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CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. In vitro, BCMAxCD3 bsAb efficiently induced polyclonal T-cell killing of primary human plasma cells and multiple myeloma (MM) cell lines expressing a range of BCMA cell surface densities. In vivo, BCMAxCD3 bsAb suppressed the growth of human MM tumors in murine xenogeneic models and showed potent combinatorial efficacy with programmed cell death protein 1 blockade. BCMAxCD3 bsAb administration to cynomolgus monkeys was well tolerated, resulting in the depletion of BCMA+ cells and mild inflammatory responses characterized by transient increases in C-reactive protein and serum cytokines. The antitumor efficacy of BCMAxCD3 bsAb was compared with BCMA-specific CAR T cells containing a BCMA-binding single-chain variable fragment derived from REGN5458. Both BCMAxCD3 bsAb and anti-BCMA CAR T cells showed similar targeted cytotoxicity of MM cell lines and primary MM cells in vitro. In head-to-head in vivo studies, BCMAxCD3 bsAb rapidly cleared established systemic MM tumors, whereas CAR T cells cleared tumors with slower kinetics. Thus, using the same BCMA-binding domain, these results suggest that BCMAxCD3 bsAb rapidly exerts its therapeutic effects by engaging T cells already in place at the tumor site, whereas anti-BCMA CAR T cells require time to traffic to the tumor site, activate, and numerically expand before exerting antitumor effects.

Disparities in cardiovascular disease (CVD) and associated health and healthcare delivery outcomes have been partially attributed to differential risk factors, and to prevention and treatment inequities within racial and ethnic (including language) minority groups and low socioeconomic status (SES) populations in urban and rural settings. Digital health interventions (DHIs) show promise in promoting equitable access to high-quality care, optimal utilization, and improved outcomes; however, their potential role and impact has not been fully explored. The role of DHIs to mitigate drivers of the health disparities listed above in populations disproportionately affected by atherosclerotic-related CVD was systematically reviewed using published literature (January 2008–July 2020) from multiple databases. Study design, type and description of the technology, health disparities information, type of CVD, outcomes, and notable barriers and innovations associated with the technology utilized were abstracted. Study quality was assessed using the Oxford Levels of Evidence. Included studies described digital health technologies in a disparity population with CVD and reported outcomes. DHIs significantly improved health (eg, clinical, intermediate, and patient-reported) and healthcare delivery (eg, access, quality, and utilization of care) outcomes in populations disproportionately affected by CVD in 24 of 38 included studies identified from 2104 citations. Hypertension control was the most frequently improved clinical outcome. Telemedicine, mobile health, and clinical decision support systems were the most common types of DHIs identified. DHIs improved CVD-related health and healthcare delivery outcomes in racial/ethnic groups and low SES populations in both rural and urban geographies globally.

Background Disrupted circadian rhythms can have a major effect on human physiology and healthcare outcomes, with proven increases in ICU morbidity, mortality and length of stay. Methods We performed a multicentre observational study to study the nocturnal lux exposure of patients in 3 intensive care units. Results The median light intensity recorded was 1 lux over the 6-hour recording period; however, this is deceptive as it hides short periods of high lux. When looked at in shorter time segments of 30 minutes, there were significant periods of lux higher than a crude median, especially in higher acuity patients. There was a positive correlation between acuity (as estimated by SOFA score) and maximum lux (R = 0.479, p = .0001), median lux (R = 0.35, p = .006) and cumulative lux (R = 0.55, p = .000001). There was no relationship between neighbouring patient acuity and lux. Conclusions Clinicians should practice vigilance at night to provide optimal environmental conditions for patients to minimise potential harm.

Artificial intelligence (AI) represents a valuable tool that could be widely used to inform clinical and public health decision-making to effectively manage the impacts of a pandemic. The objective of this scoping review was to identify the key use cases for involving AI for pandemic preparedness and response from the peer-reviewed, preprint, and grey literature. The data synthesis had two parts: an in-depth review of studies that leveraged machine learning (ML) techniques and a limited review of studies that applied traditional modeling approaches. ML applications from the in-depth review were categorized into use cases related to public health and clinical practice, and narratively synthesized. One hundred eighty-three articles met the inclusion criteria for the in-depth review. Six key use cases were identified: forecasting infectious disease dynamics and effects of interventions; surveillance and outbreak detection; real-time monitoring of adherence to public health recommendations; real-time detection of influenza-like illness; triage and timely diagnosis of infections; and prognosis of illness and response to treatment. Data sources and types of ML that were useful varied by use case. The search identified 1167 articles that reported on traditional modeling approaches, which highlighted additional areas where ML could be leveraged for improving the accuracy of estimations or projections. Important ML-based solutions have been developed in response to pandemics, and particularly for COVID-19 but few were optimized for practical application early in the pandemic. These findings can support policymakers, clinicians, and other stakeholders in prioritizing research and development to support operationalization of AI for future pandemics.

Objectives: Non-pharmaceutical interventions (e.g. quarantine and isolation) are used to mitigate and control viral infectious disease, but their effectiveness has not been well studied. For COVID-19, disease control efforts will rely on non-pharmaceutical interventions until pharmaceutical interventions become widely available, while non-pharmaceutical interventions will be of continued importance thereafter. Methods: This rapid evidence-based review provides both qualitative and quantitative analyses of the effectiveness of social distancing non-pharmaceutical interventions on disease outcomes. Literature was retrieved from MEDLINE, Google Scholar, and pre-print databases ( BioRxiv.org , MedRxiv.org , and Wellcome Open Research). Results: Twenty-eight studies met inclusion criteria ( n = 28). Early, sustained, and combined application of various non-pharmaceutical interventions could mitigate and control primary outbreaks and prevent more severe secondary or tertiary outbreaks. The strategic use of non-pharmaceutical interventions decreased incidence, transmission, and/or mortality across all interventions examined. The pooled attack rates for no non-pharmaceutical intervention, single non-pharmaceutical interventions, and multiple non-pharmaceutical interventions were 42% (95% confidence interval = 30% – 55%), 29% (95% confidence interval = 23% – 36%), and 22% (95% confidence interval = 16% – 29%), respectively. Conclusion: Implementation of multiple non-pharmaceutical interventions at key decision points for public health could effectively facilitate disease mitigation and suppression until pharmaceutical interventions become available. Dynamics around R0 values, the susceptibility of certain high-risk patient groups to infection, and the probability of asymptomatic cases spreading disease should be considered.

Celiac disease (CD) is an immune-mediated gastrointestinal (GI) disorder driven by innate and adaptive immune responses to gluten. Presentation of CD has changed over time, with non-GI symptoms, such as anemia and osteoporosis, presenting more commonly. With improved screening and diagnostic methods, the reported prevalence of CD has increased globally, and there is considerable global variation in diagnostic and treatment practices. The objective of this study was to describe the current state of CD diagnosis and treatment patterns. A targeted review of literature from MEDLINE, Embase, the Cochrane Library, and screening of relevant conference abstracts was performed. The generally recommended diagnostic approach is GI endoscopy with small bowel biopsy; however, in selected patients, biopsy may be avoided and diagnosis based on positive serology and clinical symptoms. Diagnosis often is delayed; the average diagnostic delay after symptom onset is highly variable and can last up to 12 years. Barriers to accurate and timely diagnosis include atypical presentation, lack of physician awareness about current diagnostic criteria, misdiagnosis, and limited access to specialists. Currently, strict adherence to a gluten-free diet (GFD) is the only recommended treatment, which is not successful in all patients. Only one-third of patients are monitored regularly following diagnosis. Unmet needs for CD include improvements in the accuracy and timeliness of diagnosis, and the development of treatments for both refractory CD and GFD nonresponsive CD. Further research should investigate the impact of education about gluten-free eating and the availability of gluten-free foods support adherence and improve outcomes in patients with CD.

Introduction: Higher diabetes mellitus (DM) burden and disparities in healthcare have been linked to factors including race/ethnicity, low socioeconomic status (SES), and geographic location. Objective: To identify digital health interventions (DHIs) that improve health and healthcare delivery outcomes in populations disproportionately affected by DM. Methods: A systematic scoping review evaluated DHIs to address global health disparities in cardiovascular (CV)-related diseases/disorders or cardiovascular disease (CVD). A subgroup analysis was performed to identify the impact of DHIs in DM populations. Pre-post DM-specific health (clinical/intermediate and patient-reported) and healthcare delivery outcomes (quality, utilization, and access to care including DHI technical evaluations) were abstracted. Results: In the subgroup analysis, 21 of the 58 included studies (out of 4,298 relevant citations) examined DM populations. DM-specific health data were obtained from 13 of those studies examining primary (e.g., weight loss), secondary (e.g., diabetic retinopathy screening), tertiary (e.g., glucose control), or quaternary (e.g., overmedicalization) preventive DHIs. DHIs primarily targeted Black (29%), Hispanic (24%), low SES (62%), and/or rural (52%) populations in the United States (52%). DHIs commonly used electronic health records (28%) and decision support systems (19%). Eleven (85%) studies showed DHIs significantly improved outcomes, nine (70%) studies had no effect, and seven (54%) studies negatively impacted disparity populations. Eight (62%) studies were high-quality (e.g., RCTs). No trends could be identified to find associations of DHI type nor disparity group with preventive intervention success. Conclusions: Preventive DHIs improved both health and healthcare delivery outcomes in DM-specific disparities identified in racial/ethnic groups and low SES populations in both rural and urban geographies globally. Disclosure K. Craig: Other Relationship; Self; Medtronic. K.B. Rhee: Employee; Self; IBM.

The canine detection community is a diverse one, ranging from scientific fields such as behavior, genetics, veterinary medicine, chemistry, and biology to applications in law enforcement, military, medicine, and agricultural/environmental detection. This diversity has allowed for a flourishing and innovative community, yet it has also led to little acceptance and agreement on terminology. This is especially true when discussing the variety of training aids used in olfactory-based exercises. In general, authentic materials and pseudo-scents are the most commonly discussed, with the former accepted widely for training and certification, and the latter more often disregarded. However, as advances are made in the creation of training materials, alternative training aids are being introduced that do not fit into either of these categories. The misconceptions surrounding how these alternative training aids are manufactured has led to confusion on their classification, and therefore their reliance as an effective tool. This manuscript will review the existing language surrounding canine training aids, address relevant research revealing effectiveness, and clarify the different types based on their manufacture, chemical nature, and fundamental function.

Background Hospital performance quality assessments inform patients, providers, payers, and purchasers in making healthcare decisions. These assessments have been developed by government, private and non-profit organizations, and academic institutions. Given the number and variability in available assessments, a knowledge gap exists regarding what assessments are available and how each assessment measures quality to identify top performing hospitals. This study aims to: (a) comprehensively identify current hospital performance assessments, (b) compare quality measures from each methodology in the context of the Institute of Medicine’s (IOM) six domains of STEEEP (safety, timeliness, effectiveness, efficiency, equitable, and patient-centeredness), and (c) formulate policy recommendations that improve value-based, patient-centered care to address identified gaps. Methods A scoping review was conducted using a systematic search of MEDLINE and the grey literature along with handsearching to identify studies that provide assessments of US-based hospital performance whereby the study cohort examined a minimum of 250 hospitals in the last two years (2017–2019). Results From 3058 unique records screened, 19 hospital performance assessments met inclusion criteria. Methodologies were analyzed across each assessment and measures were mapped to STEEEP. While safety and effectiveness were commonly identified measures across assessments, efficiency, and patient-centeredness were less frequently represented. Equity measures were also limited to risk- and severity-adjustment methods to balance patient characteristics across populations, rather than stand-alone indicators to evaluate health disparities that may contribute to community-level inequities. Conclusions To further improve health and healthcare value-based decision-making, there remains a need for methodological transparency across assessments and the standardization of consensus-based measures that reflect the IOM’s quality framework. Additionally, a large opportunity exists to improve the assessment of health equity in the communities that hospitals serve.

To assess the impact of organization-directed workplace interventions on physician burnout, including stress or job satisfaction in all settings, we conducted a systematic review of the literature published from January 1, 2007, to October 3, 2018, from multiple databases. Manual searches of grey literature and bibliographies were also performed. Of the 633 identified citations, 50 met inclusion criteria. Four unique categories of organization-directed workplace interventions were identified. Teamwork involved initiatives to incorporate scribes or medical assistants into electronic health record (EHR) processes, expand team responsibilities, and improve communication among physicians. Time studies evaluated the impact of schedule adjustments, duty hour restrictions, and time-banking initiatives. Transitions referred to workflow changes such as process improvement initiatives or policy changes within the organization. Technology related to the implementation or improvement of EHRs. Of the 50 included studies, 35 (70.0%) reported interventions that successfully improved the 3 measures of physician burnout, job satisfaction, and/or stress. The largest benefits resulted from interventions that improved processes, promoted team-based care, and incorporated the use of scribes/medical assistants to complete EHR documentation and tasks. Implementation of EHR interventions to improve clinical workflows worsened burnout, but EHR improvements had positive effects. Time interventions had mixed effects on burnout. The results of our study suggest that organization-directed workplace interventions that improve processes, optimize EHRs, reduce clerical burden by the use of scribes, and implement team-based care can lessen physician burnout. Benefits of process changes can enhance physician resiliency, augment care provided by the team, and optimize the coordination and communication of patient care and health information.

The prevalence of celiac disease (CD) has rapidly increased over recent decades, but costs related to CD remain poorly quantified. This systematic review assessed the economic burden of CD in North America and Europe. MEDLINE, EMBASE, EconLit, and the Cochrane Library databases were systematically searched to identify English-language literature from 2007 to 2018 that assessed costs, cost effectiveness, and health resource utilization for CD. Forty-nine studies met the inclusion criteria, of which 28 (57.1%) addressed costs of testing and diagnosis; 33 (67.3%) were from Europe. The cost per positive CD diagnosis of testing patients already undergoing esophagogastroduodenoscopy for other indications ranged from 1300 Canadian dollars ($Can) in Canada (2016 value) to €44,712 in the Netherlands (2013 value). Adding the CD test was cost effective when it combined diagnostic modalities (e.g., serology and biopsy). Direct annual excess costs to a US payer per diagnosed CD patient totaled $US6000 (2013 value) more than for a person without CD, chiefly due to outpatient care. Hospitalizations, emergency visits, and medication use were more common with CD. After initiating a gluten-free diet (GFD), patients visited primary care providers less often, used more medications, and missed fewer days from school and work. Most of the few available economic studies of CD assess testing and diagnosis costs, especially in Europe. Methods of testing generally are considered cost effective when they combine diagnostic modalities in symptomatic patients. Most costs to a payer of managing CD derive from outpatient care. Following GFD initiation, patients lose fewer days from work and school than pretreatment.

Background Contact tracing in association with quarantine and isolation is an important public health tool to control outbreaks of infectious diseases. This strategy has been widely implemented during the current COVID-19 pandemic. The effectiveness of this nonpharmaceutical intervention is largely dependent on social interactions within the population and its combination with other interventions. Given the high transmissibility of SARS-CoV-2, short serial intervals, and asymptomatic transmission patterns, the effectiveness of contact tracing for this novel viral agent is largely unknown. Objective This study aims to identify and synthesize evidence regarding the effectiveness of contact tracing on infectious viral disease outcomes based on prior scientific literature. Methods An evidence-based review was conducted to identify studies from the PubMed database, including preprint medRxiv server content, related to the effectiveness of contact tracing in viral outbreaks. The search dates were from database inception to July 24, 2020. Outcomes of interest included measures of incidence, transmission, hospitalization, and mortality. Results Out of 159 unique records retrieved, 45 (28.3%) records were reviewed at the full-text level, and 24 (15.1%) records met all inclusion criteria. The studies included utilized mathematical modeling (n=14), observational (n=8), and systematic review (n=2) approaches. Only 2 studies considered digital contact tracing. Contact tracing was mostly evaluated in combination with other nonpharmaceutical interventions and/or pharmaceutical interventions. Although some degree of effectiveness in decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality was observed, these results were highly dependent on epidemic severity (R0 value), number of contacts traced (including presymptomatic and asymptomatic cases), timeliness, duration, and compliance with combined interventions (eg, isolation, quarantine, and treatment). Contact tracing effectiveness was particularly limited by logistical challenges associated with increased outbreak size and speed of infection spread. Conclusions Timely deployment of contact tracing strategically layered with other nonpharmaceutical interventions could be an effective public health tool for mitigating and suppressing infectious outbreaks by decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality.

Patients with critical illness have disrupted circadian rhythms, which can lead to increased morbidity, mortality and length of intensive care unit stay. Light intensity within the intensive care unit influences the circadian rhythm and may therefore impact on patient outcome. We performed an observational single-centre pilot study monitoring nocturnal light exposure of intensive care unit patients between November and December 2016. As there are currently no medical guidance on recommended light levels, we audited our findings against building regulation standards. The median light intensity was 1.5 lux, which is below the 20 lux standards; however, there were significant outliers. There was positive correlation between patient illness severity based on SOFA score and maximum lux (R = 0.45, P = 0.026); however, there was no relationship between patient illness severity and median lux exposure (R = 0.23, P = 0.28). As illness severity increased so did the time spent greater than 20 lux (R = 0.59, P = 0.0021), and the individual occasions where lux breached the 20 lux limit (R = 0.52, P = 0.009). There was no relationship between illness severity of neighbouring patients and maximum lux (R = −0.11, P = 0.69) or neighbouring illness severity and median lux (R = −0.04, P = 0.87). This preliminary work will form the basis of future projects, including national guidance and evaluating the impact of environmental light on patient-centred outcomes.

PURPOSE Many cancer registries do not capture recurrence; thus, outcome studies have often relied on time-intensive and costly manual chart reviews. Our goal was to build an effective and efficient method to reduce the numbers of chart reviews when identifying subsequent breast cancer (BC) using pathology and electronic health records. We evaluated our methods in an independent sample. METHODS We developed methods for identifying subsequent BC (recurrence or second primary) using a cohort of 17,245 women diagnosed with early-stage BC from 2 health plans. We used a combination of information from pathology report reviews and an automated data algorithm to identify subsequent BC (for those lesions without pathologic confirmation). Test characteristics were determined for a developmental (N=175) and test (N=500) set. RESULTS Sensitivity and specificity of our hybrid approach were robust [96.7% (87.6%-99.4%) and 92.1% (85.1%-96.1%), respectively] in the developmental set. In the test set, the sensitivity, specificity, and negative predictive value were also high [96.9% (88.4%-99.5%), 92.4% (89.4%-94.6%), and 99.5% (98.0%-99.0%), respectively]. The positive predictive value was lower (65.6%, 55.2%-74.8%). Chart review was required for 10.9% of the 17,245 women; 2946 (17.0%) women developed subsequent BC over a 14-year period. The date of subsequent BC identified by the algorithm was concordant with full chart reviews. CONCLUSIONS We developed an efficient and effective hybrid approach that decreased the number of charts needed to be manually reviewed by approximately 90%, to determine subsequent BC occurrence and disease-free survival time.

Celiac disease (CD) is an immune-mediated gastrointestinal disorder driven by innate and adaptive immune responses to gluten. Patients with CD are at an increased risk of several neurological manifestations, frequently peripheral neuropathy and gluten ataxia. A systematic literature review of the most commonly reported neurological manifestations (neuropathy and ataxia) associated with CD was performed. MEDLINE, Embase, the Cochrane Library, and conference proceedings were systematically searched from January 2007 through September 2018. Included studies evaluated patients with CD with at least one neurological manifestation of interest and reported prevalence, and/or incidence, and/or clinical outcomes. Sixteen studies were included describing the risk of gluten neuropathy and/or gluten ataxia in patients with CD. Gluten neuropathy was a neurological manifestation in CD (up to 39%) in 13 studies. Nine studies reported a lower risk and/or prevalence of gluten ataxia with a range of 0%–6%. Adherence to a gluten-free diet appeared to improve symptoms of both neuropathy and ataxia. The prevalence of gluten neuropathy and gluten ataxia in patients with CD varied in reported studies, but the increased risk supports the need for physicians to consider CD in patients with ataxia and neurological manifestations of unknown etiology.

We present an overview of the literature on the patterns of mental health service use and the unmet need for care in individuals with schizophrenia with a focus on studies in the United States. We also present new data on the longitudinal course of treatments from a study of first-admission patients with schizophrenia. In epidemiological surveys, approximately 40% of the respondents with schizophrenia report that they have not received any mental health treatments in the preceding 6–12 months. Clinical epidemiological studies also find that many patients virtually drop out of treatment after their index contact with services and receive little mental health care in subsequent years. Clinical studies of patients in routine treatment settings indicate that the treatment patterns of these patients often fall short of the benchmarks set by evidence-based practice guidelines, while at least half of these patients continue to experience significant symptoms. The divergence from the guidelines is more pronounced with regard to psychosocial than medication treatments and in outpatient than in inpatient settings. The expansion of managed care has led to further reduction in the use of psychosocial treatments and, in some settings, continuity of care. In conclusion, we found a substantial level of unmet need for care among individuals with schizophrenia both at community level and in treatment settings. More than half of the individuals with this often chronic and disabling condition receive either no treatment or suboptimal treatment. Recovery in this patient population cannot be fully achieved without enhancing access to services and improving the quality of available services. The recent expansion of managed care has made this goal more difficult to achieve.

To facilitate continued clinical competence, the American Board of Medical Specialties and the American Board of Psychiatry and Neurology are implementing multifaceted Maintenance of Certification programs, which include requirements for self-assessments of practice. Because psychiatrists may want to gain experience with self-assessment, two sample performance-in-practice tools are presented that are based on recommendations of the American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder and the US Departments of Veterans Affairs and Defense (VA/DoD) Clinical Practice Guideline for the Management of Post-Traumatic Stress. One of these sample tools provides a traditional chart review approach to assessing care (Appendix A); the other sample tool presents an approach that permits a real-time evaluation of practice (Appendix B). Both tools focus on treatment of posttraumatic stress disorder (PTSD) among adults age 18 ...

Substance abuse among individuals with schizophrenia is common and is often associated with poor clinical outcomes. Comprehensive, integrated pharmacological and psychosocial treatments have been shown to improve these outcomes. While a growing number of studies suggest that second-generation antipsychotic medications may have beneficial effects on the treatment of co-occurring substance use disorders, this review suggests that the literature is still in its infancy. Few existing well controlled trials support greater efficacy of second-generation antipsychotics compared with first-generation antipsychotics or any particular second-generation antipsychotic. This article focuses on and reviews studies involving US FDA-approved medications for co-occurring substance abuse problems among individuals with schizophrenia.Comprehensive treatment for individuals with schizophrenia and co-occurring substance use disorders must include specialized, integrated psychosocial intervention. Most approaches use some combination of cognitive-behavioural therapy, motivational enhancement therapy and assertive case management. The research on antipsychotic and other pharmacological treatments is also reviewed, as well as psychosocial treatments for individuals with schizophrenia and co-occurring substance use disorders, and clinical recommendations to optimize care for this population are offered.

GOALS: The authors examined assault frequency and risk factors in health care. METHODS: The authors conducted a cross-sectional questionnaire survey in 142 hospitals. Analyses are presented at the level of the individual and aggregated by facility. RESULTS: Thirteen percent of employees described at least 1 assault in the last year; the proportion assaulted per facility ranged from 1% to 26%. Patients were the most common assaulters. Working in geriatrics, mental health, and rehabilitation or in nursing represented a high risk for assault. Hours of work and work patterns represented major risk factors for assault, as were higher measures of organizational stress. The penetration of training in alternate dispute resolution strategies was associated with lower rates of assaults. CONCLUSIONS: Although work in health care is associated with high rates of assaults, closer scrutiny suggests specific possible intervention strategies.

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led us to suggest that DR commonly suppresses translation, while stimulating an ancient reproduction-related process., Author Summary Dietary restriction has been shown to extend lifespan in diverse, evolutionarily distant species, yet its underlying mechanisms remain unknown. We first constructed a database of genes essential for the life-extending effects of dietary restriction in various model organisms and then studied their interactions using a variety of network and systems biology approaches. This enabled us to predict novel genes related to dietary restriction, which we validated experimentally in yeast. By comparing large-scale data compilations (interactomes and transcriptomes) from multiple organisms, we were able to condense this -omics information to the most conserved essential elements, eliminating species-specific adaptive responses. These results lead us to the rather surprising conclusion that lifespan extension by a restricted diet commonly may exploit an ancient rejuvenation process derived from gametogenesis.

Summary Objectives: The purpose of this study was to quantify and determine the degree to which dogs experience negative displacement of the paw during movement initiation on natural surfaces, the frequency of that displacement, and whether or not the negative displacement could yield injuries. Methods: Seven retired racing Greyhound dogs were selected to participate in sprint starts on two natural (non-vegetated and vegetated) surfaces. Kinematic analysis was conducted to quantify the displacements. Results: All dogs in all trials experienced a negative paw displacement in at least one or more limbs. Significant effects were found for negative displacement across surfaces, limb, and for the surface x limb interactions. Rear paw negative displacement was -6.68 ± 2.55% body length (BL) for the non-vegetated surface and -5.29 ± 1.92% BL for the vegetated surface. Front paw negative displacement was -21.42 ± 2.62% BL for the non-vegetated surface and -17.25 ± 3.82% BL for the vegetated surface. There was no significant difference between average torso velocity on the two track surfaces. This study verified that the paw does negatively displace (moves backwards) during movement initiation. The magnitude of the displacements suggests that multiple injury mechanisms could be present. Clinical relevance: These findings demonstrate the extreme kinematics placed on the canine body during movement initiation, which might further the understanding of the mechanism of injury and contribute to enhanced surgical and rehabilitation techniques.

The authors attempt to better understand the recent decline in the number of applicants to addiction psychiatry training.The Corresponding Committee on Training and Education in Addiction Psychiatry of APA's Council on Addiction Psychiatry sent out a 14-question anonymous e-mail survey to all postgraduate-year 2 (PGY-2) through PGY-4 APA Members-in-Training. The questions explored residents' beliefs and attitudes toward addiction psychiatry and sought their opinion on how training in addiction psychiatry can be made more attractive to them.Of 2,511 eligible psychiatric residents surveyed nationally, 276 (10.6%) residents responded to the survey. Residents who responded had a generally positive impression of addiction psychiatrists but expressed much less favorable attitudes toward the practice of addiction psychiatry. Respondents provided three major subsets of suggestions: employment security and compensation, optimize PGY-1-4 addiction training, and fellowship training issues.These findings may be used to improve addiction psychiatry training and recruitment.

The Veterans Health Administration (VHA) has successfully implemented evidence-based alcohol misuse screening with the AUDIT-C. The purpose of this study was to evaluate clinical alcohol screening during the first year after implementation. Using medical record review and mailed patient surveys collected during 2004 by VHA Office of Quality and Performance, this study analyzed concordance of screening results among patients with AUDIT-Cs in both data sources. Among 1,637 patients with AUDIT-C from both sources within 90 days, the medical record screening prevalence rate of alcohol misuse, 24.6% (95% CI: 22.5% to 26.7%), was significantly lower than the survey rate, 33.4% (31.1% to 35.7%). Of 8,312 patients identified as nondrinkers in medical records, 24% reported past year alcohol use and 5% screened positive for alcohol misuse on surveys. Lower rates of alcohol use and misuse documented in medical records compared to mailed surveys suggest further investigation and standardization of clinical screening are necessary.

Brief alcohol counseling is a top US prevention priority but has not been widely implemented. The lack of an easy performance measure for brief alcohol counseling is one important barrier to implementation. The purpose of this report is to outline important issues related to measuring performance of brief alcohol counseling in health care settings. We review the strengths and limitations of several options for measuring performance of brief alcohol counseling and describe three measures of brief alcohol counseling tested in the Veterans Affairs (VA) Health Care System. We conclude that administrative data are not well-suited to measuring performance of brief alcohol counseling. Patient surveys appear to offer the optimal approach currently available for comparing performance of brief alcohol counseling across health care systems, while more options are available for measuring performance within health care systems. Further research is needed in this important area of quality improvement.

To compare patient satisfaction of male and female users of Veterans Health Administration (VHA) services.Cross-sectional study based on secondary analysis of data from VHA's Survey of Healthcare Experiences of Patients (SHEP).National random sample of 107,995 outpatients and 112,817 inpatients in FY2004.Patient's ratings of overall quality (OQ) and unique dimensions of satisfaction. Sociodemographic and health-related patient attributes.Bivariate unadjusted analyses of the association between gender and other patient attributes and the outcomes of OQ and dimensions of satisfaction were conducted followed by multivariate analyses for each outcome, adjusting for demographic and health variables.Significant differences between female and male reporting of satisfaction were found in the unadjusted analyses with males showing greater levels of satisfaction than females (P.05). These differences disappeared or became smaller for both outpatient and inpatient services, after adjusting for covariates. For 6 of the inpatient dimensions (Transitions, Physical Comfort, Involvement Family and Friends, Courtesy, Coordination, and Access) males had higher satisfaction than females after statistical adjustment.After adjustment for patient attributes, female VHA outpatients report similar OQ with VHA services as male patients. The fact that some inpatient dimensions of satisfaction continued to show effects favoring males even after adjustment suggests areas for continued focus in improving health care quality. Covariate adjustment is essential for evaluating satisfaction with health care services. Breaking down overall satisfaction into independent aspects of services is useful. The SHEP survey has provided a useful tool for evaluating and improving satisfaction among its VHA veteran users.

BackgroundData on the two-year pattern of course of illness have been collected in the WHO study of the Determinants of Outcomes of Severe Mental Disorder (DOSMD). These data are reanalysed using recursive partitioning, a method not yet applied to psychiatric data to test the hypothesis that subjects from participating centres in developing countries had better outcomes than those in developed countries.MethodSubjects were those from the DOSMD study for whom two-year follow-up data were available (n= 1056). The classification and regression trees recursive partitioning technique was used to examine the predictor variables associated with the outcome variable two year pattern of course.ResultsPattern of course was best predicted by centre, but two developed centres (Prague and Nottingham) grouped with the developing country centres excluding Cali, having better outcomes than in the remaining developed country centres and Cali. Type of onset (insidious v. non-insidious) was the next strongest predictor, but its effect differed across these two centre groupings. Effects for some groups were modified by other predictor variables, including age, child and/or adolescent problems, and gender.ConclusionsThe predominant predictor effects on two-year pattern of course continued to be centre and type of onset, but complex interactions between these variables and other predictor variables are seen in specific centre groupings not strictly defined by ‘developing’ and ‘developed’.

OBJECTIVE: To provide an epidemiologic descriptive analysis of the acute drug treatment of inpatients with bipolar mania in state psychiatric facilities in 1990. METHODS: We surveyed the first 3 weeks of drug treatment of all inpatients with bipolar mania who were admitted to 22 New York State adult psychiatric facilities during a 6-month period (n = 528). RESULTS: Almost all patients with mania were treated with neuroleptics. The mean ± SD neuroleptic dosage was 684 ± 543 mg/d chlorpromazine equivalents. Sixty-one percent of the patients received lithium and 12% received carbamazepine or valproate. Neuroleptic dosage was related to age, with older patients receiving lower dosages. Patients receiving combination treatment of a neuroleptic with either lithium, an anticonvulsant, or a benzodiazepine received a mean neuroleptic dosage similar to that of patients treated with a neuroleptic alone. CONCLUSIONS: Although their use has been widely discouraged for mood disorders, neuroleptics have been the standard treatment for acute mania.