Accounting for the low survival of the Critically Endangered northern bald ibis Geronticus eremita on a major migratory flyway

AbstractThe poor survival rate of immature northern bald ibises Geronticus eremita during their first years spent outside the natal site is driving the last known wild colony of the migratory eastern population to extinction. To inform emergency conservation action for this Critically Endangered species we investigated the distribution range and behaviour of immature birds in passage and wintering areas, and the threats to which they are subject. We integrated recent satellite telemetry data with visual observations spanning 130 years. We assessed threats across the range, using satellite tracking and field surveys. Our results show that during the years before they return to the natal site in Syria, immature northern bald ibises reside away from the recently identified adult wintering site in the central Ethiopian highlands. They occur mainly across the northernmost 70–80% of the adult migratory range. Historical records suggest that immature birds spend more time along the western Arabian Peninsula now than in the past. This range shift exposes them for longer periods to threats, such as hunting and electrocution on power lines, which are absent from the wintering site used by adult birds. We suggest that other threatened and declining bird species sharing the same flyway probably face the same threats during migration

Performance of a multi-disciplinary emergency department observation protocol for acetaminophen overdose.

The availability of 20-h N-acetylcysteine (NAC) infusion for low-risk acetaminophen (APAP) overdose enabled our center to implement an Emergency Department observation unit (OU) protocol as an alternative to hospitalization. Our objective was to evaluate our early experience with this protocol. This retrospective cohort study included all patients treated for low-risk APAP overdose in our academic hospital between 2006 and 2011. Cases were identified using OU and pharmacy records. Successful OU discharge was defined as disposition with no inpatient admission. Differences in medians with 95 % confidence intervals were used for comparisons. One hundred ninety-six patients received NAC for APAP overdose with a mean age of 35 years (SD 14); 73 % were white, and 43 % were male. Twenty (10 %) received care in the OU; 3/20(15 %) met criteria for inclusion in the OU protocol and 13/20(65 %) were discharged successfully. Out of the 196 patients, 10 met criteria for inclusion in the OU protocol but instead received care in the inpatient setting. The median total length of stay from presentation to ED discharge was 41 h for all patients treated in the OU, compared to 68 h for ten patients who met criteria for inclusion in the OU protocol but who were admitted (difference 27 h, 95 % CI 18-72 h). ED observation for APAP overdose can be a viable alternative to inpatient admission. Most patients were successfully discharged from the OU. This evaluation identified both over- and under-utilization of the OU. OU treatment resulted in shorter median length of stay than inpatient admission

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Vereckei criteria as a diagnostic tool amongst emergency medicine residents to distinguish between ventricular tachycardia and supra-ventricular tachycardia with aberrancy

SummaryBackgroundAccurate electrocardiographic (ECG) differentiation of ventricular tachycardia (VT) from supraventricular tachycardia with aberrancy (SVT-A) on ECG is key to therapeutic decision-making in the emergency department (ED) setting.ObjectiveThe goal of this study was to test the accuracy and agreement of emergency medicine residents to differentiate VT from SVT-A using the Vereckei criteria.MethodsSix emergency medicine residents volunteered to participate in the review of 114 ECGs from 86 patients with a diagnosis of either VT or SVT-A based on an electrophysiology study. The resident reviewers initially read 12-lead ECGs blinded to clinical information, and then one week later reviewed a subset of the same 12-lead ECGs unblinded to clinical information.ResultsOne reviewer was excluded for failing to follow study protocol and one reviewer was excluded for reviewing less than 50 blinded ECGs. The remaining four reviewers each read 114 common ECGs blinded to clinical data and their diagnostic accuracy for VT was 74% (sensitivity 70%, specificity 80%), 75% (sensitivity 76%, specificity 73%), 61% (sensitivity 81%, specificity 25%), and 68% (sensitivity 84%, specificity 40%). The intraclass correlation coefficient (ICC) was 0.31 (95% CI 0.22–0.42). Eliminating two of the four reviewers who left a disproportionately high number of ECGs unclassified resulted in an increase in overall mean diagnostic accuracy (70–74%) and agreement (0.31–0.50) in the two remaining reviewers. Three reviewers read 45 common ECGs unblinded to clinical information and had accuracies for VT 93%, 93% and 78%.ConclusionThe new single lead Vereckei criteria, when applied by emergency medicine residents achieved only fair-to-good individual accuracy and moderate agreement. The addition of clinical information resulted in substantial improvement in test characteristics. Further improvements (accuracy and simplification) of algorithms for differentiating VT from SVT-A would be helpful prior to clinical implementation

Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial.

BACKGROUND: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock. METHODS AND DESIGN: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018

Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown. OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments. DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024. EXPOSURE: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg). MAIN OUTCOMES AND MEASURES: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity. RESULTS: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P \u3c .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P \u3c .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P \u3c .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure. CONCLUSIONS AND RELEVANCE: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

Prevalence and demographics of methicillin resistant Staphylococcus aureus in culturable skin and soft tissue infections in an urban emergency department

<p>Abstract</p> <p>Background</p> <p>The rising incidence of methicillin resistant <it>Staph. aureus </it>(MRSA) infections is a concern for emergency practitioners. While studies have examined MRSA in inpatients, few have focused on emergency department populations. We sought to describe predictors of MRSA skin infections in an emergency department population.</p> <p>Methods</p> <p>This was a prospective observational cohort study conducted over three months in 2005. A convenience sample of patients with culturable skin infections presenting to a busy, urban emergency department was enrolled. Demographic and risk factor information was collected by structured interview. The predictive value of each risk factor for MRSA, as identified by culture, was tested using univariable logistic regression, and a multivariable predictive model was developed.</p> <p>Results</p> <p>Patients were 43% black, 40% female and mean age was 39 years (SD 14 years). Of the 182 patients with cultures, prevalence of MRSA was 58% (95%CI 50% to 65%). Significant predictors of MRSA were youth, lower body mass index, sexual contact in the past month, presence of an abscess cavity, spontaneous infection, and incarceration. The multivariable model had a C-statistic of 0.73 (95%CI 0.67 to 0.79) with four significant variables: age, group living, abscess cavity, and sexual contact within one month.</p> <p>Conclusion</p> <p>In this population of emergency department patients, MRSA skin infection was related to youth, recent sexual contact, presence of abscess, low body mass index, spontaneity of infection, incarceration or contact with an inmate, and group home living.</p

Best Practices for Biostatistical Consultation and Collaboration in Academic Health Centers

Given the increasing level and scope of biostatistics expertise needed at academic health centers today, we developed best practices guidelines for biostatistics units to be more effective in providing biostatistical support to their institutions, and in fostering an environment in which unit members can thrive professionally. Our recommendations focus on the key areas of: 1) funding sources and mechanisms; 2) providing and prioritizing access to biostatistical resources; and 3) interacting with investigators. We recommend that the leadership of biostatistics units negotiate for sufficient long-term infrastructure support to ensure stability and continuity of funding for personnel, align project budgets closely with actual level of biostatistical effort, devise and consistently apply strategies for prioritizing and tracking effort on studies, and clearly stipulate with investigators prior to project initiation policies regarding funding, lead time, and authorship

Contributions to early HIV diagnosis among patients linked to care vary by testing venue

<p>Abstract</p> <p>Objective</p> <p>Early HIV diagnosis reduces transmission and improves health outcomes; screening in non-traditional settings is increasingly advocated. We compared test venues by the number of new diagnoses successfully linked to the regional HIV treatment center and disease stage at diagnosis.</p> <p>Methods</p> <p>We conducted a retrospective cohort study using structured chart review of newly diagnosed HIV patients successfully referred to the region's only HIV treatment center from 1998 to 2003. Demographics, testing indication, risk profile, and initial CD4 count were recorded.</p> <p>Results</p> <p>There were 277 newly diagnosed patients meeting study criteria. Mean age was 33 years, 77% were male, and 46% were African-American. Median CD4 at diagnosis was 324. Diagnoses were earlier via partner testing at the HIV treatment center (N = 8, median CD4 648, p = 0.008) and with universal screening by the blood bank, military, and insurance companies (N = 13, median CD4 483, p = 0.05) than at other venues. Targeted testing by health care and public health entities based on patient request, risk profile, or patient condition lead to later diagnosis.</p> <p>Conclusion</p> <p>Test venues varied by the number of new diagnoses made and the stage of illness at diagnosis. To improve the rate of early diagnosis, scarce resources should be allocated to maximize the number of new diagnoses at screening venues where diagnoses are more likely to be early or alter testing strategies at test venues where diagnoses are traditionally made late. Efforts to improve early diagnosis should be coordinated longitudinally on a regional basis according to this conceptual paradigm.</p