ObjectivesTo investigate mortality in adults with intellectual disabilities: rates, causes, place, demographic and clinical predictors.DesignCohort study with record linkage to death data.SettingGeneral community.Participants961/1023 (94%) adults (16–83 years; mean=44.1 years; 54.6% male) with intellectual disabilities, clinically examined in 2001–2004; subsequently record-linked to their National Health Service number, allowing linkage to death certificate data, 2018.Outcome measuresStandardised mortality ratios (SMRs), underlying and all contributing causes of death, avoidable deaths, place, and demographic and clinical predictors of death.Results294/961 (30.6%) had died; 64/179 (35.8%) with Down syndrome, 230/783 (29.4%) without Down syndrome. SMR overall=2.24 (1.98, 2.49); Down syndrome adults=5.28 (3.98, 6.57), adults without Down syndrome=1.93 (1.68, 2.18); male=1.69 (1.42, 1.95), female=3.48 (2.90, 4.06). SMRs decreased as age increased. More severe intellectual disabilities increased SMR, but ability was not retained in the multivariable model. SMRs were higher for most International Statistical Classification of Diseases and Related Health Problems, 10th Revision chapters. For adults without Down syndrome, aspiration/reflux/choking and respiratory infection were the the most common underlying causes of mortality; for Down syndrome adults ‘Down syndrome’, and dementia were most common. Amenable deaths (29.8%) were double that in the general population (14%); 60.3% died in hospital. Mortality risk related to percutaneous endoscopic gastrostomy/tube fed, Down syndrome, diabetes, lower respiratory tract infection at cohort-entry, smoking, epilepsy, hearing impairment, increasing number of prescribed drugs, increasing age. Bowel incontinence reduced mortality risk.ConclusionsAdults with intellectual disabilities with and without Down syndrome have different SMRs and causes of death which should be separately reported. Both die younger, from different causes than other people. Some mortality risks are similar to other people, with earlier mortality reflecting more multimorbidity; amenable deaths are also common. This should inform actions to reduce early mortality, for example, training to avoid aspiration/choking, pain identification to address problems before they are advanced, and reasonable adjustments to improve healthcare quality.

Aim The contemporary incidence of heart failure (HF) in patients with chronic coronary syndrome is unclear. We aimed to study the incidence and predictors of cardiovascular (CV) death, HF hospitalization or new‐onset HF not requiring hospitalization, in patients included in the CLARIFY registry. Methods and results CLARIFY is a contemporary, international registry of ambulatory patients with chronic coronary artery disease, conducted in 45 countries. At baseline, data on demographics, ethnicity, CV risk factors, medical history, cardiac parameters and medication were collected. Patients were followed up yearly up to 5 years. In this analysis, 26 769 patients with no HF history were included. At 5‐year follow‐up, 4393 patients (16.4%) reached the primary endpoint comprising CV death, HF hospitalization, or new‐onset HF. Only 16.7% of them (n = 732) required hospitalization for HF. All‐cause death occurred in 6.6% of patients (61.4% were CV). Age over 70 years, left ventricular ejection fraction <50%, Canadian Cardiovascular Society class ≥2 angina, atrial fibrillation or paced rhythm on the ECG, body mass index <20 kg/m2, and a history of stroke, were the most robust predictors of the primary outcome. Age <50 years, Asian ethnicity, and percutaneous revascularization were negative predictors of the outcome. Conclusion A sizeable proportion of patients with chronic coronary syndrome develop HF, which only infrequently requires hospitalization. Early identification of patients with HF may lead to early treatment, and help to further decrease mortality and morbidity. This concept needs confirmation in future studies.

Aims Measurement of B-type natriuretic peptide (BNP) or N-terminal pro-BNP is recommended as part of the diagnostic workup of patients with suspected heart failure (HF). We evaluated the diagnostic and prognostic utility of the novel urinary proteomic classifier HF1, compared with BNP, in HF. HF1 consists of 85 unique urinary peptide fragments thought, mainly, to reflect collagen turnover. Methods and results We performed urinary proteome analysis using capillary electrophoresis coupled with mass spectrometry in 829 participants. Of these, 622 had HF (504 had chronic HF and 118 acute HF) and 207 were controls (62 coronary heart disease patients without HF and 145 healthy controls). The area under the receiver operating characteristic (ROC) curve (AUC) using HF1 for the diagnosis of HF (cases vs. controls) was 0.94 (95% CI, 0.92-0.96). This compared with an AUC for BNP of 0.98 (95% CI, 0.97-0.99). Adding HF1 to BNP increased the AUC to 0.99 (0.98-0.99), P < 0.001, and led to a net reclassification improvement of 0.67 (95% CI, 0.54-0.77), P < 0.001. Among 433 HF patients followed up for a median of 989 days, we observed 186 deaths. HF1 had poorer predictive value to BNP for all-cause mortality and did not add prognostic information when combined with BNP. Conclusions The urinary proteomic classifier HF1 performed as well, diagnostically, as BNP and provided incremental diagnostic information when added to BNP. HF1 had less prognostic utility than BNP.

IntroductionThe estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only.MethodsHere we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE).ResultsVAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model.ConclusionLimitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes.FundingNovartis Pharmaceuticals UK Limited.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0620-x) contains supplementary material, which is available to authorized users.

BackgroundThe COMPASS trial showed a reduction of ischemic events with low‐dose rivaroxaban and aspirin in chronic coronary syndromes (CCS) compared with aspirin alone, at the expense of increased bleeding.HypothesisThe CHA2DS2VaSc Score, REACH Recurrent Ischemic (RIS), and REACH Bleeding Risk Score (BRS) could identify patients with a favorable trade‐off between ischemic and bleeding events, among COMPASS‐eligible patients.MethodsWe identified the COMPASS‐eligible population within the CLARIFY registry (>30.000 patients with CCS). High‐bleeding risk patients (REACH BRS > 10) were excluded, as in the COMPASS trial. Patients were categorized as low (0–1) or high (≥ 2) CHA2DS2VaSc; low (0–12) or intermediate (13–19) REACH RIS, and low (0–6) or intermediate (7–10) REACH BRS. Ischemic outcome was the composite of cardiovascular death, myocardial infarction or stroke. Bleeding was defined as serious bleeding (haemorrhagic stroke, hospitalization for bleeding, transfusion).ResultsThe COMPASS‐eligible population comprised 5.142 patients with ischemic and bleeding outcome of 2.3 (2.1–2.5) and 0.5 (0.4–0.6) per 100 patient‐years, respectively. Patients with intermediate REACH RIS (n = 1934 [37.6%]) had the higher ischemic risk (3.0 [2.6–3.4]) with similar bleeding risk (0.5 [0.4–0.7]) as the overall population. Patients with low CHA2DS2VaSc (n = 229 [4.4%]) had a very low ischemic risk (0.6 [0.3–1.3]) with similar bleeding risk (0.5 [0.2–1.1]).ConclusionsIntermediate REACH RIS identified potential optimal candidates for adjunction of low‐dose rivaroxaban while patients with low CHA2DS2VaSc score .appears unlikely to benefit from the COMPASS regimen. None of the three risk scores predicted the occurrence of serious bleeding.