Yale New Haven Hospital

BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. RESULTS: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. CONCLUSIONS: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

CONTEXT: Patients who have atrial fibrillation (AF) have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. OBJECTIVE: To assess the predictive value of classification schemes that estimate stroke risk in patients with AF. DESIGN, SETTING, AND PATIENTS: Two existing classification schemes were combined into a new stroke-risk scheme, the CHADS( 2) index, and all 3 classification schemes were validated. The CHADS( 2) was formed by assigning 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and by assigning 2 points for history of stroke or transient ischemic attack. Data from peer review organizations representing 7 states were used to assemble a National Registry of AF (NRAF) consisting of 1733 Medicare beneficiaries aged 65 to 95 years who had nonrheumatic AF and were not prescribed warfarin at hospital discharge. MAIN OUTCOME MEASURE: Hospitalization for ischemic stroke, determined by Medicare claims data. RESULTS: During 2121 patient-years of follow-up, 94 patients were readmitted to the hospital for ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c statistic greater than 0.5, the 2 existing classification schemes predicted stroke better than chance: c of 0.68 (95% confidence interval [CI], 0.65-0.71) for the scheme developed by the Atrial Fibrillation Investigators (AFI) and c of 0.74 (95% CI, 0.71-0.76) for the Stroke Prevention in Atrial Fibrillation (SPAF) III scheme. However, with a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS( 2) index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS( 2) score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. CONCLUSION: The 2 existing classification schemes and especially a new stroke risk index, CHADS( 2), can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

BACKGROUND: In patients with melanoma, ipilimumab (an antibody against cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]) prolongs overall survival, and nivolumab (an antibody against the programmed death 1 [PD-1] receptor) produced durable tumor regression in a phase 1 trial. On the basis of their distinct immunologic mechanisms of action and supportive preclinical data, we conducted a phase 1 trial of nivolumab combined with ipilimumab in patients with advanced melanoma. METHODS: We administered intravenous doses of nivolumab and ipilimumab in patients every 3 weeks for 4 doses, followed by nivolumab alone every 3 weeks for 4 doses (concurrent regimen). The combined treatment was subsequently administered every 12 weeks for up to 8 doses. In a sequenced regimen, patients previously treated with ipilimumab received nivolumab every 2 weeks for up to 48 doses. RESULTS: A total of 53 patients received concurrent therapy with nivolumab and ipilimumab, and 33 received sequenced treatment. The objective-response rate (according to modified World Health Organization criteria) for all patients in the concurrent-regimen group was 40%. Evidence of clinical activity (conventional, unconfirmed, or immune-related response or stable disease for ≥24 weeks) was observed in 65% of patients. At the maximum doses that were associated with an acceptable level of adverse events (nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram), 53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrent-regimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible. Among patients in the sequenced-regimen group, 18% had grade 3 or 4 adverse events related to therapy and the objective-response rate was 20%. CONCLUSIONS: Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; ClinicalTrials.gov number, NCT01024231.).

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is known about TAVR in low-risk patients. METHODS: We performed a randomized noninferiority trial in which TAVR with a self-expanding supraannular bioprosthesis was compared with surgical aortic-valve replacement in patients who had severe aortic stenosis and were at low surgical risk. When 850 patients had reached 12-month follow-up, we analyzed data regarding the primary end point, a composite of death or disabling stroke at 24 months, using Bayesian methods. RESULTS: ). CONCLUSIONS: In patients with severe aortic stenosis who were at low surgical risk, TAVR with a self-expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months. (Funded by Medtronic; ClinicalTrials.gov number, NCT02701283.).

Table 1dProperties of currently available glucose-lowering agents that may guide treatment choice in individual patients with type 2 diabetes mellitus Class Compound(s) Cellular mechanism

In 2012, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) published a position statement on the management of hyperglycemia in patients with type 2 diabetes (1,2). This was needed because of an increasing array of antihyperglycemic drugs and growing uncertainty regarding their proper selection and sequence. Because of a paucity of comparative effectiveness research on long-term treatment outcomes with many of these medications, the 2012 publication was less prescriptive than prior consensus reports. We previously described the need to individualize both treatment targets and treatment strategies, with an emphasis on patient-centered care and shared decision making, and this continues to be our position, although there are now more head-to-head trials that show slight variance between agents with regard to glucose-lowering effects. Nevertheless, these differences are often small and would be unlikely to reflect any definite differential effect in an individual patient. The ADA and EASD have requested an update to the position statement incorporating new data from recent clinical trials. Between June and September of 2014, the Writing Group reconvened, including one face-to-face meeting, to discuss the changes. An entirely new statement was felt to be unnecessary. Instead, the group focused on those areas where revisions were suggested by a changing evidence base. This briefer article should therefore be read as an addendum to the previous full account (1,2). Glucose control remains a major focus in the management of patients with type 2 diabetes. However, this should always be in the context of a comprehensive cardiovascular risk factor reduction program, to include smoking cessation and the adoption of other healthy lifestyle habits, blood pressure control, lipid management with priority to statin medications, and, in some circumstances, antiplatelet therapy. Studies have conclusively determined that reducing hyperglycemia decreases the onset and progression of …

BACKGROUND: Medical practitioners use survival models to explore and understand the relationships between patients' covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. METHODS: We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient's covariates and treatment effectiveness in order to provide personalized treatment recommendations. RESULTS: We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient's covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient's features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it's personalized treatment recommendations would increase the survival time of a set of patients. CONCLUSIONS: The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient's characteristics on their risk of failure.

The Guideline for Hand Hygiene in Health-Care Settings provides health-care workers (HCWs) with a review of data regarding handwashing and hand antisepsis in health-care settings. In addition, it provides specific recommendations to promote improved hand-hygiene practices and reduce transmission of pathogenic microorganisms to patients and personnel in health-care settings. This report reviews studies published since the 1985 CDC guideline (Garner JS, Favero MS. CDC guideline for handwashing and hospital environmental control, 1985. Infect Control 1986;7:231-43) and the 1995 APIC guideline (Larson EL, APIC Guidelines Committee. APIC guideline for handwashing and hand antisepsis in health care settings. Am J Infect Control 1995;23:251-69) were issued and provides an in-depth review of hand-hygiene practices of HCWs, levels of adherence of personnel to recommended handwashing practices, and factors adversely affecting adherence. New studies of the in vivo efficacy of alcohol-based hand rubs and the low incidence of dermatitis associated with their use are reviewed. Recent studies demonstrating the value of multidisciplinary hand-hygiene promotion programs and the potential role of alcohol-based hand rubs in improving hand-hygiene practices are summarized. Recommendations concerning related issues (e.g., the use of surgical hand antiseptics, hand lotions or creams, and wearing of artificial fingernails) are also included.

The exceptionally rapid development of highly flexible, reusable artificial intelligence (AI) models is likely to usher in newfound capabilities in medicine. We propose a new paradigm for medical AI, which we refer to as generalist medical AI (GMAI). GMAI models will be capable of carrying out a diverse set of tasks using very little or no task-specific labelled data. Built through self-supervision on large, diverse datasets, GMAI will flexibly interpret different combinations of medical modalities, including data from imaging, electronic health records, laboratory results, genomics, graphs or medical text. Models will in turn produce expressive outputs such as free-text explanations, spoken recommendations or image annotations that demonstrate advanced medical reasoning abilities. Here we identify a set of high-impact potential applications for GMAI and lay out specific technical capabilities and training datasets necessary to enable them. We expect that GMAI-enabled applications will challenge current strategies for regulating and validating AI devices for medicine and will shift practices associated with the collection of large medical datasets. This review discusses generalist medical artificial intelligence, identifying potential applications and setting out specific technical capabilities and training datasets necessary to enable them, as well as highlighting challenges to its implementation.

4. Does inpatient management of hyperglycemia represent a safety concern? 5. What systems need to be in place to achieve these recommendations? 6. Is treatment of inpatient hyperglycemia cost-effective? 7. What are the optimal strategies for transition to outpatient care? 8. What are areas for future research?

BACKGROUND: The growing use of imaging procedures in the United States has raised concerns about exposure to low-dose ionizing radiation in the general population. METHODS: We identified 952,420 nonelderly adults (between 18 and 64 years of age) in five health care markets across the United States between January 1, 2005, and December 31, 2007. Utilization data were used to estimate cumulative effective doses of radiation from imaging procedures and to calculate population-based rates of exposure, with annual effective doses defined as low (< or = 3 mSv), moderate (> 3 to 20 mSv), high (> 20 to 50 mSv), or very high (> 50 mSv). RESULTS: During the study period, 655,613 enrollees (68.8%) underwent at least one imaging procedure associated with radiation exposure. The mean (+/-SD) cumulative effective dose from imaging procedures was 2.4+/-6.0 mSv per enrollee per year; however, a wide distribution was noted, with a median effective dose of 0.1 mSv per enrollee per year (interquartile range, 0.0 to 1.7). Overall, moderate effective doses of radiation were incurred in 193.8 enrollees per 1000 per year, whereas high and very high doses were incurred in 18.6 and 1.9 enrollees per 1000 per year, respectively. In general, cumulative effective doses of radiation from imaging procedures increased with advancing age and were higher in women than in men. Computed tomographic and nuclear imaging accounted for 75.4% of the cumulative effective dose, with 81.8% of the total administered in outpatient settings. CONCLUSIONS: Imaging procedures are an important source of exposure to ionizing radiation in the United States and can result in high cumulative effective doses of radiation.

BACKGROUND: Small studies suggest that telemonitoring may improve heart-failure outcomes, but its effect in a large trial has not been established. METHODS: We randomly assigned 1653 patients who had recently been hospitalized for heart failure to undergo either telemonitoring (826 patients) or usual care (827 patients). Telemonitoring was accomplished by means of a telephone-based interactive voice-response system that collected daily information about symptoms and weight that was reviewed by the patients' clinicians. The primary end point was readmission for any reason or death from any cause within 180 days after enrollment. Secondary end points included hospitalization for heart failure, number of days in the hospital, and number of hospitalizations. RESULTS: The median age of the patients was 61 years; 42.0% were female, and 39.0% were black. The telemonitoring group and the usual-care group did not differ significantly with respect to the primary end point, which occurred in 52.3% and 51.5% of patients, respectively (difference, 0.8 percentage points; 95% confidence interval [CI], -4.0 to 5.6; P=0.75 by the chi-square test). Readmission for any reason occurred in 49.3% of patients in the telemonitoring group and 47.4% of patients in the usual-care group (difference, 1.9 percentage points; 95% CI, -3.0 to 6.7; P=0.45 by the chi-square test). Death occurred in 11.1% of the telemonitoring group and 11.4% of the usual care group (difference, -0.2 percentage points; 95% CI, -3.3 to 2.8; P=0.88 by the chi-square test). There were no significant differences between the two groups with respect to the secondary end points or the time to the primary end point or its components. No adverse events were reported. CONCLUSIONS: Among patients recently hospitalized for heart failure, telemonitoring did not improve outcomes. The results indicate the importance of a thorough, independent evaluation of disease-management strategies before their adoption. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00303212.).

Interview with Dr. Harlan Krumholz on a condition of generalized risk after patients are discharged from the hospital. (17:28)Download Patients who were recently hospitalized experience a period of generalized risk for myriad adverse health events. Their condition may be characterized as a post-hospital syndrome, an acquired condition of vulnerability not necessarily linked to the original illness.

Abstract Structural variants (SVs) rearrange large segments of DNA 1 and can have profound consequences in evolution and human disease 2,3 . As national biobanks, disease-association studies, and clinical genetic testing have grown increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD) 4 have become integral in the interpretation of single-nucleotide variants (SNVs) 5 . However, there are no reference maps of SVs from high-coverage genome sequencing comparable to those for SNVs. Here we present a reference of sequence-resolved SVs constructed from 14,891 genomes across diverse global populations (54% non-European) in gnomAD. We discovered a rich and complex landscape of 433,371 SVs, from which we estimate that SVs are responsible for 25–29% of all rare protein-truncating events per genome. We found strong correlations between natural selection against damaging SNVs and rare SVs that disrupt or duplicate protein-coding sequence, which suggests that genes that are highly intolerant to loss-of-function are also sensitive to increased dosage 6 . We also uncovered modest selection against noncoding SVs in cis -regulatory elements, although selection against protein-truncating SVs was stronger than all noncoding effects. Finally, we identified very large (over one megabase), rare SVs in 3.9% of samples, and estimate that 0.13% of individuals may carry an SV that meets the existing criteria for clinically important incidental findings 7 . This SV resource is freely distributed via the gnomAD browser 8 and will have broad utility in population genetics, disease-association studies, and diagnostic screening.

BACKGROUND: Google Trends is a novel, freely accessible tool that allows users to interact with Internet search data, which may provide deep insights into population behavior and health-related phenomena. However, there is limited knowledge about its potential uses and limitations. We therefore systematically reviewed health care literature using Google Trends to classify articles by topic and study aim; evaluate the methodology and validation of the tool; and address limitations for its use in research. METHODS AND FINDINGS: PRISMA guidelines were followed. Two independent reviewers systematically identified studies utilizing Google Trends for health care research from MEDLINE and PubMed. Seventy studies met our inclusion criteria. Google Trends publications increased seven-fold from 2009 to 2013. Studies were classified into four topic domains: infectious disease (27% of articles), mental health and substance use (24%), other non-communicable diseases (16%), and general population behavior (33%). By use, 27% of articles utilized Google Trends for casual inference, 39% for description, and 34% for surveillance. Among surveillance studies, 92% were validated against a reference standard data source, and 80% of studies using correlation had a correlation statistic ≥0.70. Overall, 67% of articles provided a rationale for their search input. However, only 7% of articles were reproducible based on complete documentation of search strategy. We present a checklist to facilitate appropriate methodological documentation for future studies. A limitation of the study is the challenge of classifying heterogeneous studies utilizing a novel data source. CONCLUSION: Google Trends is being used to study health phenomena in a variety of topic domains in myriad ways. However, poor documentation of methods precludes the reproducibility of the findings. Such documentation would enable other researchers to determine the consistency of results provided by Google Trends for a well-specified query over time. Furthermore, greater transparency can improve its reliability as a research tool.

The Guideline for Hand Hygiene in Health-Care Settings provides health-care workers (HCWs) with a review of data regarding handwashing and hand antisepsis in health-care settings. In addition, it provides specific recommendations to promote improved hand-hygiene practices and reduce transmission ofpathogenic microorganisms to patients and personnel in health-care settings. This report reviews studies published since the 1985 CDC guideline (Garner JS, Favero MS. CDC guideline for handwashing and hospital environmental control, 1985. Infect Control 1986;7:231-43) and the 1995 APIC guideline (Larson EL, APIC Guidelines Committee. APIC guideline for handwashing and hand antisepsis in health care settings. Am J Infect Control 1995;23:251-69) were issued and provides an in-depth review of hand-hygiene practices of HCWs, levels of adherence of personnel to recommended handwashing practices, and factors adversely affecting adherence. New studies of the in vivo efficacy of alcohol-based hand rubs and the low incidence of dermatitis associated with their use are reviewed. Recent studies demonstrating the value of multidisciplinary hand-hygiene promotion programs and the potential role of alcohol-based hand rubs in improving hand-hygiene practices are summarized. Recommendations concerning related issues (e.g., the use of surgical hand antiseptics, hand lotions or creams, and wearing of artificial fingernails) are also included.

BACKGROUND: Anemia may have adverse effects in patients with coronary artery disease. However, the benefit of blood transfusion in elderly patients with acute myocardial infarction and various degrees of anemia is uncertain. METHODS: We conducted a retrospective study of data on 78,974 Medicare beneficiaries 65 years old or older who were hospitalized with acute myocardial infarction. Patients were categorized according to the hematocrit on admission (5.0 to 24.0 percent, 24.1 to 27.0 percent, 27.1 to 30.0 percent, 30.1 to 33.0 percent, 33.1 to 36.0 percent, 36.1 to 39.0 percent, or 39.1 to 48.0 percent), and data were evaluated to determine whether there was an association between the use of transfusion and 30-day mortality. RESULTS: Patients with lower hematocrit values on admission had higher 30-day mortality rates. Blood transfusion was associated with a reduction in 30-day mortality among patients whose hematocrit on admission fell into the categories ranging from 5.0 to 24.0 percent (adjusted odds ratio, 0.22; 95 percent confidence interval, 0.11 to 0.45) to 30.1 to 33.0 percent (adjusted odds ratio, 0.69; 95 percent confidence interval, 0.53 to 0.89). It was not associated with a reduction in 30-day mortality among those whose hematocrit values fell in the higher ranges. In one of seven subgroup analyses (among patients who survived at least two days), transfusion was not associated with a reduction in mortality for patients with hematocrit values of 30.1 percent or higher. CONCLUSIONS: Blood transfusion is associated with a lower short-term mortality rate among elderly patients with acute myocardial infarction if the hematocrit on admission is 30.0 percent or lower and may be effective in patients with a hematocrit as high as 33.0 percent on admission.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder. METHODS AND RESULTS: Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence interval, 51-59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval, 2.6%-6.9%) compared with myocardial infarction associated with obstructive coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative assessment of 46 publications evaluating the underlying pathophysiology responsible for MINOCA revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in 14%. CONCLUSIONS: MINOCA should be considered as a working diagnosis with multiple potential causes that require evaluation so that directed therapies may improve its guarded prognosis.

BACKGROUND: Female athletes are at significantly greater risk of anterior cruciate ligament (ACL) injury than male athletes in the same high-risk sports. Decreased trunk (core) neuromuscular control may compromise dynamic knee stability. HYPOTHESES: (1) Increased trunk displacement after sudden force release would be associated with increased knee injury risk; (2) coronal (lateral), not sagittal, plane displacement would be the strongest predictor of knee ligament injury; (3) logistic regression of factors related to core stability would accurately predict knee, ligament, and ACL injury risk; and (4) the predictive value of these models would differ between genders. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: In this study, 277 collegiate athletes (140 female and 137 male) were prospectively tested for trunk displacement after a sudden force release. Analysis of variance and multivariate logistic regression identified predictors of risk in athletes who sustained knee injury. RESULTS: Twenty-five athletes (11 female and 14 male) sustained knee injuries over a 3-year period. Trunk displacement was greater in athletes with knee, ligament, and ACL injuries than in uninjured athletes (P < .05). Lateral displacement was the strongest predictor of ligament injury (P = .009). A logistic regression model, consisting of trunk displacements, proprioception, and history of low back pain, predicted knee ligament injury with 91% sensitivity and 68% specificity (P = .001). This model predicted knee, ligament, and ACL injury risk in female athletes with 84%, 89%, and 91% accuracy, but only history of low back pain was a significant predictor of knee ligament injury risk in male athletes. CONCLUSIONS: Factors related to core stability predicted risk of athletic knee, ligament, and ACL injuries with high sensitivity and moderate specificity in female, but not male, athletes.

BACKGROUND: Despite advances in resuscitation care in recent years, it is not clear whether survival and neurologic function after in-hospital cardiac arrest have improved over time. METHODS: We identified all adults who had an in-hospital cardiac arrest at 374 hospitals in the Get with the Guidelines-Resuscitation registry between 2000 and 2009. Using multivariable regression, we examined temporal trends in risk-adjusted rates of survival to discharge. Additional analyses explored whether trends were due to improved survival during acute resuscitation or postresuscitation care and whether they occurred at the expense of greater neurologic disability in survivors. RESULTS: Among 84,625 hospitalized patients with cardiac arrest, 79.3% had an initial rhythm of asystole or pulseless electrical activity, and 20.7% had ventricular fibrillation or pulseless ventricular tachycardia. The proportion of cardiac arrests due to asystole or pulseless electrical activity increased over time (P<0.001 for trend). Risk-adjusted rates of survival to discharge increased from 13.7% in 2000 to 22.3% in 2009 (adjusted rate ratio per year, 1.04; 95% confidence interval [CI], 1.03 to 1.06; P<0.001 for trend). Survival improvement was similar in the two rhythm groups and was due to improvement in both acute resuscitation survival and postresuscitation survival. Rates of clinically significant neurologic disability among survivors decreased over time, with a risk-adjusted rate of 32.9% in 2000 and 28.1% in 2009 (adjusted rate ratio per year, 0.98; 95% CI, 0.97 to 1.00; P=0.02 for trend). CONCLUSIONS: Both survival and neurologic outcomes after in-hospital cardiac arrest have improved during the past decade at hospitals participating in a large national quality-improvement registry. (Funded by the American Heart Association.).