Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland.

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21·3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.

Impact of a Prior Cancer Diagnosis on Quality of Care and Survival Following Acute Myocardial Infarction: Retrospective Population-Based Cohort Study in England.

BACKGROUND: An increasing proportion of patients with cancer experience acute myocardial infarction (AMI). We investigated differences in quality of AMI care and survival between patients with and without previous cancer diagnoses. METHODS: A retrospective cohort study using Virtual Cardio-Oncology Research Initiative data. Patients aged 40+ years hospitalized in England with AMI between January 2010 and March 2018 were assessed, ascertaining previous cancers diagnosed within 15 years. Multivariable regression was used to assess effects of cancer diagnosis, time, stage, and site on international quality indicators and mortality. RESULTS: Of 512 388 patients with AMI (mean age, 69.3 years; 33.5% women), 42 187 (8.2%) had previous cancers. Patients with cancer had significantly lower use of ACE (angiotensin-converting enzyme) inhibitors/angiotensin receptor blockers (mean percentage point decrease [mppd], 2.6% [95% CI, 1.8-3.4]) and lower overall composite care (mppd, 1.2% [95% CI, 0.9-1.6]). Poorer quality indicator attainment was observed in patients with cancer diagnosed in the last year (mppd, 1.4% [95% CI, 1.8-1.0]), with later stage disease (mppd, 2.5% [95% CI, 3.3-1.4]), and with lung cancer (mppd, 2.2% [95% CI, 3.0-1.3]). Twelve-month all-cause survival was 90.5% in noncancer controls and 86.3% in adjusted counterfactual controls. Differences in post-AMI survival were driven by cancer-related deaths. Modeling improving quality indicator attainment to noncancer patient levels showed modest 12-month survival benefits (lung cancer, 0.6%; other cancers, 0.3%). CONCLUSIONS: Measures of quality of AMI care are poorer in patients with cancer, with lower use of secondary prevention medications. Findings are primarily driven by differences in age and comorbidities between cancer and noncancer populations and attenuated after adjustment. The largest impact was observed in recent cancer diagnoses (<1 year) and lung cancer. Further investigation will determine whether differences reflect appropriate management according to cancer prognosis or whether opportunities to improve AMI outcomes in patients with cancer exist.

Acute heart failure presentation, management, and outcomes in cancer patients: a national longitudinal study.

AIMS: Currently, little evidence exists on survival and quality of care in cancer patients presenting with acute heart failure (HF). The aim of the study is to investigate the presentation and outcomes of hospital admission with acute HF in a national cohort of patients with prior cancer. METHODS AND RESULTS: This retrospective, population-based cohort study identified 221 953 patients admitted to a hospital in England for HF during 2012-2018 (12 867 with a breast, prostate, colorectal, or lung cancer diagnosis in the previous 10 years). We examined the impact of cancer on (i) HF presentation and in-hospital mortality, (ii) place of care, (iii) HF medication prescribing, and (iv) post-discharge survival, using propensity score weighting and model-based adjustment. Heart failure presentation was similar between cancer and non-cancer patients. A lower percentage of patients with prior cancer were cared for in a cardiology ward [-2.4% age point difference (ppd) (95% CI -3.3, -1.6)] or were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists (ACEi/ARB) for heart failure with reduced ejection fraction [-2.1 ppd (-3.3, -0.9)] than non-cancer patients. Survival after HF discharge was poor with median survival of 1.6 years in prior cancer and 2.6 years in non-cancer patients. Mortality in prior cancer patients was driven primarily by non-cancer causes (68% of post-discharge deaths). CONCLUSION: Survival in prior cancer patients presenting with acute HF was poor, with a significant proportion due to non-cancer causes of death. Despite this, cardiologists were less likely to manage cancer patients with HF. Cancer patients who develop HF were less likely to be prescribed guideline-based HF medications compared with non-cancer patients. This was particularly driven by patients with a poorer cancer prognosis.

Glycosylated haemoglobin and prognosis in 10,536 people with cancer and pre-existing diabetes: a meta-analysis with dose-response analysis.

AIMS: To assess whether glycaemic control is associated with prognosis in people with cancer and pre-existing diabetes. METHODS: In this pre-registered systematic review (PROSPERO: CRD42020223956), PubMed and Web of Science were searched on 25th Nov 2021 for studies investigating associations between glycosylated haemoglobin (HbA1c) and prognosis in people with diabetes and cancer. Summary relative risks (RRs) and 95% Confidence Intervals (CIs) for associations between poorly controlled HbA1c or per 1-unit HbA1c increment and cancer outcomes were estimated using a random-effects meta-analysis. We also investigated the impact of potential small-study effects using the trim-and-fill method and potential sources of heterogeneity using subgroup analyses. RESULTS: Fifteen eligible observational studies, reporting data on 10,536 patients with cancer and pre-existing diabetes, were included. Random-effects meta-analyses indicated that HbA1c ≥ 7% (53 mmol/mol) was associated with increased risks of: all-cause mortality (14 studies; RR: 1.14 [95% CI: 1.03-1.27]; p-value: 0.012), cancer-specific mortality (5; 1.68 [1.13-2.49]; p-value: 0.011) and cancer recurrence (8; 1.68 [1.18-2.38; p-value: 0.004]), with moderate to high heterogeneity. Dose-response meta-analyses indicated that 1-unit increment of HbA1c (%) was associated with increased risks of all-cause mortality (13 studies; 1.04 [1.01-1.08]; p-value: 0.016) and cancer-specific mortality (4; 1.11 [1.04-1.20]; p-value: 0.003). All RRs were attenuated in trim-and-fill analyses. CONCLUSIONS: Our findings suggested that glycaemic control might be a modifiable risk factor for mortality and cancer recurrence in people with cancer and pre-existing diabetes. High-quality studies with a larger sample size are warranted to confirm these findings due to heterogeneity and potential small-study effects. In the interim, it makes clinical sense to recommend continued optimal glycaemic control.

Development of 2 Short Patient-Report Questionnaires of Patient Safety in Primary Care.

OBJECTIVES: The Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) is a valid and reliable instrument (61 items across 5 domains) of patients' perceptions of safety. Stakeholder feedback has supported shorter versions for improving choice and facilitating uptake of routine patient-centered evaluation. We sought to develop 2 shorter versions of PREOS-PC: one including the shortest possible scales that met established measurement performance standards and a screening version including a single item per domain. METHODS: A total of 1244 patients from 45 general practices across England completed PREOS-PC questionnaires. All scale items in PREOS-PC underwent Item Response Theory analysis, applying standard criteria for the item reduction. Cognitive debriefing from 10 patient interviews allowed for the assessment of the instruments' readability. The instruments' psychometrics properties were reassessed in a validation sample of 1557 patients in 21 English general practices. RESULTS: "PREOS-PC Compact" includes 25 items and 2 open-ended questions across the 5 domains, 44% of the length of the original instrument. "PREOS-PC Screen" consists of 6 items: the best-performing single items for 2 domains, 1 item modified from original items for each of the remaining 3 domains, and 1 open-ended question. The evaluation of the instruments confirmed they were acceptable to patients and met standards for readability; construct, convergent, and divergent validity; and reliability. CONCLUSIONS: PREOS-PC Compact meets high-performance standards while reducing patient burden for routine monitoring of patient safety in primary care. PREOS-PC Screen is a concise tool apt for incorporation into audits and to target more in-depth review as needed.

In-Hospital Complications in Pregnancies Conceived by Assisted Reproductive Technology.

Background Assisted reproductive technology (ART) has emerged as a common treatment option for infertility, a problem that affects an estimated 48 million couples worldwide. Advancing maternal age with increasing prepregnancy cardiovascular risk factors, such as chronic hypertension, obesity, and diabetes, has raised concerns about pregnancy complications associated with ART. However, in-hospital complications following pregnancies conceived by ART are poorly described. Methods and Results To assess the patient characteristics, obstetric outcomes, vascular complications and temporal trends of pregnancies conceived by ART, we analyzed hospital deliveries conceived with or without ART between January 1, 2008, and December 31, 2016, from the United States National Inpatient Sample database. We included 106 248 deliveries conceived with ART and 34 167 246 deliveries conceived without ART. Women who conceived with ART were older (35 versus 28 years; P<0.0001) and had more comorbidities. ART-conceived pregnancies were independently associated with vascular complications (acute kidney injury: adjusted odds ratio [aOR], 2.52; 95% CI 1.99-3.19; and arrhythmia: aOR, 1.65; 95% CI, 1.46-1.86), and adverse obstetric outcomes (placental abruption: aOR, 1.57; 95% CI, 1.41-1.74; cesarean delivery: aOR, 1.38; 95% CI, 1.33-1.43; and preterm birth: aOR, 1.26; 95% CI, 1.20-1.32), including in subgroups without cardiovascular disease risk factors or without multifetal pregnancies. Higher hospital charges ($18 705 versus $11 983; P<0.0001) were incurred compared with women who conceived without ART. Conclusions Pregnancies conceived by ART have higher risks of adverse obstetric outcomes and vascular complications compared with spontaneous conception. Clinicians should have detailed discussions on the associated complications of ART in women during prepregnancy counseling.

Measuring multimorbidity in research: Delphi consensus study.

Objective: To develop international consensus on the definition and measurement of multimorbidity in research. Design: Delphi consensus study. Setting: International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021. Participants: Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels. Results: 150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction. Conclusions: Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.

Socioeconomic Status and Outcomes in Heart Failure With Reduced Ejection Fraction From Asia.

BACKGROUND: Little is known regarding the impact of socioeconomic factors on the use of evidence-based therapies and outcomes in patients with heart failure with reduced ejection fraction across Asia. METHODS: We investigated the association of both patient-level (household income, education levels) and country-level (regional income level by World Bank classification, income disparity by Gini index) socioeconomic indicators on use of guideline-directed therapy and clinical outcomes (composite of 1-year mortality or HF hospitalization, quality of life) in the prospective multinational ASIAN-HF study (Asian Sudden Cardiac Death in Heart Failure). RESULTS: Among 4540 patients (mean age: 60±13 years, 23% women) with heart failure with reduced ejection fraction, 39% lived in low-income regions; 34% in regions with high-income disparity (Gini ≥42.8%); 64.4% had low monthly household income (

Outcome trends in people with heart failure, type 2 diabetes mellitus and chronic kidney disease in the UK over twenty years.

BACKGROUND: Heart failure (HF) together with type 2 diabetes (T2D) and chronic kidney disease (CKD) are major pandemics of the twenty first century. It is not known in people with new onset HF, what the distinct and combined associations are between T2D and CKD comorbidities and cause-specific hospital admissions and death, over the past 20 years. METHODS: An observational study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics in England (1998-2017). Participants were people aged ≥30 years with new onset HF. Exposure groups were HF with: (i) no T2D and no CKD (reference group); (ii) CKD-only (estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2); (iii) T2D-only; (iv) T2D and CKD. CKD severity groups were: CKD-3a (eGFR 45-59); CKD-3b (30-44); CKD-4 (15-29); CKD-5 (<15). Outcomes were cardiovascular and non-cardiovascular hospitalisations and all-cause death. FINDINGS: In 87,709 HF patients (mean age, 78 years; 49% female), 40% had CKD-only, 12% T2D-only, and 16% both. Age-standardised first-year CVD hospitalisation rates were significantly higher in HF patients with CKD-only (46.4; 95% CI 44.9,47.9 per 100 person years) and T2D-only (49.2; 46.7,58.8) than in the reference group (35.1; 34.0,36.1); the highest rate was in patients with T2D-CKD-5: 89.1 (65.8,112.4). Similar patterns were observed for non-CVD hospitalisations and deaths. Group differences remained significant after adjustment for potential confounders. Median survival was highest in the reference (4.4 years) and HF-T2D-only (4.1 years) groups, compared to HF-CKD-only (2.2 years). HF-T2D-CKD group survival ranged from 2.8 (CKD-3a) to 0.7 years (CKD-5). Over time, CVD hospitalisation rates significantly increased for HF-CKD-only (+26%) and reduced (-24%) for HF-T2D-only groups; no reductions were observed in any of the HF-T2D-CKD groups. Trends were similar for non-CVD hospitalisations and death: whilst death rates significantly reduced for HF-T2D-only (-37%), improvement was not observed in any of the T2D-CKD groups. INTERPRETATION: In a cohort of people with new onset HF, hospitalisations and deaths are high in patients with T2D or CKD, and worst in those with both comorbidities. Whilst outcomes have improved over time for patients with HF and comorbid T2D, similar trends were not seen in those with comorbid CKD. Strategies to prevent and manage CKD in people with HF are urgently needed. FUNDING: NIHR fellowship [reference: NIHR 30011].

Risk Factors for Heart Failure: 20-Year Population-Based Trends by Sex, Socioeconomic Status, and Ethnicity.

BACKGROUND: There are multiple risk factors for heart failure, but contemporary temporal trends according to sex, socioeconomic status, and ethnicity are unknown. METHODS: Using a national UK general practice database linked to hospitalizations (1998-2017), 108 638 incident heart failure patients were identified. Differences in risk factors among patient groups adjusted for sociodemographic factors and age-adjusted temporal trends were investigated using logistic and linear regression. RESULTS: Over time, a 5.3 year (95% CI, 5.2-5.5) age difference between men and women remained. Women had higher blood pressure, body mass index, and cholesterol than men (P<0.0001). Ischemic heart disease prevalence increased for all to 2006 before reducing in women by 0.5% per annum, reaching 42.7% (95% CI, 41.7-43.6), but not in men, remaining at 57.7% (95% CI, 56.9-58.6; interaction P=0.002). Diabetes mellitus prevalence increased more in men than in women (interaction P<0.0001). Age between the most deprived (74.6 years [95% CI, 74.1-75.1]) and most affluent (79.9 [95% CI, 79.6-80.2]) diverged (interaction P<0.0001), generating a 5-year gap. The most deprived had significantly higher annual increases in comorbidity numbers (+0.14 versus +0.11), body mass index (+0.14 versus +0.11 kg/m2), and lower smoking reductions (-1.2% versus -1.7%) than the most affluent. Ethnicity trend differences were insignificant, but South Asians were overall 6 years and the black group 9 years younger than whites. South Asians had more ischemic heart disease (+16.5% [95% CI, 14.3-18.6]), hypertension (+12.5% [95% CI, 10.5-14.3]), and diabetes mellitus (+24.3% [95% CI, 22.0-26.6]), and the black group had more hypertension (+12.3% [95% CI, 9.7-14.8]) and diabetes mellitus (+13.1% [95% CI, 10.1-16.0]) but lower ischemic heart disease (-10.6% [95% CI, -13.6 to -7.6]) than the white group. CONCLUSIONS: Population groups show distinct risk factor trend differences, indicating the need for contemporary tailored prevention programs.

Trends in Cause-Specific Outcomes Among Individuals With Type 2 Diabetes and Heart Failure in the United Kingdom, 1998-2017.

Importance: The phenotype of individuals with type 2 diabetes and heart failure (HF) is changing. Successful public health interventions for type 2 diabetes mean that patients more frequently present with HF without a prior ischemic event, which is likely to change outcomes, but trends in cause-specific outcomes are unknown. Objective: To investigate cause-specific outcomes and trends associated with type 2 diabetes among individuals with incident HF. Design, Setting, and Participants: This cohort study used UK primary care data, linked to hospital admissions and mortality, for 87 709 patients with incident HF from 1998 to 2017. Patients were 30 years or older and observed to death or July 31, 2017. Data analysis was conducted in March and April 2019. Exposure: Preexisting type 2 diabetes at diagnosis of HF. Individuals with type 1 diabetes were excluded. Main Outcomes and Measures: All-cause, cardiovascular (CVD), and non-CVD unplanned hospitalizations and mortality rates. Results: Of 87 709 patients with HF (43 173 [49.2%] women; 78 211 [89.2%] white), 20 858 (23.8%) had type 2 diabetes (median [interquartile range] age, 78.0 [70.0 to 84.0] years), and 66 851 (76.2%) had no diabetes (median [interquartile range] age, 80.0 [72.0 to 86.0] years). In patients with HF, type 2 diabetes was associated with an increase in the risk of unplanned hospital admission (adjusted incidence rate ratio for CVD hospitalizations: 1.24; 95% CI, 1.19 to 1.30; for non-CVD hospitalizations: 1.26; 95% CI, 1.22 to 1.30) and an increase in the risk of mortality (adjusted hazard ratio for CVD mortality: 1.06; 95% CI, 1.02 to 1.10; for non-CVD mortality: 1.24; 95% CI, 1.19 to 1.29). Age-standardized mortality risk at 1 year was 35.6% (95% CI, 35.1% to 36.1%) in the type 2 diabetes group vs 29.2% (95% CI, 29.0% to 29.5%) in the group with no diabetes. During the study period (ie, 1998 to 2017), associations of type 2 diabetes with hospitalization and mortality rates decreased for CVD outcomes but not for non-CVD outcomes. Age-adjusted hospitalization rates during the first year following HF diagnosis increased similarly for both groups over time (eg, HF with type 2 diabetes, 1998 to 2001: 133.3 per 100 person-years; 95% CI, 102.2 to 105.4 per 100 person-years; 2012 to 2015: 152.5 per 100 person-years; 95% CI, 145.5 to 159.5 per 100 person-years; P for difference in trend = .06), but trends diverged by cause. For example, hospitalizations for HF decreased for patients with type 2 diabetes at approximately the same annual rate (-2.2%; 95% CI, -3.9% to -0.5%) as they increased for those without diabetes (1.7%; 95% CI, 1.1% to 2.3%; P for difference in trend < .001). After 2004, a trend emerged showing a greater increase in non-CVD admissions among patients with HF and type 2 diabetes than among patients with no diabetes (2.3% [95% CI, 0.9% to 3.6%] vs 1.1% [95% CI, 0.8% to 1.4%]). In contrast to hospitalization rates, mortality rates reduced over time in both groups, but the reduction was greater among those with type 2 diabetes than without (-1.4% [95% CI, -1.8% to -0.9%] vs -0.7% [95% CI, -1.2% to -0.2%]; P for difference in trend < .001). Conclusions and Relevance: In this study, the higher risk of all cause-specific outcomes and emerging non-CVD trends associated with patients with type 2 diabetes who experienced HF indicated an urgent need for earlier comorbidity management and patient-centered multimorbidity care.

Bleeding After Hospital Discharge Following Acute Coronary Syndrome: Incidence, Types, Timing, and Predictors.

Background The incidence and predictors of bleeding after acute coronary syndrome are unclear within the real-world setting. Our objective was to determine the incidence, types, timing, and predictors of bleeding complications following hospital discharge after acute coronary syndrome. Methods and Results We used the Clinical Practice Research Datalink, with linkage to Hospital Episode Statistics, to determine the incidence, timing, and types of bleeding events within 12 months after hospital discharge for acute coronary syndrome. We assessed independent associations between postdischarge bleeding and baseline patient characteristics using a competing risk regression model, accounting for death as a competing event. Among 27 660 patients surviving to hospital discharge, 3620 (13%) experienced bleeding complications at a median time of 123 days (interquartile range, 45-223 days) after discharge. The incidence of bleeding was 162/1000 person-years (95% CI, 157-167/1000 person-years) within the first 12 months after hospital discharge. Bruising (949 bleeds [26%]) was the most common type of first bleeding event, followed by gastrointestinal bleed (705 bleeds [20%]), whereas intracranial bleed was relatively rare (81 bleeds [2%]). Significant predictors of postdischarge bleeding included history of bleeding complication, oral anticoagulant prescription, history of peripheral vascular disease, chronic obstructive pulmonary disease, and advanced age (>80 years). Predictors for postdischarge bleeding varied, depending on the anatomic site of the bleeding event. Conclusions Bleeding complications after hospital discharge for acute coronary syndrome are common. Patients who experience these bleeding events have distinct baseline characteristics, which vary by anatomic site of the bleed. These characteristics can inform risk-benefit considerations in deciding on favorable combination and duration of secondary antithrombotic therapy.

20-year trends in cause-specific heart failure outcomes by sex, socioeconomic status, and place of diagnosis: a population-based study.

BACKGROUND: Heart failure is an important public health issue affecting about 1 million people in the UK, but contemporary trends in cause-specific outcomes among different population groups are unknown. METHODS: In this retrospective, population-based study, we used the UK Clinical Practice Research Datalink and Hospital Episodes Statistics databases to identify a cohort of patients who had a diagnosis of incident heart failure between Jan 1, 1998, and July 31, 2017. Patients were eligible for inclusion if they were aged 30 years or older with a first code for heart failure in their primary care or hospital record during the study period. We assessed cause-specific admission to hospital (ie, hospitalisation) and mortality, by age, sex, socioeconomic status, and place of diagnosis (ie, hospital vs community diagnosis). We calculated outcome rates separately for the first year (first-year rates) and for the second-year onwards (subsequent-year rates). Patients were followed up until death or study end. This study is registered with Clinical Practice Research Datalink Independent Scientific Advisory Committee, protocol number 18_037R. FINDINGS: We identified 88 416 individuals with incident heart failure over the study period, of whom 43 461 (49%) were female. The mean age was 77·8 years (SD 11·3) and median follow-up was 2·4 years (IQR 0·5 to 5·7). Age-adjusted first-year rates of hospitalisation increased by 28% for all-cause admissions, from 97·1 (95% CI 94·3 to 99·9) to 124·2 (120·9 to 127·5) per 100 person-years; by 28% for heart failure-specific admissions, from 17·2 (16·2 to 18·2) to 22·1 (20·9 to 23·2) per 100 person-years; and by 42% for non-cardiovascular admissions, from 59·2 (57·2 to 61·2) to 83·9 (81·3 to 86·5) per 100 person-years. 167 641 (73%) of 228 113 hospitalisations were for non-cardiovascular causes and annual rate increases were higher for women (3·9%, 95% CI 2·8 to 4·9) than for men (1·4%, 0·6 to 2·1; p<0·0001); and for patients diagnosed with heart failure in hospital (2·4%, 1·4 to 3·3) than those diagnosed in the community (1·2%, 0·3 to 2·2). Annual increases in hospitalisation due to heart failure were 2·6% (1·9 to 3·4) for women compared with stable rates in men (0·6%, -0·9 to 2·1), and 1·6% (0·6 to 2·6) for the most deprived group compared with stable rates for the most affluent group (1·2%, -0·3 to 2·8). A significantly higher risk of all-cause hospitalisation was found for the most deprived than for the most affluent (incident rate ratio 1·34, 95% CI 1·32 to 1·35) and for the hospital-diagnosed group than for the community-diagnosed group (1·76, 1·73 to 1·80). Age-adjusted first-year rates of all-cause mortality decreased by 6% from 24·5 (95% CI 23·4 to 39·2) to 23·0 (22·0 to 24·1) per 100 person-years. Annual change in mortality was -1·4% (95% CI -2·3 to -0·5) in men but was stable for women (0·3%, -0·5 to 1·1), and -2·7% (-3·2 to -2·2) for the community-diagnosed group compared with -1·1% (-1·8 to -0·4) in the hospital-diagnosed group (p<0·0001). A significantly higher risk of all-cause mortality was seen in the most deprived group than in the most affluent group (hazard ratio 1·08, 95% CI 1·05 to 1·11) and in the hospital-diagnosed group than in the community-diagnosed group (1·55, 1·53 to 1·58). INTERPRETATION: Tailored management strategies and specialist care for patients with heart failure are needed to address persisting and increasing inequalities for men, the most deprived, and for those who are diagnosed with heart failure in hospital, and to address the worrying trends in women. FUNDING: Wellcome Trust.

Incidence and prognostic impact of post discharge bleeding post acute coronary syndrome within an outpatient setting: a systematic review.

OBJECTIVE: The primary objective was to determine the incidence of bleeding events post acute coronary syndrome (ACS) following hospital discharge. The secondary objective was to determine the prognostic impact of bleeding on mortality, major adverse cardiovascular events (MACE), myocardial re-infarction and rehospitalisation in the postdischarge setting. DESIGN: A narrative systematic review. DATA SOURCE: Medline, Embase, Amed and Central (Cochrane) were searched up to August 2018. STUDY SELECTION: For the primary objective, randomised controlled trials (RCT) and observational studies reporting on the incidence of bleeding post hospital discharge were included. For the secondary objective, RCTs and observational studies that compared patients with bleeding versus those without bleeding post hospital discharge vis-à-vis mortality, MACE, myocardial re-infarction and rehospitalisation were included. RESULTS: 53 studies (36 observational studies and 17 RCTs) with a combined cohort of 714 458 participants for the primary objectives and 187 317 for the secondary objectives were included. Follow-up ranged from 1 month to just over 4 years. The incidence of bleeding within 12 months post hospital discharge ranged from 0.20% to 37.5% in observational studies and between 0.96% and 39.4% in RCTs. The majority of bleeds occurred in the initial 3 months after hospital discharge with bruising the most commonly reported event. Major bleeding increased the risk of mortality by nearly threefold in two studies. One study showed an increased risk of MACE (HR 3.00,95% CI 2.75 to 3.27; p<0.0001) with bleeding and another study showed a non-significant association with rehospitalisation (HR 1.20,95% CI 0.95 to 1.52; p=0.13). CONCLUSION: Bleeding complications following ACS management are common and continue to occur in the long term after hospital discharge. These bleeding complications may increase the risk of mortality and MACE, but greater evidence is needed to assess their long-term effects. PROSPERO REGISTRATION NUMBER: CRD42017062378.

Cardiometabolic Polygenic Risk Scores and Osteoarthritis Outcomes: A Mendelian Randomization Study Using Data From the Malmö Diet and Cancer Study and the UK Biobank.

OBJECTIVE: To investigate the causal role of cardiometabolic risk factors in osteoarthritis (OA) using associated genetic variants. METHODS: We studied 27,691 adults from the Malmö Diet and Cancer Study (MDCS) and replicated novel findings among 376,435 adults from the UK Biobank. Trait-specific polygenic risk scores for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, triglyceride levels, body mass index (BMI), fasting plasma glucose (FPG) levels, and systolic blood pressure (BP) were used to test the associations of genetically predicted elevations in each trait with incident OA diagnosis (n = 3,559), OA joint replacement (n = 2,780), or both (total OA; n = 4,226) in Mendelian randomization (MR) analyses in the MDCS, and with self-reported and/or hospital-diagnosed OA (n = 65,213) in the UK Biobank. Multivariable MR, MR-Egger, and weighted median MR were used to adjust for potential pleiotropic biases. RESULTS: In the MDCS, genetically predicted elevation in LDL cholesterol level was associated with a lower risk of OA diagnosis (odds ratio [OR] 0.83 [95% confidence interval (95% CI) 0.73-0.95] per 1SD increase) and total OA (OR 0.87 [95% CI 0.78-0.98]), which was supported by multivariable MR for OA diagnosis (OR 0.84 [95% CI 0.75-0.95]) and total OA (0.87 [95% CI 0.78-0.97]), and by conventional 2-sample MR for OA diagnosis (OR 0.86 [95% CI 0.75-0.98]). MR-Egger indicated no pleiotropic bias. Genetically predicted elevation in BMI was associated with an increased risk of OA diagnosis (OR 1.65 [95% CI 1.14-2.41]), while MR-Egger indicated pleiotropic bias and a larger association with OA diagnosis (OR 3.25 [1.26-8.39]), OA joint replacement (OR 3.81 [95% CI 1.39-10.4]), and total OA (OR 3.41 [95% CI 1.43-8.15]). No associations were observed between genetically predicted HDL cholesterol level, triglyceride level, FPG level, or systolic BP and OA outcomes. The associations with LDL cholesterol levels were replicated in the UK Biobank (OR 0.95 [95% CI 0.93-0.98]). CONCLUSION: Our MR study provides evidence of a causal role of lower LDL cholesterol level and higher BMI in OA.

Conceptualizing multiple drug use in patients with comorbidity and multimorbidity: proposal for standard definitions beyond the term polypharmacy.

With older and aging populations, patients experience multiple chronic diseases at the same time. Individual chronic disease guidelines often recommend pharmacological therapies as a key intervention, resulting in patients being prescribed multiple regular medications for their different diseases. Although the term "polypharmacy" has been applied to the use of multiple medications, there is no consistent definition, and this term is now being used all inclusively. To improve both scientific rigor and optimal patient care, it is crucial that a standard terminology is used, which reclassifies the term "polypharmacy" into distinct phenotypes relating to the index chronic disease, additional conditions to the index (comorbidity), or the experience of multiple chronic conditions at the same time (multimorbidity). Using three exemplar index conditions; heart failure, type 2 diabetes, and breast cancer, we propose the reclassification of the term "polypharmacy" into three distinct phenotypes. First, index drug or multi-index drug therapy, where each index condition creates multiple drug use for that condition; second, codrug therapy, where addition of other comorbid conditions increases the multiple drug use and may influence the management of the index disease and third, multidrug therapy, where adult population with multimorbidity may be on many drugs. This article reviews guidelines for the individual exemplars to develop the basis for the new terms and then develops the pharmacoepidemiology of multiple drug use further by reviewing the evidence on the relationship between the phenotypic classification and important outcomes. The importance of standardizing "polypharmacy" terminology for the scientific agenda and clinical practice is that it relates to an index condition or disease safety outcomes including drug interactions, adverse side effects in hospital admissions, and related "polypill" concept.

Do frailty measures improve prediction of mortality and morbidity following transcatheter aortic valve implantation? An analysis of the UK TAVI registry.

OBJECTIVES: Previous studies indicate frailty to be associated with poor outcomes following transcatheter aortic valve implantation (TAVI), but there is limited evidence from multicentre registries. The aim was to investigate the independent association of frailty with TAVI outcomes, and the prognostic utility of adding frailty into existing clinical prediction models (CPMs). DESIGN: The UK TAVI registry incorporated three frailty measures since 2013: Canadian Study of Health and Ageing, KATZ and poor mobility. We investigated the associations between these frailty measures with short-term and long-term outcomes, using logistic regression to estimate multivariable adjusted ORs, and Cox proportional hazards models to explore long-term survival. We compared the predictive performance of existing TAVI CPMs before and after updating them to include each frailty measure. SETTING: All patients who underwent a TAVI procedure in England or Wales between 2013 and 2014. PARTICIPANTS: 2624 TAVI procedures were analysed in this study. PRIMARY AND SECONDARY OUTCOMES: The primary endpoints in this study were 30-day mortality and long-term survival. The Valve Academic Research Consortium (VARC)-2 composite early safety endpoint was considered as a secondary outcome. RESULTS: KATZ <6 (OR 2.10, 95% CI 1.39 to 3.15) and poor mobility (OR 2.15, 95% CI 1.41 to 3.28) predicted 30-day mortality after multivariable adjustment. All frailty measures were associated with increased odds of the VARC-2 composite early safety endpoint. We observed a significant increase in the area under the receiver operating characteristic curves by approximately 5% after adding KATZ <6 or poor mobility into the TAVI CPMs. Risk stratification agreement was significantly improved by the addition of each frailty measure, with an increase in intraclass correlation coefficient of between 0.15 and 0.31. CONCLUSION: Frailty was associated with worse outcomes following TAVI, and incorporating frailty metrics significantly improved the predictive performance of existing CPMs. Physician-estimated frailty measures could aid TAVI risk stratification, until more objective scales are routinely collected.

Comorbidity health pathways in heart failure patients: A sequences-of-regressions analysis using cross-sectional data from 10,575 patients in the Swedish Heart Failure Registry.

BACKGROUND: Optimally treated heart failure (HF) patients often have persisting symptoms and poor health-related quality of life. Comorbidities are common, but little is known about their impact on these factors, and guideline-driven HF care remains focused on cardiovascular status. The following hypotheses were tested: (i) comorbidities are associated with more severe symptoms and functional limitations and subsequently worse patient-rated health in HF, and (ii) these patterns of association differ among selected comorbidities. METHODS AND FINDINGS: The Swedish Heart Failure Registry (SHFR) is a national population-based register of HF patients admitted to >85% of hospitals in Sweden or attending outpatient clinics. This study included 10,575 HF patients with patient-rated health recorded during first registration in the SHFR (1 February 2008 to 1 November 2013). An a priori health model and sequences-of-regressions analysis were used to test associations among comorbidities and patient-reported symptoms, functional limitations, and patient-rated health. Patient-rated health measures included the EuroQol-5 dimension (EQ-5D) questionnaire and the EuroQol visual analogue scale (EQ-VAS). EQ-VAS score ranges from 0 (worst health) to 100 (best health). Patient-rated health declined progressively from patients with no comorbidities (mean EQ-VAS score, 66) to patients with cardiovascular comorbidities (mean EQ-VAS score, 62) to patients with non-cardiovascular comorbidities (mean EQ-VAS score, 59). The relationships among cardiovascular comorbidities and patient-rated health were explained by their associations with anxiety or depression (atrial fibrillation, odds ratio [OR] 1.16, 95% CI 1.06 to 1.27; ischemic heart disease [IHD], OR 1.20, 95% CI 1.09 to 1.32) and with pain (IHD, OR 1.25, 95% CI 1.14 to 1.38). Associations of non-cardiovascular comorbidities with patient-rated health were explained by their associations with shortness of breath (diabetes, OR 1.17, 95% CI 1.03 to 1.32; chronic kidney disease [CKD, OR 1.23, 95% CI 1.10 to 1.38; chronic obstructive pulmonary disease [COPD], OR 95% CI 1.84, 1.62 to 2.10) and with fatigue (diabetes, OR 1.27, 95% CI 1.13 to 1.42; CKD, OR 1.24, 95% CI 1.12 to 1.38; COPD, OR 1.69, 95% CI 1.50 to 1.91). There were direct associations between all symptoms and patient-rated health, and indirect associations via functional limitations. Anxiety or depression had the strongest association with functional limitations (OR 10.03, 95% CI 5.16 to 19.50) and patient-rated health (mean difference in EQ-VAS score, -18.68, 95% CI -23.22 to -14.14). HF optimizing therapies did not influence these associations. Key limitations of the study include the cross-sectional design and unclear generalisability to other populations. Further prospective HF studies are required to test the consistency of the relationships and their implications for health. CONCLUSIONS: Identification of distinct comorbidity health pathways in HF could provide the evidence for individualised person-centred care that targets specific comorbidities and associated symptoms.

Preterm Delivery and Future Risk of Maternal Cardiovascular Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Preterm delivery (<37 weeks gestational age) affects 11% of all pregnancies, but data are conflicting whether preterm birth is associated with long-term adverse maternal cardiovascular outcomes. We aimed to systematically evaluate and summarize the evidence on the relationship between preterm birth and future maternal risk of cardiovascular diseases. METHODS AND RESULTS: A systematic search of MEDLINE and EMBASE was performed to identify relevant studies that evaluated the association between preterm birth and future maternal risk of composite cardiovascular disease, coronary heart disease, stroke, and death caused by cardiovascular or coronary heart disease and stroke. We quantified the associations using random effects meta-analysis. Twenty-one studies with over 5.8 million women, including over 338 000 women with previous preterm deliveries, were identified. Meta-analysis of studies that adjusted for potential confounders showed that preterm birth was associated with an increased risk of maternal future cardiovascular disease (risk ratio [RR] 1.43, 95% confidence interval [CI], 1.18, 1.72), cardiovascular disease death (RR 1.78, 95% CI, 1.42, 2.21), coronary heart disease (RR 1.49, 95% CI, 1.38, 1.60), coronary heart disease death (RR 2.10, 95% CI, 1.87, 2.36), and stroke (RR 1.65, 95% CI, 1.51, 1.79). Sensitivity analysis showed that the highest risks occurred when the preterm deliveries occurred before 32 weeks gestation or were medically indicated. CONCLUSIONS: Preterm delivery is associated with an increase in future maternal adverse cardiovascular outcomes, including a 2-fold increase in deaths caused by coronary heart disease. These findings support the assessment of preterm delivery in cardiovascular risk assessment in women.

Consumer segmentation and time interval between types of hospital admission: a clinical linkage database study.

Background: Healthcare policies target unplanned hospital admissions and 30-day re-admission as key measures of efficiency, but do not focus on factors that influence trajectories of different types of admissions in the same patient over time. Objectives: To investigate the influence of consumer segmentation and patient factors on the time intervals between different types of hospital admission. Research design, subjects and measures: A cohort design was applied to an anonymised linkage database for adults aged 40 years and over (N = 58 857). Measures included Mosaic segmentation, multimorbidity defined on six chronic condition registers and hospital admissions over a 27-month time period. Results: The shortest mean time intervals between two consecutive planned admissions were: 90 years and over (160 days (95% confidence interval (CI): 146-175)), Mosaic groups 'Twilight subsistence' (171 days (164-179)) or 'Welfare borderline' and 'Municipal dependency' (177 days (172-182)) compared to the reference Mosaic groups (186 days (180-193)), and multimorbidity count of four or more (137 days (130-145)). Mosaic group 'Twilight subsistence' (rate ratio (RR) 1.22 (95% CI: 1.08-1.36)) or 'Welfare borderline' and 'Municipal dependency' RR 1.20 (1.10-1.31) were significantly associated with higher rate to an unplanned admission following a planned event. However, associations between patient factors and unplanned admissions were diminished by adjustment for planned admissions. Conclusion: Specific consumer segmentation and patient factors were associated with shorter time intervals between different types of admissions. The findings support innovation in public health approaches to prevent by a focus on long-term trajectories of hospital admissions, which include planned activity.