LG-AS. The favourable effect of initial AVR strategy was also seen in patients with LG-AS with left ventricular ejection fraction of ≥50%.

ObjectiveTo compare two cohorts of middle-aged men from the general population born 30 years apart for incidence and predictors of heart failure (HF).MethodsTwo population samples of men, born in 1913 (n=855) and in 1943 (n=797), were examined at 50 years of age and followed up for 21 years (1963–1994 and 1993–2014). Cox regression analysis was used to examine the impact of different factors on the risk of developing HF.ResultsEighty men born in 1913 (9.4%) and 42 men born in 1943 (5.3%) developed HF during follow-up; adjusted HRs comparing the two cohorts (born 1943 vs 1913) were: 0.46 (95% CI 0.28 to 0.74, p=0.002). In both cohorts, higher body mass index, higher diastolic blood pressure, treatment for hypertension, onset of either atrial fibrillation (AF), ischaemic heart disease and diabetes mellitus were associated with higher risk of HF. Higher heart rate was associated with an increased risk only in men born in 1913, whereas higher systolic blood pressure (SBP), smoking, higher glucose, higher cholesterol and physical inactivity were associated with an increased risk in men born in 1943. AF contributed higher risk of incident HF, whereas SBP and physical inactivity contributed lower risk in men born in 1943 compared with men born in 1913.ConclusionsMen born in 1943 had half the risk of HF after their 50s than those born 30 years earlier. AF, obesity, ischaemic heart disease, diabetes and hypertension remain important precursors of HF.

ObjectiveTo examine the relationship between Mediterranean diet and risk of later-onset Crohn’s disease (CD) or ulcerative colitis (UC).DesignWe conducted a prospective cohort study of 83 147 participants (age range: 45–79 years) enrolled in the Cohort of Swedish Men and Swedish Mammography Cohort. A validated food frequency questionnaire was used to calculate an adherence score to a modified Mediterranean diet (mMED) at baseline in 1997. Incident diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modelling to calculate HRs and 95% CI.ResultsThrough December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC with an average follow-up of 17 years. Higher mMED score was associated with a lower risk of CD (Ptrend=0.03) but not UC (Ptrend=0.61). Compared with participants in the lowest category of mMED score (0–2), there was a statistically significant lower risk of CD (HR=0.42, 95% CI 0.22 to 0.80) but not UC (HR=1.08, 95% CI 0.74 to 1.58). These associations were not modified by age, sex, education level, body mass index or smoking (all Pinteraction >0.30). The prevalence of poor adherence to a Mediterranean diet (mMED score=0–2) was 27% in our cohorts, conferring a population attributable risk of 12% for later-onset CD.ConclusionIn two prospective studies, greater adherence to a Mediterranean diet was associated with a significantly lower risk of later-onset CD.

Cardiologists’ perception of the risk of stroke in rheumatic heart disease (RHD) is influenced more by anecdote and opinion than by the evidence.1 Despite data indicating a similar, if not a lower risk of stroke, even among the potentially highest-risk patients with RHD (those with mitral stenosis (MS) and atrial fibrillation (AF)),1 there is a pervasive belief that they may be at the ‘highest risk of thromboembolism’.2 As a consequence, in current practice, any patient with significant valvular heart disease and AF (valvular AF) becomes a candidate for long-term oral anticoagulation, without further risk stratification . The perception of very high stroke risk in RHD is also reinforced by estimates of stroke burden, which are based on extrapolation from the proportion of stroke admissions who have RHD (3%–8%),3 rather than the proportion of strokes attributable to RHD in the community (1%–2%).4 Contemporary data on stroke risk in RHD are therefore needed to realign risk perceptions to reality, to aid in risk stratification and to help make decisions on long-term anticoagulation. The study by Vasconcelos and colleagues in this issue of Heart is therefore a welcome addition to the literature in this area.5 Patients with valvular AF have a risk of stroke similar to that of those with non-valvular AF. Data from the Framingham study showed that the absolute risk of stroke was 4.5 per 100 patient-years among patients with MS and AF, similar to the risk in those with non-valvular AF (4.2 per 100 patient-years).6 In passing, it is worth noting that most references …

PurposeTo determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea.MethodsData regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020.ResultsOut of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500–1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses.ConclusionAdults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.

ObjectiveTo investigate if marital status is associated with risk of cardiovascular disease (CVD) and to explore the potential influence of leucocyte telomere length (LTL), a marker of biological ageing, on such association.DesignPopulation-based prospective cohort studySettingsSwedish Twin Registry.ParticipantsBased on the Screening Across the Lifespan Twin Study from the Swedish Twin Registry, we included 10 058 twins born between 1900 and 1958 who underwent an interview between 1998 and 2002 during which information about marital status was collected. Blood samples from these participants were subsequently collected between 2004 and 2008 and used for LTL assessment using quantitative PCR technique.Main outcome measuresIncident cases of CVD were identified through the Swedish Patient Register and Causes of Death Register through December 31, 2016. Multivariable linear regression and Cox proportional hazards regression models were used to estimate the regression coefficients (βs) and HRs with 95% CIs respectively. Potential confounders included age, sex, educational attainment and body mass index.ResultsA total of 2010 participants were diagnosed with CVD during a median follow-up of 9.8 years. LTL was shorter among individuals living singly, including those who were divorced or separated (β:−0.014, 95% CI: −0.035, 0.007), widowed (β:−0.035, 95% CI: −0.061, –0.010), or living alone (β:−0.033, 95% CI: −0.052, –0.014), than individuals who were married or cohabitating. One SD increase of LTL was associated with a lower risk of CVD (HR: 0.79, 95% CI: 0.66, 0.93). Individuals who were divorced or separated, widowed, or living alone had a higher risk of CVD than individuals who were married or cohabitating. The summary HR of CVD was 1.21 (95% CI: 1.08, 1.35) when comparing individuals who were living singly, regardless of reason, with the individuals who were married or cohabitating. LTL appeared to mediate little of the association between marital status and CVD (HR additionally adjusted for LTL: 1.20; 95% CI: 1.08, 1.34).ConclusionsLiving singly, regardless of reason, was associated with a shorter LTL and a higher risk of CVD. The association between marital status and CVD was however not greatly attributable to telomere shortening.

ObjectiveTo investigate the association of running participation and the dose of running with the risk of all-cause, cardiovascular and cancer mortality.DesignSystematic review and meta-analysis.Data sourcesJournal articles, conference papers and doctoral theses indexed in Academic Search Ultimate, CINAHL, Health Source: Nursing/Academic Edition, MasterFILE Complete, Networked Digital Library of Theses and Dissertations, Open Access Theses and Dissertations, PsycINFO, PubMed/MEDLINE, Scopus, SPORTDiscus and Web of Science.Eligibility criteria for selecting studiesProspective cohort studies on the association between running or jogging participation and the risk of all-cause, cardiovascular and/or cancer mortality in a non-clinical population of adults were included.ResultsFourteen studies from six prospective cohorts with a pooled sample of 232 149 participants were included. In total, 25 951 deaths were recorded during 5.5–35 year follow-ups. Our meta-analysis showed that running participation is associated with 27%, 30% and 23% lower risk of all-cause (pooled adjusted hazard ratio (HR)=0.73; 95% confidence interval (CI) 0.68 to 0.79), cardiovascular (HR=0.70; 95% CI 0.49 to 0.98) and cancer (HR=0.77; 95% CI 0.68 to 0.87) mortality, respectively, compared with no running. A meta-regression analysis showed no significant dose–response trends for weekly frequency, weekly duration, pace and the total volume of running.ConclusionIncreased rates of participation in running, regardless of its dose, would probably lead to substantial improvements in population health and longevity. Any amount of running, even just once a week, is better than no running, but higher doses of running may not necessarily be associated with greater mortality benefits.

AimTo examine the association between socioeconomic position and the risk of atrial fibrillation (AF) in different stages of life in a population of Danish citizens.MethodsRegister-based study. We followed all individuals turning 35, 50, 65 or 80 years from 1 January 1996 to 31 December 2005 until AF, death, emigration or the end of study period (31 December 2015). Exposure was education and income. We used Cox regression for the HRs (95% CI) and the pseudo-observation method for the adjusted risk difference (RD) (%).ResultsA total of 2 173 857 participants were enrolled and 151 340 incident cases of AF occurred over a median of 13.6 years of follow-up. Adjusted HR (95% CI) of incident AF for the youngest age group with the highest education (ref lowest) was 0.62 (0.50 to 0.77) (women) and 0.85 (0.76 to 0.96) (men). The associations attenuated with increasing age, that is, HRs for the oldest age group were 1.04 (0.97 to 1.10) and 0.98 (0.96 to 1.04), respectively. The corresponding adjusted RDs (%) were: −0.28 (−0.43 to −0.14), −0.18 (−0.36 to −0.01), 3.04 (−0.55 to 6.64) and −0.74 (−3.38 to 2.49), respectively. Similar but weaker associations were found for income.ConclusionHigher level of education and income was associated with a lower risk of being diagnosed with AF in young individuals but the association decreased with increasing age and was almost absent for the oldest age cohort. However, since AF is relatively rare in the youngest the RDs were low.

ObjectiveThere is controversy regarding the effect of napping on cardiovascular disease (CVD), with most studies failing to consider napping frequency. We aimed to assess the relationship of napping frequency and average nap duration with fatal and non-fatal CVD events.Methods3462 subjects of a Swiss population based cohort with no previous history of CVD reported their nap frequency and daily nap duration over a week, and were followed over 5.3 years. Fatal and non-fatal CVD events were adjudicated. Cox regressions were performed to obtain HRs adjusted for major cardiovascular risk factors and excessive daytime sleepiness or obstructive sleep apnoea.Results155 fatal and non-fatal events occurred. We observed a significantly lower risk for subjects napping 1–2 times weekly for developing a CVD event (HR 0.52, 95% CI 0.28 to 0.95) compared with non-napping subjects, in unadjusted as well as adjusted models. The increased HR (1.67, 95% CI 1.10 to 2.55) for subjects napping 6–7 times weekly disappeared in adjusted models (HR 0.89, 95% CI 0.58 to 1.38). Neither obstructive sleep apnoea nor excessive daytime sleepiness modified this lower risk. No association was found between nap duration and CVD events.ConclusionSubjects who nap once or twice per week have a lower risk of incident CVD events, while no association was found for more frequent napping or napping duration. Nap frequency may help explain the discrepant findings regarding the association between napping and CVD events.

ObjectiveFaecal immunochemical test (FIT) shows promise as a non-invasive triage test for colorectal cancer (CRC) in the symptomatic population. The aim of this study was to assess the use of FIT within the recent NG12 and DG30 National Institute for Health and Care Excellence (NICE) guidelines.DesignA single-centre prospective study of patients referred to University Hospitals Coventry and Warwickshire NHS Trust via the 2-week wait (TWW) pathway between January 2015 and March 2016 was conducted. 612 patients were reviewed, of which 519 were found to meet the NG12 criteria and 79 met the DG30 criteria. Data included age, sex, symptoms, colonoscopy or CT colonography, histology and FIT results.Main outcome measuresFIT was performed in all patients and sensitivity, specificity, positive predictive value and negative predictive value, with 95% CI, for cancers and adenomas within each pathway (TWW, NG12 and DG30) was calculated.ResultsCRC sensitivity in TWW pathway patients, NG12 and DG30 group was 86.84% (95% CI 71.91% to 95.59%), 84.85% (95% CI 68.1% to 94.89%) and 100% (95% CI 47.82% to 100%), respectively. Specificity was 82.23% (95% CI 78.85% to 85.27%), 81.28% (95% CI 77.52% to 84.65%) and 91.89% (95% CI 83.18% to 96.97%), respectively. Adenoma sensitivity in the groups was 30.69% (95% CI 29.9% to 40.66%), 30.77% (95% CI 21.51% to 41.32%) and 25% (95% CI 3.19% to 65.09%), respectively.ConclusionUse of FIT within the remit of the NG12 NICE guidelines shows a high sensitivity and specificity and may be an effective triage tool when considering whether to perform investigations. However, there is still a miss rate. FIT within DG30 has excellent sensitivity and improved specificity; however, DG30 targets lower risk groups and accounts for only 13% of the entire referrals for suspected cancer. Therefore, managing the larger, higher risk NG12 group may require the addition of another test or marker to ensure that CRC is not missed.

BackgroundA life course approach has been suggested as the most appropriate to establish the total impact of socioeconomic status (SES) on adult health outcomes; however, such an approach has been poorly used within Mediterranean populations. We aimed to examine the SES trajectories from childhood to adulthood associated with mortality risk in a large general population-based cohort and to test potential pathways (eg, inflammation) underlying such associations.MethodsLongitudinal analyses on 22 194 subjects recruited in the Moli-sani Study, Italy (2005–2010). Low and high SES in childhood, educational attainment (low/high) and SES during adulthood (measured by a score including material resources and dichotomised as low/high) were used to define overall trajectories.ResultsOver 8.3 years of follow-up, 1155 deaths occurred. In the group with poor childhood SES, an upward trajectory in both educational and material circumstances was associated with lower risk of all-cause death (HR=0.64; 95% CI 0.47 to 0.87), as opposed to subjects who remained stably low (low education and adulthood SES). Subjects with high childhood SES, but not educational achievement, were at increased risk of total and cardiovascular disease (CVD) death, although reporting higher material SES in adult life, as compared with the stably high SES group (HR=1.44; 1.02 to 2.02 and HR=1.90; 1.10 to 3.28, respectively). Inflammatory markers marginally accounted for such associations.ConclusionFor individuals with low SES in early life, an educational and material upward trajectory over the life course was associated with lower mortality risk. In the high SES childhood group, lack of a higher educational attainment appeared to be unfavourably associated with survival.

BackgroundEvidence on the role of very low or very high volumes of leisure time physical activity (PA) on the risk of all-cause and cause-specific mortality is limited. We aimed to examine the associations of different levels of leisure time PA with the risk of all-cause, cardiovascular disease (CVD) and cancer-specific mortality.MethodsData were from 12 waves of the National Health Interview Surveys (1997–2008) linked to the National Death Index records through 31 December 2011. A total of 88 140 eligible participants aged 40–85 years were included.ResultsCompared with inactive individuals, those performing 10–59 min/week of PA had 18% lower risk of all-cause mortality (hazard ratio (HR): 0.82, 95% confidence interval (CI): 0.72–0.95). Those who reported 1–2 times (150–299 min/week) the recommended level of leisure time PA had 31% (HR: 0.69, 95%CI: 0.63–0.75) reduced risk of all-cause mortality. Importantly, the continued benefits were observed among those performing leisure time PA 10 or more times (≥1500 min/week) the recommended minimum level (HR: 0.54, 95% CI: 0.45–0.64). For 10–59, 150–299 and ≥1500 min/week of PA, the corresponding HRs (95% CIs) for CVD-specific mortality were 0.88 (0.67–1.17), 0.63 (0.52–0.78) and 0.67 (0.45–0.99), respectively: for cancer-specific mortality were 0.86 (0.66–1.11), 0.76 (0.64–0.89) and 0.53 (0.39–0.73), respectively. In addition, there was a larger reduction in all-cause and cause-specific mortality for vigorous vs. moderate intensity PA.ConclusionsWe found that beneficial association between leisure time PA and mortality starts from a low dose. Doing more vigorous exercise could lead to additional health benefits.

The UK Transcatheter Aortic Valve Implantation (TAVI) registry has collected data about every TAVI procedure performed in the UK. The latest data are from 2016 when 3250 procedures (49.5 pmp) were performed. There has been no change in the mean age of patients but there has been a shift to lower risk with fall in mean Logistic Euroscore since 2012. The switch from general anaesthetic to conscious sedation has been rapid, and propensity-adjusted analysis has not shown a difference in outcomes. In-hospital mortality has fallen to 1.8% in 2016, and relative survival analysis has shown outcome the same as the matched general population to 3 years. The UK TAVI registry has provided valuable benchmarks, and a risk adjustment model that includes frailty measures has been successfully developed and is available online.

Background/aimsTo evaluate the associations of dietary consumption with the 10-year incidence of diabetic retinopathy (DR) progression in working-aged Australians with diabetes.MethodsWe obtained longitudinal data of all diabetic subjects aged 45–65 years from the baseline of the 45 and Up Study and linked this data with Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme claims until 2016. Retinal photocoagulation (RPC), as determined based on the MBS data, was used as a proxy measure of DR progression. Dietary measurements were assessed via self-reported consumption of meat, dairy products, whole-meal bread, breakfast cereal, vegetables, fruit and fruit juice using a self-administered questionnaire at baseline. Cox regression was used to assess the association between dietary consumption and incident RPC during the follow-up period.ResultsA total of 8122 participants were included in the current analysis with a mean age of 57.2±5.2 years. During a mean follow-up of 8.6 years, 314 participants (3.8% of baseline) received RPC. Higher consumption of cheese and whole-meal bread was associated with a lower risk of incident RPC, with the HRs of the highest quartiles versus the lowest being 0.58 (95% CI 0.41 to 0.83; test for trend, p=0.007) and 0.64 (0.46 to 0.89; p=0.04), respectively. Body mass index, insulin treatment and gender were significant modifiers for the association between cheese/whole-meal bread and RPC.ConclusionConsumption of cheese and whole-meal bread could reduce the risk of DR progression among the working-aged Australian population with diabetes.

ObjectiveTo assess the cumulative incidence of restenosis and stroke after stenting for cervical carotid artery stenosis.MethodsWe reviewed PubMed, ScienceDirect, and Scopus and included all studies reporting restenosis after stenting. The cumulative incidence of restenosis at 6 and 12 months was calculated. We also estimated the cumulative incidence of ipsilateral stroke within 30 days after stenting. Random effect meta-analysis and meta-regression were performed using relevant study level covariates. Sources of heterogeneity were investigated.ResultsAmong 7765 records, 40 studies were selected. 15 943 patients and 16 337 carotid arteries were considered. The overall pooled cumulative incidence of restenosis >50% at 12 months was 5.7% (95% CI 3.8% to 8.6%), >70% at 12 months was 5.2% (95% CI 3.3% to 8.2%), >50% at 6 months was 3.9% (95% CI 2.2% to 6.8%), and ipsilateral stroke within 30 days after stenting was 1.6% (95% CI 1.0% to 2.5%) without association with the use of an embolic protection device. We did not identify any relevant source of heterogeneity of the cumulative incidence of restenosis >50% at 12 months. Mean age explained 80.9% (R2=80.9%, p=0.01) of heterogeneities of restenosis >70% at 12 months. The presence of hostile neck explained 53.9% (R2=53.9%, p=0.03) of heterogeneities of restenosis >50% at 6 months.ConclusionThis meta-analysis showed a low cumulative rate of restenosis at 12 months and ipsilateral stroke within 30 days after stenting. Older patients and those with hostile neck present a lower risk of in-stent restenosis. The use of an embolic protection device was not associated with a lower risk of stroke.

ObjectivesWe examined the dose–response relationship between physical activity (PA) and incidence of cardiovascular disease (CVD) risk factors in adults in Taiwan.MethodsThis study included 1 98 919 participants, aged 18–97 years, free of CVD, cancer and diabetes at baseline (1997–2013), who were followed until 2016. At baseline, participants were classified into five PA levels: inactive’ (0 metabolic equivalent of task (MET)-h/week), ‘lower insufficiently active’ (0.1–3.75 MET-h/week), ‘upper insufficiently active’ (3.75–7.49 MET-h/week), ‘active’ (7.5–14.99 MET-h/week) and ‘highly active’ (≥15 MET-h/week]. CVD risk factors were assessed at baseline and at follow-up by physical examination and laboratory tests. Analyses were performed with Cox regression and adjusted for the main confounders.ResultsDuring a mean follow-up of 6.0±4.5 years (range 0.5–19 years), 20 447 individuals developed obesity, 19 619 hypertension, 21 592 hypercholesterolaemia, 14 164 atherogenic dyslipidaemia, 24 275 metabolic syndrome and 8548 type 2 diabetes. Compared with inactive participants, those in the upper insufficiently active (but not active) category had a lower risk of obesity (HR 0.92; 95% CI 0.88 to 0.95), atherogenic dyslipidaemia (0.96; 0.90 to 0.99), metabolic syndrome (0.95; 0.92 to 0.99) and type 2 diabetes (0.91; 0.86 to 0.97). Only highly active individuals showed a lower incidence of CVD risk factors than their upper insufficiently active counterparts.ConclusionCompared with being inactive, doing half the recommended amount of PA is associated with a lower incidence of several common biological CVD risk factors. Given these benefits, half the recommended amount of PA is an evidence based target for inactive adults.

ObjectiveTo describe the characteristics and outcomes of patients with a clinical diagnosis of COVID-19 and false-negative SARS-CoV-2 reverse transcription-PCR (RT-PCR), and develop and internally validate a diagnostic risk score to predict risk of COVID-19 (including RT-PCR-negative COVID-19) among medical admissions.DesignRetrospective cohort study.SettingTwo hospitals within an acute NHS Trust in London, UK.ParticipantsAll patients admitted to medical wards between 2 March and 3 May 2020.OutcomesMain outcomes were diagnosis of COVID-19, SARS-CoV-2 RT-PCR results, sensitivity of SARS-CoV-2 RT-PCR and mortality during hospital admission. For the diagnostic risk score, we report discrimination, calibration and diagnostic accuracy of the model and simplified risk score and internal validation.Results4008 patients were admitted between 2 March and 3 May 2020. 1792 patients (44.8%) were diagnosed with COVID-19, of whom 1391 were SARS-CoV-2 RT-PCR positive and 283 had only negative RT-PCRs. Compared with a clinical reference standard, sensitivity of RT-PCR in hospital patients was 83.1% (95% CI 81.2%–84.8%). Broadly, patients with false-negative RT-PCR COVID-19 and those confirmed by positive PCR had similar demographic and clinical characteristics but lower risk of intensive care unit admission and lower in-hospital mortality (adjusted OR 0.41, 95% CI 0.27–0.61). A simple diagnostic risk score comprising of age, sex, ethnicity, cough, fever or shortness of breath, National Early Warning Score 2, C reactive protein and chest radiograph appearance had moderate discrimination (area under the receiver–operator curve 0.83, 95% CI 0.82 to 0.85), good calibration and was internally validated.ConclusionRT-PCR-negative COVID-19 is common and is associated with lower mortality despite similar presentation. Diagnostic risk scores could potentially help triage patients requiring admission but need external validation.

Treatment guidelines and population-based recommendations evolve from research vetted by the scientific community. Healthcare providers require practice guidelines resulting from rigorous review of the totality of evidence. Open discussion/debate among experts is fundamental and encouraged, but blatant disregard for scientific process can lead to confusion and public distrust. A recent example is the controversy among scientists, healthcare professionals and the public about dietary saturated fat (SFA) recommendations to lower risk of cardiovascular disease (CVD). ### Dietary recommendations for SFA from authoritative organisations More than 60 years ago (in 1957), the American Heart Association (AHA) proposed that modifying dietary fat could reduce the incidence of coronary heart disease (CHD). This was based on research, including controlled feeding studies, and endpoint measures of blood lipids and blood pressure.1 In 1980, the first Dietary Guidelines for Americans recommended ‘avoiding too much SFA’.2 For decades, research has substantiated this consistent dietary recommendation from authoritative organisations to decrease SFA to reduce CVD risk.3–6 Current dietary guidelines for SFA and evidence ratings are summarised in table 1. While the strong evidence to reduce SFA specifically targets decreasing low-density lipoprotein (LDL)-cholesterol, it is very much germane to CVD risk reduction. View this table: Table 1 Authoritative recommendations for saturated fat and evidence ratings ### Challenging practice guidelines and population-based recommendations: the SFA SAGA In 2010, a meta-analysis of 21 prospective epidemiological studies totalling 347 747 subjects reported that higher intake of SFA was not associated with an increased risk of CHD, stroke or CVD.7 Aspects of this methodology were widely …

ObjectiveTo evaluate the association between statin use and risk of biliary tract cancers (BTC).DesignThis is a nested case–control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.ResultsWe included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007).ConclusionCompared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.

Objective To examine the comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis (OM) in adult cancer patients. Methods We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489. Results A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance. Conclusions This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.

BackgroundPipeline embolization devices (PEDs) are increasingly used in the treatment of cerebral aneurysms. Yet, major ischemic or hemorrhagic complications after PED treatment associated with antiplatelet regimens are not well-established.ObjectiveTo investigate the risk of ischemic and hemorrhagic complications associated with common antiplatelet regimens following PED treatment, and to examine whether platelet function testing (PFT) is associated with a lower risk of these complications.MethodsWe searched Medline, Embase, and Cochrane from 2009 to 2017. Twenty-nine studies were included that had reported a uniform antiplatelet regimen protocol and had provided data on major ischemic and hemorrhagic complications following PED treatment. Random-effect meta-analysis was used to pool overall ischemic and hemorrhagic event rates across studies. The rate of these complications with respect to the antithrombotic regimen and PFT was assessed by χ2 proportional tests.ResultsOverall, 2002 patients (age 55.9 years, 76% female) were included. A low-dose acetylsalicylic acid (ASA) regimen before and after PED treatment was associated with a higher rate of late ischemic complications than with high-dose ASA therapy (2.62 (95% CI 1.46 to 4.69) and 2.56 (1.41 to 4.64), respectively). Duration of post-procedure clopidogrel therapy ConclusionHigh-dose ASA therapy and clopidogrel treatment for at least 6 months were associated with a reduced incidence of ischemic events, without affecting the risk of hemorrhagic events.

BackgroundAngiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer.MethodsWe searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing therapy with conventional chemotherapy alone or no further treatment. Our main outcomes were the progression-free survival (PFS), overall survival (OS), and common adverse events.ResultsFifteen trials were included (N = 8721 participants). For newly diagnosed ovarian cancer, combination treatment with angiogenesis inhibitors and chemotherapy yielded a lower risk of disease progression (hazard ratio [HR], 0.83; 95% confidence interval (CI), 0.71–0.97) and no improved OS (HR, 0.95; 95% CI, 0.86–1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR, 0.72; 95% CI, 0.65–0.81) and OS (HR, 0.84; 95%CI, 0.74–0.96). In recurrent patients, the combined HR was 0.58 (95% CI, 0.52–0.65) for PFS, and for OS, the combined HR was 0.86 (95% CI, 0.79–0.94). We found no significant improvement for either PFS (HR, 0.80; 95% CI, 0.63–1.01) or OS (HR, 1.06; 95% CI, 0.88–1.28) in the pure maintenance therapy.In the overall population, angiogenesis inhibitors increased the incidence of gastrointestinal perforation (risk ratio [RR], 2.57; 95% CI, 1.66–3.97), hypertension (RR, 7.60; 95% CI, 2.79–20.70), arterial thromboembolism (RR, 2.27; 95% CI, 1.34–3.84), proteinuria (RR, 4.31; 95% CI, 2.15–8.64), and complication of wound healing (RR, 1.72, 95% CI, 1.12–2.63).ConclusionsCombination treatment with angiogenesis inhibitors and chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and recurrent ovarian cancer, with an increased incidence of common adverse events. Conversely, we detected no statistically significant survival benefit in the pure maintenance setting. The main limitation of the review is clinical heterogeneity across the studies.

ObjectiveTo examine the associations between egg consumption and cardiovascular disease (CVD), ischaemic heart disease (IHD), major coronary events (MCE), haemorrhagic stroke as well as ischaemic stroke.MethodsDuring 2004–2008, over 0.5 million adults aged 30–79 years were recruited from 10 diverse survey sites in China. Participants were asked about the frequency of egg consumption and were followed up via linkages to multiple registries and active investigation. Among 461 213 participants free of prior cancer, CVD and diabetes, a total of 83 977 CVD incident cases and 9985 CVD deaths were documented, as well as 5103 MCE. Stratified Cox regression was performed to yield adjusted hazard ratios for CVD endpoints associated with egg consumption.ResultsAt baseline, 13.1% of participants reported daily consumption (usual amount 0.76 egg/day) and 9.1% reported never or very rare consumption (usual amount 0.29 egg/day). Compared with non-consumers, daily egg consumption was associated with lower risk of CVD (HR 0.89, 95% CI 0.87 to 0.92). Corresponding multivariate-adjusted HRs (95% CI) for IHD, MCE, haemorrhagic stroke and ischaemic stroke were 0.88 (0.84 to 0.93), 0.86 (0.76 to 0.97), 0.74 (0.67 to 0.82) and 0.90 (0.85 to 0.95), respectively. There were significant dose-response relationships of egg consumption with morbidity of all CVD endpoints (P for linear trend ConclusionAmong Chinese adults, a moderate level of egg consumption (up to

BackgroundThe American Heart Association (AHA) developed a simplified assessment tool based on seven ideal cardiovascular health (CVH) metrics, but the relationship between the AHA defined ideal CVH metrics and cardiovascular risk in Chinese population has not been well estimated.MethodsThe baseline survey were conducted among 938 Chinese men and women from four urban and rural population samples in China, aged 35–59 years in 1983–1984. The cohort was followed up for multiple cardiovascular endpoints up to 2005. Cox proportional hazard models were used to test the associations accounting for multiple covariates. Outcomes were collected in 1987–2005 and data analysed in 2017.ResultsDuring a median of 20.3 years follow-up, 68 non-fatal CVD events and 139 deaths (29 CVD deaths) occurred. The multivariable adjusted HRs and 95% CIs for all CVD in the groups with three and 4–7 ideal CVH metrics were 0.59 (95% CI 0.33 to 1.04) and 0.24 (95% CI 0.12 to 0.47), when the group with 0–2 ideal CVH metrics as the reference. Results also showed that participants with 4–7 ideal CVH metrics had a 54% (95% CI 24% to 72%) lower risk of all-cause mortality in comparison with those with 0–2 ideal metrics.ConclusionsThe number of ideal CVH metrics was inversely associated with the risk of cardiovascular morbidity and mortality in this Chinese general population.

BackgroundIntravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).MethodsThis phase III, multicentre, randomised, double-blind, placebo-controlled study (BEL113750; NCT01345253) was conducted in 49 centres across China, Japan and South Korea (May 2011–September 2015). Patients with SLE were randomised 2:1 to intravenous belimumab 10 mg/kg or placebo, plus SoC, every 4 weeks until Week 48. The primary endpoint was the SLE Responder Index (SRI) 4 response rate at Week 52. Secondary endpoints were the percentage of patients with ≥4 point reduction in Safety of Oestrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), SRI7, time to first severe flare and number of days prednisone (or equivalent) dose ≤7.5 mg/day and/or reduced by 50% from baseline. Safety was assessed.ResultsThe modified intent-to-treat population included 677 patients (belimumab n=451, placebo n=226). At Week 52, the SRI4 response rate was higher with belimumab versus placebo (53.8% vs 40.1%; OR: 1.99 (95% CI: 1.40, 2.82; P=0.0001)). The percentages of patients with a ≥4 point reduction in SELENA-SLEDAI and an SRI7 response were significantly greater for belimumab versus placebo. Patients in the belimumab group had a 50% lower risk of experiencing a severe flare than those receiving placebo (P=0.0004). In patients with baseline prednisone dose >7.5 mg/day, there was a significant reduction in steroid use favouring belimumab (P=0.0228). The incidence of adverse events was similar between groups.ConclusionsIn patients with SLE from North East Asia, belimumab significantly improved disease activity, while reducing prednisone use, with no new safety issues.