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Hospital readmission is a key metric of hospital quality, such as for comparing Veterans Affairs (VA) hospitals to private sector hospitals. To calculate readmission rates, one must first identify individual hospitalizations. However, in the VA Corporate Data Warehouse (CDW), data are organized by “bedded stays,” that is, any stay in a healthcare facility where a patient is provided a bed, not hospitalizations. Thus, CDW data poses several challenges to identifying hospitalizations including: (1) bedded stays include both non-acute inpatient stays (i.e. nursing home, mental health) and acute inpatient hospital care; (2) transfers between VA facilities appear as separate bedded stays; and (3) VA care may also be fragmented by non-VA care. Thus, we sought to develop a rigorous method to identify acute hospitalizations using the VA CDW. We examined all VA bedded stays with an admission date in 2009. Non-acute portions of a stay were dropped. VA to VA transfers were merged when consecutive discharge and admission dates were within one calendar day. Finally, hospitalizations that occurred in a non-VA facility were merged. The 30-day readmission rate was calculated at each step of the algorithm to demonstrate the impact. The total number of VA medical hospitalizations in 2009 with live discharges was 505,861. The 30-day readmission rate after adjusting for VA to VA transfers and incorporating non-VA care was 18.3% (95% confidence interval (CI): 18.2, 18.4%).

BACKGROUND AND OBJECTIVES Drug courts provide an array of substance use treatments and community-based services for probationers struggling with substance use disorders. We assessed substance use treatment services utilization and related expenditures and relapse and recidivism outcomes and identified predictors of cost of provision of substance use treatment services in a matched cohort of Massachusetts probationers in drug courts and traditional courts. METHODS This was an observational quasi-experimental study with 542 propensity-score-matched probationers initiating drug court between August 1, 2015 and February 28, 2018 and a minimum 6-month follow-up period. RESULTS A significantly greater proportion of probationers in drug courts were female, self-reported opioids as their primary drug of choice, had a history of substance use treatment, and a high and very high risk of recidivism than their counterparts in traditional courts. We estimated that the provision of substance use treatment services was $1498 more expensive for probationers in drug courts than traditional courts (p = .054). There were no statistically significant differences in relapse or recidivism rates between court systems. DISCUSSION AND CONCLUSIONS Probationer's age, gender, risk of recidivism at court intake, and enrollment length were strong predictors of expenditures on substance use treatment services. SCIENTIFIC SIGNIFICANCE This was the first study to assess substance use treatment services utilization and outcomes among probationers in drug courts and traditional courts. Drug courts served the needs of probationers disproportionally impacted by nonserious drug-related offenses struggling with substance use disorders who were at a high and very high risk of recidivism at court intake.

Next-generation sequencing (NGS) technologies are now established in clinical laboratories as a primary testing modality in genomic medicine. These technologies have reduced the cost of large-scale sequencing by several orders of magnitude. It is now cost-effective to analyze an individual with disease-targeted gene panels, exome sequencing, or genome sequencing to assist in the diagnosis of a wide array of clinical scenarios. While clinical validation and use of NGS in many settings is established, there are continuing challenges as technologies and the associated informatics evolve. To assist clinical laboratories with the validation of NGS methods and platforms, the ongoing monitoring of NGS testing to ensure quality results, and the interpretation and reporting of variants found using these technologies, the American College of Medical Genetics and Genomics (ACMG) has developed the following technical standards.

Objective:The seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG antibody was evaluated among employees of a Veterans Affairs healthcare system to assess potential risk factors for transmission and infection.Methods:All employees were invited to participate in a questionnaire and serological survey to detect antibodies to SARS-CoV-2 as part of a facility-wide quality improvement and infection prevention initiative regardless of clinical or nonclinical duties. The initiative was conducted from June 8 to July 8, 2020.Results:Of the 2,900 employees, 51% participated in the study, revealing a positive SARS-CoV-2 seroprevalence of 4.9% (72 of 1,476; 95% CI, 3.8%–6.1%). There were no statistically significant differences in the presence of antibody based on gender, age, frontline worker status, job title, performance of aerosol-generating procedures, or exposure to known patients with coronavirus infectious disease 2019 (COVID-19) within the hospital. Employees who reported exposure to a known COVID-19 case outside work had a significantly higher seroprevalence at 14.8% (23 of 155) compared to those who did not 3.7% (48 of 1,296; OR, 4.53; 95% CI, 2.67–7.68; P < .0001). Notably, 29% of seropositive employees reported no history of symptoms for SARS-CoV-2 infection.Conclusions:The seroprevalence of SARS-CoV-2 among employees was not significantly different among those who provided direct patient care and those who did not, suggesting that facility-wide infection control measures were effective. Employees who reported direct personal contact with COVID-19–positive persons outside work were more likely to have SARS-CoV-2 antibodies. Employee exposure to SARS-CoV-2 outside work may introduce infection into hospitals.

Klawitter, L, Vincent, BM, Choi, BJ, Smith, J, Hammer, KD, Jurivich, DA, Dahl, LJ, and McGrath, R. Handgrip strength asymmetry and weakness are associated with future morbidity accumulation in americans. J Strength Cond Res 36(1): 106-112, 2022-Identifying strength asymmetries in physically deconditioned populations may help in screening and treating persons at risk for morbidities linked to muscle dysfunction. Our investigation sought to examine the associations between handgrip strength (HGS) asymmetry and weakness on accumulating morbidities in aging Americans. The analytic sample included 18,506 Americans aged ≥50 years from the 2006-2016 Health and Retirement Study. Handgrip strength was measured on each hand with a handgrip dynamometer, and persons with an imbalance in strength10% between hands had HGS asymmetry. Men with HGS26 kg and women with HGS16 kg were considered as weak. Subjects reported the presence of healthcare provider-diagnosed morbidities: hypertension, diabetes, cancer, chronic lung disease, cardiovascular disease, stroke, arthritis, and psychiatric problems. Covariate-adjusted ordinal generalized estimating equations analyzed the associations for each HGS asymmetry and weakness group on future accumulating morbidities. Of those included in our study, subjects at baseline were aged 65.0 ± 10.2 years, 9,570 (51.7%) had asymmetric HGS, and 996 (5.4%) were weak. Asymmetry alone and weakness alone were associated with 1.09 (95% confidence interval [CI]: 1.04-1.14) and 1.27 (CI: 1.11-1.45) greater odds for future accumulating morbidities, respectively. Having both HGS asymmetry and weakness was associated with 1.46 (CI: 1.29-1.65) greater odds for future accumulating morbidities. Handgrip-strength asymmetry, as another potential indicator of impaired muscle function, is associated with future morbidity status during aging. Exercise professionals and related practitioners should consider examining asymmetry and weakness with handgrip dynamometers as a simple and noninvasive screening method for helping to determine muscle dysfunction and future chronic disease risk.

BACKGROUND Hospital-specific template matching is a newer method of hospital performance measurement that may be fairer than regression-based benchmarking. However, it has been tested in only limited research settings. OBJECTIVE The objective of this study was to test the feasibility of hospital-specific template matching assessments in the Veterans Affairs (VA) health care system and determine power to detect greater-than-expected 30-day mortality. RESEARCH DESIGN Observational cohort study with hospital-specific template matching assessment. For each VA hospital, the 30-day mortality of a representative subset of hospitalizations was compared with the pooled mortality from matched hospitalizations at a set of comparison VA hospitals treating sufficiently similar patients. The simulation was used to determine power to detect greater-than-expected mortality. SUBJECTS A total of 556,266 hospitalizations at 122 VA hospitals in 2017. MEASURES A number of comparison hospitals identified per hospital; 30-day mortality. RESULTS Each hospital had a median of 38 comparison hospitals (interquartile range: 33, 44) identified, and 116 (95.1%) had at least 20 comparison hospitals. In total, 8 hospitals (6.6%) had a significantly lower 30-day mortality than their benchmark, 5 hospitals (4.1%) had a significantly higher 30-day mortality, and the remaining 109 hospitals (89.3%) were similar to their benchmark. Power to detect a standardized mortality ratio of 2.0 ranged from 72.5% to 79.4% for a hospital with the fewest (6) versus most (64) comparison hospitals. CONCLUSIONS Hospital-specific template matching may be feasible for assessing hospital performance in the diverse VA health care system, but further refinements are needed to optimize the approach before operational use. Our findings are likely applicable to other large and diverse multihospital systems.

BACKGROUND: Screening for dementia in relevant healthcare settings may help in identifying low cognitive functioning for comprehensive cognitive assessments and subsequent dementia treatment after diagnosis. AIMS: This study sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally-representative sample of older Americans with a cognitive impairment consistent with dementia (CICD) by healthcare utilization. METHODS: The unweighted analytical sample included 1514 Americans aged ≥ 65 years that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010–2016 waves of the Health and Retirement Study. An adapted Telephone Interview of Cognitive Status assessed cognitive functioning. Those with scores ≤ 6 had a CICD. Dementia-related diagnosis was self-reported. Respondents indicated if they visited a physician, received home healthcare, or experienced an overnight nursing home stay in the previous two years. RESULTS: The prevalence of no reported dementia-related diagnosis in persons with a CICD who visited a physician was 89.9% (95% confidence interval (CI): 85.4%−93.1%). Likewise, the prevalence of no reported diagnosis in those with a CICD who received home healthcare was 84.3% (CI: 75.1–90.5%). For persons with a CICD that had an overnight nursing home stay, the prevalence of no reported dementia-related diagnosis was 83.0% (CI: 69.1–91.4%). DISCUSSION: Although the prevalence of no reported dementia-related diagnosis in individuals with a CICD differed across healthcare settings, the prevalence was generally high nonetheless. CONCLUSIONS: We recommend increased awareness and efforts be given to dementia screenings in various clinical settings.

Purpose The ability of a single technology, next-generation sequencing, to provide both sequence and copy number variant (CNV) results has driven the merger of clinical cytogenetics and molecular genetics. Consequently, the distinction between the definition of a sequence variant and a CNV is blurry. As the 2015 American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) standards and guidelines for interpretation of sequence variants address CNV classification only sparingly, this study focused on adapting ACMG/AMP criteria for single-gene CNV interpretation. Methods CNV-specific modifications of the 2015 ACMG/AMP criteria were developed and their utility was independently tested by three diagnostic laboratories. Each laboratory team interpreted the same 12 single-gene CNVs using three systems: (1) without ACMG/AMP guidance, (2) with ACMG/AMP criteria, and (3) with new modifications. A replication study of 12 different CNVs validated the modified criteria. Results The adapted criteria system presented here showed improved concordance and usability for single-gene CNVs compared with using the ACMG/AMP interpretation guidelines focused on sequence variants. Conclusion These single-gene CNV criteria modifications could be used as a supplement to the ACMG/AMP guidelines for sequence variants, allowing for a streamlined workflow and a step toward a uniform classification system for both sequence and copy number alterations.

Background: HIV is a worldwide disease and affects all systems of the body. Despite the high burden of Paediatric HIV in Nigeria, few studies have been done on Otolaryngological disorders in children living with HIV. This study aimed to determine the pattern and prevalence of Otorhinolaryngological disorders among HIV positive paediatric patients and to compare them with age and sex-matched control. Methods: This was a descriptive cross-sectional case-control study carried out among 130 HIV positive and 130 HIV negative children aged 6 to 15 years at the University of Port Harcourt Teaching Hospital (UPTH). Eligible patients were recruited via a systematic sampling method and matched with HIV negative controls and an interviewer-administered questionnaire was used to extract relevant information. All patients had Otorhinolaryngological examination and CD4 count determination, while children with tonsillar enlargement underwent X-ray of the post nasal space. HIV patients were graded for severity using WHO clinical Staging. Results: A higher proportion of the HIV positive patients had allergic rhinitis (66.9% vs.30.8%, p=0.01), pharyngitis (40.8% vs.18.5%, p=0.01), tonsillitis (34.6% vs.20.8%, p=0.013), adenotonsilar disease (24.6% vs. 13.8%, p=0.028), cervical lymphadenopathy (15.4% vs. 5.4%, p=0.001) and otitis media (5.4% vs. 0.8%, p=0.031). There was a significantly higher prevalence of ORL disorders among HIV positive children (95.4%) compared to HIV negative children (78.5%). (P=0.001). Conclusion: Pattern of ORL disorder appeared similar in both HIV-positive and -negative children. However, the overall high prevalence of the findings among the HIV-positive children required regular ORL assessment in these children.

Handgrip strength is considered a biomarker of nutritional status and strength capacity, which are both linked to heart complications. However, it is not well understood how weakness, as measured by handgrip strength, factors into common heart conditions seen in aging adults such as chronic heart failure (CHF). The purpose of this study was to determine the association between weakness and incident CHF for aging Americans. Longitudinal-Panel. Physical measures were completed during enhanced face-to-face interviews. The core interview was typically conducted over the telephone. Data from 17,431 adults aged at least 50 years who identified as Black or White, completed interviews without a proxy, and participated in at least one wave of the 2006–2014 waves of the Health and Retirement Study were included. Handgrip strength was measured with a hand-held dynamometer. Healthcare provider diagnosed CHF was self-reported at each wave. Sex- and race-specific maximal handgrip strength cut-points were used for determining weakness (Black men

Discovering how certain health factors contribute to functional declines may help to promote successful aging. To determine the independent and joint associations of handgrip strength (HGS) and cognitive function with instrumental activities of daily living (IADL) and activities of daily living (ADL) disability decline in aging Americans. Data from 18,391 adults aged 50 years and over who participated in at least one wave of the 2006–2014 waves of the Health and Retirement Study were analyzed. A hand-held dynamometer assessed HGS and cognitive functioning was examined with a modified version of the Telephone Interview of Cognitive Status. IADL and ADL abilities were self-reported. Participants were stratified into four distinct groups based on their HGS and cognitive function status. Separate covariate-adjusted multilevel models were conducted for the analyses. Participants who were weak, had a cognitive impairment, and had both weakness and a cognitive impairment had 1.70 (95% confidence interval (CI) 1.57–1.84), 1.97 (CI 1.74–2.23), and 3.13 (CI 2.73–3.59) greater odds for IADL disability decline, respectively, and 2.26 (CI 2.03–2.51), 1.26 (CI 1.05–1.51), and 4.48 (CI 3.72–5.39) greater odds for ADL disability decline, respectively. HGS and cognitive functioning were independently and jointly associated with IADL and ADL disability declines. Individuals with both weakness and cognitive impairment demonstrated substantially higher odds for functional decline than those with either risk factor alone. Including measures of both HGS and cognitive functioning in routine geriatric assessments may help to identify those at greatest risk for declining functional capacity.

Background To study patient physiology throughout a period of acute hospitalization, we sought to create accessible, standardized nationwide data at the level of the individual patient-facility-day. This methodology paper summarizes the development, organization, and characteristics of the Veterans Affairs Patient Database 2014–2017 (VAPD 2014–2017). The VAPD 2014–2017 contains acute hospitalizations from all parts of the nationwide VA healthcare system with daily physiology including clinical data (labs, vitals, medications, risk scores, etc.), intensive care unit (ICU) indicators, facility, patient, and hospitalization characteristics. Methods The VA data structure and database organization represents a complex multi-hospital system. We define a single-site hospitalization as one or more consecutive stays with an acute treating specialty at a single facility. The VAPD 2014–2017 is structured at the patient-facility-day level, where every patient-day in a hospital is a row with separate identification variables for facility, patient, and hospitalization. The VAPD 2014–2017 includes daily laboratory, vital signs, and inpatient medication. Such data were validated and verified through lab value range and comparison with patient charts. Sepsis, risk scores, and organ dysfunction definitions were standardized and calculated. Results We identified 565,242 single-site hospitalizations (SSHs) in 2014; 558,060 SSHs in 2015; 553,961 SSHs in 2016; and 550,236 SSHs in 2017 at 141 VA hospitals. The average length of stay was four days for all study years. In-hospital mortality decreased from 2014 to 2017 (1.7 to 1.4%), 30-day readmission rates increased from 15.3% in 2014 to 15.6% in 2017; 30-day mortality also decreased from 4.4% in 2014 to 4.1% in 2017. From 2014 to 2017, there were 107,512 (4.8%) of SSHs that met the Center for Disease Control and Prevention’s Electronic Health Record-based retrospective definition of sepsis. Conclusion The VAPD 2014–2017 represents a large, standardized collection of granular data from a heterogeneous nationwide healthcare system. It is also a direct resource for studying the evolution of inpatient physiology during both acute and critical illness. Electronic supplementary material The online version of this article (10.1186/s12874-019-0740-x) contains supplementary material, which is available to authorized users.

Significance Sex differences in infection outcome are a widely observed phenomenon. While it is known that biological sex can influence an animal’s response to infection, the mechanisms through which these differences emerge are less clear. Here, we describe a mechanism through which heightened regulation of the IMD signaling pathway by female—but not male—Drosophila melanogaster reduces the cost of immune activity at the expense of resistance to bacterial infection. Through the masculinization of the main organ responsible for antimicrobial peptide activity in the fly (fat body), this work demonstrates that this heightened immune regulation is mediated by sex-determining pathways., Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is the sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune- versus microbe-induced pathology and whether these may differ for the sexes. Here, by measuring metabolic and physiological outputs in Drosophila melanogaster with wild-type and mutant immune responses, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB, a negative regulator of the immune deficiency (IMD) pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB, females are more resistant to infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.

Background: Dementia screening is an important step for appropriate dementia-related referrals to diagnosis and treat possible dementia. Objective: We sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally representative sample of older Americans with a cognitive impairment consistent with dementia (CICD). Methods: The weighted analytical sample included 6,036,224 Americans aged at least 65 years old that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010–2016 Health and Retirement Study. The adapted Telephone Interview of Cognitive Status assessed cognitive functioning. Those with scores≤6 were considered as having a CICD. Healthcare provider dementia-related diagnosis was self-reported. Age, sex, educational achievement, and race and ethnicity were also self-reported. Results: The overall estimated prevalence of no reported dementia-related diagnosis for older Americans with a CICD was 91.4%(95%confidence interval (CI): 87.7%–94.1%). Persons with a CICD who identified as non-Hispanic black had a high prevalence of no reported dementia-related diagnosis (93.3%; CI: 89.8%–95.6%). The estimated prevalence of no reported dementia-related diagnosis was greater in males with a CICD (99.7%; CI: 99.6%–99.8%) than females (90.2%; CI: 85.6%–93.4%). Moreover, the estimated prevalence of no reported dementia-related diagnosis for non-high school graduates with a CICD was 93.5%(CI: 89.3%–96.1%), but 90.9%(CI: 84.7%–94.7%) for those with at least a high school education. Conclusion: Dementia screening should be encouraged during routine geriatric health assessments. Continued research that evaluates the utility of self-reported dementia-related measures is also warranted.

Objective To examine associations between local and systemic symptoms and the wear of the tin weld of Essure implants. Design study of a series of cases. Settings Two French hospitals. Participants Eighteen patients explanted by hysterectomy and salpingectomy for removal of their Essure implants between September 2019 and July 2020, have had a common anatomopathological process. Main outcome measures anatomopathological examination by optical microscopy and mineralogical analysis of the fallopian tube or uterine horn with scanning electron microscopy coupled with energy dispersive X-ray (SEM-EDX). Evaluation of local and systemic symptoms with a questionnaire. Examination of blood metal assays (nickel, chromium, and tin). Results anatomopathological examination highlights foreign body granulomas, fibrosis, adenomyosis, nonspecific inflammation, cysts and myomas in the Fallopian tubes, uterine horns, or both and mentions the presence of foreign bodies in seven cases. SEM-EDX analyses showed, systematically, the presence of tin particles integrated in the wall near the weld, generally in clusters, and with a size ranging from about one micron to several dozen microns. The questionnaire shows that the most frequent local symptoms were pelvic pain, urinary disorders, bleeding, and pains during intercourse. The most common systemic symptoms were: asthenia, visual disturbances, amnesia, giddiness, dorsal pains, headaches, and joint pains. The majority of local and systemic symptoms decreased after explantation, but sometimes incompletely. Before explantation, high levels of nickel, tin and chromium were observed in 11/17, 1/7 and 2/17 patients. After explantation, tin levels were high in 3/11 patients. Conclusions our new anatomopathological process systematically demonstrates the presence of tin particles in tissue near the weld. These particles could be responsible for granulomatous inflammations as well as local symptoms. Many of the systemic symptoms are consistent with chronic organotin poisoning but further studies are needed to find out whether tin from the solder can be converted to organotin in the patients' bodies.

OBJECTIVES To evaluate biomarkers of oxidative stress in dogs with copper-associated hepatitis (CAH) as compared with healthy controls, and to evaluate if these markers correlate with hepatic copper concentrations and hepatic histopathologic features. MATERIALS AND METHODS Prospective study. Plasma reactive metabolite concentrations, plasma antioxidant potential, and plasma and urine isoprostane concentrations were determined in Labrador retrievers with copper-associated hepatitis (n=9) as well as in breed- and sex-matched (n=9) and age- and sex-matched (n=9) healthy control populations. Possible correlations between markers of oxidative stress and hepatic histopathological features also were investigated. RESULTS Reactive metabolites (median, range) were over twofold greater in dogs with copper-associated hepatitis (87.2 RFU/μL, 60.9 to 185.6 RFU/μL) as compared to breed- and sex-matched (38.2 RFU/μL, 22.4 to 116.8 RFU/μL) and age- and sex-matched controls (32.0 RFU/μL, 18.5 to 127.4 RFU/μL). Antioxidant potential was decreased in copper-associated hepatitis dogs (6.5 TE/μL, 5.1 to 7.7 TE/μL) as compared to breed- and sex-matched controls (8.2 TE/μL, 5.3 to 11.8 TE/μL). Both reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio were positively correlated with hepatic copper concentrations. Plasma and urine isoprostanes were variable and not significantly different between populations. CLINICAL SIGNIFICANCE Labrador retrievers with copper-associated hepatitis have altered oxidant status. Plasma reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio could be useful biomarkers. However, neither plasma nor urine isoprostanes were useful biomarkers for copper-associated hepatitis.

Background: Engaging in healthy behaviors may help to preserve function during aging; however, it is not well understood how sleeping time is associated with functional capacity in older adults.Aims We sought to determine the association of sleeping time on functional limitation in a national sample of older Americans. Methods: The analytical sample included 6020 adults aged at least 65 years who participated in the 2007–2016 waves of the National Health and Nutrition Examination Survey. Respondents indicated their hours of sleep/weeknight and were categorized as9 h of sleep/weeknight. Ability to complete 19 functional tasks including basic activities of daily living, instrumental activities of daily living, leisure and social activities, lower extremity mobility activities, and general physical activities were also self-reported. A covariate-adjusted logistic model analyzed the associations between each sleeping time category and functional limitation. Results: Relative to those reporting 7–8 h of sleep/weeknight, older Americans reporting9 h of sleep/weeknight had 1.66 [95% confdence interval (CI): 1.05, 2.62], 1.25 (CI: 1.02, 1.52), 1.59 (CI: 1.19, 2.12), and 2.99(CI: 1.96, 4.56) greater odds for functional limitation, respectively. Discussion: Sleep should be recognized as a health factor that may reflect functional capacity in older adults. Health careproviders should discuss the importance of optimal sleep with their older patients and older adults should practice healthy sleeping behaviors for preserving function. Conclusions: Not meeting optimal sleep recommendations is associated with functional limitations in older Americans. Refereed/Peer-reviewed

Background: The PACIFIC trial demonstrated that consolidation durvalumab significantly improved PFS and OS (the primary endpoints) vs. placebo in patients with unresectable, stage III NSCLC whose disease had not progressed after platinum-based, concurrent chemoradiotherapy (CRT). We report exploratory analyses of outcomes from PACIFIC by age. Patients and Methods: Patients were randomized 2:1 (1-42 days post-CRT) to receive 12-months’ durvalumab (10 mg/kg intravenously every-2-weeks) or placebo. We analyzed PFS and OS (unstratified Cox-proportional-hazards models), safety and patient-reported outcomes (PROs: symptoms, functioning, and global-health-status/quality-of-life) in subgroups defined by a post-hoc 70-year age threshold. Data cut-off for PFS was February 13, 2017 and for OS, safety and PROs was March 22, 2018. Results: Overall, 158 of 713 (22.2%) and 555 of 713 (77.8%) randomized patients were aged ?70 and

Background Evaluating handgrip strength (HGS) asymmetry may help to improve the prognostic value of HGS. This study sought to determine the associations of HGS asymmetry and weakness on future activities of daily living (ADL) disability in a national sample of aging Americans. Methods The analytic sample included 18,468 Americans aged ≥50 years from the 2006–2016 waves of the Health and Retirement Study. A handgrip dynamometer measured HGS. Those with HGS >10% stronger on either hand were considered as having any HGS asymmetry. Individuals with HGS >10% stronger on their dominant hand were considered as having dominant HGS asymmetry, while those with HGS >10% stronger on their nondominant hand were classified as having nondominant HGS asymmetry. Men with HGS Results Relative to those with symmetric HGS and no weakness, each HGS asymmetry and weakness group had increased odds for future ADL disability: 1.11 (95% confidence interval [CI]: 1.02–1.20) for any HGS asymmetry alone, 1.42 (CI: 1.16–1.74) for weakness alone, and 1.81 (CI: 1.52–2.16) for both any HGS asymmetry and weakness. Most weakness and HGS asymmetry dominance groups had increased odds for future ADL disability: 1.30 (CI: 1.13–1.50) for nondominant HGS asymmetry alone, 1.42 (CI: 1.16–1.74) for weakness alone, 1.72 (CI: 1.29–2.29) for both weakness and nondominant HGS asymmetry, and 1.86 (CI: 1.52–2.28) for both weakness and dominant HGS asymmetry. Conclusions HGS asymmetry and weakness together may increase the predictive utility of handgrip dynamometers.

Background Evaluating asymmetries in muscle function could provide important insights for fall risk assessments. We sought to determine the associations of (i) handgrip strength (HGS) asymmetry and (ii) leg extension power (LEP) asymmetry on risk of incident recurrent falls and fractures in older men. Method There were 5 730 men with HGS asymmetry data and 5 347 men with LEP asymmetry data from the Osteoporotic Fractures in Men (MrOS) study. A handgrip dynamometer measured HGS and a Nottingham Power Rig ascertained LEP. Percent difference in maximal HGS between hands was calculated, and asymmetric HGS was defined as men in the highest quartile of dissimilarity for HGS between hands. The same approach was used to determine asymmetric LEP. Participants self-reported falls every 4 months after the baseline exam, and persons with ≥2 falls in the first year were considered recurrent fallers. Fractures and their dates of occurrence were self-reported and confirmed with radiographic reports. Results Older men in the highest HGS asymmetry quartile had a 1.20 (95% confidence interval [CI]: 1.01–1.43) relative risk for incident recurrent falls. Likewise, men in the highest HGS asymmetry quartile had a higher risk for incident fractures: 1.41 (CI: 1.02–1.96) for hip, 1.28 (CI: 1.04–1.58) for major osteoporotic, and 1.24 (CI: 1.06–1.45) for nonspine. There were no significant associations between LEP asymmetry and recurrent falls or fractures. Conclusions Asymmetric HGS could be a novel risk factor for falls and fractures that is more feasible to measure than LEP. Fall risk assessments should consider evaluating muscle function, including HGS asymmetry.

Background Hyperoxia produces reactive oxygen species, apoptosis, and vasoconstriction, and is associated with adverse outcomes in patients with heart failure and cardiac arrest. Our aim was to evaluate the association between hyperoxia and mortality in patients (pts) receiving positive pressure ventilation (PPV) in the cardiac intensive care unit (CICU). Methods Patients admitted to our medical center CICU who received any PPV (invasive or non-invasive) from 2001 through 2012 were included. Hyperoxia was defined as time-weighted mean of PaO2 >120mmHg and non-hyperoxia as PaO2 ≤120mmHg during CICU admission. Primary outcome was in-hospital mortality. Multivariable logistic regression was used to assess the association between hyperoxia and in-hospital mortality adjusted for age, female sex, Oxford Acute Severity of Illness Score, creatinine, lactate, pH, PaO2/FiO2 ratio, PCO2, PEEP, and estimated time spent on PEEP. Results Among 1493 patients, hyperoxia (median PaO2 147mmHg) during the CICU admission was observed in 702 (47.0%) pts. In-hospital mortality was 29.7% in the non-hyperoxia group and 33.9% in the hyperoxia group ((log rank test, p=0.0282, see figure). Using multivariable logistic regression, hyperoxia was independently associated with in-hospital mortality (OR 1.507, 95% CI 1.311–2.001, p=0.00508). Post-hoc analysis with PaO2 as a continuous variable was consistent with the primary analysis (OR 1.053 per 10mmHg increase in PaO2, 95% CI 1.024–1.082, p=0.0002). Conclusions In a large CICU cohort, hyperoxia was associated with increased mortality. Trials of titration of supplemental oxygen across the full spectrum of critically ill cardiac patients are warranted. Funding Acknowledgement Type of funding source: None

Objectives: Examining strength asymmetries in assessments of muscle function may improve screenings for limitations in independent living tasks such as instrumental activities of daily living (IADL). We sought to determine the associations between handgrip strength (HGS) asymmetry and future IADL limitations in aging Americans. Design: Longitudinal panel. Setting and Participants: Secondary analyses of data from participants aged at least 50 years from the 2006-2016 waves of the Health and Retirement Study. The analytic sample included 18,235 Americans who identified hand dominance and had measures of HGS for both hands in a single wave. Methods: Hand dominance was self-reported, and a handgrip dynamometer measured HGS on each hand. The highest HGS values on each hand were used to calculate the HGS asymmetry ratio: (nondominant HGS/dominant HGS). Individuals with HGS asymmetry ratio 1.20 had HGS asymmetry. Persons with HGS asymmetry ratio 1.20 had nondominant HGS asymmetry. Persons with HGS asymmetry ratio

Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune-induced versus microbe-induced pathology, and whether these may differ for the sexes. Here, through measuring metabolic and physiological outputs in wild-type and immune-compromised Drosophila melanogaster, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB, a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB, females are more resistant of infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.

The origins and causes of infection pathologies are often not understood. Despite this, the study of infection and immunity relies heavily on the ability to discern between potential sources of pathology. Work in the fruit fly has supported the assumption that mortality resulting from bacterial invasion is largely due to direct host-pathogen interactions, as lower pathogen loads are often associated with reduced pathology, and bacterial load upon death is predictable. However, the mechanisms through which these interactions bring about host death are complex. Here we show that infection with the bacterium Francisella novicida leads to metabolic dysregulation and, using treatment with a bacteriostatic antibiotic, we show that this pathology is the result of direct interaction between host and pathogen. We show that mutants of the immune deficiency immune pathway fail to exhibit similar metabolic dysregulation, supporting the idea that the reallocation of resources for immune-related activities contributes to metabolic dysregulation. Targeted investigation into the cross-talk between immune and metabolic pathways has the potential to illuminate some of this interaction.

Purpose Integrating genomic sequencing in clinical care requires standardization of variant interpretation practices. The Clinical Genome Resource has established expert panels to adapt the American College of Medical Genetics and Genomics/Association for Molecular Pathology classification framework for specific genes and diseases. The Cardiomyopathy Expert Panel selected MYH7, a key contributor to inherited cardiomyopathies, as a pilot gene to develop a broadly applicable approach. Methods Expert revisions were tested with 60 variants using a structured double review by pairs of clinical and diagnostic laboratory experts. Final consensus rules were established via iterative discussions. Results Adjustments represented disease-/gene-informed specifications (12) or strength adjustments of existing rules (5). Nine rules were deemed not applicable. Key specifications included quantitative frameworks for minor allele frequency thresholds, the use of segregation data, and a semiquantitative approach to counting multiple independent variant occurrences where fully controlled case-control studies are lacking. Initial inter-expert classification concordance was 93%. Internal data from participating diagnostic laboratories changed the classification of 20% of the variants (n = 12), highlighting the critical importance of data sharing. Conclusion These adapted rules provide increased specificity for use in MYH7-associated disorders in combination with expert review and clinical judgment and serve as a stepping stone for genes and disorders with similar genetic and clinical characteristics.

Objectives: The primary purpose of this study was to determine the time-varying associations between decreased handgrip strength (HGS) and individual instrumental activities of daily living (IADL) impairments for a nationally-representative sample of aging adults in the United States. Design: Longitudinal-Panel. Setting: Detailed interviews were completed in person and core interviews were typically completed over the telephone. Participants: A total of 15,336 participants aged at least 50 years who participated in the 2006 wave of the Health and Retirement Study were followed biennially for 8-years. Measurements: A hand-held dynamometer assessed HGS and performance in IADLs were self-reported. Results: Every 5-kilogram decrease in HGS was associated with an increased odds ratio for the following IADL impairments: 1.11 (95% confidence interval (CI): 1.09, 1.13) for using a map, 1.10 (CI: 1.07, 1.12) for grocery shopping, 1.09 (CI: 1.05, 1.14) for taking medications, 1.07 (CI: 1.05, 1.09) for preparing hot meals, 1.06 (CI: 1.04, 1.08) for managing money, and 1.05 (CI: 1.02, 1.09) for using a telephone. Conclusions: Decreased HGS was associated with each IADL impairment, and slightly different associations were observed in individual IADL tasks for aging adults in the United States. Our findings suggest that decreased HGS, which is reflective of reduced function of the neuromuscular system, is associated with diminished performance in autonomous living tasks during aging. Losses in HGS may lead to the development of an IADL impairment. Therefore, health-care providers working with aging adults should utilize measures of HGS as a screening tool for identifying future deficits in neuromuscular functioning. Interventions designed to preserve IADLs in aging adults should also include measures of HGS for detecting early changes in IADL capacity, and intervening at the onset of HGS declines may help aging adults retain their ability to live autonomously.

Purpose We sought to measure inpatient healthcare utilization among U.S. Veteran Affairs beneficiaries surviving sepsis hospitalization, and to examine how post-sepsis utilization varies by select patient characteristics. Materials and methods Retrospective cohort study of 26,561 Veterans who survived sepsis hospitalization in 2009. Using difference-in-differences analysis, we compared changes in healthcare utilization in one year before and one year after sepsis hospitalization by Veteran age, illness severity, and recent nursing facility use. Results Median days in a healthcare facility increased from 5 to 10. Veterans with recent nursing facility use spent a median 65 days (or 86% of days alive) in a healthcare facility in the year after sepsis. Older age, greater illness severity, and recent nursing home use were each associated with spending more days, and a greater proportion of days alive, in a healthcare facility during the year after sepsis. However, none of these characteristics was associated with a greater rise in utilization after sepsis. Conclusions Veterans surviving sepsis experience high rates of post-sepsis mortality and significant increases in healthcare facility use. Recent nursing facility use is strongly predictive of greater post-sepsis healthcare utilization.

Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolve interpretation differences by analyzing a subset of variants. ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the American College of Medical Genetics and Genomics–Association for Molecular Pathology (ACMG-AMP) guidelines, and then compared interpretations. At least two of the participating laboratories interpreted 6,169 variants in ClinVar, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing; 12.8% (31) of reassessed variants remained discordant owing to differences in the application of the ACMG-AMP guidelines. Participating laboratories increased their overall concordance from 88.3 to 91.7%, indicating that sharing variant interpretations in ClinVar—thereby allowing identification of differences and motivation to resolve those differences—is critical to moving toward more consistent variant interpretations. Genet Med advance online publication 09 March 2017

McGrath, RP, Kraemer, WJ, Vincent, BM, Hall, OT, and Peterson, MD. Muscle strength is protective against osteoporosis in an ethnically diverse sample of adults. J Strength Cond Res 31(9): 2586-2589, 2017-The odds of developing osteoporosis may be affected by modifiable and nonmodifiable factors such as muscle strength and ethnicity. This study sought to (a) determine whether increased muscle strength was associated with decreased odds of osteoporosis and (b) identify whether the odds of osteoporosis differed by ethnicity. Data from the 2013 to 2014 National Health and Nutrition Examination Survey were analyzed. Muscle strength was measured with a hand-held dynamometer, and dual-energy x-ray absorptiometry was used to assess femoral neck bone mineral density. A T-score of ≤2.5 was used to define osteoporosis. Separate covariate-adjusted logistic regression models were performed on each sex to determine the association between muscle strength and osteoporosis. Odds ratios (ORs) were also generated to identify if the association between muscle strength and osteoporosis differed by ethnicity using non-Hispanic blacks as the reference group. There were 2,861 participants included. Muscle strength was shown to be protective against osteoporosis for men (OR: 0.94; 95% confidence interval [CI]: 0.94-0.94) and women (OR: 0.90; CI: 0.90-0.90). Although ORs varied across ethnicities, non-Hispanic Asian men (OR: 6.62; CI: 6.51-6.72) and women (OR: 6.42; CI: 6.37-6.48) were at highest odds of osteoporosis. Increased muscle strength reduced the odds of osteoporosis among both men and women in a nationally representative, ethnically diverse sample of adults. Non-Hispanic Asians had the highest odds of developing osteoporosis. Irrespective of sex or ethnicity, increased muscle strength may help protect against the odds of developing osteoporosis.

SummaryBackground Several studies document reliable brain health benefits of acute exercise bouts. However, no prior studies have explored such effects among those living with co-morbid overweight/obesity and type 2 diabetes (T2DM), both of which are conditions associated with cognitive performance decrements. Purpose To examine the impact of a 30-min bout of moderate-intensity aerobic exercise on executive function among adults with overweight/obesity and T2DM, employing a widely used experimental paradigm. Methods Thirty adults with overweight/obesity and T2DM were randomly assigned to moderate (30% maximal heart rate reserve) and minimal (r.p.m. 30–50; work load 5) intensity aerobic exercise. Pre-exercise to post-exercise changes in Stroop interference and Go/No-Go scores were compared across conditions. Results Primary analyses revealed no overall effect of exercise condition on changes in Stroop or Go/No-Go performance. Post-hoc moderation analyses indicated that Stroop interference scores were reduced, following moderate exercise among female participants and among those who were more physically active. Conclusion The current study revealed no reliable benefit of acute aerobic exercise for overweight and obese individuals living with T2DM overall. There may be limited benefits for women and more and active subgroups, but the precise nature of such benefits remains unclear.

Aim Childhood immune thrombocytopenia (ITP) has been associated with low bleeding rates and a high frequency of spontaneous remission. Although current guidelines suggest that most patients are just observed, children still receive platelet-enhancing therapies for fear of bleeding complications. We hypothesised that a standardised protocol with a step-down approach would reduce hospitalisation and treatment use. Method A retrospective chart review was performed on patients diagnosed with acute ITP between January 2010 and December 2014, before (n = 54) and after (n = 37) the standardised protocol, which was introduced in January 2013. Management and events during the first 3 months following diagnosis were recorded. Results The protocol resulted in a 34% decrease in the hospitalisation rate (p < 0.001) at diagnosis. Prednisone treatment duration at diagnosis was also significantly reduced (13.1 versus 5.8 days, p = 0.004). Children over 3 years of age were 3.8 times less likely to be hospitalised (95% CI 1.94–7.61) and 2.3 times less likely to receive treatment (95% CI 1.2–4.3). There was no difference in the rate of persistent ITP (38% versus 30%, p = 0.43) or serious bleeding complications (7% versus 5%, p = 0.70). Conclusion Our ITP management protocol significantly reduced hospitalisation rates and length of prednisone treatment without any increase in disease complications.

OBJECTIVES: Quantifying the association between muscle weakness and mortality with carefully matched cohorts will help to better establish the impact of weakness on premature death. We utilized a matched cohort analysis in a national sample of older Americans to determine if those who were weak had a higher risk for mortality compared to control groups with incrementally higher strength capacities. DESIGN: Longitudinal-Panel. SETTING: Detailed interviews that included physical measures were conducted in person, while core interviews were often performed over the telephone. PARTICIPANTS: Data from 19,729 Americans aged at least 50-years from 2006-2014 waves of the Health and Retirement Study were analyzed. MEASURES: A hand-grip dynamometer was used to assess handgrip strength (HGS) in each participant. Men with HGS

Assessment of the clinical benefit of cancer treatments can be highly subjective, influenced by both perspective and context. Such assessments are required in regulatory and policy decision-making, but consistency between jurisdictions is often lacking. Clear and consistent standards for determining when a treatment offers a meaningful benefit, relative to the current standard of care, can help to address issues of equity and transparency in health technology assessment. For metastatic colorectal cancer (MCRC), no standardized Canadian definition of clinically meaningful benefit has yet been proposed. Colorectal Cancer Canada therefore convened a group of medical oncologists expert in colorectal cancer to review the literature about clinical significance. The resulting consensus is intended to apply to any therapeutic agent being considered in the setting of chemotherapy-refractory MCRC. It was agreed that overall survival is the appropriate measure of clinical efficacy in chemorefractory MCRC. As quantitative targets for efficacy, an improvement of 2 months or more in median overall survival or a hazard ratio for survival of 0.75 or lower (or both) are proposed as the threshold for clinically meaningful benefit. That threshold could be influenced by a treatment’s effect on quality of life. Treatment toxicity is also relevant to the assessment of clinical benefit in this setting, specifically when significant differences in treatment tolerability are evident.

SummaryBackground Perioperative pediatric adverse events have been challenging to study within and across institutions due to varying definitions, low event rates, and incomplete capture. Aim The aim of this study was to determine perioperative adverse event prevalence and to evaluate associated case characteristics and potential contributing factors at an academic pediatric quaternary-care center. Methods At the Children's Hospital of Philadelphia (CHOP), perioperative adverse events requiring rapid response assistance are termed Anesthesia Now (AN!) events. They have been accurately captured and entered into a quality improvement database since 2010. Adverse events involving open heart and cardiac catheterization cases are managed separately and not included in this database. We conducted a retrospective case–control study utilizing Compurecord (Phillips Healthcare, Andover, MA, USA), EPIC (EPIC, Verona, WI, USA), and Chartmaxx (MedPlus, Mason, OH, USA) systems matching AN! event cases to noncardiac controls (1 : 2) based on surgical date. Results From April 16, 2010 to September 25, 2012, we documented 213 AN! events in the noncardiac perioperative complex and remote sites at our main hospital. AN! prevalence was 0.0043 (1 : 234) with a 95% confidence interval (CI) (0.0037, 0.0049). Respiratory events, primarily laryngospasm, were most common followed by events of cardiovascular etiology. Median age was lower in the AN! group than in controls, 2.86 years (interquartile range 0.94, 10.1) vs 6.20 (2.85, 13.1), P < 0.0001. Odds ratios (with 95% CI) for age, 0.969 (0.941, 0.997); American Society of Anesthesiologists physical status, 1.67 (1.32, 2.12); multiple (≥2) services, 2.27 (1.13, 4.55); nonoperating room vs operating room location, 0.240 (0.133, 0.431); and attending anesthesiologist's experience, 0.976 (0.959, 0.992) were all significant. Conclusions Decreased age, increased comorbidities, multiple (vs single) surgical services, operating room (vs nonoperating room) location, and decreased staff experience were associated with increased risk of AN! events, which were predominantly respiratory in origin.

Supplemental Digital Content is available in the text, Template matching is a proposed approach for hospital benchmarking, which measures performance based on matching a subset of comparable patient hospitalizations from each hospital. We assessed the ability to create the required matched samples and thus the feasibility of template matching to benchmark hospital performance in a diverse healthcare system. Nationwide Veterans Affairs (VA) hospitals, 2017. Observational cohort study. We used administrative and clinical data from 668,592 hospitalizations at 134 VA hospitals in 2017. A standardized template of 300 hospitalizations was selected, and then 300 hospitalizations were matched to the template from each hospital. There was substantial case-mix variation across VA hospitals, which persisted after excluding small hospitals, hospitals with primarily psychiatric admissions, and hospitalizations for rare diagnoses. Median age ranged from 57 to 75 years across hospitals; percent surgical admissions ranged from 0.0% to 21.0%; percent of admissions through the emergency department, 0.1% to 98.7%; and percent Hispanic patients, 0.2% to 93.3%. Characteristics for which there was substantial variation across hospitals could not be balanced with any matching algorithm tested. Although most other variables could be balanced, we were unable to identify a matching algorithm that balanced more than ∼20 variables simultaneously. We were unable to identify a template matching approach that could balance hospitals on all measured characteristics potentially important to benchmarking. Given the magnitude of case-mix variation across VA hospitals, a single template is likely not feasible for general hospital benchmarking.

Introduction Patients are at risk for medication problems after hospital admissions, particularly those with critical illness. Medication problems include continuation of acute medications and discontinuation of chronic medications after discharge. Little is known across a national integrated health care system about the extent of these two medication problems. Objective To examine the extent of statin medication discontinuation and new antipsychotic medication use after hospital discharge. Design Retrospective cohort study. Setting Veterans Affairs healthcare system. Participants Veterans with an inpatient hospitalization from January 1, 2014-December 31, 2016, survived at least 180 days post-discharge, and received at least one medication through the VA outpatient pharmacy within one year around admission were included. Hospitalizations were grouped into: 1) direct admission to the intensive care unit (ICU) and a diagnosis of sepsis, 2) direct admission to the ICU without sepsis diagnosis, and 3) no ICU stay during the hospitalization. Main outcome measures Statin medication discontinuation and new antipsychotic use at six months post-hospital discharge. Results A total of 520,187 participants were included in the statin medication and 910,629 in the antipsychotic medication cohorts. Statin discontinuation ranged from 10–15% and new antipsychotic prescription fills from 2–4% across the three hospitalization groups, with highest rates in the ICU admission and sepsis diagnosis group. Statin discontinuation and new antipsychotic use after a hospitalization varied by hospital, with worse performing hospitals having 11% higher odds of discontinuing a statin (median odds ratio at hospital-level, adjusted for patient differences, aMOR: 1.11 (95% CI: 1.09, 1.13)) and 29% higher odds of new antipsychotic use (aMOR, 1.29 (95% CI: 1.24, 1.34)). Risk-adjusted hospital rates of these two medication changes were not correlated (p = 0.49). Conclusions Systemic variation in the rates of statin medication continuation and new antipsychotic use were found.

Objectives Factors that are responsible for age-related neurologic deterioration of noncognitive and cognitive processes may have a shared cause. We sought to examine the temporal, directional associations of handgrip strength and cognitive function in a national sample of aging Americans. Design Longitudinal panel. Setting Enhanced interviews that included physical, biological, and psychosocial measures were completed in person. Core interviews were often conducted over the telephone. Participants The analytic sample included 14,775 Americans aged at least 50 years who participated in at least 2 waves of the 2006-2016 waves of the Health and Retirement Study. Measures Handgrip strength was measured with a hand-held dynamometer. Participants were considered cognitively intact, mildly impaired, or severely impaired according to the Telephone Interview of Cognitive Status questionnaire. Separate lagged general estimating equations analyzed the directional associations of handgrip strength and cognitive function. Results The overall time to follow-up was 2.1 ± 0.4 years. Every 5 kg higher handgrip strength was associated with 0.97 [95% confidence interval (CI) 0.93, 0.99] lower odds for both future cognitive impairment and worse cognitive impairment. Those who were not weak had 0.54 (CI 0.43, 0.69) lower odds for future cognitive impairment and 0.57 (CI 0.46, 0.72) lower odds for future worse cognitive impairment. Conversely, any (β = −1.09; CI –1.54, −0.64), mild (β = −0.85; CI –1.34, −0.36), and severe cognitive impairment (β = −2.34; CI –3.25, −1.42) predicted decreased handgrip strength. Further, the presence of any, mild, and severe cognitive impairment was associated with 1.82 (CI 1.48, 2.24), 1.65 (CI 1.31, 2.08), and 2.53 (CI 1.74, 3.67) greater odds for future weakness, respectively. Conclusions/Implications Strength capacity and cognitive function may parallel each other, whereby losses of functioning in 1 factor may forecast losses of functioning in the other. Handgrip strength could be used for assessing cognitive status in aging Americans and strength capacity should be monitored in those with cognitive impairment.

Purpose To determine the time-varying associations between 1) decreased handgrip strength and disabilities in each activity of daily living (ADL) function, and 2) disaggregated ADL limitations and time to mortality in older adults. Methods A United States nationally representative sample of 17,747 older adults from the Health and Retirement Study were followed up for 8 yr. Maximal handgrip strength was measured with a hand-held dynamometer. Ability to perform ADL was self-reported. Date of death was identified by the National Death Index and exit interviews. Separate covariate-adjusted hierarchical logit models were used to examine the time-varying associations between decreased handgrip strength and each ADL outcome. Distinct covariate-adjusted Cox models were used to analyze the time-varying associations between disaggregated ADL limitations and time to mortality. Results Every 5-kg decrease in handgrip strength was associated with increased odds for the following ADL limitations: 20% for eating, 14% for walking, 14% for bathing, 9% for dressing, 8% for transferring, and 6% for toileting. The presence of a bathing, walking, toileting, eating, and dressing ADL disability was associated with a 47%, 43%, 32%, 30%, and 19% higher hazard for mortality, respectively. A transferring ADL disability was not significantly associated with mortality. Conclusions Decreased handgrip strength was associated with increased odds for each ADL limitation, and in turn, most individual ADL impairments were associated with a higher hazard for mortality in older adults. These findings provide insights into the disabling process by identifying which ADL limitations are most impacted by decreased handgrip strength and the subsequent time to mortality for each ADL disability.

Resume Introduction L’inhalation de corps etranger est une complication peu frequente des soins dentaires. Lorsqu’elle survient directement au cours du soin, il s’agit en general d’un outil utilise par le praticien tel que les petits tournevis servant pour la fixation d’implants dentaires. Observation Un patient de 59 ans a ete adresse dans les suites de l’inhalation asymptomatique d’une petite fraise au cours d’un acte de chirurgie dentaire. Du fait de son caractere acere, l’objet necessitait une extraction rapide. Il a ete localise au niveau d’une branche sous-segmentaire de la bronche postero-basale gauche (B10b) et a pu etre extrait au bronchoscope souple au cours d’une anesthesie generale courte sans intubation. Aucune lesion de la muqueuse endobronchique n’a ete constatee. Conclusion L’inhalation de corps etranger au cours des soins dentaires est peu frequente et parfois asymptomatique. Leur forme parfois aceree rend leur ablation indispensable.

Background Severe blood loss is a common complication of craniofacial reconstruction surgery. The antifibrinolytic e-aminocaproic acid (EACA) reduces transfusion requirements in children undergoing cardiac surgery and in older children undergoing spine surgery. Tranexamic acid (TXA), another antifibrinolytic with a similar mechanism of action, has been shown to reduce blood loss and transfusion requirements in children undergoing craniofacial surgery. However, TXA has been associated with an increase in post-operative seizures and is more expensive than EACA. There is currently little published data evaluating the efficacy of EACA in children undergoing craniofacial surgery. Methods This is a retrospective study of prospectively collected data from our craniofacial perioperative registries for children under 6 years of age who underwent anterior or posterior cranial vault reconstruction. We compared calculated blood loss, blood donor exposures, and post-operative drain output between subjects who received EACA and those who did not. Results The registry queries returned data from 152 subjects. Eighty-six did not receive EACA and 66 received EACA. The EACA group had significantly lower calculated blood loss (82 ± 43 vs. 106 ± 63 ml/kg, P = 0.01), fewer intraoperative blood donor exposures (median 2, interquartile range 1-2 vs. median 2, interquartile range 1-3; P = 0.02) and lower surgical drain output in the first post-operative 24 h (28 ml/kg vs. 37 ml/kg, P = 0.001) than the non-EACA group. Conclusion In this analysis of prospectively captured observational data, EACA administration was associated with less calculated blood loss, intraoperative blood donor exposures, and post-operative surgical drain output.

We designed a phase i study of concurrent chemoradiotherapy (ccrt) with docetaxel (D) and cisplatin (C), followed by consolidation dc, for unresectable stage iii non-small cell lung cancer (nsclc). Patients with histologically proven and unresectable stage iii nsclc were eligible. During ccrt, C was given every 3 weeks (75 mg/m2) and D given weekly. The starting dose of D was 20 mg/m2, escalated in cohorts of 3 to define the maximum tolerated dose (mtd). Radiotherapy was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidation dc, which were dose escalated if ccrt was tolerated. Twenty-six patients were enrolled, with 1 excluded following evidence of metastatic disease. Nineteen patients completed both phases of treatment. There were 7 grade 3 events during ccrt (5 esophagitis, 2 nausea), and 8 grade 3 events during consolidation (2 neutropenia, 2 leukopenia, 1 esophagitis, 2 nausea, and 1 pneumonitis). Three patients had grade 4 neutropenia. No patients died due to toxicities. The mtd of concurrent weekly D was 20 mg/m2. Consolidation D and C were each dose escalated to 75 mg/m2 in 8 patients. The median overall survival (os) and progression-free survival (pfs) of all patients were 33.6 months and 17.2 months, respectively, with median follow-up of 26.6 months (range 0.43&ndash, 110.8). The use of docetaxel 20 mg/m2 weekly and cisplatin 75 mg/m2 every 3 weeks concurrent with thoracic radiotherapy, followed by consolidation docetaxel and cisplatin, both given at 75 mg/m2 every 3 weeks, appears to be safe in this phase i trial.

Objectives: Muscle weakness is often linked to functional limitations in older adults. However, certain demographic characteristics, such as ethnicity, may differentially impact the association bet...