Variability in Contemporary Heparin Prescription and Activated Clotting Time Monitoring During Percutaneous Coronary Intervention: Call for Up-To-Date Evidence-Based Guidelines.

BACKGROUND: Unfractionated heparin (UFH) is the preferred anticoagulant agent in percutaneous coronary intervention (PCI) procedures for minimising the risk of thrombotic complications. Because of the narrow therapeutic range of UFH, some society guidelines have advocated the use of the activated clotting time (ACT) test to monitor anticoagulation intensity during PCI to reduce thrombotic and bleeding complications. We aimed to assess the current practice of UFH prescription and its monitoring in Australia and New Zealand (ANZ). METHOD: We conducted an anonymous voluntary cross-sectional survey of interventional cardiologists (ICs) who were members of the Cardiac Society of Australia and New Zealand in 2022. The survey included 10 questions pertaining to the current practice of anticoagulation during PCI. RESULTS: Of 430 ICs surveyed, 148 responded (response rate, 34.4%). Most ICs (84.4%) prescribed 70-100 IU/kg of UFH for PCI. Over half of ICs (58.7%) routinely measured ACT during PCI, whereas only 22.2% routinely measured ACT after PCI to guide additional UFH prescription. Among ICs who prescribed additional UFH, approximately half (48%) aimed for ACT ≥250 seconds. Factors that influenced post-PCI UFH prescription included vascular access site and concomitant antiplatelet or anticoagulant therapy. CONCLUSIONS: The contemporary practice of UFH prescription during PCI and ACT monitoring in ANZ is variable and based on outdated evidence preceding current drug-eluting stents, antiplatelet therapies, and radial-first practice. Current society guideline recommendations lack clarity and agreement, reflecting the quality of the available evidence. Up-to-date clinical trials evaluating UFH prescription and ACT monitoring are needed to optimise clinical outcomes in contemporary PCI procedures.

Effect of Concomitant Cardiac Arrest on Outcomes in Patients With Acute Coronary Syndrome-Related Cardiogenic Shock.

Patients with acute coronary syndrome (ACS)-related cardiogenic shock (CS) with or without concomitant CA may have disparate prognoses. We compared clinical characteristics and outcomes of patients with CS secondary to ACS with and without cardiac arrest (CA). Between 2014 and 2020, 1,573 patients with ACS-related CS with or without CA who underwent percutaneous coronary intervention enrolled in a multicenter Australian registry were analyzed. Primary outcome was 30-day major adverse cardiovascular and cerebrovascular events (MACCE) (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization and stroke). Long-term mortality was obtained through linkage to the National Death Index. Compared with the no-CA group (n = 769, 49%), the CA group (n = 804, 51%) was younger (62 vs 69 years, p <0.001) and had fewer comorbidities. Patients with CA more frequently had ST-elevation myocardial infarction (92% vs 86%), occluded left anterior descending artery (43% vs 33%), and severe preprocedural renal impairment (49% vs 42%) (all p <0.001). CA increased risk of 30-day MACCE by 45% (odds ratio 1.45, 95% confidence interval 1.05 to 2.00, p = 0.024) after adjustment. CA group had higher 30-day MACCE (55% vs 42%, p <0.001) and mortality (52% vs 37%, p <0.001). Three-year survival was lower for CA compared with no-CA patients (43% vs 52%, p <0.001). In Cox regression, CS with CA was associated with a trend toward greater long-term mortality hazard (hazard ratio 1.19, 95% confidence interval 1.00 to 1.41, p = 0.055). In conclusion, concomitant CA among patients with ACS-related CS conferred a particularly heightened short-term risk with a diminishing legacy effect over time for mortality. CS survivors continue to exhibit high sustained long-term mortality hazard regardless of CA status.

Left Ventricular End-Diastolic Pressure for the Prediction of Contrast-Induced Nephropathy and Clinical Outcomes in Patients With ST-Elevation Myocardial Infarction Who Underwent Primary Percutaneous Intervention (the ELEVATE Study).

Contrast-induced nephropathy (CIN) is an important complication of percutaneous coronary intervention (PCI). We investigated whether left ventricular end-diastolic pressure (LVEDP) in patients who underwent PCI might be additive to current risk stratification of CIN. Data from consecutive patients who underwent primary PCI for ST-elevation myocardial infarction between 2013 and 2018 at Western Health in Victoria, Australia were analyzed. CIN was defined as a 25% increase in serum creatinine from baseline or 44 µmol/L increase in absolute value within 48 hours of contrast administration. Compared with patients without CIN (n = 455, 93%), those who developed CIN (n = 35, 7%) were older (64 vs 58 years, p = 0.006), and had higher peak creatine kinase (2,862 [1,258 to 3,952] vs 1,341 U/L [641 to 2,613], p = 0.02). The CIN group had higher median LVEDP (30 [21-33] vs 25 mm Hg [20-30], p = 0.013) and higher median Mehran risk score (MRS) (5 [2-8] vs 2 [1-5], p <0.001). Patients with CIN had more in-hospital major adverse cardiovascular and cerebrovascular events (composite end point of death, new or recurrent myocardial infarction or stent thrombosis, target vessel revascularization or stroke) (23% vs 8.6%, p = 0.01), but similar 30-day major adverse cardiovascular and cerebrovascular events (20% vs 15%, p = 0.46). An LVEDP >30 mm Hg independently predicted CIN (odds ratio 3.4, 95% confidence interval 1.46 to 8.03, p = 0.005). The addition of LVEDP ≥30 mm Hg to MRS marginally improved risk prediction for CIN compared with MRS alone (area-under-curve, c-statistic = 0.71 vs c-statistic = 0.63, p = 0.08). In conclusion, elevated LVEDP ≥30 mm Hg during primary PCI was an independent predictor of CIN in patients treated for ST-elevation myocardial infarction. The addition of LVEDP to the MRS may improve risk prediction for CIN.

Sex differences among patients presenting to hospital with out-of-hospital cardiac arrest and shockable rhythm.

OBJECTIVE: Sex differences in patients presenting with out-of-hospital cardiac arrest (OHCA) and shockable rhythm might be associated with disparities in clinical outcomes. METHODS: We conducted a retrospective cohort study and compared characteristics and short-term outcomes between male and female adult patients who presented with OHCA and shockable rhythm at two large metropolitan health services in Melbourne, Australia between the period of 2014-2018. Logistic regression was used to assess the effect of sex on clinical outcomes. RESULTS: Of 212 patients, 166 (78%) were males and 46 (22%) were females. Both males and females presented with similar rates of ST-elevation myocardial infarction (44% vs 36%, P = 0.29), although males were more likely to have a history of coronary artery disease (32% vs 13%) and a final diagnosis of a cardiac cause for their OHCA (89% vs 72%), both P = 0.01. Rates of coronary angiography (81% vs 71%, P = 0.23) and percutaneous coronary intervention (51% vs 42%, P = 0.37) were comparable among males and females. No differences in rates of in-hospital mortality (38% vs 37%, P = 0.90) and 30-day major adverse cardiac and cerebrovascular events (composite of all-cause mortality, myocardial infarction, coronary revascularization and nonfatal stroke) (39% vs 41%, P = 0.79) were observed between males and females, respectively. Female sex was not associated with worse in-hospital mortality when adjusted for other variables (odds ratio 0.66, 95% confidence interval 0.28-1.60, P = 0.36). CONCLUSION: Among patients presenting with OHCA and a shockable rhythm, baseline sex and sex differences were not associated with disparities in short-term outcomes in contemporary systems of care.

Evaluation of factors associated with selection for coronary angiography and in-hospital mortality among patients presenting with out-of-hospital cardiac arrest without ST-segment elevation.

BACKGROUND: Clinical factors favouring coronary angiography (CA) selection and variables associated with in-hospital mortality among patients presenting with out-of-hospital cardiac arrest (OHCA) without ST-segment elevation (STE) remain unclear. METHODS: We evaluated clinical characteristics associated with CA selection and in-hospital mortality in patients with OHCA, shockable rhythm and no STE. RESULTS: Between 2014 and 2018, 118 patients with OHCA and shockable rhythm without STE (mean age 59; males 75%) were stratified by whether CA was performed. Of 86 (73%) patients undergoing CA, 30 (35%) received percutaneous coronary intervention (PCI). CA patients had shorter return of spontaneous circulation (ROSC) time (17 vs. 25 min) and were more frequently between 50 and 60 years (29% vs. 6.5%), with initial Glasgow Coma Scale (GCS) score >8 (24% vs. 6%) (all p < 0.05). In-hospital mortality was 33% (n = 39) for overall cohort (CA 27% vs. no-CA 50%, p = 0.02). Compared to late CA, early CA ( ≤ 2 h) was not associated with lower in-hospital mortality (32% vs. 34%, p = 0.82). Predictors of in-hospital mortality included longer defibrillation time (odds ratio 3.07, 95% confidence interval 1.44-6.53 per 5-min increase), lower pH (2.02, 1.33-3.09 per 0.1 decrease), hypoalbuminemia (2.02, 1.03-3.95 per 5 g/L decrease), and baseline renal dysfunction (1.33, 1.02-1.72 per 10 ml/min/1.73 m2 decrease), while PCI to lesion (0.11, 0.01-0.79) and bystander defibrillation (0.06, 0.004-0.80) were protective factors (all p < 0.05). CONCLUSIONS: Among patients with OHCA and shockable rhythm without STE, younger age, shorter time to ROSC and GCS >8 were associated with CA selection, while less effective resuscitation, greater burden of comorbidities and absence of treatable coronary lesion were key adverse prognostic predictors.

Adverse Impact of Peri-Procedural Stroke in Patients Who Underwent Percutaneous Coronary Intervention.

Peri-procedural stroke (PPS) is an important complication in patients who underwent percutaneous coronary intervention (PCI). The extent to which PPS impacts mortality and outcomes remains to be defined. Consecutive patients who underwent PCI enrolled in the Victorian Cardiac Outcomes Registry (2014 to 2018) were categorized into PPS and no PPS groups. The primary outcome was 30-day major adverse cardiovascular events (MACEs) (composite of mortality, myocardial infarction, stent thrombosis, and unplanned revascularization). Of 50,300 patients, PPS occurred in 0.26% patients (n = 133) (71% ischemic, and 29% hemorrhagic etiology). Patients who developed PPS were older (69 vs 66 years) compared with patients with no PPS, and more likely to have pre-existing heart failure (59% vs 29%), chronic kidney disease (33% vs 20%), and previous cerebrovascular disease (13% vs 3.6%), p <0.01. Among those with PPS, there was a higher frequency of presentation with ST-elevation myocardial infarction (49% vs 18%) and out-of-hospital cardiac arrest (14% vs 2.2%), PCI by way of femoral access (59% vs 46%), and adjunctive thrombus aspiration (12% vs 3.6%), all p = <0.001. PPS was associated with incident 30-day MACE (odds ratio [OR] 2.97, 95% confidence intervals [CIs] 1.86 to 4.74, p <0.001) after multivariable adjustment. Utilizing inverse probability of treatment weighting analysis, PPS remained predictive of 30-day MACE (OR 1.91, 95% CI 1.31 to 2.80, p = 0.001) driven by higher 30-day mortality (OR 2.0, 95% CI 1.35 to 2.96, p = 0.001). In conclusion, in this large, multi-center registry, the incidence of PPS was low; however, its clinical sequelae were significant, with a twofold increased risk of 30-day MACE and all-cause death.

Natural adaptation and human selection of northeast African sheep genomes.

African sheep manifest diverse but distinct physio-anatomical traits, which are the outcomes of natural- and human-driven selection. Here, we generated 34.8 million variants from 150 indigenous northeast African sheep genomes sequenced at an average depth of ∼54× for 130 samples (Ethiopia, Libya) and ∼20× for 20 samples (Sudan). These represented sheep from diverse environments, tail morphology and post-Neolithic introductions to Africa. Phylogenetic and model-based admixture analysis provided evidence of four genetic groups corresponding to altitudinal geographic origins, tail morphotypes and possible historical introduction and dispersal of the species into and across the continent. Running admixture at higher levels of K (6 ≤ K ≤ 25), revealed cryptic levels of genome intermixing as well as distinct genetic backgrounds in some populations. Comparative genomic analysis identified targets of selection that spanned conserved haplotype structures overlapping clusters of genes and gene families. These were related to hypoxia responses, ear morphology, caudal vertebrae and tail skeleton length, and tail fat-depot structures. Our findings provide novel insights underpinning morphological variation and response to human-driven selection and environmental adaptation in African indigenous sheep.

Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m2) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m2. RESULTS: The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups (P for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m2 (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m2 (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m2. CONCLUSIONS: The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m2. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m2.

Temporal Changes in Pollen Concentration Predict Short-Term Clinical Outcomes in Acute Coronary Syndromes.

Background Atmospheric changes in pollen concentration may affect human health by triggering various allergic processes. We sought to assess if changes in pollen concentrations were associated with different acute coronary syndrome (ACS) subtype presentations and short-term clinical outcomes. Methods and Results We analyzed data in consecutive patients presenting with ACS (unstable angina, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction) treated with percutaneous coronary intervention between January 2014 and December 2017 and enrolled in the VCOR (Victorian Cardiac Outcomes Registry). Baseline characteristics were compared among patients exposed to different grass and total pollen concentrations. The primary outcome was occurrence of ACS subtypes and 30-day major adverse cardiac and cerebrovascular events (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or stroke). Of 15 379 patients, 7122 (46.3%) presented with ST-segment-elevation myocardial infarction, 6781 (44.1%) with non-ST-segment-elevation myocardial infarction, and 1476 (9.6%) with unstable angina. The mean age was 62.5 years, with men comprising 76% of patients. No association was observed between daily or seasonal grass and total pollen concentrations with the frequency of ACS subtype presentation. However, grass and total pollen concentrations in the preceding days (2-day average for grass pollen and 7-day average for total pollen) correlated with in-hospital mortality (odds ratio [OR], 2.17 [95% CI, 1.12-4.21]; P=0.021 and OR, 2.78 [95% CI, 1.00-7.74]; P=0.05), respectively, with a trend of 2-day grass pollen for 30-day major adverse cardiac and cerebrovascular events (OR, 1.50 [95% CI, 0.97-2.32]; P=0.066). Conclusions Increased pollen concentrations were not associated with differential ACS subtype presentation but were significantly related to in-hospital mortality following percutaneous coronary intervention, underscoring a potential biologic link between pollen exposure and clinical outcomes.

Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. METHODS: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. FINDINGS: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58-1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97-1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52-1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. INTERPRETATION: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. FUNDING: AstraZeneca.

Cardiac Arrest in the Cardiac Catheterization Laboratory: Initial Experience With the Role of Simulation Setup and Training.

With rising complexity of percutaneous coronary interventions being performed, the incidence of cardiac arrest in the cardiac catheterization laboratory (CCL) is likely to increase. The authors undertook a series of multidisciplinary simulation sessions to identify practice deficiencies and propose solutions to improve patient care. Five simulation sessions were held at Western Health CCL to simulate different cardiac arrest scenarios. Participants included cardiologists, intensivists, anesthetists, nurses, and technicians. Post-simulation feedback was analyzed qualitatively. Challenges encountered were grouped into 4 areas: (1) communication and teamwork, (2) equipment, (3) vascular access and drugs, and (4) physical environment and radiation exposure. Proposed solutions included regular simulation training; increasing familiarity with the physical environment, utilization of specialized equipment; and formation of 2 team leaders to improve efficiency. Cardiac arrest in the CCL is a unique clinical event that necessitates specific training to improve technical and nontechnical skills with potential to improve clinical outcomes.

Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: Design and rationale for the DARE-19 study.

AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS: DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS: DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.

Left atrial mechanics and aortic stiffness following high intensity interval training: a randomised controlled study.

PURPOSE: High intensity interval training (HIIT) has been shown to improve important health parameters, including aerobic capacity, blood pressure, cardiac autonomic modulation and left ventricular (LV) mechanics. However, adaptations in left atrial (LA) mechanics and aortic stiffness remain unclear. METHODS: Forty-one physically inactive males and females were recruited. Participants were randomised to either a 4-week HIIT intervention (n = 21) or 4-week control period (n = 20). The HIIT protocol consisted of 3 × 30-s maximal cycle ergometer sprints with a resistance of 7.5% body weight, interspersed with 2-min of active unloaded recovery, three times per week. Speckle tracking imaging of the LA and M-Mode tracing of the aorta was performed pre and post HIIT and control period. RESULTS: Following HIIT, there was significant improvement in LA mechanics, including LA reservoir (13.9 ± 13.4%, p = 0.033), LA conduit (8.9 ± 11.2%, p = 0.023) and LA contractile (5 ± 4.5%, p = 0.044) mechanics compared to the control condition. In addition, aortic distensibility (2.1 ± 2.7 cm2 dyn-1 103, p = 0.031) and aortic stiffness index (- 2.6 ± 4.6, p = 0.041) were improved compared to the control condition. In stepwise linear regression analysis, aortic distensibility change was significantly associated with LA stiffness change R2 of 0.613 (p = 0.002). CONCLUSION: A short-term programme of HIIT was associated with a significant improvement in LA mechanics and aortic stiffness. These adaptations may have important health implications and contribute to the improved LV diastolic and systolic mechanics, aerobic capacity and blood pressure previously documented following HIIT.

Changes in Statin Prescription Patterns in Patients Admitted to an Australian Geriatric Subacute Unit.

BACKGROUND: Assessment of demographic and clinical factors influencing the decision of statin discontinuation in the elderly population admitted to subacute geriatric unit. The aim of this study is to assess the clinical factors impacting the decision-making process of statin discontinuation in the elderly. METHODS: We retrospectively assessed changes in statin discontinuation and prescription among patients (≥60 years old) discharged from a geriatric evaluation and management unit by reviewing hospital digital medical records at Western Health - The Williamstown Hospital over a 12-month period from 4 February 2012 until 4 February 2013 inclusive. The main outcome of the study was to determine the independent predictors of statin discontinuation using logistic regression analysis. RESULTS: Of the studied population, 46% were already prescribed statins prior to their admission. Statins were discontinued in 17.5% of patients at discharge. Predictors of statin de-prescription included octogenarian status, primary prevention indication, poor functional recovery, residential care facility discharge destination and lower cognitive function. The presence of previous cardiovascular disease history and the burden of comorbidities were not predictors of statin discontinuation. CONCLUSIONS: We observed that factors that conveyed poor prognosis such as advanced age, poor functional recovery, worse cognitive function, being discharged to a residential care facility as well as primary prevention indication for statin prescription are predictors of statin discontinuation in the geriatric unit.

Comparison of short-term clinical outcomes of proximal versus nonproximal lesion location in patients treated with primary percutaneous coronary intervention for ST-elevation myocardial infarction: The PROXIMITI study.

OBJECTIVES: The objective of this study was to investigate the association of proximal and nonproximal location of culprit coronary lesions with clinical outcomes of patients presenting with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). BACKGROUND: Proximal culprit lesion location in patients presenting with STEMI is associated with increased mortality when compared to distal culprit lesions in the thrombolytic era. The impact of lesion location on clinical outcomes in the era of PCI remains unclear. METHODS: We analyzed 3,283 patients with STEMI who enrolled in the Victorian Cardiac Outcomes Registry. We compared outcomes in those with proximal lesion location versus patients with nonproximal location. RESULTS: Of 3,283 participants, 1,376 (41.9%) had a proximal lesion location. Patients with proximal lesion location presented with greater rates of cardiogenic shock and out-of-hospital cardiac arrest, and left ventricular systolic dysfunction, all P < .01. Procedural success rates were similar (96% vs. 95%, P = .08). Patients with proximal lesion location had higher rates of in-hospital and 30-day mortality, major adverse cardiac events (MACE; mortality, myocardial infarction, stent thrombosis, and unplanned revascularization) and major adverse cardiac and cerebrovascular events (MACCE; MACE, and stroke) compared to the nonproximal group, all P < .001. However, on multivariable regression analysis, proximal lesion location was not independently associated with MACE during in-hospital stay or at 30-days (OR 1.32, 95% CI 0.95-1.83, P = .09 and OR 1.23, 95% CI 0.92-1.65, P = .15) respectively. CONCLUSIONS: Patients with proximal lesion location had greater hemodynamic instability and higher-risk features; however, proximal lesions per se were not independently associated with worse clinical outcomes compared to nonproximal lesions.

A randomized controlled crossover trial evaluating differential responses to antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity: The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative Markers in HYpertension program-AIM-HY INFORM trial.

BACKGROUND: Ethnicity, along with a variety of genetic and environmental factors, is thought to influence the efficacy of antihypertensive therapies. Current UK guidelines use a "black versus white" approach; in doing so, they ignore the United Kingdom's largest ethnic minority: Asians from South Asia. STUDY DESIGN: The primary purpose of the AIM-HY INFORM trial is to identify potential differences in response to antihypertensive drugs used as mono- or dual therapy on the basis of self-defined ethnicity. A multicenter, prospective, open-label, randomized study with 2 parallel, independent trial arms (mono- and dual therapy), AIM-HY INFORM plans to enroll a total of 1,320 patients from across the United Kingdom. Those receiving monotherapy (n = 660) will enter a 3-treatment (amlodipine 10 mg od; lisinopril 20 mg od; chlorthalidone 25 mg od), 3-period crossover, lasting 24 weeks, whereas those receiving dual therapy (n = 660) will enter a 4-treatment (amlodipine 5 mg od and lisinopril 20 mg od; amlodipine 5 mg od and chlorthalidone 25 mg od; lisinopril 20 mg od and chlorthalidone 25 mg od; amiloride 10 mg od and chlorthalidone 25 mg od), 4-period crossover, lasting 32 weeks. Equal numbers of 3 ethnic groups (white, black/black British, and Asian/Asian British) will ultimately be recruited to each of the trial arms (ie, 220 participants per ethnic group per arm). Seated, automated, unattended, office, systolic blood pressure measured 8 weeks after each treatment period begins will serve as the primary outcome measure. CONCLUSION: AIM-HY INFORM is a prospective, open-label, randomized trial which aims to evaluate first- and second-line antihypertensive therapies for multiethnic populations.

Genome-Wide Variation, Candidate Regions and Genes Associated With Fat Deposition and Tail Morphology in Ethiopian Indigenous Sheep.

Variations in body weight and in the distribution of body fat are associated with feed availability, thermoregulation, and energy reserve. Ethiopia is characterized by distinct agro-ecological and human ethnic farmer diversity of ancient origin, which have impacted on the variation of its indigenous livestock. Here, we investigate autosomal genome-wide profiles of 11 Ethiopian indigenous sheep populations using the Illumina Ovine 50 K SNP BeadChip assay. Sheep from the Caribbean, Europe, Middle East, China, and western, northern and southern Africa were included to address globally, the genetic variation and history of Ethiopian populations. Population relationship and structure analysis separated Ethiopian indigenous fat-tail sheep from their North African and Middle Eastern counterparts. It indicates two main genetic backgrounds and supports two distinct genetic histories for African fat-tail sheep. Within Ethiopian sheep, our results show that the short fat-tail sheep do not represent a monophyletic group. Four genetic backgrounds are present in Ethiopian indigenous sheep but at different proportions among the fat-rump and the long fat-tail sheep from western and southern Ethiopia. The Ethiopian fat-rump sheep share a genetic background with Sudanese thin-tail sheep. Genome-wide selection signature analysis identified eight putative candidate regions spanning genes influencing growth traits and fat deposition (NPR2, HINT2, SPAG8, INSR), development of limbs and skeleton, and tail formation (ALX4, HOXB13, BMP4), embryonic development of tendons, bones and cartilages (EYA2, SULF2), regulation of body temperature (TRPM8), body weight and height variation (DIS3L2), control of lipogenesis and intracellular transport of long-chain fatty acids (FABP3), the occurrence and morphology of horns (RXFP2), and response to heat stress (DNAJC18). Our findings suggest that Ethiopian fat-tail sheep represent a uniquely admixed but distinct genepool that presents an important resource for understanding the genetic control of skeletal growth, fat metabolism and associated physiological processes.

The Multiple Consultant Report: new assessment; same old problems.

BACKGROUND: In December 2013 the Multiple Consultant Report (MCR) was introduced as an assessment tool for junior doctors (i.e. doctors below specialist status) in the UK, including those undertaking core medical training (CMT). It aims to capture the views of consultant supervisors about a doctor's clinical performance. OBJECTIVE: Despite the mandatory nature of the MCR there is no published academic evaluation of this tool as an assessment of, or for, learning. The aim of this study was to explore opinions on the MCR amongst core medical trainees at a large London teaching hospital. STUDY DESIGN: Questionnaires were distributed to the entire cohort of 42 core medical trainees. Data were enriched by a focus group. Inductive thematic analysis was used to analyse the data qualitatively. FINDINGS: Twenty-two trainees (52%) completed the questionnaire. Six trainees attended a single focus group. A key issue highlighted by this study was a lack of awareness amongst trainees (and assessors) surrounding the introduction and purpose of the MCR. Ineffective feedback limited the potential impact of the assessment, but many trainees reported a perception that the MCR duplicated existing assessments. Registrars (doctors undergoing a minimum 4 years of specialty training along with higher training in general medicine) were considered better placed to offer detailed feedback regarding the clinical performance of core medical trainees, within the context of the MCR. [The MRC] aims to capture the views of consultant supervisors about a doctor's clinical performance CONCLUSIONS: The MCR has many of the weaknesses and strengths observed with existing assessments. Given this, perhaps it is time to reconsider our approach to workplace-based assessments.