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Purpose The purpose of this study was to evaluate Dance for Health, an intergenerational program to increase access to physical activity in an underserved, high risk urban community. Design and Methods Dance for Health was developed using community-based participatory research methods and evaluated using an observational study design. The program entailed two hour line dancing sessions delivered by trained dance instructors in the neighborhood recreation center. The weekly sessions were delivered for one month in the spring and one month in the fall from 2012–2016. Nurse practitioner students mentored local high school students to assess outcomes: achievement of target heart rate, Borg Rating of Perceived Exertion, number of pedometer steps during dance session, Physical Activity Enjoyment Scale, and adiposity. Analytic methods included descriptive statistics and mixed effects models. Results From 2012–2016, 521 participants ranging from 2–79 years attended Dance for Health. Approximately 50% of children and 80% of adults achieved target heart rate. Achievement of target heart rate was not related to perceived exertion, though it was related to pedometer steps in adults. All participants rated the program highly for enjoyment. There was no change in adiposity. Conclusions Dance for Health demonstrated high levels of community engagement and enjoyment. It led to adequate levels of exertion, particularly for adults. Our evaluation can inform program refinement and future intergenerational physical activity programs. Practice Implications Dance is an enjoyable, culturally appropriate, low cost method for increasing access to physical activity for children and families.

Rationale: Understanding long-term outcomes of critically ill patients may inform shared decision-making in the intensive care unit (ICU).Objectives: To quantify 6-month functional outcomes of general ICU patients, and develop a multivariable model comprising factors present during the first ICU day to predict which patients will return to their baseline function 6 months later.Methods: We conducted a prospective cohort study in three medical ICUs and two surgical ICUs in three hospitals. We enrolled patients who spent at least 3 days in the ICU and received mechanical ventilation for more than 48 hours and/or vasoactive infusions for more than 24 hours.Results: We measured 6-month outcomes including survival, return to original place of residence, and physical and cognitive function. Of 303 enrolled patients, 299 (98.7%) had complete follow-up at 6 months. Among the 169 patients (56.5%) who survived to 6 months, 82.8% returned home, 81.9% were able to toilet, 71.3% were able to ambulate 10 stairs, and 62...

Youth living with HIV (YLWH) are less likely than older adults to achieve and sustain viral suppression. While treatment guidelines recommend decreased viral load (VL) monitoring in individuals with well-controlled HIV, the appropriateness of this strategy for adolescents is unknown. We conducted a retrospective cohort study to describe longitudinal viral suppression and identify incidence of, and risk factors for, virologic failure among YLWH at a US adolescent HIV clinic from 2002 to 2015. We utilized Cox proportional hazards modeling to compare hazard ratios (HRs) for virologic failure stratified by baseline characteristics. Study participants (n = 365) were predominately African American (87%) and cisgender men and transgender women who have sex with men (80%) and the majority (79%) entered care from 2002 to 2012. Of antiretroviral therapy (ART)-treated participants (n = 201), 88% achieved viral suppression, with 29% subsequently developing virologic failure at a median 12.0 months [interquartile range (IQR) 6.9–22.4] after suppression. The cohort incidence rate of virologic failure was 200 (confidence interval [95% CI]: 151–264) per 1000 person years (PY), with a rate after ≥2 years sustained suppression of 113 (95% CI: 57–227) per 1000 PY. After adjusting for time to ART initiation, initial regimen class, and year of cohort entry, cisgender women had increased hazards of virologic failure (HR 3.2 95% CI: 1.3–7.9, p = 0.01). In conclusion, youth remained at high risk of virologic failure throughout their treatment course, with higher hazards of virologic failure among cisgender women compared with other youth. Maintaining frequent VL monitoring in YLWH may be warranted, even after prolonged viral suppression.

Clinical endpoints measured in terms of duration, such as intensive care unit (ICU) length of stay (LOS), are widely used in randomized clinical trials (RCTs) and observational research. In analyses of patient-level data from a recent RCT, in which ICU LOS was the primary endpoint, and in administrative data, we showed that additional ICU time is often accrued by patients after they are deemed ready for discharge. This "immutable" time (which cannot plausibly be altered by interventions under study) varies by day, week, and year, adding on average one-third of a day to total LOS. We then used statistical simulations, informed by the administrative data and RCT, to assess the impact of immutable time on the measurement and statistical comparison of patients' ICU LOS. These simulations demonstrated that immutable time combines with clinically necessary ICU time (neither of which is likely to be normally distributed) to produce overall LOS distributions that might either mask true treatment effects or suggest false treatment effects relative to analyses of time to discharge readiness. The extent and direction of bias were complex functions of the statistical method used, mortality rates and distributions, and the magnitude of immutable time relative to intervention-associated reductions in LOS.

Background Allergic asthmatic subjects are uniquely susceptible to acute wheezing episodes provoked by rhinovirus. However, the underlying immune mechanisms and interaction between rhinovirus and allergy remain enigmatic, and current paradigms are controversial. Objective We sought to perform a comprehensive analysis of type 1 and type 2 innate and adaptive responses in allergic asthmatic subjects infected with rhinovirus. Methods Circulating virus-specific TH1 cells and allergen-specific TH2 cells were precisely monitored before and after rhinovirus challenge in allergic asthmatic subjects (total IgE, 133-4692 IU/mL; n = 28) and healthy nonallergic controls (n = 12) using peptide/MHCII tetramers. T cells were sampled for up to 11 weeks to capture steady-state and postinfection phases. T-cell responses were analyzed in parallel with 18 cytokines in the nose, upper and lower airway symptoms, and lung function. The influence of in vivo IgE blockade was also examined. Results In uninfected asthmatic subjects, higher numbers of circulating virus-specific PD-1+ TH1 cells, but not allergen-specific TH2 cells, were linked to worse lung function. Rhinovirus infection induced an amplified antiviral TH1 response in asthmatic subjects versus controls, with synchronized allergen-specific TH2 expansion, and production of type 1 and 2 cytokines in the nose. In contrast, TH2 responses were absent in infected asthmatic subjects who had normal lung function, and in those receiving anti-IgE. Across all subjects, early induction of a minimal set of nasal cytokines that discriminated high responders (G-CSF, IFN-γ, TNF-α) correlated with both egress of circulating virus-specific TH1 cells and worse symptoms. Conclusions Rhinovirus induces robust TH1 responses in allergic asthmatic subjects that may promote disease, even after the infection resolves.

This article explores the validity of the Sustained Aeration Inflation for Infant Lungs (SAIL) randomized controlled clinical trial. The SAIL trial enrolled 460 infants out of a planned 600, but the trial was stopped early for harm. We ask here, whether there were any threats to validity in the trial as conducted. We then explore what design elements of the trial could have been improved upon. Finally, we consider what the implications are for future trials in this arena. Clinical Trial Registration: www.clinicaltrials.gov, Identifier: NCT02139800.

Aims Survival after delivery room cardiopulmonary resuscitation (DR-CPR) is not well characterized in full-term infants, and survival outcomes after DR-CPR have not been defined across the spectrum of gestation. The study objectives were to define gestational age (GA) specific survival following DR-CPR and to assess the association between GA and DR-CPR characteristics and survival outcomes. Methods Retrospective cohort study of prospectively collected data in the American Heart Association Get With the Guidelines-Resuscitation registry. Newborn infants without congenital abnormalities who received greater than 1 min of chest compressions for DR-CPR were included. GA was stratified by categorical subgroups: ≥36 weeks; 33–356/7 weeks; 29–326/7 weeks; 25–286/7 weeks; 22–246/7 weeks. The primary outcome was survival to hospital discharge; the secondary outcome was return of circulation (ROC). Results Among 1022 infants who received DR-CPR, 83% experienced ROC and 64% survived to hospital discharge. GA-stratified hospital survival rates were 83% (≥36 weeks), 66% (33–35 weeks), 60% (29–32 weeks), 52% (25–28 weeks), and 25% (22–24 weeks). Compared with GA ≥ 36 weeks, lower GA was independently associated with decreasing odds of survival (33–35 weeks: adjusted Odds Ratio [aOR] 0.46, 95% Confidence Interval [CI] 0.26–0.81; 29–32 weeks: aOR 0.40, 95% CI 0.23–0.69; 25–28 weeks: aOR 0.21, 95% CI 0.11–0.41; 22–24 weeks: aOR 0.06, 95% CI 0.03–0.10). Conclusions In this national registry of infants who received delivery room cardiopulmonary resuscitation (DR-CPR), 83% survived the event and two-thirds survived to hospital discharge. These results contribute to defining survival outcomes following DR-CPR across the continuum of gestation.

OBJECTIVE: To study the relationship between cancer patient/research participants’ perceptions of communication with their research nurse and doctor and 1) participants’ thoughts of dropping out from their cancer clinical trials (CCTs), 2) how informed they felt before and during their clinical trial participation, and 3) trust in their researchers. METHODS: We surveyed 110 adult cancer patients who were enrolled in cancer clinical trials by using 15 modified items from the Medical Communication Competence Scale measuring information exchange and relational communication. Retention was measured by two items: ever thought about dropping out (yes/no) and likelihood of remaining enrolled in the clinical trial (5-point Likert item). We asked how well informed about the trial participants felt at enrollment, at the date they filled out the survey, and about changes in the trial. RESULTS: Patient-participants with thoughts of dropping out from their CCTs rated their communication with research doctors lower than those who did not have thoughts of dropping out (4.14 versus 4.46, t=2.22, p=0.03). Patient-participants’ intention to remain enrolled was correlated with more favorable scores on relational communication (such as contributing to a trusting relationship and showing compassion) with research doctors (r=0.20, p=0.04) and nurses (r=0.25, p=0.01). Communication with doctors was also associated with how informed patient-participants felt during their clinical trials. CONCLUSIONS: Relational communication with research doctors and nurses was significantly related to thoughts about remaining enrolled or dropping out of a clinical trial among adult participants in cancer treatment clinical trials. PRACTICE IMPLICATIONS: Relational skills with cancer patients advances communication in research.

Objectives: We aimed to determine the accuracy and validity of the Ultrasonic Cardiac Output Monitor (USCOM) measurements of cardiac output (CO) compared to echocardiography in newborn infants, and the inter-rater agreement of USCOM measurements. Methods: In a single-center study we prospectively evaluated neonates undergoing an echocardiographic evaluation. USCOM measurements of CO were obtained at the pulmonary and aortic valve by 2 physicians blinded to the echocardiographic results. All echocardiographic measurements were performed blinded to USCOM measurements. We first enrolled an ascertainment cohort which was subsequently validated in an independent new cohort. Agreement between echocardiography and USCOM methods was assessed by Bland-Altman analysis. Intra-class correlation coefficients (ICC) assessed the agreement between the 2 operators. The ascertainment cohort correction factors were applied in a second validation cohort and agreement of the calibrated measures evaluated with repeat Bland-Altman comparisons. Results: A total of 50 infants were enrolled in the initial cohort and 15 in the validation cohort. There was a high degree of correlation between the USCOM operators (ICC = 0.975). USCOM measurements of CO were significantly higher compared to echocardiography (left ventricular output bias 95 ± 52 mL/kg/min and right ventricular output bias 64 ± 30 mL/kg/min). There was no difference in the subgroup of infants with and without a ductus arteriosus. After the correction was applied to the validation cohort, there was no longer a significant difference between the measures. Conclusions: CO measured by USCOM consistently overestimated the results obtained from echocardiography. USCOM is not adequate to provide absolute estimates of CO. However, it may allow longitudinal hemodynamic assessment of sick neonates.

Objective To describe the factors patients and physicians prioritize during first-trimester miscarriage management and assess what drives satisfaction with care. Methods We conducted a mixed-methods study of clinically stable women seeking surgical, medical, or expectant miscarriage treatment. Women with first-trimester fetal demise or anembryonic gestation (N=55) completed demographic and psychosocial surveys. Using purposive sampling, 45 (82%) completed in-depth interviews. Fifteen obstetricians were interviewed. Participants described factors that informed their counseling (physicians) or decision-making (patients). Content analysis used an integrated approach with inductively and deductively derived codes. Patient-derived themes were stratified by treatment choice. Associations between variables and treatment choices were analyzed. Results Thirty-four women (62%) received surgical management, 19 (35%) received medical, and two (4%) received expectant. Physicians expected that women with prior pregnancies have strong management preferences, and indeed, multigravid patients were less likely to change their initial treatment choice after counseling than primigravid patients (12% compared with 42%, odds ratio [OR] 0.18, 95% confidence interval [CI] 0.04-0.81, P=.03). Physicians favored patient-centered decisions and patients chose the treatment that they thought would least affect other responsibilities. Those ultimately receiving surgical management had a higher monthly income (adjusted OR 1.30, 95% CI 1.04-1.63, P=.023) and more social support (adjusted OR 2.45, 95% CI 1.07-5.61, P=.035) than the medical group. The surgical group cited loss acceptance, a favorable perception of surgery, and a desire to expedite the miscarriage as decisive factors. The medical group endorsed control over, and timed completion of, the miscarriage in a more intimate setting, an aversion to surgery or anesthesia, and a perception of improved fertility preservation as decisive factors. Regardless of treatment choice, satisfaction with treatment was linked to a supportive clinical team and expeditious resolution. Conclusion Prior pregnancy experiences, obligations, and sociodemographic factors influence miscarriage management decision-making. Structured counseling, especially for primigravid patients, could improve both the physician and the patient experience with miscarriage care.

Introduction Friedreich ataxia (FRDA) leads to increased risk of diabetes. Less is known regarding the dynamics of glucose homeostasis in FRDA, the influence of disease features, and the utility of oral-based metrics for capturing metabolic dysfunction. Methods To examine these dynamics, we analyzed oral and intravenous glucose tolerance test data in 42 non-diabetic patients with FRDA. Results Patients showed high insulin responsiveness to glucose and low insulin sensitivity. Genetic severity predicted overall metabolic impairment: individuals with longer guanine-adenine-adenine (GAA) repeats on the shorter allele showed a lower disposition index. Genetic severity did not predict any other variables. Measures of disposition index from intravenous and oral glucose tolerance testing did not correlate well, possibly reflecting divergent responses to oral and intravenous glucose loads. Conclusions FRDA patients demonstrate abnormal compensatory activity for managing glucose. Genetic severity impacts the global homeostatic profile, whereas relative contributions of insulin secretion and action vary from patient to patient. Muscle Nerve 54: 887-894, 2016.

STUDY OBJECTIVES The goal of this study was to examine different paradigms for determining critical closing pressures (Pcrit). Methods of determining Pcrit were compared, including direct observation of occluded (no flow) breaths versus inferring Pcrit from extrapolated data, and Pcrit generated by aggregating pressure-flow data from multiple runs versus Pcrit averaged across individual pressure-flow runs. The relationship between Pcrit and obstructive sleep apnea (OSA) was examined. METHODS A total of 351 participants with and without OSA underwent overnight polysomnography with pressure-flow measurements to determine Pcrit. A series of filters were applied to raw data to provide consistent, objective criteria for determining which data to include in Pcrit calculations. Observed Pcrit values were computed as the mean nasal pressure level at which a subject had at least two breaths with peak inspiratory flow < 50 mL/sec. Extrapolated Pcrit was calculated in two ways: (1) separately for each individual run and then averaged; and (2) using all valid data from individual runs combined into one plot. RESULTS Observed Pcrit was calculated in 67% to 69% of participants, a similar or higher proportion of study subjects compared to extrapolated Pcrit values using a ± 3 cm H2O filter. Although raw (unfiltered) extrapolated Pcrit measures were able to be calculated among a greater proportion of participants than filtered, extrapolated Pcrit values, and thus had fewer missing values, they had larger variability. Both extrapolated and observed Pcrit were higher among individuals with OSA compared to those without OSA. CONCLUSIONS Observed Pcrit provides a reliable descriptor of hypotonic upper airway collapsibility. Different methods for determining Pcrit were able to distinguish subjects with and without OSA.

SummaryEliciting knowledge from geographically dispersed experts given their time and scheduling constraints, while maintaining anonymity among them, presents multiple challenges.Describe an innovative, Internet based method to acquire knowledge from experts regarding patients who need post-acute referrals. Compare, 1) the percentage of patients referred by experts to percentage of patients actually referred by hospital clinicians, 2) experts’ referral decisions by disciplines and geographic regions, and 3) most common factors deemed important by discipline.De-identified case studies, developed from electronic health records (EHR), contained a comprehensive description of 1,496 acute care inpatients. In teams of three, physicians, nurses, social workers, and physical therapists reviewed case studies and assessed the need for post-acute care referrals; Delphi rounds followed when team members did not agree. Generalized estimating equations (GEEs) compared experts’ decisions by discipline, region of the country and to the decisions made by study hospital clinicians, adjusting for the repeated observations from each expert and case. Frequencies determined the most common case characteristics chosen as important by the experts.The experts recommended referral for 80% of the cases; the actual discharge disposition of the patients showed referrals for 67%. Experts from the Northeast and Midwest referred 5% more cases than experts from the West. Physicians and nurses referred patients at similar rates while both referred more often than social workers. Differences by discipline were seen in the factors identified as important to the decision.The method for eliciting expert knowledge enabled national dispersed expert clinicians to anonymously review case summaries and make decisions about post-acute care referrals. Having time and a comprehensive case summary may have assisted experts to identify more patients in need of post-acute care than the hospital clinicians. The methodology produced the data needed to develop an expert decision support system for discharge planning.Citation: Bowles KH, Ratcliffe S, Potashnik S, Topaz M, Holmes J, Shih N-W, Naylor MD. Using electronic case summaries to elicit multi-disciplinary expert knowledge about referrals to post-acute care.

Objective Trajectories of physiomarkers over time can be useful to define phenotypes of disease progression and as predictors of clinical outcomes. The aim of this study was to identify phenotypes of the time course of late-onset sepsis in premature infants in Neonatal Intensive Care Units. Methods We examined the trajectories of a validated continuous physiomarker, abnormal heart rate characteristics, using functional data analysis and clustering techniques. Participants We analyzed continuous heart rate characteristics data from 2989 very low birth weight infants (Result Despite the relative homogeneity of the patients, we found extreme variability in the physiomarker trajectories. We identified phenotypes that were indicative of seven and 30 day mortality beyond that predicted by individual heart rate characteristics values or baseline demographic information. Conclusion Time courses of a heart rate characteristics physiomarker reveal snapshots of illness patterns, some of which were more deadly than others.

Interventions for fall prevention must consider facility costs for purchasing durable medical equipment (DME), especially since items are expensive, possibly non- reimbursable or ineffective in falls prevention. The purpose of this study was to monetize the aggregate costs for DME used for fall care for one nursing home of elderly fallers pre- and post-intervention. The evidenced-based intervention (the Post Fall Index [PFI]) was a comprehensive post fall assessment and decision support tool used by trained nurses facility wide for one year to determine the likely fall diagnosis and appropriate interventions. The intervention was effective in reducing total and recurrent falls (32% and 25% respectively (p

Aortic valve replacement (AVR) for calcific aortic stenosis is associated with high rates of perioperative stroke and silent cerebral infarcts on diffusion-weighted magnetic resonance imaging (MRI), but cognitive outcomes in elderly AVR patients compared with individuals with cardiac disease who do not undergo surgery are uncertain.One hundred ninety AVR patients (mean age 76 ± 6 years) and 198 non-surgical participants with cardiovascular disease (mean age 74 ± 6 years) completed comprehensive cognitive testing at baseline (preoperatively) and 4 to 6 weeks and 1 year postoperatively. Surgical participants also completed perioperative stroke evaluations, including postoperative brain MRI. Mixed model analyses and reliable change scores examined cognitive outcomes. Stroke outcomes were evaluated in participants with and without postoperative cognitive dysfunction.From reliable change scores, only 12.4% of the surgical group demonstrated postoperative cognitive dysfunction at 4 to 6 weeks and 7.5% at 1 year. Although the surgical group had statistically significantly lower scores in working memory/inhibition 4 to 6 weeks after surgery, the groups did not differ at 1 year. In surgical participants, postoperative cognitive dysfunction was associated with a greater number (p0.01) and larger total volume (p0.01) of acute cerebral infarcts on MRI.In high-risk, aged participants undergoing surgical AVR for aortic stenosis, postoperative cognitive dysfunction was surprisingly limited and was resolved by 1 year in most. Postoperative cognitive dysfunction at 4 to 6 weeks was associated with more and larger acute cerebral infarcts.

Objectives Although hospital clinicians strive to effectively refer patients who require post-acute care (PAC), their discharge planning processes often vary greatly, and typically are not evidence-based. Design Quasi-experimental study employing pre-/postdesign. Aimed at improving patient-centered discharge processes, we examined the effects of the Discharge Referral Expert System for Care Transitions (DIRECT) algorithm that provides clinical decision support (CDS) regarding which patients to refer to PAC and to what level of care (home care or facility). Setting and participants Conducted in 2 hospitals, DIRECT data elements were collected in the pre-period (control) but discharging clinicians were blinded to the advice and provided usual discharge care. During the postperiod (intervention), referral advice was provided within 24 hours of admission to clinicians, and updated twice daily. Propensity modeling was used to account for differences between the pre-/post patient cohorts. Measures Outcomes compared between the control and the intervention periods included PAC referral rates, patient characteristics, and same-, 7-, 14-, and 30-day readmissions or emergency department visits. Results Although 24%–25% more patients were recommended for PAC referral by DIRECT algorithm advice, the proportion of patients receiving referrals for PAC did not significantly differ between the control (3302) and intervention (5006) periods. However, the characteristics of patients referred for PAC services differed significantly and inpatient readmission rates decreased significantly across all time intervals when clinicians had DIRECT CDS compared with without. There were no differences observed in return emergency department visits. Largest effects were observed when clinicians agreed with the algorithm to refer (yes/yes). Conclusions/Implications Our findings suggest the value of timely, automated, discharge CDS for clinicians to optimize PAC referral for those most likely to benefit. Although overall referral rates did not change with CDS, the algorithm may have identified those patients most in need, resulting in significantly lower inpatient readmission rates.

Worldwide, most new HIV infections occur through mucosal exposure. Immunoglobulin M (IgM) is the first antibody class generated in response to infectious agents; IgM is present in the systemic circulation and in mucosal fluids as secretory IgM. We sought to investigate for the first time the role of IgM in preventing AIDS virus acquisition in vivo.Recombinant polymeric monoclonal IgM was generated from the neutralizing monoclonal IgG1 antibody 33C6-IgG1, tested in vitro, and given by passive intrarectal immunization to rhesus macaques 30 min before intrarectal challenge with simian-human immunodeficiency virus (SHIV) that carries an HIV-1 envelope gene.In vitro, 33C6-IgM captured virions more efficiently and neutralized the challenge SHIV with a 50% inhibitory molar concentration (IC50) that was 1 log lower than that for 33C6-IgG1. The IgM form also exhibited significantly higher affinity and avidity compared with 33C6-IgG1. After intrarectal administration, 33C6-IgM prevented viremia in four out of six rhesus macaques after high-dose intrarectal SHIV challenge. Five out of six rhesus macaques given 33C6-IgG1 were protected at a five times higher molar concentration compared with the IgM form; all untreated controls became highly viremic. Rhesus macaques passively immunized with 33C6-IgM with breakthrough infection had notably early development of autologous neutralizing antibody responses.Our primate model data provide the first proof-of-concept that mucosal IgM can prevent mucosal HIV transmission and have implications for HIV prevention and vaccine development.

Objective To identify the prevalence of high HIV transmission potential in a cohort of youth living with HIV (YLWH), and determine the impact of insurance coverage on potential for HIV transmission. Design Retrospective cohort study of antiretroviral therapy (ART)-treated YLWH at a US adolescent HIV clinic, 2002-2015. Methods The primary exposure was presence or absence of insurance, defined as private, public or pharmacy-only coverage. The primary outcome was high HIV transmission potential, defined as time-concurrent incident bacterial sexually transmitted infections (STI) (gonorrhea, chlamydia or syphilis) and HIV RNA greater than 1500 copies/ml. Marginal structural models adjusting for baseline demographic covariates, prior history of STI and time-varying retention in care assessed the relationship between insurance status and HIV transmission potential. Results Participants (n = 240) were followed for a median of 22 (IQR 8.1-49) months after ART initiation, and were predominately African-American men and transgender women who have sex with men, with a median age at HIV diagnosis of 19 years (IQR 17-21). We identified 37 (15%) participants with at least one episode of high HIV transmission potential. Insurance coverage was associated with a greater than 50% lower odds of high HIV transmission potential (aOR 0.46, 95% CI 0.26-0.84), and history of STI at or before entry to HIV care conferred more than three-fold higher odds of high transmission potential (aOR 3.21, 95% CI 1.55-6.63). Conclusion We found 15% of YLWH to have episodic high HIV transmission potential despite receiving ART. Insurance coverage, including pharmacy-only benefits, was protective against transmission risk, suggesting a pivotal role for universal ART coverage in treatment as prevention.

We developed measures of benefits and burdens of research participation in cancer clinical trials using a sequential mixed methods design with a qualitative ( n = 32) and quantitative sample ( n = 110) of cancer clinical trial participants. Benefit–burden items (22 for benefits, 23 for burdens) were subsequently developed and assessed through cognitive interviewing for content, clarity, and meaning. Preliminary psychometric analyses support the internal consistency reliability and construct validity of Benefit (α = .90) and Burden (α = .87) research participation scales. Item response theory models supported the discrimination ability of the items on the scales. Participants who had thoughts of dropping out had lower Benefit scale scores ( p < .001) and higher Burden scores ( p < .001) than those who had no thoughts of dropping out, supporting construct validity. With further psychometric testing, the scale can be used to develop appropriate interventions to address recruitment and retention of human participants in clinical research.

Introduction: The prevalence of HIV-associated neurocognitive disorders continues to rise despite the widespread use of antiretroviral therapy. We aimed to define the risk of neurocognitive dysfunction among smokers relative to nonsmokers. Methods: We conducted a retrospective cohort study including HIV-infected adults ages 21 to 65 years. The Mental Alternation Test (MAT) was the primary outcome. The odds of cognitive impairment were compared using random-effects logistic regression to adjust for potential confounders. Results: Of 3033, 1486 (49%) were smokers. The odds ratio for the association between smoking and cognitive impairment was 1.12 (95% confidence interval: 0.85-1.49). Nonsmokers had a higher median MAT score relative to smokers ( P = .01). Conclusion: There was no evidence that HIV-infected smokers had greater neurocognitive dysfunction relative to HIV-infected nonsmokers. While tobacco use remains an important health risk issue to address in the HIV population, it may not represent a risk factor for neurocognitive impairment.

We extend a random pattern mixture joint model for longitudinal ordinal outcomes and informative dropouts. The patients are generalized to 'pattern' groups based on known covariates that are potentially surrogated for the severity of the underlying condition. The random pattern effects are defined as the latent effects linking the dropout process and the ordinal longitudinal outcome. Conditional on the random pattern effects, the longitudinal outcome and the dropout times are assumed independent. Estimates are obtained via the Expectation-maximization algorithm. We applied the model to the end-stage renal disease data. Anemia was found to be significantly affected by the baseline iron treatment when the dropout information was adjusted via the study model; as opposed to an independent or shared parameter model. Simulations were performed to evaluate the performance of the random pattern mixture model under various assumptions.

BACKGROUND ICU readmissions are associated with increased mortality and costs; however, it is unclear whether these outcomes are caused by readmissions or by residual confounding by illness severity. An assessment of temporal changes in ICU readmission in response to a specific policy change could help disentangle these possibilities. We sought to determine whether ICU readmission rates changed after 2003 Accreditation Council for Graduate Medical Education Resident Duty Hours reform ("reform") and whether there were temporally corresponding changes in other ICU outcomes. METHODS We used a difference-in-differences approach using Project IMPACT (Improved Methods of Patient Information Access of Core Clinical Tasks). Piecewise regression models estimated changes in outcomes immediately before and after reform in 274,491 critically ill medical and surgical patients in 151 community and academic US ICUs. Outcome measures included ICU readmission, ICU mortality, and in-hospital post-ICU-discharge mortality. RESULTS In ICUs with residents, ICU readmissions increased before reform (OR, 1.5; 95% CI, 1.22-1.84; P P = .03). This abrupt decline in ICU readmissions after reform differed significantly from an increase in readmissions observed in ICUs without residents at this time (difference-in-differences P CONCLUSIONS The changes in ICU readmission rates after reform, without corresponding changes in mortality, suggest that ICU readmissions are not causally related to other untoward patient outcomes. Instead, ICU readmission rates likely reflect operational aspects of care that are not patient-centered, making them less useful indicators of ICU quality.

Background and Purpose— Stroke is a potentially devastating complication of cardiac surgery. Identifying predictors of radiographic infarct may lead to improved stroke prevention for surgical patients. Methods— We reviewed 129 postoperative brain magnetic resonance imagings from a prospective study of patients undergoing surgical aortic valve replacement. Acute infarcts were classified as watershed or embolic using prespecified criteria. Results— Acute infarct on magnetic resonance imaging was seen in 79 of 129 patients (61%), and interrater reliability for stroke pathogenesis was high (κ=0.93). Embolic infarcts only were identified in 60 patients (46%), watershed only in 2 (2%), and both in 17 (13%). In multivariable logistic regression, embolic infarct was associated with aortic arch atheroma (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.0–12.0; P =0.055), old subcortical infarcts (OR, 5.5; 95% CI, 1.1–26.6; P =0.04), no history of percutaneous transluminal coronary angioplasty or coronary artery bypass graft (OR, 4.0; 95% CI, 1.2–13.7; P =0.03), and higher aortic valve gradient (OR, 1.3 per 5 mm Hg; 95% CI, 1.09–1.6; P =0.004). Watershed infarct was associated with internal carotid artery stenosis ≥70% (OR, 11.7; 95% CI, 1.8–76.8; P =0.01) and increased left ventricular ejection fraction (OR, 1.6 per 5% increase; 95% CI, 1.08–2.4; P =0.02). Conclusions— The principal mechanism of acute cerebral infarction after aortic valve replacement is embolism. There are distinct factors associated with watershed and embolic infarct, some of which may be modifiable.

Context Thyroid nodules are increasingly recognized in children and are associated with a greater risk for thyroid cancer compared with adults. Thyroid ultrasound is the favored tool for evaluation of thyroid nodules; however, there are limited data regarding the accuracy of thyroid ultrasound to confirm features associated with a low risk of thyroid cancer in children. Objectives We examined whether thyroid ultrasound is capable of accurately identifying thyroid nodules at a low risk of malignancy in children. Design and setting Using a retrospective cohort study design, we identified children age ≤18 years with thyroid nodules and adequate follow-up. Ultrasound images were reviewed independently by two blinded expert radiologists, and ultrasound characteristics were analyzed to determine optimal predictive value and reliability. Patients and results A total of 417 subjects were found to have thyroid nodules, and 152 subjects had adequate follow-up; 59 (38.8%) of these were diagnosed with thyroid cancer. We evaluated 236 individual nodules. Features most consistent with benign nodules included small size, isoechoic echogenicity, partially cystic structure, sharp or noninfiltrative margins, absent Doppler flow, and absent calcifications. Significant variability was found between expert interpretations of ultrasound features. Thyroid nodule composition appears to be the most sensitive and reliable feature for stratifying the risk of thyroid cancer. Ultrasound accurately identified benign thyroid nodules in 80.9% of subjects (95% confidence interval, 74-86.6). Conclusions Ultrasonography is useful for the evaluation of thyroid nodules, but we found no combination of ultrasound features sufficient to exclude thyroid cancer without a biopsy.

Background Symptoms drive healthcare use among adults with atrial fibrillation, but limited data are available regarding which symptoms are most problematic and which patients are most at‐risk. The purpose of this study was to: (1) identify clusters of patients with similar symptom profiles, (2) characterize the individuals within each cluster, and (3) determine whether specific symptom profiles are associated with healthcare utilization. Methods We conducted a cross‐sectional secondary data analysis of 1,501 adults from the Vanderbilt Atrial Fibrillation Registry. Participants were recruited from Vanderbilt cardiology clinics, emergency department, and in‐patient services. Subjects included in our analysis had clinically verified atrial fibrillation and a completed symptom survey. Symptom and healthcare utilization data were collected with the University of Toronto Atrial Fibrillation Severity Scale. Latent class regression analysis was used to identify symptom clusters, with clinical and demographic variables included as covariates. We used Poisson regression to examine the association between latent class membership and healthcare utilization. Results Participants were predominantly male (67%) with a mean age of 58.4 years (±11.9). Four latent classes were evident, including an Asymptomatic cluster (N = 487, 38%), Highly Symptomatic cluster (N = 142, 11%), With Activity cluster (N = 326, 25%), and Mild Diffuse cluster (N = 336, 26%). Highly Symptomatic membership was associated with the greatest rate of emergency department visits and hospitalizations (incident rate ratio 2.4, P < 0.001). Conclusions Clinically meaningful atrial fibrillation symptom profiles were identified that were associated with increased rates of emergency department visits and hospitalizations.

Decisions about who should be referred for post-acute care (PAC) are made by individual clinicians or teams for 14 million older adults per year, without national standards or guidelines. Using teams of multi-disciplinary experts we built a decision support (DS) tool that assists clinicians with these important decisions. The DS is based on two algorithms calculated from the characteristics of the patient during the hospital stay and provides a suggestion of refer or not, and which site of care is recommended. We will describe the development and testing of live DS in two hospitals. When the tool said to refer and patients did not get referred, readmission risk and ED use were 40% and 43% higher respectively, than those who did get referred. Use of DS can assure that high risk patients are identified and referred for PAC.

Background: Lipid mediators are complex molecules that demonstrate an association to inflammatory states including atherosclerotic vascular disease. Peripheral artery disease (PAD) is an atherosclerotic disease of the distal aorta and lower extremity arteries. Supervised walking therapy (SWT) is the mainstay of treatment for PAD and is hypothesized to improve claudication by suppressing inflammatory activation. Objectives: We sought to examine how lipid mediators were impacted by treadmill testing in PAD, and to identify lipid mediators that were altered by SWT. Methods: Plasma samples were collected before and after Gardner treadmill testing (GTT) in individuals with PAD; participants underwent 12 weeks of SWT and were retested. Lipid mediators were isolated using Ostro Sample Preparation Plates (Waters; Milford, MA) and quantified by UPLC-MS/MS. Results: Thirty-six participants had complete sets of plasma for analysis. The median age was 67 years (IQR: 62 - 71); there were 55 men (73%) and the median ABI was 0.64 (IQR: 0.55 - 0.76). The median peak walking time prior to SWT was 7.4 min (IQR: 4.8 - 10.3 min), which increased to 11.9 min (IQR: 8.4 - 17.1) after SWT (p < 10 -4 ). Discriminant analysis showed clear separation of pre- and post- GTT and pre- and post- SWT samples based on global lipid profiles (Figure 1). Cluster analysis demonstrated 13 distinct clusters of lipid mediators; those clusters containing carbon and arachidonic acid epoxides, and vicinal diols were significantly (FDR Conclusions: Lipid mediator profiles manifested unique response patterns to treadmill testing and were modified by supervised walking therapy. These data suggest that lipid mediators play an active role in the biology underlying improvements in lower extremity symptoms associated with SWT and may offer a novel target for therapeutic manipulation.

Introduction: Aortic valve replacement (AVR) for calcific aortic stenosis (AS) is associated with high rates of perioperative clinical stroke and “silent” acute cerebral infarcts (SACI) in older adults. The goal of this study was to determine the impact of clinical stroke and acute infarcts on cognitive outcomes. Methods: 129 elderly surgical AVR (age=74.7±6y) participants underwent perioperative evaluations by neurologists and post-surgical diffusion-weighted MRI during the first week post-op. Clinical assessments and MRI’s were reviewed by vascular neurologists, and participants were classified as having clinical stroke, SACI, or no stroke. Trained coders quantified all acute lesions on MRI (lesion number, lesion volume). Participants also completed cognitive testing at baseline, 4-6 weeks, and 1 year. The incidence of post-operative cognitive disorder (POCD) was identified using reliable change index scores calculated in reference to a comparison group of 154 nonsurgical participants with vascular disease. Results: Surgical participants who had a perioperative clinical stroke (n=34) had the largest infarct volume and performed worse than participants with SACI (n=59) and those without stroke on cognitive testing at baseline and at 4-6 weeks post-surgery (p < .05 for all). Among participants who showed an acute infarct on postop MRI (i.e., clinical stroke + silent stroke, n = 93), total acute infarct volume but not infarct number was significantly correlated with cognitive outcomes at 4-6 weeks and 1 year (r > .27 for all). Surgical participants with POCD (12.2% at 4-6 weeks; 9.2% at 1 year) were older, more likely to have had a perioperative clinical stroke, and had more and larger acute infarcts on MRI than surgical participants without POCD (p Conclusions: Cognitive outcomes and POCD are significantly associated with perioperative clinical stroke and volume of acute infarct on MRI. However, surgical participants who demonstrate small, SACI show good cognitive outcomes that are comparable to participants without perioperative infarct. Low baseline cognitive function may be a risk marker for perioperative stroke and poor cognitive outcomes in the elderly.

Background Symptom clusters have not previously been explored among individuals with atrial fibrillation of any type. Objective The purpose of this study is to determine the number of symptom clusters present among adults with chronic atrial fibrillation and to explore sociodemographic and clinical factors potentially associated with cluster membership. Methods This was a cross-sectional secondary data analysis of 335 Australian community-dwelling adults with chronic (recurrent paroxysmal, persistent, or permanent) atrial fibrillation. We used self-reported symptoms and agglomerative hierarchical cluster analysis to determine the number and content of symptom clusters present. Results There were slightly more male (52%) than female participants, with a mean (SD) age of 72 (11.25) years. Three symptom clusters were evident, including a vagal cluster (nausea and diaphoresis), a tired cluster (fatigue/lethargy, weakness, syncope/dizziness, and dyspnea/breathlessness), and a heart cluster (chest pain/discomfort and palpitations/fluttering). We compared patient characteristics among those with all the symptoms in the cluster, those with some of the symptoms in the cluster, and those with none of the symptoms in the cluster. The only statistically significant differences were in age, gender, and the use of antiarrhythmic medications for the heart cluster. Women were more likely to have the heart symptom cluster than men were. Individuals with all of the symptoms in the heart cluster were younger (69.6 vs 73.7 years; P = .029) than those with none of the symptoms in the heart cluster and were more likely to be on antiarrhythmic medications. Conclusion Three unique atrial fibrillation symptom clusters were identified in this study population.

To the Editor: With rising demand for critical care, intensivists’ time must increasingly be divided among patients (1–6). Recent studies suggest that increased strain at intensive care unit (ICU) admission leads to higher mortality in closed ICUs (7) and that increased strain at discharge leads to increases in ICU readmissions (8). These relationships between strain and outcomes could be mediated by strain-induced changes in the time intensivists devote to patients during patient care rounds (7–9). We therefore examined how the allocation of intensivists’ time during rounds changes at times of low versus high ICU strain and whether intensivists preferentially allocate time away from certain patient groups as strain increases. Some results have been previously reported in the form of an abstract (10). Methods We conducted a prospective study of patient care rounds in the 24-bed medical ICU of the Hospital of the University of Pennsylvania in 2012. Time spent performing various rounding activities was recorded in real time by trained data collectors, using a tablet computer. Methods for assessing interrater reliability can be found in the online supplement. Data collection was randomly assigned to one of two intensivist-led medical ICU teams each day and was not performed on weekends. Variables describing patient characteristics, staffing, and ICU strain were obtained from the electronic medical record and as part of a separate clinical trial (11). Our analysis focused on “cognitive rounding time” (time spent on the patient’s assessment and plan) and on total rounding time (presentation of events and data, assessment and plan, and teaching related to that patient). Three validated strain variables (5) were considered: team census (“census”), representing the number of patients rounded on by the observed team each day; number of new admissions (“admissions”) since the end of rounds the previous day; and average severity of illness (“acuity”) of patients on the team, using Acute Physiology and Chronic Health Evaluation III (APACHE III) scores (12). We constructed explanatory linear mixed-effects models for cognitive and total rounding time for each patient-day. Patients were treated as random clusters, cumulative days hospitalized in the ICU were included as a random slope and as a linear term, and attending was treated as an indicator variable (13). Patient race was obtained from the electronic medical record and could be reported by either patient or provider. We considered three race categories: black, nonblack (white or Asian), and unknown. Table 1 and Table E1 in the online supplement describe all evaluated covariates. Table 1. Descriptive Statistics We constructed separate models to determine whether time was allocated away from specific patient groups as strain increased by exploring interactions between the three strain variables and the following six patient variables: admission status (new admission vs. follow-up), patient race (black vs. nonblack), age (continuous), severity of illness (continuous), family presence on rounds, and patient sex. We then constructed a fully adjusted model with all interactions having a P value < 0.2 and used backward selection, removing nonsignificant terms (14). We used Holm tests of conditional significance given the multiple comparisons made (15). Additional details regarding the statistical analyses are available in the online supplement. Results Rounds were observed for 566 patients over the course of 114 noncontiguous weekdays, for a total of 1,295 patient-days. Intensivists rounded on a median of 11 patients (interquartile range [IQR], 10–13) each day, including two new admissions (IQR, 1–3). Median daily rounding time was 188.6 minutes (IQR, 164.8–212.6 min); 91.9 minutes (IQR, 77.9–107.3 min) were spent on cognitive rounding time (Table 1). Daily rounding time increased as census (6.3 min; 95% confidence interval [CI], 2.4–10.1 min; P = 0.002) and admissions (6.0 min; 95% CI, 0.6–11.4 min; P = 0.031) increased (Figure E1 in the online supplement); cognitive rounding time increased as census increased (2.5 min; 95% CI, 0.1–4.9 min; P = 0.045). In fully adjusted models, with increasing daily admissions, newly admitted patients received 1.38 fewer minutes (95% CI, −2.43 to −0.33 min; PHolm = 0.002) total rounding time (interaction P value = 0.01) and 0.73 fewer minutes (95% CI, −1.42 to −0.07 min; PHolm = 0.0113) cognitive rounding time per additional admission. No significant changes occurred among follow-up patients (interaction P value = 0.030; Figure E2). As census increased, each unit increase led to a 0.5-minute (95% CI, 0.87–0.13 min; PHolm = 0.0135) decrease in cognitive rounding time among new admissions, with no decrement among follow-ups (interaction P value = 0.028). The effect of census on total rounding time was modified by new admission status and race. A three-way interaction (P = 0.04) revealed that among follow-ups, nonblack patients received 3.4 minutes (95% CI, −5.6 to −1.2 min; PHolm = 0.02) more than blacks at low census (eight patients); however, the excess time spent with nonblacks disappeared as census increased (P < 0.01). In contrast, no significant differences in strain-induced decrements in rounding time were observed between black and nonblack new admissions (P = 0.22; Figure 1). These relationships persisted in two sensitivity analyses, excluding patients of indeterminate race or excluding Asians from the nonblack group (Table E2). Figure 1. Total rounding time. Models are adjusted for acuity, severity of illness measured on Day 1 of the first intensive care unit (ICU) stay, day number in ICU course, attending, data collector, order patient was rounded on (inverse), maximum team size, attending’s ... Neither patient age, sex, acuity, and severity of illness nor the presence of family on rounds affected the allocation of rounding time. Discussion This study provides the first description of how ICU physicians allocate rounding time among patients and how this allocation changes as ICUs become strained. Daily rounding time increased with increases in census and admissions, but less time was spent per patient, primarily affecting new admissions and nonblack follow-up patients. These findings are consistent with studies showing that clinicians perceive their time to be highly constrained (1, 5, 6). The observation that strain preferentially affected new admissions and nonblack follow-ups may reflect the fact that these patients received more time in general, such that further reductions were challenging. Importantly, we found that increases in ICU strain did not result in disproportionate decreases in the time allocated to other patient subgroups, suggesting that ICU physicians generally ration their time equitably. Although total rounding time was allocated away from nonblack follow-ups as census increased, the facts that nonblacks received more time overall and that similar patterns were not observed among new admissions casts doubt on this finding, representing a true racial disparity. This study had several limitations. First, data were not collected outside of morning rounds, and therefore we could not assess how strain affected time allocation at other times. Second, although a differential effect of census on time allocation was not found between newly admitted black and nonblack patients, future research should determine whether a larger sample would reveal a significant disparity. Third, severity of illness was assessed only at ICU admission, limiting severity adjustment on subsequent days; however, bias introduced by inadequate severity adjustment is unlikely to be differential across different levels of census, and therefore it is unlikely to have affected the results. Residual confounding could still be present, as severity of illness may be indirectly affected by census. Finally, data capture was not formally evaluated; however, interrater reliability was excellent. In summary, this study provides a description of how intensivists allocate their time among patients as their workloads increase, providing objective confirmation of the common perception that time is a scarce resource. However, as a single-center study, these results may not generalize to other ICUs. In addition, because we often lacked data on rounding time on the same patient over contiguous days, we could not address whether observed decreases in rounding time mediated previously observed relationships between strain and outcomes or whether they represent improved efficiency. Future research is needed to explore these questions (7, 8).

Branching curves are a technique for modeling curves that change trajectory at a change (branching) point. Currently, the estimation framework is limited to independent data, and smoothing splines are used for estimation. This article aims to extend the branching curve framework to the longitudinal data setting where the branching point varies by subject. If the branching point is modeled as a random effect, then the longitudinal branching curve framework is a Semiparametric Nonlinear Mixed Effects Model. Given existing issues with using random effects within a smoothing spline, we express the model as a B-spline Based Semiparametric Nonlinear Mixed Effects Model. Simple, clever smoothness constraints are enforced on the B-splines at the change point. The method is applied to Women’s Health data where we model the shape of the labor curve (cervical dilation measured longitudinally) before and after treatment with oxytocin (a labor stimulant).

Although commonly observed in clinical practice, the heterogeneity of obstructive sleep apnoea (OSA) clinical presentation has not been formally characterised.This study was the first to apply cluster analysis to identify subtypes of patients with OSA who experience distinct combinations of symptoms and comorbidities. An analysis of baseline data from the Icelandic Sleep Apnoea Cohort (822 patients with newly diagnosed moderate-to-severe OSA) was performed.Three distinct clusters were identified. They were classified as the “disturbed sleep group” (cluster 1), “minimally symptomatic group” (cluster 2) and “excessive daytime sleepiness group” (cluster 3), consisting of 32.7%, 24.7% and 42.6% of the entire cohort, respectively. The probabilities of having comorbid hypertension and cardiovascular disease were highest in cluster 2 but lowest in cluster 3. The clusters did not differ significantly in terms of sex, body mass index or apnoea–hypopnoea index.Patients with OSA have different patterns of clinical presentation, which need to be communicated to both the lay public and the professional community with the goal of facilitating care-seeking and early identification of OSA. Identifying distinct clinical profiles of OSA creates a foundation for offering more personalised therapies in the future.

Summary Our objective was to determine tuberculin skin test conversion rate of health care workers traveling to Botswana. The rate of tuberculin skin test conversion was 4.2% for the entire group studied or 6.87 per 1000 person weeks (95% CI, 1.87–17.60). Background International travel by health care workers traveling from low incidence countries to areas of the world where tuberculosis is highly endemic places the health care worker at an increased risk of acquiring tuberculosis. Objectives To determine the tuberculin skin test conversion rate of health care workers living in the United States with previously negative tuberculin skin test results working for less than 1 year in a hospital in Botswana where tuberculosis is highly endemic. Methods We performed a cross-sectional survey among health care workers affiliated with the University of Pennsylvania School of Medicine who participated in patient care in Botswana between July 1st 2004 and June 30th 2009. We recruited health care workers after returning from Botswana who had a documented negative tuberculin skin test in the year prior to travel, who spent at least 2 weeks but not more than 1 year and who had a documented tuberculin skin test 2–3 months post travel. The main study outcome was a positive tuberculin skin test 6–12 weeks after returning from Botswana, defined by an area of at least 10 mm induration 48–72 h after placement of the tuberculin skin test. Results 95 Subjects participated in the study and there were 4 tuberculin skin test conversions. The rate of tuberculin skin test conversion in our study population was 4.2% for the entire group studied or 6.87 per 1000 person weeks (95% CI, 1.87–17.60). Conclusions The tuberculin skin test conversion rate was higher than the reported conversion rates for those not working in a health care setting.

Rationale: Intensive care unit (ICU)-based randomized clinical trials (RCTs) among adult critically ill patients commonly fail to detect treatment benefits. Objectives: Appraise the rates of success, outcomes used, statistical power, and design characteristics of published trials. Methods: One hundred forty-six ICU-based RCTs of diagnostic, therapeutic, or process/systems interventions published from January 2007 to May 2013 in 16 high-impact general or critical care journals were studied. Measurement and Main Results: Of 146 RCTs, 54 (37%) were positive (i.e., the a priori hypothesis was found to be statistically significant). The most common primary outcomes were mortality (n = 40 trials), infection-related outcomes (n = 33), and ventilation-related outcomes (n = 30), with positive results found in 10, 58, and 43%, respectively. Statistical power was discussed in 135 RCTs (92%); 92 cited a rationale for their power parameters. Twenty trials failed to achieve at least 95% of their reported target sample size, including 11 that were stopped early due to insufficient accrual/logistical issues. Of 34 superiority RCTs comparing mortality between treatment arms, 13 (38%) accrued a sample size large enough to find an absolute mortality reduction of 10% or less. In 22 of these trials the observed control-arm mortality rate differed from the predicted rate by at least 7.5%. Conclusions: ICU-based RCTs are commonly negative and powered to identify what appear to be unrealistic treatment effects, particularly when using mortality as the primary outcome. Additional concerns include a lack of standardized methods for assessing common outcomes, unclear justifications for statistical power calculations, insufficient patient accrual, and incorrect predictions of baseline event rates.

Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P =0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P =0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.

BackgroundMedical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.MethodsWe randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.ResultsComplete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group.ConclusionsPretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).

Falls disproportionately burden frail older adults in long-term care, which is evidenced by the 60% fall rate annually in this setting. Our health systems improvement model, framed by the Health Outcomes Model for falls prevention, is targeted to achieve the triple aim of better health, better care, and better value. Highlighting evidence from three inter-related studies, this presentation describes the impact of a practice change model and its impact on patient, unit/staff, and organizational level factors as related to facility-wide falls prevention. In study one, we used an evidenced-based practice approach and assessment tool to achieve total and recurrent falls reduction over one year by 32% and 25%, respectively (p

The aging population may strain intensive care unit (ICU) capacity and adversely affect patient outcomes. Existing fluctuations in demand for ICU care offer an opportunity to explore such relationships.To determine whether transient increases in ICU strain influence patient mortality, and to identify characteristics of ICUs that are resilient to surges in capacity strain.Retrospective cohort study of 264,401 patients admitted to 155 U.S. ICUs from 2001 to 2008. We used logistic regression to examine relationships of measures of ICU strain (census, average acuity, and proportion of new admissions) near the time of ICU admission with mortality.A total of 36,465 (14%) patients died in the hospital. ICU census on the day of a patient's admission was associated with increased mortality (odds ratio [OR], 1.02 per standardized unit increase; 95% confidence interval [CI]: 1.00, 1.03). This effect was greater among ICUs employing closed (OR, 1.07; 95% CI: 1.02, 1.12) versus open (OR, 1.01; 95% CI: 0.99, 1.03) physician staffing models (interaction P value = 0.02). The relationship between census and mortality was stronger when the census was composed of higher acuity patients (interaction P value0.01). Averaging strain over the first 3 days of patients' ICU stays yielded similar results except that the proportion of new admissions was now also associated with mortality (OR, 1.04 for each 10% increase; 95% CI: 1.02, 1.06).Several sources of ICU strain are associated with small but potentially important increases in patient mortality, particularly in ICUs employing closed staffing models. Although closed ICUs may promote favorable outcomes under static conditions, they are susceptible to being overwhelmed by patient influxes.

Human adenovirus (AdHu)-based candidate AIDS vaccine can provide protection from simian immunodeficiency virus (SIV) transmission and disease progression. However, their potential use may be limited by widespread preexisting immunity to the vector. In contrast, preexisting immunity to chimpanzee adenoviruses (AdC) is relatively rare. In this study, we utilized two regimens of prime-boost immunizations with AdC serotype SAd-V23 (also called AdC6) and SAd-V24 (also called AdC7) expressing SIV Gag/Tat to test their immunogenicity and ability to protect rhesus macaques (RMs) from a repeated low-dose SIV mac239 challenge. Both AdC6 followed by AdC7 (AdC6/7) and AdC7 followed by AdC6 (AdC7/6) induced robust SIV Gag/Tat-specific T cell responses as measured by tetramer staining and functional assays. However, no significant protection from SIV transmission was observed in either AdC7/6- or AdC7/6-vaccinated RMs. Interestingly, in the RMs showing breakthrough infections, AdC7/6-SIV immunization was associated with a transient but significant ( P = 0.035 at day 90 and P = 0.033 at day 120 postinfection) reduction in the setpoint viral load compared to unvaccinated controls. None of the measured immunological markers (i.e., number or functionality of SIV-specific CD8 + and CD4 + T cell responses and level of activated and/or CCR5 + CD4 + target cells) at the time of challenge correlated with protection from SIV transmission in the AdC-SIV-vaccinated RMs. The robust immunogenicity observed in all AdC-immunized RMs and the transient signal of protection from SIV replication exhibited by AdC7/6-vaccinated RMs even in the absence of any envelope immunogen suggest that AdC-based vectors may represent a promising platform for candidate AIDS vaccines.

BACKGROUND:: Intensive care unit (ICU) readmission rates are commonly viewed as indicators of ICU quality. However, definitions of ICU readmissions vary, and it is unknown which, if any, readmissions are associated with ICU quality. OBJECTIVE:: Empirically derive the optimal interval between ICU discharge and readmission for purposes of considering ICU readmission as an ICU quality indicator. RESEARCH DESIGN:: Retrospective cohort study. SUBJECTS:: A total of 214,692 patients discharged from 157 US ICUs participating in the Project IMPACT database, 2001-2008. MEASURES:: We graphically examined how patient characteristics and ICU discharge circumstances (eg, ICU census) were related to the odds of ICU readmissions as the allowable interval between ICU discharge and readmission was lengthened. We defined the optimal interval by identifying inflection points where these relationships changed significantly and permanently. RESULTS:: A total of 2242 patients (1.0%) were readmitted to the ICU within 24 hours; 9062 (4.2%) within 7 days. Patient characteristics exhibited stronger associations with readmissions after intervals >48-60 hours. By contrast, ICU discharge circumstances and ICU interventions (eg, mechanical ventilation) exhibited weaker relationships as intervals lengthened, with inflection points at 30-48 hours. Because of the predominance of afternoon readmissions regardless of time of discharge, using intervals defined by full calendar days rather than fixed numbers of hours produced more valid results. DISCUSSION:: It remains uncertain whether ICU readmission is a valid quality indicator. However, having established 2 full calendar days (not 48 h) after ICU discharge as the optimal interval for measuring ICU readmissions, this study will facilitate future research designed to determine its validity. Copyright © 2013 by Lippincott Williams & Wilkins.

Objective To assess whether women with polycystic ovary syndrome (PCOS) follow the same age-related decline in IVF outcomes as women with tubal factor infertility over the reproductive life span. PCOS is characterized by increased ovarian reserve as assessed by antral follicle counts and anti-Mullerian hormone levels. It is unclear whether these surrogate markers of ovarian reserve reflect a true lengthening of the reproductive window. Design Retrospective cohort. Setting Not applicable. Patient(s) Women with PCOS and tubal factor infertility (42,286 cycles). Intervention(s) IVF. Main Outcome Measure(s) Pregnancy and live-birth rates. Result(s) The mean number of oocytes retrieved was higher in women with PCOS compared with in women with tubal factor (16.4 vs. 12.8; odds ratio [OR], 1.27; 95% confidence interval [CI], 1.25–1.29). The clinical pregnancy (42.5% vs. 35.8%; OR, 1.32; 95% CI, 1.27–1.38) and live-birth rates were also increased in women with PCOS (34.8% vs. 29.1%; OR, 1.30; 95% CI, 1.24–1.35). A similar rate of decline in clinical pregnancy and live-birth rates was noted in both groups (20–44 years). The implantation, clinical pregnancy, miscarriage, and live-birth rates were not significantly different for each year after age 40 in the two groups. Conclusion(s) Despite a higher oocyte yield in all age groups, women with PCOS over age 40 had similar clinical pregnancy and live-birth rates compared with women with tubal factor infertility. These findings suggest that the reproductive window may not be extended in PCOS and that patients with infertility should be treated in a timely manner despite indicators of high ovarian reserve.

Administrators play a major role in choosing and managing the use of the electronic health record (EHR). The documentation policies and EHR changes enacted or approved by administrators affect the ability to use clinical data for research. This article illustrates the challenges that can be avoided through awareness of the consequences of customization, variations in documentation policies and quality, and user interface features. Solutions are posed that assist administrators in avoiding these challenges and promoting data harmonization for research and quality improvement.

Background Population-based (PB) registries of type 1 diabetes mellitus (T1DM) in children have been essential in determining the geographic, racial, and temporal patterns of the disease. There is a paucity of PB data on the prevalence of type 1 and type 2 diabetes (T2DM) in youth. Methods The prevalence of diabetes in children was determined using a PB survey of the 628 schools in Philadelphia. Data obtained included type of diabetes, date of birth, race, gender, date of diagnosis, diabetes treatment, and most recent height and weight. Results The survey was completed by nurses at 510 schools (81% of schools) representing 252,896 children (70% of children in Philadelphia). Prevalence (per 1000) was computed. The survey identified 492 cases (355 T1DM, 88 T2DM, 49 type unknown). The overall prevalence of T1DM was 1.58 (0.73 White, 0.56 African American, 0.50 Hispanic); of T2DM was 0.35 (0.03 White, 0.28 African American, 0.05 Hispanic). Mean age at diagnosis was 8.6 and 11.9 years for T1DM and T2DM, respectively. The prevalence of T1DM was higher in boys- T2DM was higher in girls. Of children with T2DM, 25% were treated with insulin. BMI was ≥95th percentile in 20% of children weighed (10% of T1DM, 57% of T2DM). Conclusions Although the Philadelphia Pediatric Diabetes Registry is the longest ongoing US registry of its kind, these are the first PB diabetes prevalence data of children in Philadelphia. PB studies in schools are able to capture children with diabetes who are diagnosed and treated in a variety of settings. 摘要 背景 基于人口的1型糖尿病儿童登记表对于确定疾病的地理、种族以及时间规律来说很有必要。目前还缺乏有关青年人中1型与2型糖尿病患病率的基于人口的数据。 方法 在费城628所学校里采用基于人口的调查获取儿童中的糖尿病患病率。获取的数据包括糖尿病类型、出生日期、种族、性别、诊断日期、糖尿病治疗方案以及最近的身高与体重。 结果 由护士在510所学校（81%的学校）中对252896名儿童（70%的费城儿童）进行了调查。计算出（每1000名）患病率。这个调查鉴定出了492名病例（355名1型糖尿病，88名2型糖尿病，49名类型不明确）。1型糖尿病的总患病率为1.58（白人为0.73，非裔美国人为0.56，西班牙人裔为0.50）；2型糖尿病为0.35（白人为0.03，非裔美国人为0.28，西班牙人裔为0.05）。诊断1型糖尿病与2型糖尿病时的平均年龄分别为8.6岁与11.9岁。男孩中的1型糖尿病患病率更高，而女孩中的2型糖尿病患病率更高。在2型糖尿病儿童中，有25%的人使用胰岛素治疗。有20%的儿童BMI超过了第95百分位（1型糖尿病有10%，2型糖尿病有57%）。 结论 虽然费城儿科糖尿病登记表在美国同类登记表中持续时间最长，但这些是费城儿童第一份基于人口的糖尿病患病率的数据。在学校中进行的基于人口的研究能够获得在不同的机构进行诊断与治疗的儿童糖尿病数据。

OBJECTIVE The purpose of this study was to describe the incidence of type 1 diabetes in children in Philadelphia from 2000–2004, compare the epidemiology to the previous three cohorts in the Philadelphia Pediatric Diabetes Registry, and, for the first time, describe the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS Diabetes cases were obtained through a retrospective population-based registry. Hospital inpatient and outpatient records were reviewed for cases of type 1 and type 2 diabetes diagnosed from 1 January 2000 to 31 December 2004. The secondary source of validation was the School District of Philadelphia. Time series analysis was used to evaluate the changing pattern of incidence over the 20-year period. RESULTS The overall age-adjusted incidence rate in 2000–2004 of 17.0 per 100,000 per year was significantly higher than that of previous cohorts, with an average yearly increase of 1.5% and an average 5-year cohort increase of 7.8% (P = 0.025). The incidence in white children (19.2 per 100,000 per year) was 48% higher than in the previous cohort. Children aged 0–4 years had a 70% higher incidence (12.2 per 100,000 per year) than the original cohort; this increase was most marked in young black children. The overall age-adjusted incidence of type 2 diabetes was 5.8 per 100,000 per year and was significantly higher in black children. CONCLUSIONS The incidence of type 1 diabetes is rising among children in Philadelphia. The incidence rate has increased by 29% since the 1985–1989 cohort. The most marked increases were among white children ages 10–14 years and black children ages 0–4 years. The incidence of type 1 diabetes is 18 times higher than that of type 2 in white children but only 1.6 times higher in black children.