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STUDY OBJECTIVE Emergency department (ED)-based naloxone distribution and peer-based behavioral counseling have been shown to be feasible, but little is known about utilization maintenance over time and clinician, patient, and visit level factors influencing implementation. METHODS We conducted a retrospective cohort study of an ED overdose prevention program providing take-home naloxone, behavioral counseling, and treatment linkage for patients treated for an opioid overdose at two Rhode Island EDs from 2017 to 2020: one tertiary referral center and a community hospital. Utilizing a Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, we evaluated program reach, adoption, implementation modifiers, and maintenance using logistic and Poisson regression. RESULTS Seven hundred forty two patients were discharged after an opioid overdose, comprising 966 visits (median: 32 visits per month; interquartile range: 29, 41). At least one intervention was provided at most (86%, 826/966) visits. Take-home naloxone was provided at 69% of visits (637/919). Over half (51%, 495/966) received behavioral counseling and treatment referral (65%, 609/932). Almost all attending physicians provided take-home naloxone (97%, 105/108), behavioral counseling (95%, 103/108), or treatment referral (95%, 103/108) at least once. Most residents and advanced practice practitioners (APPs) provided take home naloxone (78% residents; 72% APPs), behavioral counseling (76% residents; 67% APPs), and treatment referral (80% residents; 81% APPs) at least once. Most clinicians provided these services for over half of the opioid overdose patients they cared for. Patients were twice as likely to receive behavioral counseling when treated by an attending in combination with a resident and/or APP (adjusted odds ratio: 2.29; 95% confidence interval, 1.68, 3.12) compared to an attending alone. There was no depreciation in use over time. CONCLUSIONS ED naloxone distribution, behavioral counseling, and referral to treatment can be successfully integrated into usual emergency care and maintained over time with high reach and adoption. Further work is needed to identify low-cost implementation strategies to improve services use and dissemination across clinical settings.

Importance A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. Objectives To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later. Design, Setting, and Participants The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021. Main Outcomes and Measures The PTSD Checklist forDSM-5was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE. Results A total of 1003 patients (median [interquartile range] age, 34.5 [24-43] years; 715 [weighted 67.9%] female; 100 [weighted 10.7%] Hispanic, 537 [weighted 52.7%] non-Hispanic Black, 324 [weighted 32.2%] non-Hispanic White, and 42 [weighted 4.4%] of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean [SE] area under the curve [AUC], 0.815 [0.031]) and calibration (mean [SE] integrated calibration index, 0.040 [0.002]; mean [SE] expected calibration error, 0.039 [0.002]) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean [SE], 0.789 [0.025] using the Northeast as the test sample and 0.809 [0.023] using the Midwest as the test sample) and calibration (mean [SE] integrated calibration index, 0.048 [0.003] using the Northeast as the test sample and 0.024 [0.001] using the Midwest as the test sample; mean [SE] expected calibration error, 0.034 [0.003] using the Northeast as the test sample and 0.025 [0.001] using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms. Conclusions and Relevance The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.

Background Emergency department (ED) visits for opioid-related overdoses continue to rise across the United States, particularly among Black, Latinx, and American Indian/Alaskan Native communities. A minority of people with opioid use disorder (OUD) engages in formal addiction treatment and there are racial disparities in treatment access. ED visits for opioid overdose are crucial opportunities to link individuals with OUD to harm reduction and treatment services. However, we know little about whether racial inequities exist in ED treatment after opioid overdose. Methods This observational, cross-sectional study examined differences in services provided to overdose patients who were discharged after an ED visit for opioid overdose by patient race-ethnicity. Primary outcomes included provision of take-home naloxone, ED-based behavioral counseling, and linkage to treatment. Race-ethnicity differences in post-overdose ED services were evaluated using chi-square analyses, and multivariable logistic regression analyses were conducted to examine associations of race-ethnicity with receiving post-overdose services, controlling for other institutional-, provider-, and patient-level factors. Results From September 2017 to February 2020, 734 patients were discharged from the ED for an opioid-related overdose. Most patients were White non-Latinx (70.0%), 8.9% were Black non-Latinx, 3.3% were Other race non-Latinx, and 18.0% were Latinx. Take-home naloxone was the most frequent intervention provided to patients while behavioral counseling was the lowest across all race-ethnicity categories. There were no statistically significant differences in provision of take-home naloxone and treatment referral based on patient race-ethnicity. However, a lower proportion of discharged Black non-Latinx patients received behavioral counseling compared to patients of other race-ethnicities, and the odds of receiving behavioral counseling was significantly higher for White non-Latinx (OR: 1.75; 95% CI: 1.00, 3.06); Latinx (OR: 2.06; 95% CI: 1.05, 4.06); and Other race non-Latinx (OR: 3.29; 95% CI: 1.18, 9.15) patients compared to Black non-Latinx patients. Conclusion Black non-Latinx patients discharged from the ED for an opioid-related overdose were less likely to receive behavioral counseling compared to non-Black patients. Possible reasons for this decreased provision of behavioral counseling include provider bias, patient mistrust of the medical and behavioral health care systems, and limited provider training in addiction medicine and motivational interviewing. These inequities add to the known racial disparities in ED patient care. Further research should elucidate barriers to behavioral counseling within ED settings and factors contributing to racial inequities in post-overdose emergency care.

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. Approach: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. Results: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. Significance: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.

Background Emergency departments (EDs) in the US have increasingly incorporated interventions that seek to reduce opioid-related morbidity and mortality. However, many of these interventions are underutilized. This study examined ED provider-identified barriers and facilitators to policy-prescribed service provision for patients treated for an opioid overdose in Rhode Island EDs, and opportunities to improve care delivery. Methods Semi-structured qualitative interviews were conducted with 55 ED providers (management and clinical staff) across Rhode Island EDs from November 2019 to July 2020. Thematic analysis of interviews focused on gaps and best practices in post-overdose care delivery, including social and structural factors driving access to, and uptake of, services. Results Participants highlighted how automatic service delivery (opt out vs. opt in) and the integration of peer-based services enhanced post-overdose service provision. However, social and structural factors (e.g. insurance barriers, limited outpatient treatment resources) and gaps in provider knowledge of medications for opioid use disorder created barriers to care. Addressing long ED wait times and establishing dedicated care teams for patients following an overdose were seen as critical to improving ED service delivery. Conclusion Our findings suggest that post-overdose service delivery within EDs is a useful approach for connecting patients to services, particularly when peer support specialists are involved. However, standardizing service delivery approaches and improving provider education of harm reduction services must be prioritized alongside state-level policy changes to improve access to care for ED patients.

Background To minimize the spread of COVID-19, health and ancillary care providers altered service delivery patterns. These changes included an increase in reliance on telemedicine modalities, a reduction in services or hours of operation, and prohibiting guests and nonessential personnel from healthcare settings. We describe a rapid environmental assessment with senior emergency department (ED) practitioners in Rhode Island to understand how COVID-related procedural changes impact the provision of post-overdose care in ED. Methods Semi-structured interviews were conducted with 14 senior healthcare practitioners in EDs across Rhode Island from June to July 2020. Interviews were part of a larger, ongoing study examining the implementation and effectiveness of post-opioid overdose care in EDs and sought to understand how COVID-19 had impacted the provision of services for people who use drugs (PWUD). Results COVID-related policy changes challenged the provision of services to PWUD in the ED, and extended challenges in connecting people with OUD to services in the community. Specifically, challenges included transitions to telehealth modalities, required COVID tests for treatment services, and gaps in community resources. Conclusions This study underscores opportunities to improve the delivery of services amid overlapping public health crises for PWUD, including bolstering the use of telemedicine in EDs and across the care continuum.

Background Opioid-related harms are increasing among older adults. Until we better understand the factors contributing to this trend, we will be unable to design and implement effective interventions to optimally manage opioid use and its potential harms among older adults. Although considerable research has been done in younger or mixed-age populations, the degree to which it is directly applicable to older adults is uncertain. Objectives To provide a framework for understanding how to reduce adverse outcomes of opioid use among older adults, and to describe the evidence available for different factors associated with and interventions to reduce adverse outcomes related to opioid use in this population. Approach With input from a diverse panel of content experts and other stakeholders, we developed a conceptual framework and evidence map to characterize empirical studies of factors associated with opioid-related outcomes and interventions to reduce opioid-related harms in older adults. We identified relevant literature among older adults (age ≥60 years) for an evidence map by systematically searching PubMed, PsycINFO, and CINAHL for studies published in English between 2000 and May 6, 2020. Findings We identified 5,933 citations, from which we identified 41 studies with multivariable models of factors associated with opioid-related outcomes and 16 studies of interventions in older adults. More than half (22/41) of the multivariable analysis studies evaluated factors associated with long-term opioid use (which, though not a harm per se, may increase the risk of harms if not appropriately managed). Prior or early postoperative opioid use, or greater amounts of prescribed opioids (high number of opioid prescriptions or higher opioid dose), were consistently (100% agreement) and strongly (measure of association ≥2.0) associated with long-term opioid use. Back pain, depression, concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), and fibromyalgia also had consistent, but weaker, associations with long-term opioid use. Several factors were mostly associated (>75% agreement) with long-term opioid use, including benzodiazepine use, comorbidity scores, (generally undefined) substance misuse, tobacco use, and low income. However, studies were mostly consistent that alcohol abuse and healthcare utilization were not associated with long-term opioid use. Gender, age among older adults, Black race, dementia, rural/nonurban residence, prescription of long-acting opioids, unmarried status, and use of muscle relaxants were variably associated ( Six studies examined factors associated with opioid-related disorders, although only one study evaluated factors associated with opioid use disorder. Alcohol misuse and gender were variably associated with opioid misuse (examined by three studies each). All other evaluations of specific pairs of associated factors and outcomes of interest were evaluated by only one or two studies each. These included analyses of factors associated with multiple opioid prescribers, mental health outcomes, physical health outcomes, all-cause hospitalization, opioid-related hospitalization, nonopioid-specific hospitalization, emergency department visits, opioid overdose, all-cause death, opioid-related death, and nonopioid-related death. The evidence on interventions directed at older adults is sparse. Of the 16 studies of opioid-related interventions in older adults, six examined screening tools to predict opioid-related harms, but none of these tools was tested in clinical practice to assess real-world results. Two studies found that prescription drug monitoring programs are associated with less opioid use in communities. Other studied interventions include multidisciplinary pain education for patients, an educational pamphlet for patients, implementation of an opioid safety initiative, provision of patient information and pain management training for clinicians, a bundle of educational modalities for clinicians, free prescription acetaminophen, a nationally mandated tamper-resistant opioid formulation, and motivational interview training for nursing students. Few intervention studies evaluated pain or other patient-centered outcomes such as disability and functioning. Conclusions The evidence base that is directly applicable to older adults who are prescribed opioids or have opioid-related disorders is limited. Fundamental research is necessary to determine which factors may predict clinically important, patient-centered, opioid-related outcomes. Studies to date have identified numerous possible factors associated with long-term opioid use (whether appropriate or not), but analyses of other opioid-related outcomes in older adults are relatively sparse. Research is also needed to identify interventions to reduce opioid prescribing where harms outweigh benefits (including screening tools), reduce opioid-related harms and disorders, and treat existing misuse or opioid use disorder among older adults.

Study Objectives Many patients in Emergency Departments (EDs) after motor vehicle collisions (MVCs) develop post-traumatic stress disorder (PTSD) or major depressive episode (MDE). This report from the AURORA study focuses on associations of pre-MVC sleep problems with these outcomes 8 weeks after MVC mediated through peritraumatic distress and dissociation and 2-week outcomes. Methods A total of 666 AURORA patients completed self-report assessments in the ED and at 2 and 8 weeks after MVC. Peritraumatic distress, peritraumatic dissociation, and pre-MVC sleep characteristics (insomnia, nightmares, daytime sleepiness, and sleep duration in the 30 days before the MVC, trait sleep stress reactivity) were assessed retrospectively in the ED. The survey assessed acute stress disorder (ASD) and MDE at 2 weeks and at 8 weeks assessed PTSD and MDE (past 30 days). Control variables included demographics, MVC characteristics, and retrospective reports about PTSD and MDE in the 30 days before the MVC. Results Prevalence estimates were 41.0% for 2-week ASD, 42.0% for 8-week PTSD, 30.5% for 2-week MDE, and 27.2% for 8-week MDE. Pre-MVC nightmares and sleep stress reactivity predicted 8-week PTSD (mediated through 2-week ASD) and MDE (mediated through the transition between 2-week and 8-week MDE). Pre-MVC insomnia predicted 8-week PTSD (mediated through 2-week ASD). Estimates of population attributable risk suggest that blocking effects of sleep disturbance might reduce prevalence of 8-week PTSD and MDE by as much as one-third. Conclusions Targeting disturbed sleep in the immediate aftermath of MVC might be one effective way of reducing MVC-related PTSD and MDE.

African Americans experience a greater burden of acute pain than non-Hispanic white individuals across of variety of acute medical conditions, but it is unknown whether this is the case after trauma. We evaluated pain, pain-related characteristics (eg, peritraumatic distress), and analgesic treatment in 2 cohorts of individuals (African American [n = 931] and non-Hispanic white [n = 948]) presenting to the emergency department (ED) after a motor vehicle collision. We performed a propensity-matched analysis (n = 796 in each group) to assess racial differences in acute pain in the ED. In multivariable models conducted within the matched sample, race was associated with moderate to severe axial pain (odds ratio [OR] 3.2; 95% confidence interval [CI]: 2.1-5.0, P < 0.001) and higher average numerical rating scale scores (1.3; 95% CI: 1.1-1.6; P < 0.001). After adjustment for pain and other covariates, non-Hispanic white patients were more likely to receive an opioid analgesic in the ED (OR 2.0; 95% CI: 1.4-3.0, P < 0.001) or at discharge (OR 4.9; 95% CI: 3.4-7.1, P < 0.001) and also less likely to receive an NSAID in the ED (OR 0.54; 95% CI: 0.38-0.78; P = 0.001) or at discharge (0.31; 95% CI: 0.43-0.84). Racial differences in the severity of acute posttraumatic pain after a motor vehicle collision are not explained by factors such as socioeconomic status or crash characteristics. Despite a higher burden of acute pain, African Americans were less likely to receive opioid analgesics and more likely to receive NSAIDs. Further work is needed to understand the relationship between pain severity, disparities in analgesic treatment, and longer term outcomes, such as post-motor vehicle collision chronic pain.

Background: The majority of individuals with Opioid Use Disorder (OUD) do not receive any formal substance use treatment. Due to limited engagement and access to traditional treatment, there is increasing evidence that patients with OUDs turn to online social platforms to access peer support and obtain health-related information about addiction and recovery. Interacting with peers before and during recovery is a key component of many evidence-based addiction recovery programs, and may improve self-efficacy and treatment engagement as well as reduce relapse. Commonly-used online social platforms are limited in utility and scalability as an adjunct to addiction treatment; lack effective content moderation (e.g., misinformed advice, maliciousness or “trolling”); and lack common security and ethical safeguards inherent to clinical care. Methods: This present study will develop a novel, artificial-intelligence (AI) enabled, mobile treatment delivery method that fulfills the need for a robust, secure, technology-based peer support platform to support patients with OUD. Forty adults receiving outpatient buprenorphine treatment for OUD will be asked to pilot a smartphone-based mobile peer support application, the “Marigold App”, for a duration of six weeks. The program will use (1) a prospective cohort study to obtain text message content and feasibility metrics, and (2) qualitative interviews to evaluate usability and acceptability of the mobile platform. Anticipated findings and future directions: The Marigold mobile platform will allow patients to access a tailored chat support group 24/7 as a complement to different forms of clinical OUD treatment. Marigold can keep groups safe and constructive by augmenting chats with AI tools capable of understanding the emotional sentiment in messages, automatically “flagging” critical or clinically relevant content. This project will demonstrate the robustness of these AI tools by adapting them to catch OUD-specific “flags” in peer messages while also examining the adoptability of the platform itself within OUD patients.

African Americans experience an increased burden of motor vehicle collision (MVC), post-MVC musculoskeletal pain, and vitamin D insufficiency. In this prospective multicenter study, we tested the hypothesis that African Americans (n = 133) presenting to the emergency department after MVC with low peritraumatic vitamin D levels would have worse chronic musculoskeletal pain outcomes compared to individuals with sufficient vitamin D. Vitamin D levels were assessed in the early aftermath of MVC through enzyme-linked immunosorbent assay, and pain severity was assessed using the 0 to 10 numeric rating scale at 6 weeks, 6 months, and 1 year. In repeated-measures analysis, African American MVC survivors with vitamin D insufficiency experienced more severe chronic pain (β = 1.18, P = 0.031). In secondary analyses, we assessed for evidence that the effect of vitamin D on post-MVC pain outcomes is mediated, at least in part, by the influence of vitamin D on genetic variants in genes involved in immune system regulation (IL-10 and NLRP3). Genotyping was performed using a genome-wide microarray using collected DNA samples. Secondary analyses suggest that the effect of vitamin D on post-MVC pain outcomes may be influenced by genetic variation in IL-10 and NLRP3. Further studies are needed to assess the impact of vitamin D insufficiency on pain outcomes in African Americans experiencing MVC and other common trauma exposures, to assess factors affecting this relationship, and to assess the efficacy of administering vitamin D in the immediate aftermath of MVC to prevent chronic pain. Such low-cost, nonopioid interventions are urgently needed to address chronic pain development after MVC.

Background Studies from high-income countries (HIC) support restrictive blood transfusion thresholds in medical patients. In low- and middle-income countries (LMIC), the etiologies of anemia and baseline health states differ greatly; optimal transfusion thresholds are unknown. This study evaluated the association of packed red blood cell (PRBC) transfusion with mortality outcomes across hemoglobin levels amongst emergency center (EC) patients presenting with medical pathology in Kigali, Rwanda. Methods This retrospective cohort study was performed using a random sample of patients presenting to the EC at the University Teaching Hospital of Kigali. Patients ≥15 years of age, treated for medical emergencies during 2013–16, with EC hemoglobin measurements were included. The relationship between EC PRBC transfusion and patient mortality was evaluated using logistic regression, with stratified analyses performed at hemoglobin levels of 7 mg/dL and 5 mg/dL. Results Of 3609 cases sampled, 1116 met inclusion. The median age was 42 years (IQR 29, 60) and 45.2% were female. Transfusion occurred in 12.1% of patients. Hematologic (24.4%) and gastrointestinal pathologies (20.7%) were the primary diagnoses of those transfused. Proportional mortality was higher amongst those receiving transfusions, although not statistically significant (23.7% vs 17.0%, p = 0.06). No significant difference in adjusted odds of overall mortality by PRBC transfusion was found. In stratified analysis, patients receiving EC transfusions with a hemoglobin >5.0 mg/dL, had 2.21 times the odds of mortality (95% CI 1.51–3.21) as compared to those ≤5.0 mg/dL. Conclusions No association between PRBC transfusion and odds of mortality was observed amongst EC patients in this LMIC setting. An increased mortality association was found for patients receiving PRBC transfusions with an initial hemoglobin >5 mg/dL. Results suggest benefits from PRBC transfusion are limited as compared to HIC. Further research evaluating emergent transfusion thresholds for medical pathologies should be performed in LMICs to guide practice.

Objective Current Infectious Disease Society of America (IDSA) guidelines for the management of purulent skin or soft tissue infections do not account for patient age in treatment recommendations. The study objective was to determine if age was associated with outpatient treatment failure for purulent skin infection after adjusting for IDSA treatment guidelines. Methods We conducted a multicenter retrospective study of adult patients treated for a purulent skin infection and discharged home from four emergency departments between April and September 2014. Patients were followed for one month to assess for treatment failure (defined as need for a change in antibiotics, surgical intervention, or hospitalization). We used multivariable logistic regression to examine the role of patient age on treatment failure adjusting for demographic variables (gender, race), comorbidities and severity of infection. Results A total of 467 patients met inclusion criteria (mean age 37.9 years [SD 14.0], 48.2% of whom were women). Overall, 12.4% failed initial therapy. Patients 65 years and older (n = 35) were almost 4 times more likely to fail initial ED therapy in follow-up compared with younger patients (adjusted Odds Ratio (OR) 3.87, 95% Confidence Interval (CI) 1.24–12.10). After adjustment, for every 10 years of advancing age there was a 43% increased odds of failing initial treatment (OR 1.43 95% CI 1.09–1.88). Conclusion Elderly patients with purulent skin infections, whose providers followed the 2014 IDSA guidelines, were more likely to fail initial treatment than younger patients. This study suggests that there is a need to re-evaluate treatment guidelines in elderly patients.

Background Despite increased concern about prescription opioid misuse among older adults, there is limited work examining the best means to identify misuse by older adults. The goal of this investigation was to examine the performance the Prescription Drug Use Questionnaire Patient Version (PDUQp), in detecting prescription opioid misuse and prescription opioid use disorders among adult emergency department (ED) patients aged 50 years and older. Methods This was a cross-sectional study of a random sample of adult ED patients, aged 50 years and older. All participants were without cognitive impairment and reported prescription opioid use within the past 30 days. We evaluated the sensitivity, specificity, predictive values, and receiver operating characteristics of the PDUQp against a standard definition of opioid misuse and DSM-5 criteria for prescription opioid use disorder. Results Overall, 112 participants completed the study; 74 were aged 50–64 years and 38 were aged 65 years and older. Over half of the participants satisfied DSM-5 criteria for prescription opioid use disorder, with slightly less participants reporting misuse. Overall, the respective sensitivity and specificity of the PDUQp was: 44% and 79% (Receiver Operating Characteristic [ROC] area under the curve: 0.61) for prescription opioid misuse, 38% and 81% (ROC area under the curve: 0.64) for the presence of any prescription opioid use disorder, and 56% and 75% (ROC area under the curve: 0.71) for moderate to severe prescription opioid use disorder. Conclusions Based on this preliminary work, the PDUQp may be a viable instrument to screen for prescription opioid misuse and prescription opioid use disorder, but it likely requires modifications to optimize its predictive ability in adults over age 50 years.

Objectives To examine the association between use of opioids versus other analgesics with death and functioning after hip fracture in older nursing home (NH) residents. Design Retrospective cohort using national Medicare fee-for-service claims linked to the Minimum Data Set. Setting US NHs. Participants NH residents aged ≥65 years who became a long-stay resident (>100 days in the NH) between January 2008 and December 2009, had a hospitalized hip fracture, and returned to the NH. Exposure New use of opioid versus nonopioid analgesics (acetaminophen or nonsteroidal anti-inflammatory drugs) within 14 days post hip fracture. Measurements Follow-up began on the index date and continued until the first occurrence of death, significant functional decline (3-point increase on MDS Activities of Daily Living scale), or 120 days of follow-up. Odds ratios (ORs) with 95% confidence intervals (CIs) for outcomes were estimated using inverse probability of treatment–weighted multinomial logistic regression models. Results Among the 2755 NH residents with a hip fracture included in our study, 1155 (41.9%) were opioid users, and 1600 (58.1%) were nonopioid analgesic users. The mean age was 86.3 years, 73.8% were female, and 86.0% were white. Opioid use was associated with a significantly lower likelihood of death (OR = 0.47, 95% CI 0.39-0.56) and a nonsignificant decrease in functional decline (OR = 0.77, 95% CI 0.58-1.03). Conclusion A rigorous study that addresses the limitations of this study is critical to validate our preliminary findings and provide evidence about the effect of using opioid versus nonopioid analgesics to optimize acute pain in NH residents with a hip fracture.

While nausea often develops following exposure to trauma, little is known regarding the relationship between peri-traumatic nausea and prospective risk for developing posttraumatic stress disorder (PTSD). We examined the association between peri-traumatic nausea and PTSD symptom development in three independent cohorts. Participants were recruited from (1) the Emergency Departments (ED) at Grady Memorial Hospital (GMH) in Atlanta, GA, (2) from multiple other ED sites in the TRYUMPH Research Network, and (3) from the ED during evaluation for suspected acute coronary syndrome in the REACH cohort. Administration of IV ondansetron, the most predominant antiemetic used at GMH, was used as a surrogate marker for nausea in the initial GMH cohort; nausea was then directly assessed in the internal validation at GMH, and within the replication TRYUMPH Research Network and REACH cohorts. In the GMH cohort (N = 363), ondansetron administration was associated with increased 1- and 3-month posttrauma PTSD symptoms in adjusted models (all p’s

Study objective We describe characteristics of patients with in–emergency department (ED) opioid-related adverse drug events, medication errors, and harm resulting from medication errors; identify patient-, provider-, and system-based factors associated with in-ED opioid-related medication errors and harm; and create a list of strategies to prevent future events. Methods This retrospective study was conducted at 2 urban academic EDs. Potential iatrogenic opioid overdoses were identified by querying the ED electronic medical record for cases when naloxone was administered after an opioid was administered in the ED. Cases involving medication errors resulting in harm were reviewed qualitatively for common patient-, provider-, and systems-based factors that might have contributed to the event. Results Of 73 ED patients with in-ED opioid-related adverse events that required reversal with naloxone, 43 had a medication error resulting in harm. Patient-, provider-, and systems-based factors that might have contributed to the events included chronic health conditions that could predispose an individual to an opioid-related adverse event, failure to adjust opioid dosing in the elderly and for hepatic or renal impairment, multiple doses and routes of administration of opioids, coadministration of opioids with other sedating medications, and systems-based problems with patient handoffs and pharmacy oversight. Conclusion We identified patient-, provider-, and systems-based factors related to opioid-related adverse drug events and medication errors among ED patients who had received naloxone. The results from our assessment can be used to inform educational and policy initiatives aimed to prevent in-ED opioid-related adverse drug events and medication errors.

Objective Evaluate the sensitivity and specificity of pelvic ultrasound (US) and abdominopelvic computed tomography (CT) for the identification of ovarian torsion in women presenting to the emergency department with acute lower abdominal or pelvic pain. Materials and methods This is a retrospective study of 20 cases of ovarian torsion and 20 control patients, all of whom had both US and CT performed in the emergency department. Two radiologists who were blinded to clinical data interpreted all studies as (1) demonstrating an abnormal ovary or not, and (2) suggestive of torsion or not. Sensitivity, specificity and interobserver variation were calculated for each imaging modality. Results Pelvic US was interpreted as demonstrating an abnormal ovary in 90.0% of ovarian torsion cases by reader 1, and in 100.0% by reader 2, whereas CT was interpreted as revealing an abnormal ovary in 100.0% of torsion cases by both readers. Pelvic US for ovarian torsion was 80.0% sensitive (95% CI, 58.4–91.9%) and 95.0% specific (95% CI, 76.4–99.1%) for reader 1, while 80.0% sensitive (95% CI, 58.4–91.9%) and 85.0% specific (95% CI, 64.0–95.0%) for reader 2. Interobserver agreement for pelvic US was fair (Kappa = 0.60). Abdominopelvic CT for ovarian torsion was 100.0% sensitive (95% CI, 83.9–100.0%) and 85.0% specific (95% CI, 64.0–94.5%) for reader 1, while 90.0% sensitive (95% CI, 69.9–97.2%) and 90.0% specific (95% CI, 69.9–97.2%) for reader 2. Interobserver agreement was excellent (Kappa = 0.85). Conclusion The diagnostic performance of CT is not shown to be significantly different from that of US in identifying ovarian torsion in this study. These results suggest that when CT demonstrates findings of ovarian torsion, the performance of another imaging exam (i.e. US) that delays therapy is unlikely to improve preoperative diagnostic yield.

IntroductionEffective approaches to increase engagement in treatment for opioid use disorder (OUD) and reduce the risk of recurrent overdose and death following emergency department (ED) presentation for opioid overdose remain unknown. As such, we aim to compare the effectiveness of behavioural interventions delivered in the ED by certified peer recovery support specialists relative to those delivered by licensed clinical social workers (LCSWs) in promoting OUD treatment uptake and reducing recurrent ED visits for opioid overdose.Methods and analysisAdult ED patients who are at high risk for opioid overdose (ie, are being treated for an opioid overdose or identified by the treating physician as having OUD) (n=650) will be recruited from two EDs in a single healthcare system in Providence, Rhode Island into a two-arm randomised trial with 18 months of follow-up postrandomisation. Eligible participants will be randomly assigned (1:1) in the ED to receive a behavioural intervention from a certified peer recovery support specialist or a behavioural intervention from an LCSW. The primary outcomes are engagement in formal OUD treatment within 30 days of the initial ED visit and recurrent ED visits for opioid overdose within 18 months of the initial ED visit, as measured through statewide administrative records.Ethics and disseminationThis protocol was approved by the Rhode Island Hospital institutional review board (Approval Number: 212418). Data will be presented at national and international conferences and published in peer-reviewed journals.Trial registration numberNCT03684681.

IntroductionChronic musculoskeletal pain affects a substantial portion of adults visiting the emergency department (ED). Current treatment is limited in scope and does not effectively reduce musculoskeletal pain in patients. The study will evaluate the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor Food and Drug Administration approved for the treatment of chronic pain, as a promising option in its prevention. The proposed study may present a well-tolerated and effective non-opioid treatment for patients with acute musculoskeletal pain that may also be effective in preventing the transition to persistent or chronic musculoskeletal pain.Methods and analysisThe primary outcome of this study will be to assess the tolerability and preliminary effectiveness of duloxetine in patients with acute musculoskeletal pain. The study will take place at two EDs in Rhode Island, USA. The study will involve randomisation to one of three arms: duloxetine 30 mg, duloxetine 60 mg or placebo. Tolerability will be assessed by comparing the proportion of participants that report an adverse event and that drop-out across the three study arms. Effectiveness will be determined by self-reported pain over 6 weeks of follow-up. Specifically, we will compare the proportion of participants with persistent pain (ongoing pain at 6-week follow-up), across the three study arms. 60 adults (aged 18–59) presenting to the ED with acute axial musculoskeletal pain within 7 days of onset are expected to be enrolled in the proposed study.Ethics and disseminationEthics approval was obtained by the Institutional Review Board (IRB). These results will be published in a peer reviewed scientific journal and presented at one or more scientific conferences.Trial registration numberNCT03315533.

Each year millions of Americans present to the emergency department (ED) for care after a motor vehicle collision (MVC); the majority (>90%) are discharged to home after evaluation. Acute musculoskeletal pain is the norm in this population, and such patients are typically discharged to home with prescriptions for oral opioid analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). The influence of acute pain management on subsequent pain outcomes in this common ED population is unknown. We evaluated the effect of opioid analgesics vs NSAIDs initiated from the ED on the presence of moderate to severe musculoskeletal pain and ongoing opioid use at 6 weeks in a large cohort of adult ED patients presenting to the ED after MVC (n = 948). The effect of opioids vs NSAIDs was evaluated using an innovative quasi-experimental design method using propensity scores to account for covariate imbalances between the 2 treatment groups. No difference in risk for moderate to severe musculoskeletal pain at 6 weeks was observed between those discharged with opioid analgesics vs NSAIDs (risk difference = 7.2% [95% confidence interval: -5.2% to 19.5%]). However, at follow-up participants prescribed opioids were more likely than those prescribed NSAIDs to report use of prescription opioids medications at week 6 (risk difference = 17.5% [95% confidence interval: 5.8%-29.3%]). These results suggest that analgesic choice at ED discharge does not influence the development of persistent moderate to severe musculoskeletal pain 6 weeks after an MVC, but may result in continued use of prescription opioids. Supported by NIAMS R01AR056328 and AHRQ 5K12HS022998.

Objective: In response to persistent public health concerns regarding prescription opioids, many states and healthcare systems have implemented legislation and policies intended to regulate or guide opioid prescribing. The overall impact of these policies is still uncertain. The aim of this systematic review was to examine the existing evidence of provider-level and patient-level outcomes preimplementation and postimplementation of policies and legislation constructed to impact provider prescribing practices around opioid analgesics. Design: A systematic search of MEDLINE, EMBASE, the Web of Science, and the Cochrane Database of Systematic Reviews was conducted to identify studies evaluating the impact of opioid prescribing policies on provider-level and patient-level outcomes. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Eleven studies were included in the review. A meta-analysis was not possible due to between-study heterogeneity. Six of the studies assessed state-level policies, and five were at the level of the healthcare system or hospital. Studies showed temporal associations between policy implementation and reductions in opioid prescribing, as well as opioid-related overdoses. Results were mixed regarding the impact of policies on misuse. The majority of the studies were judged to be of low quality based on the GRADE criteria. Conclusions: There is low to moderate quality evidence suggesting that the presence of opioid prescribing policy will reduce the amount and strength of opioid prescribed. The presence of these policies may impact the number of overdoses, but there is no clear evidence to suggest that it reduces opioid misuse.

Victoria Leytin, Francesca L Beaudoin Department of Emergency Medicine, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USADate of preparation: 6th December 2010 Conflict of interest: None declaredClinical question: Is there evidence that hip protectors and vitamin D with calcium supplementation reduce hip fractures in the elderly?Results: The results are that vitamin D and calcium supplementation reduce incidence of hip fractures. Hip protectors provide some benefit in reducing hip fractures in elderly patients in residential facilities.Implementation: Primary care providers should assess patients for the risk of hip fracture and consider using hip protectors and nutritional supplementaton in selected individuals to prevent fractures.Keywords: hip fracture, hip protector, vitamin D, calcium

Emergency department (ED) patients are more likely than the general population to use and misuse tobacco, alcohol, and drugs.1,2 Among ED patients, the prevalence of tobacco use has been reported to be as high as 48%.2 In 2010, almost one out of every 10 ED visits was directly or indirectly a consequence of alcohol use, a figure that has nearly doubled since 1995.1 In 2011, the Drug Abuse Warning Network (DAWN) estimated that 2.5 million ED visits (approximately 2% to 3% of all visits) were directly due to misuse or abuse of illicit and prescription drugs,3 and approximately 13% of ED patients screened positive for problematic drug use.4 Sex differences have received growing attention as being an important component in the etiology and consequences of substance abuse and dependence.5–8 One large multistate ED study demonstrated that male sex was associated with greater severity of tobacco, alcohol, and drug use, which mirrors what is known about the general population.9 Apart from this study, little is known about sex-specific differences in the patterns of substance use and need for interventions among ED patients. This knowledge deficit about substance use related to sex was highlighted as a research priority at the 2014 Academic Emergency Medicine consensus conference “Gender-Specific Research in Emergency Care.”10 Understanding sex differences may be a pivotal factor in designing effective screening, brief interventions, and referral to treatment (SBIRT) approaches to address substance use among ED patients.11 In the ED, some SBIRT models have been shown to reduce alcohol use and its associated negative consequences, using the reason for the ED visit as a “teachable moment.”12,13 In settings other than EDs, primary care-based SBIRTs have shown differential effects of these approaches between men and women.14 In addition, women generally have been underrepresented in this line of research. As research and clinical implementation of SBIRT expands, there likely will be a role for sex-specific SBIRT trials, particularly if significant differences between sexes in the prevalence, patterns, or severity of substance use exist. Substance abuse may also manifest in variable behaviors between men and women (i.e., social or financial problems), and knowledge of these behaviors might supply important content for interventions and treatment. Additional work is needed to identify sex differences and examine factors that might account for these differences in substance use among ED patients. The primary aim of this investigation was to determine if sex differences exist in the prevalence of lifetime and past 3-month use of tobacco, alcohol, and drugs among a large random sample of adult ED patients. In addition, we also examined sex differences in: 1) the frequency of tobacco, alcohol, and drug use among those who used these substances within the past 3 months; 2) the severity of substance use within each substance category; 3) the need for interventions (brief or intensive) per World Health Organization (WHO) guidelines to decrease or eliminate substance use; and 4) patterns of substance use associated with the need for intervention.

During exercise, obese individuals oxidize less glycogen and more fat than their lean counterparts, but the shift in substrate use may be mediated by insulin resistance rather than body fat per se. In addition, individuals with Type 2 diabetes are not resistant to contraction-mediated glucose uptake during exercise, but in vivo studies uncomplicated by hyperglycemia are lacking. The purpose of this study was to compare blood glucose uptake and the balance between carbohydrate and fat utilization during exercise in insulin-resistant (IR) and insulin-sensitive (IS) women of equivalent body fatness and maximal oxygen consumption (V̇o2 max). Twelve overweight sedentary women were divided into two groups with similar body mass index (IR = 28.5 ± 1.6, IS = 27.5 ± 1.9), lean mass (IR = 42.4 ± 1.8 kg, IS = 41.5 ± 1.9 kg), and V̇o2 max (IR = 29.7 ± 3.5 ml·kg−1·min−1, IS = 30.7 ± 3.9 ml·kg−1·min−1) but a markedly different composite insulin sensitivity index (IR = 3.0 ± 0.7, IS = 7.7 ± 0.9). Blood glucose kinetics and substrate oxidation were assessed by stable isotope dilution and indirect calorimetry during 50 min of treadmill walking at 45% V̇o2 max. Total carbohydrate oxidation and estimated muscle glycogen use were significantly lower in the IR group. Blood glucose uptake was the same in the IR and IS groups. These data suggest that insulin resistance, independent of body fat, spares muscle glycogen and shifts substrate oxidation toward less carbohydrate use during exercise. Insulin-resistant individuals with normoglycemia appear to have no defect in blood glucose uptake during exercise.

Little is known about gender differences in the treatment of pain after motor vehicle collisions (MVCs) in an emergency department (ED). We aimed to describe gender differences in pain experiences and treatment, specifically the use of opioids and benzodiazepines after ED discharge, for MVC-related pain.This was a secondary analysis of previously collected data from the CRASH Injury studies. We included patients who were seen and discharged from an ED after an MVC and who were enrolled in 1 of 2 multicenter longitudinal prospective cohort studies (1 black/non-Hispanic and 1 white/non-Hispanic). First, we compared the experience of pain as defined by self-reported moderate-to-severe axial pain, widespread pain, number of somatic symptoms, pain catastrophizing, and peritraumatic distress between women and men using bivariate analyses. We then determined whether there were gender differences in the receipt of prescription medications for post-MVC pain symptoms (opioids and benzodiazepines) using multivariate logistic regression adjusting for demographic characteristics, pain, and collision characteristics.In total, 1878 patients were included: 61.4% were women. More women reported severe symptoms on the pain catastrophizing scale (36.8% vs 31.0%; P = 0.032) and peritraumatic distress following the MVC (59.7% vs 42.5%; P0.001), and women reported more somatic symptoms than men (median, 3.9; interquartile range, 3.7-4.0 vs median, 3.3; interquartile range, 3.1-3.5; P0.001). Unadjusted, similar proportions of women and men were given opioids (29.2% vs 29.7%; P = 0.84). After adjusting for covariates, women and men remained equally likely to receive a prescription for opioids (relative risk = 0.83; 95% confidence interval, 0.58-1.19). Women were less likely than men to receive a benzodiazepine at discharge from an ED (relative risk = 0.53; 95% confidence interval, 0.32-0.88).In a large, multicenter study of ED patients treated for MVC, there were gender differences in the acute psychological response to MVC with women reporting more psychological and somatic symptoms. Women and men were equally likely to receive opioid prescriptions at discharge. Future research should investigate potential gender-specific interventions to reduce both posttraumatic distress and the risk of developing negative long-term outcomes like chronic pain.

Background Scabies, a highly pruritic and contagious mite infestation of the skin, is endemic among tropical regions and causes a substantial proportion of skin disease among lower-income countries. Delayed treatment can lead to bacterial superinfection, and treatment of close contacts is necessary to prevent reinfestation. We describe scabies incidence and superinfection among children in American Samoa (AS) to support scabies control recommendations. Methodology/Principal Findings We reviewed 2011–2012 pharmacy records from the only AS pharmacy to identify children aged ≤14 years with filled prescriptions for permethrin, the only scabicide available in AS. Medical records of identified children were reviewed for physician-diagnosed scabies during January 1, 2011–December 31, 2012. We calculated scabies incidence, bacterial superinfection prevalence, and reinfestation prevalence during 14–365 days after first diagnosis. We used log binomial regression to calculate incidence ratios for scabies by age, sex, and county. Medical record review identified 1,139 children with scabies (incidence 29.3/1,000 children aged ≤14 years); 604 (53%) had a bacterial superinfection. Of 613 children who received a scabies diagnosis during 2011, 94 (15.3%) had one or more reinfestation. Scabies incidence varied significantly among the nine counties (range 14.8–48.9/1,000 children). Children aged

A small leg length inequality, either true or functional, can be implicated in the pathogenesis of numerous spinal disorders. The correction of a leg length inequality with the goal of treating a spinal pathology is often achieved with the use of a shoe lift. Little research has focused on the impact of this correction on the three-dimensional (3D) postural organisation. The goal of this study is to quantify in control subjects the 3D postural changes to the pelvis, trunk, scapular belt and head, induced by a shoe lift. The postural geometry of 20 female subjects (X = 22, sigma = 1.2) was evaluated using a motion analysis system for three randomised conditions: control, and right and left shoe lift. Acute postural adaptations were noted for all subjects, principally manifested through the tilt of the pelvis, asymmetric version of the left and right iliac bones, and a lateral shift of the pelvis and scapular belt. The difference in the version of the right and left iliac bones was positively associated with the pelvic tilt. Postural adaptations were noted to vary between subjects for rotation and postero-anterior shift of the pelvis and scapular belt. No notable differences between conditions were noted in the estimation of kyphosis and lordosis. The observed systematic and variable postural adaptations noted in the presence of a shoe lift reflects the unique constraints of the musculoskeletal system. This suggests that the global impact of a shoe lift on a patient's posture should also be considered during treatment. This study provides a basis for comparison of future research involving pathological populations.

Study Objectives The purposes of this study were to determine the prevalence of prescription opioid misuse in a cohort of discharged emergency department (ED) patients who received prescription opioids and to examine factors predictive of misuse. Methods This prospective observational study enrolled a sample of ED patients aged 18 to 55 years who were discharged with a prescription opioid. Participants completed surveys at baseline in the ED, then 3 and 30 days later. Follow-up surveys contained questions about opioid use and misuse, including screening questions from the National Epidemiologic Survey on Alcohol and Related Conditions. Patients were categorized as misusers if they (1) self-escalated their dose, (2) obtained additional prescription opioids without a prescription, or (3) used for a reason besides pain. Results Of the 85 patients who completed follow-ups, 36 (42%) reported misuse at either 3 or 30 days. There was no difference in demographic variables, pain scores, analgesic treatment, or discharge diagnoses between misusers and nonmisusers. Self-escalation of dose was the most common category of misuse (33/36; 92%). Taking prescription opioids without a doctor's prescription was reported by 39% (14/36), and taking pain medications for a reason other than pain was reported by 36% (13/36). The presence of disability, chronic pain, preexisting prescription opioid use, oxycodone use, and past 12-month risk of substance abuse were associated with misuse. Conclusions Prescription opioid misuse was prevalent among this cohort of ED patients. A heterogeneous mixture of behaviors was captured. Future research should focus on the etiologies of misuse with directed screening and interventions to decrease misuse.

Infected hepatocytes are important targets for malaria vaccines. To identify Plasmodium yoelii proteins expressed in infected hepatocytes, we immunized BALB/c ByJ mice with P. yoelii liver stage schizonts and produced a panel of monoclonal antibodies (Mabs). An IgG1 Mab, navy yoelii liver stage 3 (NYLS3), had the strongest reactivity against liver stage parasites and was selected for further characterization. The Mab does not recognize P. yoelii sporozoites, but recognizes liver stages parasites within 6 hr of invasion of mouse hepatocytes and throughout the hepatic and asexual erythrocytic stages of the parasite life cycle as determined by the immunofluorescent antibody test. This Mab is species-specific, and it reacts with liver stages of P. yoelii but does not react with liver stages of other Plasmodium species. The protein recognized by this Mab is present on the parasitophorous vacuole membrane of infected hepatocytes and erythrocytes as demonstrated by immunoelectron microscopy and has a relative molecular weight of 17 kDa as demonstrated by immunoblot of an extract of infected erythrocytes. It is therefore designated P. yoelii hepatic and erythrocytic stage protein, 17 kDa or PyHEP17. When added to primary cultures of mouse hepatocytes 24 hr after inoculation with P. yoelii sporozoites, when all sporozoites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver-stage parasites. Intravenous injection of NYLS3 into mice delays the onset and reduces the density of blood-stage parasitemia after sporozoite or blood-stage challenge. The P. falciparum and P. vivax homologs of PyHEP17 may therefore be important targets for vaccines designed to attack the hepatic and erythrocytic stages of the parasite life cycle.

During the influenza season patients are labeled as having an influenza-like illness (ILI) which may be either a viral or bacterial infection. We hypothesize that C-reactive protein (CRP) levels among patients with ILI diagnosed with a bacterial infection will be higher than patients diagnosed with an influenza or another viral infection.We enrolled a convenience sample of adults with ILI presenting to an urban academic emergency department from October to March during the 2008 to 2011 influenza seasons. Subjects had nasal aspirates for viral testing, and serum CRP. Bacterial infection was determined by positive blood cultures, radiographic evidence of pneumonia, or a discharge diagnosis of bacterial infection. Receiver operating characteristic curve, analysis of variance, and Student t test were used to analyze results.Over 3 influenza seasons there were 131 total patients analyzed (48 influenza infection, 42 other viral infection and 41 bacterial infection). CRP values were 25.65 mg/L (95% CI, 18.88-32.41) for influenza, 18.73 mg/L (95% CI, 12.97-24.49) for viral and 135.96 mg/L (95% CI, 99.38-172.54) for bacterial. There was a significant difference between the bacterial group, and both the influenza and other viral infection groups (P.001). The receiver operating characteristic curve for CRP as a determinant of bacterial infection had an area under the curve of 0.978, whereby a CRP value of20 had a sensitivity of 100% and80 had a specificity of 100%.C-reactive protein is both a sensitive and specific marker for bacterial infection in patients presenting with ILI during the influenza season.

Background: Although the underlying pathology is initially confined to the lungs, the associated emotional responses to chronic obstructive pulmonary disease (COPD) contribute greatly to the resulting morbidity. The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms. Methods: We conducted a 12-week, randomized double- blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Questionnaire (CRQ), an evaluative COPD-specific quality-oflife questionnaire, was the primary outcome. Results: 23 patients were randomized and 15 completed the trial (8 on Paroxetine; 7 on placebo). In the per-protocol analysis, we observed statistically and clinically significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ: emotional function (adjusted mean difference: 1.1; 95% confidence interval [CI]: 0.0 - 2.2) and mastery (difference: 1.1; CI: 0.4 - 1.8). Dyspnea and fatigue improved, but to an extent that did not reach statistical significance. In the intention-to-treat analysis, none of the differences in CRQ scores was significant. Paroxetine was not associated to any worsening of respiratory symptoms. Conclusions: The results of this small randomized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present. This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD.

Importance Liposuction is one of the most common cosmetic surgery procedures in the United States. Tumescent liposuction, in which crystalloid fluids, lidocaine, and epinephrine are infused subcutaneously before cannula-assisted aspiration of fat, can be performed without intravenous or general anesthesia, often at outpatient facilities. However, some of these facilities are not subject to state or federal regulation and may not adhere to appropriate infection control practices. Objective To describe an outbreak of severe group A Streptococcus (GAS) infections among persons undergoing tumescent liposuction at 2 outpatient cosmetic surgery facilities not subject to state or federal regulation. Design Outbreak investigation (including cohort analysis of at-risk patients), interviews using a standardized questionnaire, medical record review, facility assessment, and laboratory analysis of GAS isolates. Setting and Participants Patients undergoing liposuction at 2 outpatient facilities, one in Maryland and the other in Pennsylvania, between July 1 and September 14, 2012. Main Outcomes and Measures Confirmed invasive GAS infections (isolation of GAS from a normally sterile site or wound of a patient with necrotizing fasciitis or streptococcal toxic shock syndrome), suspected GAS infections (inflamed surgical site and either purulent discharge or fever and chills in a patient with no alternative diagnosis), postsurgical symptoms and patient-reported experiences related to his or her procedure, and emm types, T-antigen types, and antimicrobial susceptibility of GAS isolates. Results We identified 4 confirmed cases and 9 suspected cases, including 1 death (overall attack rate, 20% [13 of 66]). One instance of likely secondary GAS transmission to a household member occurred. All confirmed case patients had necrotizing fasciitis and had undergone surgical debridement. Procedures linked to illness were performed by a single surgical team that traveled between the 2 locations; 2 team members (1 of whom reported recent cellulitis) were colonized with a GAS strain that was indistinguishable by laboratory analysis of the isolates from the case patients. Facility assessments and patient reports indicated substandard infection control, including errors in equipment sterilization and infection prevention training. Conclusions and Relevance This outbreak of severe GAS infections was likely caused by transmission from colonized health care workers to patients during liposuction procedures. Additional oversight of outpatient cosmetic surgery facilities is needed to assure that they maintain appropriate infection control practices and other patient protections.

Malaria was transmitted to only 5 of 10 volunteers bitten by 1-2 Anopheles stephensi carrying sporozoites of the 3D7 clone of the NF54 strain of Plasmodium falciparum in their salivary glands. Parasites were detectable by culture in blood taken 7-10 days following exposure and by thick blood film 14-16.5 days after exposure. Infectivity did not correlate with the numbers of sporozoites in the salivary glands.

ABSTRAcr: Two colonized populations of Anopheles albimanus isolated from the Suchiate region, Chiapas State, Mexico, were compared for their susceptibility to coindigenous Plasmodium vivax. Groups of mosquitoes were fed in vitro with either autologous donor blood or the same blood cells substituted with serum negative for antigametocyte antibody. Significant differences in susceptibility between the 2 colonies were encountered if the autologous blood from a patient was fed to mosquitoes: mean infection rates of AnA2-positive groups was double that in AnAl mosquitoes. Consistent for both colonies, only 23.6% of samples positive from malarianegative serum-substituted blood were infected with an autologous blood feed. Vector competence in these mosquito populations was partially linked to the human population's immune response to the parasite. The susceptibility of mosquito populations to coindigenous species of Plasmodium is an important variable in the determination of transmission levels in an endemic area. The real de

A method consisting of filtration of up to 100 macerated mosquitoes in a batch, followed by fixation with glutaraldehyde and concentration of filtrate by centrifugation has been developed to rapidly assess malaria infection in anopheline mosquitoes. Determination of the presence of sporozoites is made by observation of a sample of the final filtrate with a phase microscope. The method is simple and field adaptable, essential factors for the application of any technique to large scale field operations. Application of the technique in El Gancho, Chiapas, Mexico, in February 1984 yielded an infection rate for Anopheles albimanus of 0.9% for intradomicile-collected human bait mosquitoes and 0.1% for peridomicile-collected human bait mosquitoes.

The circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum may be the most promising target for the development of a malaria vaccine. In this study, proteins composed of 16, 32, or 48 tandem copies of a tetrapeptide repeating sequence found in the CS protein were efficiently expressed in the bacterium Escherichia coli. When injected into mice, these recombinant products resulted in the production of high titers of antibodies that reacted with the authentic CS protein on live sporozoites and blocked sporozoite invasion of human hepatoma cells in vitro. These CS protein derivatives are therefore candidates for a human malaria vaccine.

The exoerythrocytic stages of Plasmodium lophurae and P. fallax were grown in cell cultures derived from embryonic mouse livers. Liver cell monolayers were maintained in continuous culture with frequent subculturing for extended periods of time. Morphologically, the main cell type was a large, flat cell which closely resembled in shape the mouse parenchymal cell, although small colonies of spindle-shaped cells could also be found. Mammalian cells were labelled with thymidine- 3 H prior to infection with avian merozoites so they could be positively distinguished from any avian cells which might be present in the merozoite inoculum as contaminants. Merozoites were observed inside the labelled mammalian cells within three hours and large forms were seen at 48 hr. The mammalian cells supported parasite growth comparable to that observed in avian cell cultures.

Previous work demonstrated that corticosterone induces relapse of avian malaria, and that this effect varies markedly from winter to spring. In the present study, English sparrows with latent Plasmodium relictum infections were treated in winter with corticosterone, gonadotropin, corticosterone + gonadotropin, or a control regimen consisting of the oil vehicle. Gonadotropin neither induced relapse nor potentiated the induction of relapse by corticosterone. These data cast doubt on the hypothesis that spring relapse in malarial infections is mediated by seasonal changes in reproductive hormone levels.

A method is described wherebyP. berghei sprorozoites may be obtained from the salivary glands of infected femaleA. stephensi mosquitoes. The method is relatively easy to master, requires minimal handling of biological material, and is done with ordinary laboratory equipment. In addition, the sporozoites are rendered relatively free of contaminating micro-organisms and the entire operation may be performed aseptically.