Institute of Health Services and Policy Research

Abstract Rationale Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. Objectives To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. Methods The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Measurements and Main Results Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159–1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg. Conclusions NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).

BACKGROUND: The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel. METHODS: The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2). RESULTS: Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis. CONCLUSIONS: Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.

CONTEXT: Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. OBJECTIVE: To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks. DESIGN, SETTING, AND PARTICIPANTS: Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years). MAIN OUTCOME MEASURES: Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. RESULTS: Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. CONCLUSIONS: Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

BACKGROUND: Evidence from observational studies that the use of surgical safety checklists results in striking improvements in surgical outcomes led to the rapid adoption of such checklists worldwide. However, the effect of mandatory adoption of surgical safety checklists is unclear. A policy encouraging the universal adoption of checklists by hospitals in Ontario, Canada, provided a natural experiment to assess the effectiveness of checklists in typical practice settings. METHODS: We surveyed all acute care hospitals in Ontario to determine when surgical safety checklists were adopted. Using administrative health data, we compared operative mortality, rate of surgical complications, length of hospital stay, and rates of hospital readmission and emergency department visits within 30 days after discharge among patients undergoing a variety of surgical procedures before and after adoption of a checklist. RESULTS: During 3-month periods before and after adoption of a surgical safety checklist, a total of 101 hospitals performed 109,341 and 106,370 procedures, respectively. The adjusted risk of death during a hospital stay or within 30 days after surgery was 0.71% (95% confidence interval [CI], 0.66 to 0.76) before implementation of a surgical checklist and 0.65% (95% CI, 0.60 to 0.70) afterward (odds ratio, 0.91; 95% CI, 0.80 to 1.03; P=0.13). The adjusted risk of surgical complications was 3.86% (95% CI, 3.76 to 3.96) before implementation and 3.82% (95% CI, 3.71 to 3.92) afterward (odds ratio, 0.97; 95% CI, 0.90 to 1.03; P=0.29). CONCLUSIONS: Implementation of surgical safety checklists in Ontario, Canada, was not associated with significant reductions in operative mortality or complications. (Funded by the Canadian Institutes of Health Research.).

BACKGROUND: Women with a history of certain pregnancy complications are at higher risk for cardiovascular (CVD) disease. However, most clinical guidelines only recommend postpartum follow-up of those with a history of preeclampsia, gestational diabetes mellitus, or preterm birth. This systematic review was undertaken to determine if there is an association between a broader array of pregnancy complications and the future risk of CVD. METHODS: We systematically searched PubMed, MEDLINE and EMBASE (via Ovid), CINAHL, and the Cochrane Library from inception to September 22, 2017, for observational studies of the association between the hypertensive disorders of pregnancy, placental abruption, preterm birth, gestational diabetes mellitus, low birth weight, small-for-gestational-age birth, stillbirth, and miscarriage and subsequent CVD. Likelihood ratio meta-analyses were performed to generate pooled odds ratios (OR) and 95% intrinsic confidence intervals (ICI). RESULTS: Our systematic review included 84 studies (28 993 438 patients). Sample sizes varied from 250 to 2 000 000, with a median follow-up of 7.5 years postpartum. The risk of CVD was highest in women with gestational hypertension (OR 1.7; 95% ICI, 1.3-2.2), preeclampsia (OR 2.7; 95% ICI, 2.5-3.0), placental abruption (OR 1.8; 95% ICI, 1.4-2.3), preterm birth (OR 1.6; 95% ICI, 1.4-1.9), gestational diabetes mellitus (OR 1.7; 95% ICI, 1.1-2.5), and stillbirth (OR 1.5; 95% ICI, 1.1-2.1). A consistent trend was seen for low birth weight and small-for-gestational-age birth weight but not for miscarriage. CONCLUSIONS: Women with a broader array of pregnancy complications, including placental abruption and stillbirth, are at increased risk of future CVD. The findings support the need for assessment and risk factor management beyond the postpartum period.

Background: SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease. Methods: Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m 2 . The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide). Results: Among the 97 participants (90 men [93%], mean [standard deviation] age 62.8 [9.0] years, type 2 diabetes mellitus duration 11.0 [8.2] years, estimated glomerular filtration rate 88.4 [16.9] mL/min/1.73m 2 , LV mass indexed to body surface area 60.7 [11.9] g/m 2 ), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m 2 and 0.01 g/m 2 for those assigned empagliflozin and placebo, respectively (adjusted difference −3.35 g/m 2 ; 95% CI, −5.9 to −0.81g/m 2 , P =0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference −6.8mmHg, 95% CI −11.2 to −2.3mmHg, P =0.003), diastolic blood pressure (adjusted difference −3.2mmHg; 95% CI, −5.8 to −0.6mmHg, P =0.02) and elevation of hematocrit ( P =0.0003). Conclusions: Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02998970.

The most commonly used tool for self-report of pruritus intensity is the visual analogue scale (VAS). Similar tools are the numerical rating scale (NRS) and verbal rating scale (VRS). In the present study, initiated by the International Forum for the Study of Itch assessing reliability of these tools, 471 randomly selected patients with chronic itch (200 males, 271 females, mean age 58.44 years) recorded their pruritus intensity on VAS (100-mm line), NRS (0-10) and VRS (four-point) scales. Re-test reliability was analysed in a subgroup of 250 patients after one hour. Statistical analysis showed a high reliability and concurrent validity (r>0.8; p<0.01) for all tools. Mean values of all scales showed a high correlation. In conclusion, high reliability and concurrent validity was found for VAS, NRS and VRS. On re-test, higher correlation and less missing values were observed. A training session before starting a clinical trial is recommended.

BACKGROUND: A single-item measure of self-rated mental health (SRMH) is being used increasingly in health research and population health surveys. The item asks respondents to rate their mental health on a five-point scale from excellent to poor. This scoping study presents the first known review of the SRMH literature. METHODS: Electronic databases of Medline, CINAHL, PsycINFO, EMBASE and Cochrane Reviews were searched using keywords. The databases were also searched using the titles of surveys known to include the SRMH single item. The search was supplemented by manually searching the bibliographic sections of the included studies. Two independent reviewers coded articles for inclusion or exclusion based on whether articles included SRMH. Each study was coded by theme and data were extracted about study design, sample, variables, and results. RESULTS: Fifty-seven studies included SRMH. SRMH correlated moderately with the following mental health scales: Kessler Psychological Distress Scale, Patient Health Questionnaire, mental health subscales of the Short-Form Health Status Survey, Behaviour and Symptom Identification Scale, and World Mental Health Clinical Diagnostic Interview Schedule. However, responses to this item may differ across racial and ethnic groups. Poor SRMH was associated with poor self-rated health, physical health problems, increased health service utilization and less likelihood of being satisfied with mental health services. Poor or fair SRMH was also associated with social determinants of health, such as low socioeconomic position, weak social connections and neighbourhood stressors. Synthesis of this literature provides important information about the relationships SRMH has with other variables. CONCLUSIONS: SRMH is associated with multi-item measures of mental health, self-rated health, health problems, service utilization, and service satisfaction. Given these relationships and its use in epidemiologic surveys, SRMH should continue to be assessed as a population health measure. More studies need to examine relationships between SRMH and clinical mental illnesses. Longitudinal analyses should look at whether SRMH is predictive of future mental health problems.

Elucidation and examination of cellular subpopulations that display condition-specific behavior can play a critical contributory role in understanding disease mechanism, as well as provide a focal point for development of diagnostic criteria linking such a mechanism to clinical prognosis. Despite recent advancements in single-cell measurement technologies, the identification of relevant cell subsets through manual efforts remains standard practice. As new technologies such as mass cytometry increase the parameterization of single-cell measurements, the scalability and subjectivity inherent in manual analyses slows both analysis and progress. We therefore developed Citrus (cluster identification, characterization, and regression), a data-driven approach for the identification of stratifying subpopulations in multidimensional cytometry datasets. The methodology of Citrus is demonstrated through the identification of known and unexpected pathway responses in a dataset of stimulated peripheral blood mononuclear cells measured by mass cytometry. Additionally, the performance of Citrus is compared with that of existing methods through the analysis of several publicly available datasets. As the complexity of flow cytometry datasets continues to increase, methods such as Citrus will be needed to aid investigators in the performance of unbiased--and potentially more thorough--correlation-based mining and inspection of cell subsets nested within high-dimensional datasets.

OBJECTIVE: To ascertain patients' views on the benefits of and possible memory loss from electroconvulsive therapy. DESIGN: Descriptive systematic review. DATA SOURCES: Psychinfo, Medline, Web of Science, and Social Science Citation Index databases, and bibliographies. STUDY SELECTION: Articles with patients' views after treatment with electroconvulsive therapy. DATA EXTRACTION: 26 studies carried out by clinicians and nine reports of work undertaken by patients or with the collaboration of patients were identified; 16 studies investigated the perceived benefit of electroconvulsive therapy and seven met criteria for investigating memory loss. DATA SYNTHESIS: The studies showed heterogeneity. The methods used were associated with levels of perceived benefit. At least one third of patients reported persistent memory loss. CONCLUSIONS: The current statement for patients from the Royal College of Psychiatrists that over 80% of patients are satisfied with electroconvulsive therapy and that memory loss is not clinically important is unfounded.

OBJECTIVE: To characterize the incidence of vulvar carcinoma in situ and vulvar cancer over time. METHODS: We used the Surveillance Epidemiology and End Results database to assess trends in the incidence of vulvar cancer over a 28-year period (1973 through 2000) and determined whether there had been a change in incidence over time. Information collected included patient characteristics, primary tumor site, tumor grade, and follow-up for vital status. We calculated the incidence rates by decade of age, used chi(2) tests to compare demographic characteristics, and tested for trends in incidence over time. RESULTS: A total of 13,176 in situ and invasive vulvar carcinomas were identified; 57% of the women were diagnosed with in situ, 44% with invasive disease. Vulvar carcinoma in situ increased 411% from 1973 to 2000. Invasive vulvar cancer increased 20% during the same period. The incidence rates for in situ and invasive vulvar carcinomas are distributed differently across the age groups. In situ carcinoma incidence increases until the age of 40-49 years and then decreases, whereas invasive vulvar cancer risk increases as a woman ages, increasing more quickly after 50 years of age. CONCLUSION: The incidence of in situ vulvar carcinoma is increasing. The incidence of invasive vulvar cancer is also increasing but at a much lower rate.

BACKGROUND: There is a need for a brief and simple screen for personality disorders that can be used in routine psychiatric assessments. AIMS: To test the concurrent validity and test-retest reliability of a brief screen for personality disorder. METHOD: Sixty psychiatric patients were administered a brief screening interview for personality disorder. On the same day, they were interviewed with an established assessment for DSM-IV personality disorder. Three weeks later, the brief screening interview was repeated in order to examine test-retest reliability. RESULTS: A score of 3 on the screening interview correctly identified the presence of DSM-IV personality disorder in 90% of participants. The sensitivity and specificity were were 0.94 and and 0.85 respectively. CONCLUSIONS: The study provides preliminary evidence of the usefulness of the screen in routine clinical settings.

RATIONALE: Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design. OBJECTIVES: To stratify patients for post-ICU disability and recovery to 1 year after critical illness. METHODS: We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling. MEASUREMENTS AND MAIN RESULTS: The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year. CONCLUSIONS: ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00896220).

BACKGROUND: The respective roles of generalist and specialist physicians in the care of patients is currently a matter of debate. Information is limited about the knowledge and practices of generalist and specialist physicians regarding conditions that both groups treat, such as myocardial infarction. METHODS: We therefore surveyed 1211 cardiologists, internists, and family practitioners in the states of New York and Texas about four treatments demonstrated by randomized clinical trials to be associated with improved survival after myocardial infarction (thrombolytic therapy, immediate and long-term use of aspirin, and long-term use of beta-blockers) and two treatments for which such evidence is lacking (diltiazem for patients with pulmonary congestion and prophylactic lidocaine). We asked physicians about the effect of each treatment on survival and the likelihood that they would prescribe each class of drugs. RESULTS: For the four beneficial treatments, the cardiologists believed more strongly than the internists and family physicians that survival was improved by the treatment, and they were more likely to prescribe these drugs (P < 0.001). For example, 94.1 percent of cardiologists said they were very likely to prescribe thrombolytic agents to treat an acute myocardial infarction, as compared with 82.0 percent of internists and 77.3 percent of family practitioners. Conversely, for the two treatments for which trials showed no evidence of a survival benefit, cardiologists were less likely than internists and family practitioners to think there was such a benefit and less likely to prescribe the drugs (P < 0.001). For example, 4.7 percent of cardiologists reported that they were very likely to use prophylactic lidocaine, as compared with 13.1 percent of internists, and 16.5 percent of family practitioners. When we used logistic regression to adjust for potential confounders, all the differences between the cardiologists and the internists and family practitioners remained significant (P < 0.02). CONCLUSIONS: Internists and family practitioners are less aware of or less certain about key advances in the treatment of myocardial infarction than are cardiologists. This finding underscores the need to improve the dissemination of information from clinical trials to generalist physicians, particularly if they are to have an enlarged role in the evolving health care system.

empagliflozin ◼ erythrocytes ◼ erythropoietin ◼ iron ◼ sodium-glucose transporter 2 inhibitors S odium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve cardiovascular outcomes, including hospitalization for heart failure and mortality, in people with and without diabetes mellitus. 1,2The mechanisms underlying this benefit remain unclear.Although several hypotheses have been suggested (including SGLT2 inhibitormediated diuresis and natriuresis, reduction in blood pressure and afterload, direct effects on myocardial sodium and calcium handling, alterations in myocardial energetics, reduction in left ventricular mass, and improved progenitor cell response), 3 a mediation analysis from the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) suggests that an increase in hematocrit may account for more than half of the mortality benefit observed.The consistent observation of an increase in hematocrit, even in those without diabetes mellitus, has led to the hypothesis that SGLT2 inhibitors may increase erythropoiesis via enhanced erythropoietin secretion by the kidney. 4This SGLT2 inhibitor-mediated increase in erythropoietin production (and resultant rise in hematocrit) could lead to systemic organ protection by virtue of its capacity as a circulating pleiotropic cytokine, known to favorably influence cardiomyocyte mitochondrial function, angiogenesis, cell proliferation, and inflammation.In addition, an increase in erythropoietin-induced hematocrit may improve myocardial function by directly enhancing myocardial and systemic tissue oxygen delivery.In this substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes) CardioLink-6 randomized clinical trial in which 6 months of empagliflozin treatment was associated with significant reduction in left ventricular mass index, 5 we measured erythropoietin levels, red blood cell (RBC) morphology, and indices of iron stores in individuals with type 2 diabetes mellitus and stable coronary artery disease who were randomized to either empagliflozin 10 mg daily or placebo for 6 months.The St Michael's Hospital Research Ethics Board approved the study, and all subjects gave informed consent.Blood samples were collected at baseline, after 1 month of treatment, and at the end of the study (6 months).Erythropoietin levels were measured from frozen sera with a 2-site immunoenzymatic chemiluminescent assay, and the data were analyzed with a linear mixed-effects model that included treatment group, visit, and treatment-by-visit interaction, and baseline values as fixed effects.Iron indices, ferritin, and complete blood counts were measured at baseline and at 6 months with standard spectrophotometric, 2-site immunoenzymatic, and flow cytometric techniques, with data analyzed using ANCOVA adjusted for baseline values.Values of P<0.05 were considered significant.

Assessing the calibration of methods for estimating the probability of the occurrence of a binary outcome is an important aspect of validating the performance of risk‐prediction algorithms. Calibration commonly refers to the agreement between predicted and observed probabilities of the outcome. Graphical methods are an attractive approach to assess calibration, in which observed and predicted probabilities are compared using loess‐based smoothing functions. We describe the Integrated Calibration Index (ICI) that is motivated by Harrell's E max index, which is the maximum absolute difference between a smooth calibration curve and the diagonal line of perfect calibration. The ICI can be interpreted as weighted difference between observed and predicted probabilities, in which observations are weighted by the empirical density function of the predicted probabilities. As such, the ICI is a measure of calibration that explicitly incorporates the distribution of predicted probabilities. We also discuss two related measures of calibration, E50 and E90, which represent the median and 90th percentile of the absolute difference between observed and predicted probabilities. We illustrate the utility of the ICI, E50, and E90 by using them to compare the calibration of logistic regression with that of random forests and boosted regression trees for predicting mortality in patients hospitalized with a heart attack. The use of these numeric metrics permitted for a greater differentiation in calibration than was permissible by visual inspection of graphical calibration curves.

OBJECTIVE: School connectedness, or the feeling of closeness to school personnel and the school environment, decreases the likelihood of health risk behaviors during adolescence. The objective of this study was to identify factors differentiating youth who do and do not feel connected to their schools in an effort to target school-based interventions to those at highest health risk. METHODS: The study population consisted of all students attending the 7th through 12th grades of 8 public schools. The students were asked to complete a modified version of the in-school survey designed for the National Longitudinal Study of Adolescent Health (Add Health). The school connectedness score (SCS) was the summation of 5 survey items. Bivariate analyses were used to evaluate the association between SCS and 13 self-reported variables. Stepwise linear regression was conducted to identify the set of factors best predicting connectedness, and logistic regression analysis was performed to identify students with SCS >1 standard deviation below the mean. RESULTS: Of the 3491 students receiving surveys, 1959 (56%) submitted usable surveys. The sample was 47% white and 38% black. Median age was 15. Median grade was 9th. The SCS was normally distributed with a mean of 15.7 and a possible range of 5 to 25. Of the 12 variables associated with connectedness, 7 (gender, race, extracurricular involvement, cigarette use, health status, school nurse visits, and school area) entered the linear regression model. All but gender were significant in the logistic model predicting students with SCS >1 standard deviation below the mean. CONCLUSIONS: In our sample, decreasing school connectedness was associated with 4 potentially modifiable factors: declining health status, increasing school nurse visits, cigarette use, and lack of extracurricular involvement. Black race, female gender, and urban schools were also associated with lower SCS. Further work is needed to better understand the link between these variables and school connectedness. If these associations are found in other populations, school health providers could use these markers to target youth in need of assistance.

OBJECTIVES: Age and stroke severity are major determinants of stroke outcomes, but systematically incorporating these prognosticators in the routine practice of acute ischemic stroke can be challenging. We evaluated the effect of an index combining age and stroke severity on response to IV tissue plasminogen activator (tPA) among patients in the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke trials. METHODS: We created the Stroke Prognostication using Age and NIH Stroke Scale (SPAN) index by combining age in years plus NIH Stroke Scale (NIHSS) ≥100. We applied the SPAN-100 index to patients in the NINDS tPA stroke trials (parts I and II) to evaluate its ability to predict clinical response and risk of intracerebral hemorrhage (ICH) after thrombolysis. The main outcome measures included ICH (any type) and a composite favorable outcome (defined as a modified Rankin Scale score of 0 or 1, NIHSS ≤1, Barthel index ≥95, and Glasgow Outcome Scale score of 1) at 3 months. Bivariate and multivariable logistic regression analyses were used to determine the association between SPAN-100 and outcomes of interest. RESULTS: Among 624 patients in the NINDS trials, 62 (9.9%) participants were SPAN-100 positive. Among those receiving tPA, ICH rates were higher for SPAN-100-positive patients (42% vs 12% in SPAN-100-negative patients; p < 0.001); similarly, ICH rates were higher in SPAN-100-positive patients (19% vs 5%; p = 0.005) among those not receiving tPA. SPAN-100 was associated with worse outcomes. The benefit of tPA, defined as favorable composite outcome at 3 months, was present in SPAN-100-negative patients (55.4% vs 40.2%; p < 0.001), but not in SPAN-100-positive patients (5.6% tPA vs 3.9%; p = 0.76). Similar trends were found for secondary outcomes (e.g., symptomatic ICH, catastrophic outcome, discharge home). CONCLUSION: The SPAN-100 index could be a simple method for estimating the clinical response and risk of hemorrhagic complications after tPA for acute ischemic stroke. These results need further confirmation in larger contemporary datasets.

BACKGROUND: The burden of hypertension is escalating, and control rates are poor in low- and middle-income countries. Cardiovascular mortality is high in rural areas. METHODS: We conducted a cluster-randomized, controlled trial in rural districts in Bangladesh, Pakistan, and Sri Lanka. A total of 30 communities were randomly assigned to either a multicomponent intervention (intervention group) or usual care (control group). The intervention involved home visits by trained government community health workers for blood-pressure monitoring and counseling, training of physicians, and care coordination in the public sector. A total of 2645 adults with hypertension were enrolled. The primary outcome was reduction in systolic blood pressure at 24 months. Follow-up at 24 months was completed for more than 90% of the participants. RESULTS: At baseline, the mean systolic blood pressure was 146.7 mm Hg in the intervention group and 144.7 mm Hg in the control group. At 24 months, the mean systolic blood pressure fell by 9.0 mm Hg in the intervention group and by 3.9 mm Hg in the control group; the mean reduction was 5.2 mm Hg greater with the intervention (95% confidence interval [CI], 3.2 to 7.1; P<0.001). The mean reduction in diastolic blood pressure was 2.8 mm Hg greater in the intervention group than in the control group (95% CI, 1.7 to 3.9). Blood-pressure control (<140/90 mm Hg) was achieved in 53.2% of the participants in the intervention group, as compared with 43.7% of those in the control group (relative risk, 1.22; 95% CI, 1.10 to 1.35). All-cause mortality was 2.9% in the intervention group and 4.3% in the control group. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, a multicomponent intervention that was centered on proactive home visits by trained government community health workers who were linked with existing public health care infrastructure led to a greater reduction in blood pressure than usual care among adults with hypertension. (Funded by the Joint Global Health Trials scheme; COBRA-BPS ClinicalTrials.gov number, NCT02657746.).

OBJECTIVES: To measure the effects of outpatient geriatric evaluation and management (GEM) on high-risk older persons' functional ability and use of health services. DESIGN: Randomized clinical trial. SETTING: Ambulatory clinic in a community hospital. PARTICIPANTS: A population-based sample of community-dwelling Medicare beneficiaries age 70 and older who were at high risk for hospital admission in the future (N = 568). INTERVENTION: Comprehensive assessment followed by interdisciplinary primary care. MEASUREMENTS: Functional ability, restricted activity days, bed disability days, depressive symptoms, mortality, Medicare payments, and use of health services. Interviewers were blinded to participants' group status. RESULTS: Intention-to-treat analysis showed that the experimental participants were significantly less likely than the controls to lose functional ability (adjusted odds ratio (aOR) = 0.67, 95% confidence interval (CI) = 0.47-0.99), to experience increased health-related restrictions in their daily activities (aOR = 0.60, 95% CI = 0.37-0.96), to have possible depression (aOR = 0.44, 95% CI = 0.20-0.94), or to use home healthcare services (aOR = 0.60, 95% CI = 0.37-0.92) during the 12 to 18 months after randomization. Mortality, use of most health services, and total Medicare payments did not differ significantly between the two groups. The intervention cost $1,350 per person. CONCLUSION: Targeted outpatient GEM slows functional decline.