Citations

ABSTRACT Background The Accreditation Council for Graduate Medical Education (ACGME) has mandated revisions to residents' work hours to improve patient safety and enhance resident education and wellness. The impact on clinical outcomes on a national level is poorly understood. Objective We examined data from before and after the ACGME 2011 duty hour revision and looked for differences between teaching and nonteaching US hospitals. Methods A retrospective observational study of patients admitted to hospitals in the 2-year periods before and after the 2011 duty hour revision was conducted, utilizing a nationally representative data set. We compared patient and hospital characteristics using standardized differences. With nonteaching hospitals serving as the control group, we used multiple group interrupted time series segmented regression analysis to test for postrevision level and trend changes in mortality, length of stay (LOS), and costs. Results We examined more than 117 million hospitalizations. At teaching and nonteaching hospitals, trends in mortality and LOS in prerevision and postrevision periods were not significantly different (all P > .05). A significant monthly reduction in cost per hospitalization was noted postrevision at teaching hospitals (P = .019) but not at nonteaching hospitals (P = .62). In the 2 years following the 2011 revision, there was a monthly reduction in cost per hospitalization (–$52.28; 95% confidence interval –$116.90 to –$12.32; P = .026) at teaching relative to nonteaching hospitals. Conclusions There were no differences in mortality or LOS between teaching and nonteaching hospitals. However, there was a small decrease in cost per hospitalization at teaching hospitals following the 2011 revision.

OBJECTIVE To evaluate the efficacy and safety of inclisiran by diabetes status. RESEARCH DESIGN AND METHODS ORION-1 (ClinicalTrials.gov, NCT02597127) randomized 501 subjects with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalents and high LDL cholesterol (LDL-C), despite maximally tolerated LDL-C–lowering therapies, to one or two doses of placebo or inclisiran. Levels of lipids and proprotein convertase subtilisin/kexin type 9 (PCSK9) at baseline and day 180 were compared. RESULTS Inclisiran was associated with marked declines in LDL-C (median −28% to −52%, P < 0.0001 and −28% to −55%, P < 0.005 for all doses in the without- and with-diabetes groups, respectively) and PCSK9. The inclisiran-treated groups also had lower apolipoprotein B, non-HDL cholesterol, and lipoprotein(a) but higher HDL cholesterol. Inclisiran had an adverse profile similar to that of placebo, and adverse events were proportionally balanced in the baseline with- and without-diabetes groups. CONCLUSIONS PCSK9-targeted siRNA-driven strategies may provide a novel therapeutic option for managing dyslipidemia in the presence and absence of diabetes.

Background: The ORION-1 trial (Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol [LDL-C]) demonstrated that inclisiran, an siRNA therapeutic that targets protease proprotein convertase subtilisin/kexin type 9 mRNA within hepatocytes, produces significant low-density lipoprotein cholesterol reduction. The effects of inclisiran on other lipids are less well described. Methods: ORION-1 was a phase 2 trial assessing 6 different inclisiran dosing regimens versus placebo. Participants with elevated low-density lipoprotein cholesterol despite receiving maximally tolerated statin therapy received a single-dose (200, 300, or 500 mg) or 2-dose starting regimen (100, 200, or 300 mg on days 1 and 90) of inclisiran or placebo. This prespecified analysis reports the percentage reductions in non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein (apo) B, very-low-density lipoprotein cholesterol, lipoprotein(a), triglycerides, HDL-C, and apo A1 at the primary efficacy time point (day 180) with mixed-effect models for repeated measures. Additional prespecified analyses report time course of changes from baseline at each visit to day 210, interindividual variation in response, and lipid goal attainment. Results: The mean age of the 501 participants was 63 years, 65% were male, 69% had atherosclerotic cardiovascular disease, 73% used statins, and mean low-density lipoprotein cholesterol was 128 mg/dL. A single dose of inclisiran reduced apo B, non–HDL-C, and very-low-density lipoprotein cholesterol over 210 days. A second dose of inclisiran provided additional lowering of these lipids. At day 180, non–HDL-C was lowered dose-dependently: by 25% from 148±43 to 110±45 mg/dL in the 200-mg single-dose group and by 46% from 161±58 to 91±58 mg/dL in the 2-dose 300-mg group. For the same dosing regimens, apo B was reduced by 23% from 101±23 to 78±29 mg/dL and by 41% from 106±31 to 65±33 mg/dL ( P <0.001 for all groups versus placebo). In the 300-mg 2-dose group, all individuals experienced apo B and non–HDL-C reductions. There was larger interindividual variation in very-low-density lipoprotein cholesterol, triglycerides, and lipoprotein(a) reductions. In the 300-mg 2-dose group, the percentages of patients achieving guideline-recommended apo B goals for high- and very-high-risk patients at day 180 were 78% and 90%; 68% and 83% of participants achieved non–HDL-C <100 and <130 mg/dL. Conclusions: Inclisiran produces significant and prolonged reductions in atherogenic lipoproteins, suggesting that inhibiting the synthesis of protease proprotein convertase subtilisin/kexin type 9 through siRNA may be a viable alternative to other approaches that target protease proprotein convertase subtilisin/kexin type 9. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02597127.

Background Optimal methods of mortality risk stratification in patients in the cardiac intensive care unit ( CICU ) remain uncertain. We evaluated the ability of the Sequential Organ Failure Assessment ( SOFA ) score to predict mortality in a large cohort of unselected patients in the CICU. Methods and Results Adult patients admitted to the CICU from January 1, 2007, to December 31, 2015, at a single tertiary care hospital were retrospectively reviewed. SOFA scores were calculated daily, and Acute Physiology and Chronic Health Evaluation ( APACHE )‐ III and APACHE ‐ IV scores were calculated on CICU day 1. Discrimination of hospital mortality was assessed using area under the receiver‐operator characteristic curve values. We included 9961 patients, with a mean age of 67.5±15.2 years; all‐cause hospital mortality was 9.0%. Day 1 SOFA score predicted hospital mortality, with an area under the receiver‐operator characteristic curve value of 0.83; area under the receiver‐operator characteristic curve values were similar for the APACHE ‐ III score, and APACHE ‐ IV predicted mortality ( P >0.05). Mean and maximum SOFA scores over multiple CICU days had greater discrimination for hospital mortality ( P <0.01). Patients with an increasing SOFA score from day 1 and day 2 had higher mortality. Patients with day 1 SOFA score <2 were at low risk of mortality. Increasing tertiles of day 1 SOFA score predicted higher long‐term mortality ( P <0.001 by log‐rank test). Conclusions The day 1 SOFA score has good discrimination for short‐term mortality in unselected patients in the CICU, which is comparable to APACHE ‐ III and APACHE ‐ IV . Advantages of the SOFA score over APACHE include simplicity, improved discrimination using serial scores, and prediction of long‐term mortality.

Background The Effects of the P‐Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention for Non‐ST‐Segment Elevation Myocardial Infarction ( SELECT ‐ ACS ) trial suggested beneficial effects of inclacumab, a monoclonal antibody directed against P‐selectin, on periprocedural myocardial damage. This study evaluated the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and percutaneous coronary intervention ( PCI ). Methods and Results Patients (n=544) enrolled in the SELECT ‐ ACS trial and randomized to receive 1 infusion of placebo or inclacumab (5 or 20 mg/kg, administered between 1 and 24 hours before PCI ) were divided according to the time interval between study drug infusion and PCI . The primary end point was the change in troponin I from baseline at 16 and 24 hours after PCI . In patients receiving inclacumab 20 mg/kg with a short (less than median) time interval between infusion and PCI , placebo‐adjusted geometric mean percent changes in troponin I, creatine kinase–myocardial band, and peak troponin I at 24 hours were −45.6% ( P =0.005), −30.7% ( P =0.01), and −37.3% ( P =0.02), respectively. No significant changes were observed in patients with a long (greater than median) time interval between infusion and PCI . Placebo‐adjusted geometric mean percent changes in troponin I and creatine kinase–myocardial band were −43.5% ( P =0.02) and −26.0% ( P =0.07), respectively, when inclacumab 20 mg/kg was administered between 1 and 3 hours before PCI , whereas the drug had no effect with longer intervals. Conclusions Inclacumab 20 mg/kg significantly reduces myocardial damage after PCI in patients with non– ST ‐segment elevation myocardial infarction, and benefits are larger when the infusion is administered <3 hours before PCI . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01327183.

Background: Patients hospitalized for first acute coronary syndrome (ACS) are frequently discharged on multiple new medications. The short-term tolerability of these medications is unknown. Methods: This single-center cohort study assessed 30-day health-care utilization and how it may be impacted by medication prescribing trends. We included Olmsted County patients presenting with ACS and previously undiagnosed coronary artery disease in 2008 to 2009. All health-care contacts were reviewed 30 days after index hospital discharge for potential adverse medication effects including documented hypotension or bradycardia, or symptoms likely attributed to the medications. Results: The study included 86 patients; their mean age was 63 (standard deviation: 15.5 years). Antianginal or antihypertensive cardiovascular (CV) medications were prescribed to 98% of patients at discharge; 76% were prescribed 2 or more. There were 233 health-care contacts in 30 days; 90 (39%) of these contacts were unscheduled. More CV medications tended to be prescribed to patients with unscheduled contacts, both pre-ACS ( P = .045) and upon hospital discharge ( P = .051). Hypotension and/or bradycardia at follow-up occurred in 52 patients (60%). Surprisingly, there was no association between hypotension and/or bradycardia at follow-up and increased health-care utilization ( P = .12). Potential adverse drug effects were reported in 34 (40%) patients. These patients had significantly more total health-care contacts ( P < .001) and unscheduled health-care contacts (median 0 vs 1.5; P < .001). Conclusions: Symptoms of adverse drug effects were associated with more frequent health-care utilization after ACS. Clinicians need to consider this while striving to increase patient compliance with post-ACS medications and optimize care transitions.

Objectives To determine the incidence and 1‐year outcomes of an elderly population with perioperative atrial arrhythmia (PAA) within 7 days of hip fracture surgery. Design Retrospective cohort study. Setting The Rochester Epidemiology Project (REP). Participants Elderly adults consecutive undergoing hip fracture repair from 1988 to 2002 in Olmsted County, Minnesota (N = 1,088, mean age 84.0 ± 7.4, 80.2% female). Measurements Baseline clinical variables were analyzed in relation to survival using Cox proportional hazards methods for comparison. Results Sixty‐one participants (5.6%) developed PAA within the first 7 days. During 1 year of follow‐up, 239 (22%) participants died. PAA was associated with greater mortality (45% vs 21%; hazard ratio (HR) = 2.8, 95% confidence interval (CI) = 1.9–4.2). Other mortality risk factors were male sex (HR = 2.0, 95% CI = 1.5–2.6), congestive heart failure (HR = 2.1, 95% CI = 1.7–2.8), chronic renal insufficiency (HR = 2.0, 95% CI = 1.5–2.8), dementia (HR = 2.9, 95% CI = 2.2–3.7), and American Society of Anesthesiologists risk Class III, IV, or V (HR = 3.3, 95% CI = 1.9–5.9). Conclusion Elderly adults undergoing hip fracture surgery who develop PAA within 7 days have significantly higher 1‐year mortality than those who do not. Further studies are indicated to determine whether prevention of PAA will reduce mortality in this population.