Search

Background: Female urologists report higher rates of work-related physical discomfort compared to male urologists. We compared ergonomics during simulated ureteroscopy, the most common surgery for kidney stones, between male and female urologists., Methods: Surface electromyography was used to measure muscle activation during common ureteroscopic tasks in urology trainees and staff with different surgeon positions and ureteroscopes. Subjective workload was assessed using the NASA Task Load Index (NASA-TLX). Paired t-tests, Wilcoxon rank-sum tests, and multivariate regressions were used to compare muscle activation by gender for each trial condition., Results: There was no difference in age or distribution of training level between genders, though men had larger glove sizes. Across all conditions, women required greater muscle activation in multiple muscle groups and had greater NASA-TLX scores compared to men., Conclusions: There may be gender differences in ergonomics during ureteroscopy based on muscle activation and subjective workload, suggesting potential for personalizing surgical ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI., Methods: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T)., Results: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores., Conclusions: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP., Significance: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI., Competing Interests: Conflicts of Interest The authors report no potential conflict of interests., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Cerebellum shares robust di-synaptic dentato-thalamo-cortical (DTC) connections with the contralateral motor cortex. Preclinical studies have shown that DTC are excitatory in nature. Structural integrity of DTC is associated with better upper extremity (UE) motor function in people with stroke, indicating DTC are important for cerebellar influences on movement. However, there is a lack of understanding of physiologic influence of DTC in humans, largely due to difficulty in accessing the dentate nucleus., Objective: Characterize DTC physiology using dentate nucleus deep brain stimulation (DBS) combined with transcranial magnetic stimulation (TMS) in stroke., Methods: Nine chronic stroke survivors with moderate-to-severe UE impairment (Fugl-Meyer 13-38) underwent a paired DBS-TMS experiment before receiving experimental dentate nucleus DBS in our first-in-human phase I trial (Baker et al., 2023, Nature Medicine). Conditioning DBS pulses were given to dentate nucleus 1 to 10 ms prior to supra-threshold TMS pulses given to ipsilesional motor cortex. Effects were assessed on motor evoked potentials (MEPs). Size of DBS-conditioned MEPs was expressed relative to TMS MEPs, where values >1 indicate facilitation., Results: Dentate nucleus DBS led to facilitation of MEPs at short-latency intervals (3.5 and 5 ms, P  = .049 and .021, respectively), a phenomenon we have termed dentato-cortical facilitation (DCF). Higher DCF was observed among patients with more severe UE impairment. Diffusion tensor imaging revealed microstructure of thalamo-cortical portion of DTC was related to higher corticomotor excitability., Conclusions: Our in vivo investigation reveals for the first time in humans the intrinsic excitatory properties of DTC, which can serve as a novel therapeutic target for post-stroke motor recovery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Andre G. Machado is a consultant and has intellectual property licensed to Enspire DBS. Kenneth B. Baker is a consultant to Enspire DBS. Enspire DBS funded part of the clinical trial. The remaining authors report no competing interests.

Melioidosis, caused by Burkholderia pseudomallei , is a rare but potentially fatal bacterial disease endemic to tropical and subtropical regions worldwide. It is typically acquired through contact with contaminated soil or fresh water. Before this investigation, B. pseudomallei was not known to have been isolated from the environment in the continental United States. Here, we report on three patients living in the same Mississippi Gulf Coast county who presented with melioidosis within a 3-year period. They were infected by the same Western Hemisphere B. pseudomallei strain that was discovered in three environmental samples collected from the property of one of the patients. These findings indicate local acquisition of melioidosis from the environment in the Mississippi Gulf Coast region., (Copyright © 2023 Massachusetts Medical Society.)

The SARS-CoV-2 Delta variant, first identified in October 2020, quickly became the dominant variant worldwide. We used publicly available data to explore the relationship between illness and death (peak case rates, death rates, case-fatality rates) and selected predictors (percentage vaccinated, percentage of the population >65 years, population density, testing volume, index of mitigation policies) in 45 high-income countries during the Delta wave using rank-order correlation and ordinal regression. During the Delta-dominant period, most countries reported higher peak case rates (57%) and lower peak case-fatality rates (98%). Higher vaccination coverage was protective against peak case rates (odds ratio 0.95, 95% CI 0.91-0.99) and against peak death rates (odds ratio 0.96, 95% CI 0.91-0.99). Vaccination coverage was vital to preventing infection and death from COVID-19 during the Delta wave. As new variants emerge, public health authorities should encourage the uptake of COVID-19 vaccination and boosters.

Background: In conflict-affected settings, access to health care for displaced populations is constrained by barriers including geographical, cultural, communication, logistical, financial and insecurity. A six year humanitarian crises in the North West and South West regions of Cameroon has caused 27% of health facilities to be non-functional. The eleven year crisis in North-East Nigeria, has caused the closure of 26% of health facilities. These closure of health facilities and population displacement led to health care delivery using humanitarian funding by multiple different agencies. However, there is a paucity of evidence on the selection and design of the primary health care delivery models used in humanitarian settings. To ensure efficient use of resources and quality of services, model of care selection should be evidence based and informed by the specific humanitarian context. This research protocol aims to explore how primary health care models are selected by humanitarian organizations., Methods: We will conduct a cross sectional quantitative survey to map the range of primary health care delivery models used by humanitarian organisations in Cameroon and Nigeria. Using in-depth interviews and focus group discussions with staff from humanitarian organizations and internally displaced persons, we will explore the factors influencing the selection of primary health care models in these settings and determine the coverage and gaps in services across the different primary health care models. Quantitative data will be analysed in a descriptive manner and qualitative data will be analysed thematically., Discussion: Different models of care have been reported to be used by humanitarian organisations in conflict-affected settings, yet evidence on how different models are selected is lacking. A detailed understanding of the rationale for selection, the design and quality considerations of the strategies used to deliver health care will be obtained using a survey, in-depth interviews and focus group discussions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Omam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Acanthamoeba is a free-living ameba that can cause severe disease affecting the central nervous system, skin, sinuses, and other organs, particularly in immunocompromised individuals. These rare but severe infections are often fatal, yet incompletely described., Methods: Cases included were either reported to the Centers for Disease Control and Prevention (CDC) Free-Living Ameba program or published in scientific literature. Characteristics of all patients in the United States with laboratory-confirmed non-keratitis Acanthamoeba infections were described using descriptive statistics, and associations with survival were determined using χ 2 and Fisher exact tests., Results: Of 173 patients identified, 71% were male and the median age was 44 years (range, 0-87 years). Of these, 26 (15%) survived. Most patients (88%) had at least 1 immunocompromising condition, most commonly human immunodeficiency virus (39%), cancer (28%), and solid organ or hematopoietic stem cell transplant (28%). Granulomatous amebic encephalitis (GAE) was the most common disease presentation (71%). Skin (46%), sinuses (29%), lungs (13%), and bone (6%) were also involved. Nearly half of patients (47%) had involvement of >1 organ system. Survival was less frequent among those with GAE (3%, P < .001) compared with cutaneous disease, rhinosinusitis, or multiorgan disease not including GAE. Of 7 who received the currently recommended treatment regimen, 5 (71%) survived., Conclusions: Non-keratitis Acanthamoeba infections occur primarily in immunocompromised individuals and are usually fatal. Survival may be associated with disease presentation and treatment. Providers who care for at-risk patients should be aware of the various disease manifestations to improve early recognition and treatment., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Efforts to promote COVID-19 vaccine acceptance must consider the critical role of the emergency department (ED) in providing health care to underserved patients. Focusing on patients who lacked primary care, we sought to elicit the perspectives of unvaccinated ED patients regarding COVID-19 vaccination concerns and potential approaches that might increase their vaccine acceptance., Methods: We conducted this qualitative interview study from August to November 2021 at four urban EDs in San Francisco, California; Seattle, Washington; Durham, North Carolina; and Philadelphia, Pennsylvania. We included ED patients who were ≥18 years old, fluent in English or Spanish, had not received a COVID-19 vaccine, and did not have primary care physicians or clinics. We excluded patients who were unable to complete an interview, in police custody, under suspicion of active COVID-19 illness, or presented with a psychiatric chief complaint. We enrolled until we reached thematic saturation in relevant domains. We analyzed interview transcripts with a content analysis approach focused on identifying concerns about COVID-19 vaccines and ideas regarding the promotion of vaccine acceptance and potential trusted messengers., Results: Of 65 patients enrolled, 28 (43%) identified as female, their median age was 36 years (interquartile range 29-49), and 12 (18%) interviews were conducted in Spanish. Primary concerns about COVID-19 vaccines included risk of complications, known and unknown side effects, and fear of contracting COVID-19 from vaccines. Trust played a major role for patients in deciding which sources to use for vaccine information and in engendering vaccine acceptance. Health care providers and family or friends were commonly cited as trusted messengers of information., Conclusions: We characterized concerns about COVID-19 vaccines, uncovered themes that may promote vaccine acceptance, and identified trusted messengers-primarily health care professionals. These data may inform the development of nuanced COVID-19 vaccine messaging platforms to address COVID-19 vaccine hesitancy among underserved ED populations., (© 2022 Society for Academic Emergency Medicine.)

We report 2 immunocompetent and otherwise healthy adults in the United States who had monkeypox and required hospitalization for viral myocarditis. Both patients were unvaccinated against orthopoxviruses. They had shortness of breath or chest pain and elevated cardiac biomarkers. No immediate complications were observed. They were discharged home after symptoms resolved.

Viral genomic surveillance has been a critical source of information during the COVID-19 pandemic, but publicly available data can be sparse, concentrated in wealthy countries, and often made public weeks or months after collection. We used publicly available viral genomic surveillance data submitted to GISAID and GenBank to examine sequencing coverage and lag time to submission during 2020-2021. We compared publicly submitted sequences by country with reported infection rates and population and also examined data based on country-level World Bank income status and World Health Organization region. We found that as global capacity for viral genomic surveillance increased, international disparities in sequencing capacity and timeliness persisted along economic lines. Our analysis suggests that increasing viral genomic surveillance coverage worldwide and decreasing turnaround times could improve timely availability of sequencing data to inform public health action.

Objective: To assess the effects of different surgeon positions and ureteroscope types on muscle activation as measured by surface electromyography (sEMG) during simulated ureteroscopy in an endourology box-trainer model and the kidney phantom., Methods: For this exploratory study, sEMG was used to quantify muscle activation of 3 endourology fellows during various ureteroscopic tasks. Electrodes were placed on the ureteroscope-holding side of the following muscles: thenar, forearm flexor, forearm extensor, biceps, triceps, deltoid, and trapezius. Subjects wore fitted lead aprons in an operating room and used a cystoscopy table with surgical drapes and an endoscopic video tower. Trials were completed with a disposable and reusable ureteroscope, both in the standing and sitting positions. Each subject performed an identical set of tasks in a phantom silicone kidney and ureteroscopy box trainer to recreate the procedural components of basketing, navigating a renal collecting system, and dusting. Raw EMG data for each task was processed and normalized as a percent of each subject's maximum voluntary contraction to allow comparison., Results: The forearm extensor was the most heavily utilized muscle. The trapezius and deltoid muscles were activated more during sitting whereas the forearm flexors had increased activity during standing. The heavier reusable ureteroscope had increased forearm extensor activation compared to the disposable ureteroscope., Conclusion: Preliminary data show measurable differences in muscle activation based on both surgical posture and type of ureteroscope used. This highlights the need for more extensive EMG studies to identify techniques and equipment to optimize ergonomics and potentially minimize injury during flexible ureteroscopy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States. § Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox ¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy †† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox. §§ Engaging all persons with HIV in sustained care remains a critical public health priority., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Siobhán M. O’Connor reports US Patent Application #20190212345 and #20150140670 for kits and methods for determining physiologic levels and ranges of hemoglobin or disease state. Nicola A. Hanania reports institutional support from GSK, Sanofi, Genentech, AstraZeneca, and Teva; consulting fees from AstraZeneca, GSK, Boehringer Ingelheim, Sanofi, Genentech, Teva, and Amgen; and service as editor in chief of Respiratory Medicine. Jerry Clay Goodman reports payment from the American Academy of Neurology for a course in neuropathology at the annual meeting. No other potential conflicts of interest were disclosed.

Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Daniel M. Pastula reports receipt of honoraria from the American Academy of Neurology for lectures. Amanda L. Piquet reports institutional support from Genentech, the University of Colorado, and the Rocky Mountain MS Center, royalties from Springer Nature for editorial services, consulting fees from Alexion and Genentech/Roche, honoraria from the American Academy of Neurology for educational lectures and from Medlink for a medical article, payment for expert testimony for the U.S. Department of Health and Human Services National Vaccination Injury Compensation Program from Sands Anderson, PC and from Joe Jones Law Firm, PLLC for medicolegal work, and institutional compensation for participation on a Genentech/Roche data safety monitoring board. J. David Beckham reports grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke, the National Institute for Allergy and Infectious Diseases, Roche Diagnostics, and VAMerit. Rebecca N. Kumar reports institutional grants or contracts from Regeneron and District of Columbia Department of Health, honoraria from AstraZeneca for a presentation, and a leadership role in the Infectious Disease Community of the International Society for Heart and Lung Transplantation. Princy N. Kumar reports institutional grants or contracts from Lilly, GSK, Merck, Regeneron, Gilead Sciences, Inc., American Gene Technologies, and Biohaven Pharmaceuticals; compensation for participation on Data Safety Monitoring or Advisory Boards for Johnson & Johnson, ViiV Healthcare, Gilead Sciences, Inc., and Theratechnologies, Inc.; and owns stock or stock options in Merck, Johnson & Johnson, GSK, Gilead Sciences, Inc., Pfizer, and Moderna. No other potential conflicts of interest were disclosed.

Currently, no Food and Drug Administration (FDA)-approved treatments for human monkeypox are available. Tecovirimat (Tpoxx), however, is an antiviral drug that has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox. Use of tecovirimat for treatment of monkeypox in the United States is permitted only through an FDA-regulated Expanded Access Investigational New Drug (EA-IND) mechanism. CDC holds a nonresearch EA-IND protocol that facilitates access to and use of tecovirimat for treatment of monkeypox. § The protocol includes patient treatment and adverse event reporting forms to monitor safety and ensure intended clinical use in accordance with FDA EA-IND requirements. The current multinational monkeypox outbreak, first detected in a country where Monkeypox virus infection is not endemic in May 2022, has predominantly affected gay, bisexual, and other men who have sex with men (MSM) (1,2). To describe characteristics of persons treated with tecovirimat for Monkeypox virus infection, demographic and clinical data abstracted from available tecovirimat EA-IND treatment forms were analyzed. As of August 20, 2022, intake and outcome forms were available for 549 and 369 patients, respectively; 97.7% of patients were men, with a median age of 36.5 years. Among patients with available data, 38.8% were reported to be non-Hispanic White (White) persons, 99.8% were prescribed oral tecovirimat, and 93.1% were not hospitalized. Approximately one half of patients with Monkeypox virus infection who received tecovirimat were living with HIV infection. The median interval from initiation of tecovirimat to subjective improvement was 3 days and did not differ by HIV infection status. Adverse events were reported in 3.5% of patients; all but one adverse event were nonserious. These data support the continued access to and treatment with tecovirimat for patients with or at risk for severe disease in the ongoing monkeypox outbreak., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Riad Elmor reports contract support (DCIPHER Program Management and Data Analytic Services) from Booz Allen Hamilton. No other potential conflicts of interest were disclosed.

Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Brian Pope reports travel support and provision of laboratory equipment from the Association for Public Health Laboratories and unpaid participation for service on the Awards and Nominations Committee for the Pan American Society for Clinical virology. Heba H. Mostafa reports grant support from the Maryland Department of Health, and research contract support from BioRad, DiaSorin, and Hologic. No other potential conflicts of interest were disclosed.

Study Design: A multisite, randomized, controlled, double-blinded phase I/II clinical trial., Objective: The purpose of this clinical trial is to evaluate the safety, feasibility and efficacy of pairing noninvasive transcranial direct current stimulation (tDCS) with rehabilitation to promote paretic upper extremity recovery and functional independence in persons living with chronic cervical spinal cord injury (SCI)., Setting: Four-site trial conducted across Cleveland Clinic, Louis Stokes Veterans Affairs Medical Center of Cleveland and MetroHealth Rehabilitation Rehabilitation Institute of Ohio, and Kessler Foundation of New Jersey., Methods: Forty-four adults (age ≥18 years) with tetraplegia following cervical SCI that occurred ≥1-year ago will participate. Participants will be randomly assigned to receive anodal tDCS or sham tDCS given in combination with upper extremity rehabilitation for 15 sessions each over 3-5 weeks. Assessments will be made twice at baseline separated by at least a 3-week interval, once at end-of-intervention, and once at 3-month follow-up., Primary Outcome Measure(s): Primary outcome measure is upper extremity motor impairment assessed using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) scale. Functional abilities will be assessed using Capabilities of Upper Extremity-Test (CUE-T), while functional independence and participation restrictions will be evaluated using the self-care domain of Spinal Cord Independent Measure (SCIM), and Canadian Occupational Performance Measure (COPM)., Secondary Outcome Measures: Treatment-associated change in corticospinal excitability and output will also be studied using transcranial magnetic stimulation (TMS) and safety (reports of adverse events) and feasibility (attrition, adherence etc.) will also be evaluated., Trial Registration: ClincalTrials.gov identifier NCT03892746. This clinical trial is being performed at four sites within the United States: Cleveland Clinic (lead site), Louis Stokes Cleveland Veterans Affairs Medical Center (VAMC) and MetroHealth Rehabilitation Institute in Ohio, and Kessler Foundation in New Jersey. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

The SARS-CoV-2 Delta variant emerged shortly after COVID-19 vaccines became available in 2021. We describe SARS-CoV-2 breakthrough infections in a highly vaccinated, well-monitored US Embassy community in Kampala, Uganda. Defining breakthrough infection rates in highly vaccinated populations can help determine public health messaging, guidance, and policy globally.

Background: Approximately two-thirds of stroke survivors experience chronic upper limb paresis, and of them, 50% experience severe paresis. Treatment options for severely impaired survivors are often limited. Rehabilitation involves intensively engaging the paretic upper limb, and disincentivizing use of the non-paretic upper limb, with the goal to increase excitability of the ipsilesional primary motor cortex (iM1) and suppress excitability of the undamaged (contralesional) motor cortices, presumed to have an inhibitory effect on iM1. Accordingly, brain stimulation approaches, such as repetitive transcranial magnetic stimulation (rTMS), are also given to excite iM1 and/or suppress contralesional motor cortices. But such approaches aimed at ultimately increasing iM1 excitability yield limited functional benefit in severely impaired survivors who lack sufficient ipsilesional substrate., Aim: Here, we test the premise that combining Contralaterally Controlled Functional Electrical Stimulation (CCFES), a rehabilitation technique that engages the non-paretic upper limb in delivery of neuromuscular electrical stimulation to the paretic upper limb, and a new rTMS approach that excites intact, contralesional higher motor cortices (cHMC), may have more favorable effect on paretic upper limb function in severely impaired survivors based on recruitment of spared, transcallosal and (alternate) ipsilateral substrate., Methods: In a prospective, double-blind, placebo-controlled RCT, 72 chronic stroke survivors with severe distal hand impairment receive CCFES plus cHMC rTMS, iM1 rTMS, or sham rTMS, 2X/wk for 12wks. Measures of upper limb motor impairment (Upper Extremity Fugl Meyer, UEFM), functional ability (Wolf Motor-Function Test, WMFT) and perceived disability are collected at 0, 6, 12 (end-of-treatment), 24, and 36 wks (follow-up). TMS is performed at 0, 12 (end-of-treatment), and 36 wks (follow-up) to evaluate inter-hemispheric and ipsilateral mechanisms. Influence of baseline severity is also characterized with imaging., Conclusions: Targeting of spared neural substrates and rehabilitation which engages the unimpaired limb in movement of the impaired limb may serve as a suitable combinatorial treatment option for severely impaired stroke survivors., Clinicaltrials No: NCT03870672., Competing Interests: JK is an inventor on the CCFES patent assigned to Case Western Reserve University, Patent 8,165,685: System and Method for Therapeutic Neuromuscular Electrical Stimulation. This patent was licensed to Synapse Biomedical Inc. (Oberlin, Ohio) on February 1, 2019. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mohan, Knutson, Cunningham, Widina, O'Laughlin, Arora, Li, Sakaie, Wang, Uchino and Plow.)

Background: We conducted in-depth interviews to characterize reasons for COVID-19 vaccine hesitancy in emergency department (ED) patients and developed messaging platforms that may address their concerns. In this trial, we seek to determine whether provision of these COVID-19 vaccine messaging platforms in EDs will be associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients., Methods: This is a cluster-randomized controlled trial (RCT) evaluating our COVID-19 vaccine messaging platforms in seven hospital EDs (mix of academic, community, and safety-net EDs) in four US cities. Within each study site, we randomized 30 1-week periods to the intervention and 30 1-week periods to the control. Adult patients who have not received a COVID-19 vaccine are eligible with these exclusions: (1) major trauma, intoxication, altered mental status, or critical illness; (2) incarceration; (3) psychiatric chief complaint; and (4) suspicion of acute COVID-19 illness. Participants receive an orally administered Intake survey. During intervention weeks, participants then receive three COVID-19 vaccine messaging platforms (4-min video, one-page informational flyer and a brief, scripted face-to-face message delivered by an ED physician or nurse); patients enrolled during non-intervention weeks do not receive these platforms. Approximately, an hour after intake surveys, participants receive a Vaccine Acceptance survey during which the primary outcome of acceptance of the COVID-19 vaccine in the ED is ascertained. The other primary outcome of receipt of a COVID-19 vaccine within 32 days is ascertained by electronic health record review and phone follow-up. To determine whether provision of vaccine messaging platforms is associated with a 7% increase in vaccine acceptance and uptake, we will need to enroll 1290 patients., Discussion: Highlighting the difficulties of trial implementation during the COVID-19 pandemic in acute care settings, our novel trial will lay the groundwork for delivery of public health interventions to vulnerable populations whose only health care access occurs in EDs., Conclusions: Toward addressing vaccine hesitancy in vulnerable populations who seek care in EDs, our cluster-RCT will determine whether implementation of vaccine messaging platforms is associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients., Trial Status: We began enrollment in December 2021 and expect to continue through 2022., Trial Registration: ClinicalTrials.gov NCT05142332 . Registered 02 December 2021., (© 2022. The Author(s).)

Nearly 80 million people have been forcibly displaced by persecution, violence, and disaster. Displaced populations, including refugees, face health challenges such as resource shortages, food and housing insecurity, violence, and disrupted social support. People living with HIV in refugee settings have decreased engagement with HIV services compared to non-refugee populations, and interventions are needed to enhance linkage to care. However, designing health interventions in humanitarian settings is challenging. We used Intervention Mapping (IM), a six-step method for developing theory- and evidence-based health interventions, to design a program to increase linkage to HIV care for refugees and Ugandan nationals in Nakivale Refugee Settlement in Uganda. We engaged a diverse group of stakeholders ( N  = 14) in Nakivale, including community members and humanitarian actors, in an interactive workshop focusing on IM steps 1-4. We developed a chronic care program that would integrate HIV care with services for hypertension and diabetes at accessible community sites, thereby decreasing stigma around HIV treatment and improving access to care. IM provided an inclusive, efficient method for integrating community members and program implementers in the intervention planning process, and can be used as a method-driven approach to intervention design in humanitarian settings.

We aimed to describe frequency of COVID-19 exposure risk factors among patients presenting for medical care at an urban, public hospital serving mostly uninsured/Medicare/Medicaid clients and risk factors associated with SARS-CoV-2 infection. Consenting, adult patients seeking care at a public hospital from August to November 2020 were enrolled in this cross-sectional investigation. Saliva, anterior nasal and nasopharyngeal swabs were collected and tested for SARS-CoV-2 using RT-PCR. Participant demographics, close contact, and activities ≤14 days prior to enrollment were collected through interview. Logistic regression was used to identify risk factors associated with testing positive for SARS-CoV-2. Among 1,078 participants, 51.8% were male, 57.0% were aged ≥50 years, 81.3% were non-Hispanic Black, and 7.6% had positive SARS-CoV-2 tests. Only 2.7% reported COVID-19 close contact ≤14 days before enrollment; this group had 6.79 adjusted odds of testing positive (95%CI = 2.78-16.62) than those without a reported exposure. Among participants who did not report COVID-19 close contact, working in proximity to ≥10 people (adjusted OR = 2.17; 95%CI = 1.03-4.55), choir practice (adjusted OR = 11.85; 95%CI = 1.44-97.91), traveling on a plane (adjusted OR = 5.78; 95%CI = 1.70-19.68), and not participating in an essential indoor activity (i.e., grocery shopping, public transit use, or visiting a healthcare facility; adjusted OR = 2.15; 95%CI = 1.07-4.30) were associated with increased odds of testing positive. Among this population of mostly Black, non-Hispanic participants seeking care at a public hospital, we found several activities associated with testing positive for SARS-CoV-2 infection in addition to close contact with a case. Understanding high-risk activities for SARS-CoV-2 infection among different communities is important for issuing awareness and prevention strategies., Competing Interests: YW, PR, VK, AH, and MS received funding for this study from the CDC Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Smith-Jeffcoat, Sleweon, Koh, Khalil, Schechter, Rebolledo, Kasinathan, Hoffman, Rossetti, Shragai, O'Laughlin, Espinosa, Bankamp, Bowen, Paulick, Gargis, Folster, da Silva, Biedron, Stewart, Wang, Kirking, Tate and CDC COVID-19 Emergency Response GA-10 Field.)

Self-collected specimens can expand access to SARS-CoV-2 testing. At a large inner-city hospital 1,082 participants self-collected saliva and anterior nasal swab (ANS) samples before healthcare workers collected nasopharyngeal swab (NPS) samples on the same day. To characterize patient preferences for self-collection, this investigation explored ability, comfort, and ease of ANS and saliva self-collection for SARS-CoV-2 testing along with associated patient characteristics, including medical history and symptoms of COVID-19. With nearly all participants successfully submitting a specimen, favorable ratings from most participants (at least >79% in ease and comfort), and equivocal preference between saliva and ANS, self-collection is a viable SARS-CoV-2 testing option., Competing Interests: The authors have declared that no competing interests exist.

Up to 50% of stroke survivors have persistent, severe upper extremity paresis even after receiving rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) can augment the effects of rehabilitation by modulating corticomotor excitability, but the conventional approach of facilitating excitability of the ipsilesional primary motor cortex (iM1) fails to produce motor improvement in stroke survivors with severe loss of ipsilesional substrate. Instead, the undamaged, contralesional dorsal premotor cortex (cPMd) may be a more suitable target. CPMd can offer alternate, bi-hemispheric and ipsilateral connections in support of paretic limb movement. This pilot, randomized clinical trial seeks to investigate whether rTMS delivered to facilitate cPMd in conjunction with rehabilitation produces greater gains in motor function than conventional rTMS delivered to facilitate iM1 in conjunction with rehabilitation in severely impaired stroke survivors. Twenty-four chronic (≥6 months) stroke survivors with severe loss of ipsilesional substrate (defined by the absence of physiologic evidence of excitable residual pathways tested using TMS) will be included. Participants will be randomized to receive rTMS to facilitate cPMd or iM1 in conjunction with task-oriented upper limb rehabilitation given for 2 sessions/week for 6 weeks. Assessments of primary outcome related to motor impairment (upper extremity Fugl-Meyer [UEFM]), motor function, neurophysiology, and functional neuroimaging will be made at baseline and at 6-week end-of-treatment. An additional assessment of motor outcomes will be repeated at 3-month follow-up to evaluate retention. The primary endpoint is 6-week change in UEFM. This pilot trial will provide preliminary evidence on the effects and mechanisms associated with facilitating intact cPMd in chronic severe stroke survivors. The trial is registered on clinicaltrials.gov, NCT03868410., (© 2022 S. Karger AG, Basel.)

Transcranial magnetic stimulation (TMS) is used to investigate corticomotor neurophysiology associated with functional recovery in individuals with spinal cord injury (SCI). There is insufficient evidence about test-retest measurement properties of TMS in SCI. Therefore, we investigated test-retest agreement and reliability of TMS metrics representing corticomotor excitability, output, gain, map (representation), and inhibition in individuals with cervical SCI. We collected TMS metrics from biceps and triceps muscles because of the relevance of this proximal muscle pair to the cervical SCI population. Twelve individuals with chronic C3-C6 SCI participated in two TMS sessions separated by ≥ 2 weeks. Measurement agreement was evaluated using t tests, Bland-Altman limits of agreement and relative standard error of measurement (SEM%), while reliability was investigated using intra-class correlation coefficient (ICC) and concordance correlation coefficient (CCC). We calculated the smallest detectable change for all TMS metrics. All TMS metrics except antero-posterior map coordinates and corticomotor inhibition were in agreement upon repeated measurement though limits of agreement were generally large. Measures of corticomotor excitability, output and medio-lateral map coordinates had superior agreement (SEM% < 10). Metrics representing corticomotor excitability, output, and inhibition had good-to-excellent reliability (ICC/CCC > 0.75). The smallest detectable change for TMS metrics was generally high for a single individual, but this value reduced substantially with increase in sample size. We recommend use of corticomotor excitability and recruitment curve area owing to their superior measurement properties. A modest group size (20 or above) yields more stable measurements, which may favor use of TMS metrics in group level modulation after SCI., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Historically, there has been concern that conflict may exacerbate the HIV epidemic. We conducted a systematic review to examine HIV prevalence in conflict-affected populations compared to district-level or countrywide HIV prevalence. Following PRISMA guidelines, studies presenting original HIV prevalence data published between 2005 and 2020 were drawn from PubMed, Scopus, and Embase. Data extracted included HIV prevalence, methods, dates, location, and population type. Studies were assessed for bias. Ten met criteria for data extraction; all focused on populations in sub-Saharan African. Most of the studies reported on mixed population settings while one was in a refugee camp. Six reported HIV prevalence higher than district- or country-level prevalence, while four reported lower HIV prevalence. Seven demonstrated moderate-to-high likelihood of bias in sampling, and five used methods limiting their comparability with local HIV prevalence. The relationship between armed conflict and HIV prevalence remains difficult to evaluate and likely varies by socioeconomic indicators.

We evaluated the performance of self-collected anterior nasal swab (ANS) and saliva samples compared with healthcare worker-collected nasopharyngeal swab specimens used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the same PCR diagnostic panel to test all self-collected and healthcare worker-collected samples from participants at a public hospital in Atlanta, Georgia, USA. Among 1,076 participants, 51.9% were men, 57.1% were >50 years of age, 81.2% were Black (non-Hispanic), and 74.9% reported >1 chronic medical condition. In total, 8.0% tested positive for SARS-CoV-2. Compared with nasopharyngeal swab samples, ANS samples had a sensitivity of 59% and saliva samples a sensitivity of 68%. Among participants tested 3-7 days after symptom onset, ANS samples had a sensitivity of 80% and saliva samples a sensitivity of 85%. Sensitivity varied by specimen type and patient characteristics. These findings can help physicians interpret PCR results for SARS-CoV-2.

We compared the characteristics of hospitalized and nonhospitalized patients who had coronavirus disease in Atlanta, Georgia, USA. We found that risk for hospitalization increased with a patient's age and number of concurrent conditions. We also found a potential association between hospitalization and high hemoglobin A1c levels in persons with diabetes.

The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged ≥18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age ≥65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. James M. Blum reports personal fees from Clew Medical, outside the submitted work. No other potential conflicts of interest were disclosed.

In July 2019, the Illinois Department of Public Health and the Wisconsin Department of Health Services launched a coordinated epidemiologic investigation after receiving reports of several cases of lung injury in previously healthy persons who reported electronic cigarette (e-cigarette) use, or vaping (1). This report describes features of e-cigarette product use by patients in Illinois and Wisconsin. Detailed patient interviews were conducted by telephone, in person, or via the Internet with 86 (68%) of 127 patients. Overall, 75 (87%) of 86 interviewed patients reported using e-cigarette products containing tetrahydrocannabinol (THC), and 61 (71%) reported using nicotine-containing products. Numerous products and brand names were identified by patients. Nearly all (96%) THC-containing products reported were packaged, prefilled cartridges, and 89% were primarily acquired from informal sources (e.g., friends, family members, illicit dealers, or off the street). In contrast, 77% of nicotine-containing products were sold as prefilled cartridges, and 83% were obtained from commercial vendors. The precise source of this outbreak is currently unknown (2); however, the predominant use of prefilled THC-containing cartridges among patients with lung injury associated with e-cigarette use suggests that they play an important role. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. Given the diversity of products reported and frequency of patients using both THC- and nicotine-containing e-cigarette products, additional methods such as product testing and traceback could help identify the specific cause of this outbreak., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Social reward is critical for social relationships, and yet we know little about the characteristics of social interactions that are rewarding or the neural mechanisms underlying that reward. Here, we investigate the sex-dependent role of oxytocin receptors within the ventral tegmental area (VTA) in mediating the magnitude and valence of social reward. Operant and classical conditioning tests were used to measure social reward associated with same-sex social interactions. The effects of oxytocin, selective oxytocin receptor agonists, antagonists, and vehicle injected into the VTA on social reward was determined in male and female Syrian hamsters. The colocalization of FOS and oxytocin in sites that project to the VTA following social interaction was also determined. Females find same-sex social interactions more rewarding than males and activation of oxytocin receptors in the VTA is critical for social reward in females, as well as males. These studies provide support for the hypothesis that there is an inverted U relationship between the duration of social interaction and social reward, mediated by oxytocin; and that in females the dose-response relationship is initiated at lower doses compared with males. Same-sex social interaction is more rewarding in females than in males, and an inverted U relationship mediated by oxytocin may have a critical role in assigning positive and negative valence to social stimuli. Understanding these sex differences in social reward processing may be essential for understanding the sex differences in the prevalence of many psychiatric disorders and the development of gender-specific treatments of neuropsychiatric disorders.

Background: Food allergy prevalence has continued to rise over the past decade. While studies have reported threshold doses for multiple foods, large-scale multi-food allergen studies are lacking. Our goal was to identify threshold dose distributions and predictors of severe reactions during blinded oral food challenges (OFCs) in multi-food allergic patients. Methods: A retrospective chart review was performed on all Stanford-initiated clinical protocols involving standardized screening OFCs to any of 11 food allergens at 7 sites. Interval-censoring survival analysis was used to calculate eliciting dose (ED) curves for each food. Changes in severity and ED were also analyzed among participants who had repeated challenges to the same food. Results: Of 428 participants, 410 (96%) had at least one positive challenge (1445 standardized OFCs with 1054 total positive challenges). Participants undergoing peanut challenges had the highest ED 50 (29.9 mg), while those challenged with egg or pistachio had the lowest (7.07 or 1.7 mg, respectively). The most common adverse event was skin related (54%), followed by gastrointestinal (GI) events (33%). A history of asthma was associated with a significantly higher risk of a severe reaction (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.36, 4.13). Higher values of allergen-specific IgE (sIgE) and sIgE to total IgE ratio (sIgEr) were also associated with higher risk of a severe reaction (1.49 [1.19, 1.85] and 1.84 [1.30, 2.59], respectively). Participants undergoing cashew, peanut, pecan, sesame, and walnut challenges had more severe reactions as ED increased. In participants who underwent repeat challenges, the ED did not change ( p = 0.66), but reactions were more severe ( p = 0.02). Conclusions: Participants with a history of asthma, high sIgEr, and/or high values of sIgE were found to be at higher risk for severe reactions during food challenges. These findings may help to optimize food challenge dosing schemes in multi-food allergic, atopic patients, specifically at lower doses where the majority of reactions occur. Trials Registration Number: ClinicalTrials. gov number NCT03539692; https://clinicaltrials.gov/ct2/show/NCT03539692.

Objectives: Refugees living in Uganda come from HIV-endemic countries, and many remain in refugee settlements for over a decade. Our objective was to evaluate the HIV care cascade in Nakivale Refugee Settlement and to assess correlates of linkage to care., Methods: We prospectively enrolled individuals accessing clinic-based HIV testing in Nakivale Refugee Settlement from March 2013 to July 2014. Newly HIV-diagnosed clients were followed for 3 months post-diagnosis. Clients underwent a baseline survey. The following outcomes were obtained from HIV clinic registers in Nakivale: clinic attendance ('linkage to HIV care'), CD4 testing, antiretroviral therapy (ART) eligibility, and ART initiation within 90 days of testing. Descriptive data were reported as frequency with 95% confidence interval (CI) or median with interquartile range (IQR). The impact of baseline variables on linkage to care was assessed with logistic regression models., Results: Of 6850 adult clients tested for HIV, 276 (4%; CI: 3-5%) were diagnosed with HIV infection, 148 (54%; CI: 47-60%) of those were linked to HIV care, 54 (20%; CI: 15-25%) had a CD4 test, 22 (8%; CI: 5-12%) were eligible for ART, and 17 (6%; CI: 3-10%) initiated ART. The proportions of refugees and nationals at each step of the cascade were similar. We identified no significant predictors of linkage to care., Conclusions: Less than a quarter of newly HIV-diagnosed clients completed ART assessment, considerably lower than in other reports from sub-Saharan Africa. Understanding which factors hinder linkage to and engagement in care in the settlement will be important to inform interventions specific for this environment., (© 2017 British HIV Association.)

Objectives: The objective was to measure the variation in missed diagnosis and costs of care for older acute myocardial infarction (AMI) patients presenting to emergency departments (EDs) and to identify the hospital and ED characteristics associated with this variation., Methods: Using 2004-2005 Medicare inpatient and outpatient records, the authors identified a cohort of AMI patients age 65 years and older who presented to the ED for initial care. The primary outcome was missed diagnosis of AMI, i.e., AMI hospital admission within 7 days of an ED discharge for a condition suggestive of cardiac ischemia. Costs were defined as Medicare hospital payments for all services associated with and immediately resulting from the ED evaluation. The effect of ED and hospital characteristics on quality and costs were estimated using multilevel models with hospital random effects., Results: There were 371,638 AMI patients age 65 and older included in the study, of whom 4,707 were discharged home from their initial ED visits and subsequently admitted to the hospital. The median unadjusted hospital-level missed diagnosis percentage was 0.52% (interquartile range [IQR] = 0 to 3.45%). ED characteristics protective of adverse outcomes include higher ED chest pain acuity (adjusted odds ratio [aOR] = 0.23, 99% confidence interval [CI] = 0.19 to 0.27) and American Board of Emergency Medicine (ABEM) certification (aOR = 0.60, 99% CI = 0.50 to 0.73). Protective hospital characteristics include larger hospital size (aOR = 0.46, 99% CI = 0.37 to 0.57) and academic status (aOR = 0.74, 99% CI = 0.58 to 0.94). All of these characteristics were associated with higher costs as well., Conclusions: The proportion of missed AMI diagnoses and cost of care for patients age 65 years and older presenting to EDs with AMI varies across hospitals. Hospitals with more board-certified emergency physicians (EPs) and higher average acuity are associated with significantly higher quality. All hospital characteristics associated with better ED outcomes are associated with higher costs., (© 2014 by the Society for Academic Emergency Medicine.)

Radical hysterectomy, a procedure used in the treatment of women with cervical cancer, is frequently a cause of either temporary or permanent bladder dysfunction in the postoperative period. Four major types of dysfunction are seen: hypertonus of the bladder muscle, loss of sensation of bladder fullness, difficulty initiating micturition, and bladder hypotonia. Nursing interventions can affect adaptation to some of these problems and prevention of others. A review of rehabilitative literature is used to develop a rationale for nursing care using Levine's Conservation Principles as a conceptual framework.

Studies in cell culture systems have demonstrated synergistic cytotoxicity of thymidine and its in vivo metabolite thymine with cisplatin. We have conducted a Phase I trial to assess the toxic effects and tolerable doses of thymidine plus cisplatin in patients with advanced cancer. Twenty such patients were treated with varying doses of thymidine infused continuously during Days 1-5 of a 28-day cycle. Cisplatin at a dose of 100 mg/m2 was administered on Day 3 of the cycle. Using this schedule, the maximally tolerated dose of thymidine was 60 g/m2/day. Hematological toxicity was dose limiting with median granulocyte and platelet nadirs of 1,500/mm3 and 55,000/mm3, respectively. Central nervous system and gastrointestinal toxicity was also prominent. Plasma and urine thymidine and thymine concentrations were determined using a high-performance liquid chromatography assay. At the maximally tolerated thymidine dose, steady state plasma thymidine concentrations approached or exceeded 1 mM in all patients, and thymine levels of 1-2 mM were achievable. These concentrations approach those demonstrated to produce synergistic cytotoxicity with cisplatin in vitro. Further pharmacokinetic analysis revealed that there is a progressive fall in thymidine plasma clearance with increasing dose and that cisplatin administration is followed by a significant fall in plasma thymidine clearance. No clear-cut relationships between platelet nadir and thymidine pharmacokinetics could be found, although nonlinear regression analysis did reveal a significant correlation between steady-state plasma thymidine concentration and platelet nadir. The recommended thymidine dose for Phase II trials of this combination is 60 g/m2/day in patients with little or no prior therapy.