Search

INTRODUCTION: Post-exposure prophylaxis (PEP) is an efficacious prevention method when initiated promptly after an HIV exposure. Yet, PEP has been underutilized, even among healthcare workers (HCWs) with occupational exposure in sites with PEP policies and procedures and access to PEP medications. It is important to understand the dynamics of uneven PEP use in what appears to be an optimal context to better protect the health and wellbeing of HCWs. METHODS: We conducted a scoping review to elucidate factors influencing HCWs use of PEP after occupational exposure. We searched PubMed, PsychInfo and Google Scholar for peer-reviewed literature published in English from 2014 to 2022 using the terms HIV, postexposure/post-exposure prophylaxis, acceptability, healthcare workers, and values and preferences. An inductive narrative review of the resulting 53 studies identified core themes. RESULTS: Nearly all studies (96%) with various HCW types and settings occurred in low- and middle-income countries (LMICs) in Africa and Asia. Identified themes arrayed along a trajectory of PEP use experience: awareness/knowledge; acceptability; availability/access; uptake/use; adherence/completion. Across studies, awareness of PEP for HIV prevention was high, knowledge about drug regimens and healthcare facility policies was moderate to low; acceptability of PEP was moderate to high; PEPs perceived accessibility/availability was inconsistent and varied by geographic location and setting; HCWs uptake of PEP was low, affected by not knowing how to report an exposure and being unaware of PEP availability; and adherence/completion of PEP regimens was moderate to low, impeded by side effects and a belief that completing regimens was unnecessary to avert seroconversion. HCWs consistently expressed concern about HIV stigma. DISCUSSION: Findings are limited by the inconsistent use of constructs across studies and a lack of clarity about reporting exposure events. Multi-level approaches are needed to address the interplay of individual, social and structural barriers that diminish HCWs PEP use. Improved training, incident reporting, 24-hour access to non-stigmatizing PEP services and monitoring of adherence/completion are essential to optimizing HCWs PEP use. CONCLUSIONS: Lessons from HCWs experience in LMICs may inform understanding of PEP under-use among people in these settings with non-occupational exposures.

Reprint. Originally appeared in Perspectives on History, vol. 61, no. 8(November 2023).

BACKGROUND: Patients hospitalized with COVID-19 can clinically deteriorate after a period of initial stability, making optimal timing of discharge a clinical and operational challenge. OBJECTIVE: To determine risks for post-discharge readmission and death among patients hospitalized with COVID-19. DESIGN: Multicenter retrospective observational cohort study, 2020-2021, with 30-day follow-up. PARTICIPANTS: Adults admitted for care of COVID-19 respiratory disease between March 2, 2020, and February 11, 2021, to one of 180 US hospitals affiliated with the HCA Healthcare system. MAIN MEASURES: Readmission to or death at an HCA hospital within 30 days of discharge was assessed. The area under the receiver operating characteristic curve (AUC) was calculated using an internal validation set (33% of the HCA cohort), and external validation was performed using similar data from six academic centers associated with a hospital medicine research network (HOMERuN). KEY RESULTS: The final HCA cohort included 62,195 patients (mean age 61.9 years, 51.9% male), of whom 4704 (7.6%) were readmitted or died within 30 days of discharge. Independent risk factors for death or readmission included fever within 72 h of discharge; tachypnea, tachycardia, or lack of improvement in oxygen requirement in the last 24 h; lymphopenia or thrombocytopenia at the time of discharge; being ≤ 7 days since first positive test for SARS-CoV-2; HOSPITAL readmission risk score ≥ 5; and several comorbidities. Inpatient treatment with remdesivir or anticoagulation were associated with lower odds. The models AUC for the internal validation set was 0.73 (95% CI 0.71-0.74) and 0.66 (95% CI 0.64 to 0.67) for the external validation set. CONCLUSIONS: This large retrospective study identified several factors associated with post-discharge readmission or death in models which performed with good discrimination. Patients 7 or fewer days since test positivity and who demonstrate potentially reversible risk factors may benefit from delaying discharge until those risk factors resolve.

Inpatient pain management is challenging for clinicians and inequities are prevalent. We examined sex concordance between physicians and patients to determine if discordance was associated with disparate opioid prescribing on hospital discharge. We examined 15,339 hospitalizations from 2013 to 2021. Adjusting for patient, clinical, and hospitalization-level characteristics, we calculated the odds of a patient receiving an opioid on discharge and the days of opioids prescribed across all hospitalizations and for patients admitted with a common pain diagnosis. We did not find an overall association between physician-patient sex concordance and discharge opioid prescriptions. Compared to concordant sex pairs, patients in discordant pairs were not significantly less likely to receive an opioid prescription (odds ratio: 1.04; 95% confidence interval [CI]: 0.95, 1.15) and did not receive significantly fewer days of opioids (2.1 fewer days of opioids; 95% CI: -4.4, 0.4). Better understanding relationships between physician and patient characteristics is essential to achieve more equitable prescribing.

BACKGROUND: The field of toxicology has witnessed substantial advancements in recent years, particularly with the adoption of new approach methodologies (NAMs) to understand and predict chemical toxicity. Class-based methods such as clustering and classification are key to NAMs development and application, aiding the understanding of hazard and risk concerns associated with groups of chemicals without additional laboratory work. Advances in computational chemistry, data generation and availability, and machine learning algorithms represent important opportunities for continued improvement of these techniques to optimize their utility for specific regulatory and research purposes. However, due to their intricacy, deep understanding and careful selection are imperative to align the adequate methods with their intended applications. OBJECTIVES: This commentary aims to deepen the understanding of class-based approaches by elucidating the pivotal role of chemical similarity (structural and biological) in clustering and classification approaches (CCAs). It addresses the dichotomy between general end point-agnostic similarity, often entailing unsupervised analysis, and end point-specific similarity necessitating supervised learning. The goal is to highlight the nuances of these approaches, their applications, and common misuses. DISCUSSION: Understanding similarity is pivotal in toxicological research involving CCAs. The effectiveness of these approaches depends on the right definition and measure of similarity, which varies based on context and objectives of the study. This choice is influenced by how chemical structures are represented and the respective labels indicating biological activity, if applicable. The distinction between unsupervised clustering and supervised classification methods is vital, requiring the use of end point-agnostic vs. end point-specific similarity definition. Separate use or combination of these methods requires careful consideration to prevent bias and ensure relevance for the goal of the study. Unsupervised methods use end pointagnostic similarity measures to uncover general structural patterns and relationships, aiding hypothesis generation and facilitating exploration of datasets without the need for predefined labels or explicit guidance. Conversely, supervised techniques demand end point-specific similarity to group chemicals into predefined classes or to train classification models, allowing accurate predictions for new chemicals. Misuse can arise when unsupervised methods are applied to end point-specific contexts, like analog selection in read-across, leading to erroneous conclusions. This commentary provides insights into the significance of similarity and its role in supervised classification and unsupervised clustering approaches. https://doi.org/10.1289/EHP14001, Introduction Chemical hazard and risk assessments aim to estimate toxicological outcomes and evaluate the potential risks that chemicals may pose to human health and the environment. However, studying chemicals one-by-one [...]

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Paraganglioma is derived from the paraganglia tissue in the neck, along the sympathetic trunk, and in the pelvis. Paraganglioma has malignant potential and can metastasize to remote organs such as the liver, lungs, and bones. Most metachronous metastases occur within several years after the initial diagnosis of paraganglioma. Here, we report the case of a 71-year-old male patient who developed bony metastasis 52 years after the resection of a large paraganglioma at the aortic bifurcation. The biopsy-proven paraganglioma metastasis to the lesser trochanter of left femur presented as an avulsion fracture. His normetanephrine level was elevated. DOTATATE PET (positron emission tomography) did not find any other metastatic lesions. The bony metastasis was treated with radiation therapy. We believe that the patient had one of the longest gaps ever reported, 52 years, between the initial diagnosis and metastasis of paraganglioma. This case highlights the importance of long-term surveillance of patients with paraganglioma for metastasis.

Introduction: Image guided radiotherapy allows for particularly conformal tumour irradiation through precise patient positioning. Becoming the standard for radiotherapy, this increases imaging doses to the patient. The Halcyon 3.0 linear accelerator (Varian Medical Systems, Palo Alto, CA) requires daily imaging due to its geometry. For this reason, the accelerator is equipped with on-line kV and MV imaging. However, daily CBCT images required for irradiation apply additional radiation, which increases the dose to normal tissue and therefore can affect the patient's secondary cancer risk. In this study, actual organ doses were measured for the kV system, and a comparison of normal tissue doses for all available kV CBCT protocols was presented to demonstrate differences in imaging doses across entities and protocols. In addition, effective dose and secondary cancer risk from imaging are evaluated. Material and methods: Measurements were performed with thermoluminescent dosimeters in an anthropomorphic phantom positioned according to each entity (brain, head and neck, breast, lung, pelvis). CBCT images were obtained, using all available pre-set protocols without further adjustment of the parameters. Measured doses for each position and each protocol were then compared and secondary cancer risk of relevant and specifically radiosensitive organs was calculated. Results: It was found that imaging doses for protocols such as Pelvis and Head could be reduced by up to half using the corresponding Fast and Low Dose modes, respectively. On the other hand, larger field sizes or the Large mode yielded higher doses than their initial protocols. Image Gently was found to spare normal tissue best, however it is not suitable for certain entities due to low image quality or insufficient projection data. Discussion: By using appropriate kV-CBCT protocols, it is possible to reduce imaging doses to a significant extent and therefore spare healthy tissue. Combined with studies of image quality, the results of this study could lead to adjustments in workflow regarding the choice of protocols used in daily routine. This could prevent unnecessary radiation exposure and reduce secondary cancer risk.

BACKGROUND: Prescribing non-opioid pain medications, such as non-steroidal anti-inflammatory (NSAIDs) medications, has been shown to reduce pain and decrease opioid use, but it is unclear how to effectively encourage multimodal pain medication prescribing for hospitalised patients. Therefore, the aim of this study is to evaluate the effect of prechecking non-opioid pain medication orders on clinician prescribing of NSAIDs among hospitalised adults. METHODS: This was a cluster randomised controlled trial of adult (≥18 years) hospitalised patients admitted to three hospital sites under one quaternary hospital system in the USA from 2 March 2022 to 3 March 2023. A multimodal pain order panel was embedded in the admission order set, with NSAIDs prechecked in the intervention group. The intervention group could uncheck the NSAID order. The control group had access to the same NSAID order. The primary outcome was an increase in NSAID ordering. Secondary outcomes include NSAID administration, inpatient pain scores and opioid use and prescribing and relevant clinical harms including acute kidney injury, new gastrointestinal bleed and in-hospital death. RESULTS: Overall, 1049 clinicians were randomised. The study included 6239 patients for a total of 9595 encounters. Both NSAID ordering (36 vs 43%, p

BACKGROUND: Few hospitals have built surveillance for diagnostic errors into usual care or used comparative quantitative and qualitative data to understand their diagnostic processes and implement interventions designed to reduce these errors. OBJECTIVES: To build surveillance for diagnostic errors into usual care, benchmark diagnostic performance across sites, pilot test interventions, and evaluate the programs impact on diagnostic error rates. METHODS AND ANALYSIS: Achieving diagnostic excellence through prevention and teamwork (ADEPT) is a multicenter, real-world quality and safety program utilizing interrupted time-series techniques to evaluate outcomes. Study subjects will be a randomly sampled population of medical patients hospitalized at 16 US hospitals who died, were transferred to intensive care, or had a rapid response during the hospitalization. Surveillance for diagnostic errors will occur on 10 events per month per site using a previously established two-person adjudication process. Concurrent reviews of patients who had a qualifying event in the previous week will allow for surveys of clinicians to better understand contributors to diagnostic error, or conversely, examples of diagnostic excellence, which cannot be gleaned from medical record review alone. With guidance from national experts in quality and safety, sites will report and benchmark diagnostic error rates, share lessons regarding underlying causes, and design, implement, and pilot test interventions using both Safety I and Safety II approaches aimed at patients, providers, and health systems. Safety II approaches will focus on cases where diagnostic error did not occur, applying theories of how people and systems are able to succeed under varying conditions. The primary outcome will be the number of diagnostic errors per patient, using segmented multivariable regression to evaluate change in y-intercept and change in slope after initiation of the program. ETHICS AND DISSEMINATION: The study has been approved by the University of California, San Francisco Institutional Review Board (IRB), which is serving as the single IRB. Intervention toolkits and study findings will be disseminated through partners including Vizient, The Joint Commission, and Press-Ganey, and through national meetings, scientific journals, and publications aimed at the general public.

Abstract Background The World Health Organization (WHO) supports the use of Sugar-Sweetened Beverage Taxes (SSBTs) as a fiscal lever to help reduce sugar consumption and tackle obesity. Obesity is associated with a range of adverse health outcomes. In response to increasing levels of obesity in Ireland, an SSBT was introduced in 2018. Previous research in Ireland has noted that the pass-through rate of the SSBT in retail (off-site consumption) settings was poor. However, to date, no research has examined the SSBT pass-through rate in hospitality (on-site consumption) venues in Ireland. Methods This research examines the SSBT pass-through rate on Coca-Cola versus diet versions of Coca-Cola in a convenience sample of 100 hospitality venues in two provincial Irish cities. Results Wilcoxon signed rank test analysis revealed that regular Coca-Cola was significantly more expensive compared to the price charged for diet versions of Coca-Cola. However, in 85.6% of cases the same price was charged for both full-sugar and sugar-free drinks. The mean pass-through rate of the SSBT was 33.8%. Conclusion The effective functioning of the SSBT is premised on persistent price differences between soft drink prices based on sugar content. However, this is barely evident in the hospitality sector in Ireland. A number of recommendations are suggested, including both increasing the SSBT, and increasing it annually in line with inflation.

Abstract This article describes primary data and resources available from the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, a novel arm of the Human Connectome Project (HCP). Data were collected from 215 adolescents (14–17 years old), 152 of whom had current diagnoses of anxiety and/or depressive disorders at study intake. Data include cross-sectional structural (T1- and T2-weighted), functional (resting state and three tasks), and diffusion-weighted magnetic resonance images. Both unprocessed and HCP minimally-preprocessed imaging data are available within the data release packages. Adolescent and parent clinical interview data, as well as cognitive and neuropsychological data are also included within these packages. Release packages additionally provide data collected from self-report measures assessing key features of adolescent psychopathology, including: anxious and depressive symptom dimensions, behavioral inhibition/activation, exposure to stressful life events, and risk behaviors. Finally, the release packages include 6- and 12-month longitudinal data acquired from clinical measures. Data are publicly accessible through the National Institute of Mental Health Data Archive (ID: #2505).

OBJECTIVE: We used machine learning to identify the highest impact components of emergency department (ED) pediatric readiness for predicting in-hospital survival among children cared for in US trauma centers. BACKGROUND: ED pediatric readiness is associated with improved short-term and long-term survival among injured children and part of the national verification criteria for US trauma centers. However, the components of ED pediatric readiness most predictive of survival are unknown. METHODS: This was a retrospective cohort study of injured children below 18 years treated in 458 trauma centers from January 1, 2012, through December 31, 2017, matched to the 2013 National ED Pediatric Readiness Assessment and the American Hospital Association survey. We used machine learning to analyze 265 potential predictors of survival, including 152 ED readiness variables, 29 patient variables, and 84 ED-level and hospital-level variables. The primary outcome was in-hospital survival. RESULTS: There were 274,756 injured children, including 4585 (1.7%) who died. Nine ED pediatric readiness components were associated with the greatest increase in survival: policy for mental health care (+8.8% change in survival), policy for patient assessment (+7.5%), specific respiratory equipment (+7.2%), policy for reduced-dose radiation imaging (+7.0%), physician competency evaluations (+4.9%), recording weight in kilograms (+3.2%), life support courses for nursing (+1.0%-2.5%), and policy on pediatric triage (+2.5%). There was a 268% improvement in survival when the 5 highest impact components were present. CONCLUSIONS: ED pediatric readiness components related to specific policies, personnel, and equipment were the strongest predictors of pediatric survival and worked synergistically when combined.

BackgroundCisgender women represent over half of people living with HIV globally. However, current research efforts toward a cure for HIV focus predominantly on cisgender men. The under-representation of women in HIV cure clinical studies is particularly problematic given data suggesting that sex-dependent phenotypes limit scientific discovery.ObjectiveWe aimed to generate considerations to increase the meaningful involvement of women in HIV cure-related research.Materials and methodsWe conducted in-depth interviews with biomedical researchers and community members to better understand factors that could increase the meaningful involvement of women in HIV cure clinical trials. Participants were affiliated with academia, industry, community advisory boards, and community-based organizations, and were identified using listings from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories. We used conventional content analysis to analyze the qualitative data.ResultsWe recruited 27 participants, of whom 11 were biomedical researchers and 16 were community members. Participants included 25 cisgender women, 1 transgender woman, and 1 cisgender man. Key considerations emerged, including the need to ensure that HIV cure studies reflect HIV epidemiologic trends and having accurate representation by sex and gender in HIV cure research. To increase the meaningful involvement of women, recommendations included instituting intentional enrollment goals, frequent and mandatory reporting on enrollment, and incentives for sites to enroll women. Additional themes included the need for agency and self-determination, attention to lived experiences, trauma and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and physical). Participants noted that women would be willing to participate in HIV cure trials, related procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women-centered and holistic clinical trial designs that account for intersectionality.ConclusionsOur empirical inquiry extends recent calls to action to increase diversity of people involved in HIV cure research. Redressing the under-inclusion of women in HIV cure research is an urgent imperative. The entire field must mobilize and reform to achieve this goal. Meaningfully involving women across the gender spectrum in HIV cure research is needed to ensure that interventions are safe, effective, scalable, and acceptable for all people with HIV.

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce pain and has become a core strategy to decrease opioid use, but there is a lack of data to describe encouraging use when admitting patients using electronic health record systems. OBJECTIVE: Assess an electronic health record system to increase ordering of NSAIDs for hospitalized adults. DESIGNS, SETTINGS AND PARTICIPANTS: We performed a cluster randomized controlled trial of clinicians admitting adult patients to a health system over a 9-month period. Clinicians were randomized to use a standard admission order set. INTERVENTION: Clinicians in the intervention arm were required to actively order or decline NSAIDs; the control arm was shown the same order but without a required response. MAIN OUTCOME AND MEASURES: The primary outcome was NSAIDs ordered and administered by the first full hospital day. Secondary outcomes included pain scores and opioid prescribing. RESULTS: A total of 20,085 hospitalizations were included. Among these hospitalizations, patients had a mean age of 58 years, and a Charlson comorbidity score of 2.97, while 50% and 56% were female and White, respectively. Overall, 52% were admitted by a clinician randomized to the intervention arm. NSAIDs were ordered in 2267 (22%) interventions and 2093 (22%) control admissions (p = .10). Similarly, there were no statistical differences in NSAID administration, pain scores, or opioid prescribing. Average pain scores (0-5 scale) were 3.36 in the control group and 3.39 in the intervention group (p = .46). There were no differences in clinical harms. CONCLUSIONS AND RELEVANCE: Requiring an active decision to order an NSAID at admission had no demonstrable impact on NSAID ordering. Multicomponent interventions, perhaps with stronger decision support, may be necessary to encourage NSAID ordering.

Most HIV cure studies remain in the early stage of investigation and may carry clinical risks to the participants and, in some cases, their partners. Surprisingly little sociobehavioral research has investigated the perceptions of couples-including HIV serodifferent couples-around HIV cure research, including factors that would influence recruitment and retention in trials. We conducted a qualitative study to explore perceptions of diverse HIV serodifferent partners in the United States. We recruited 10 diverse HIV serodifferent couples (20 participants). We found participants had learned to cope with the reality of HIV, including protections during sex, and ascribed both positive and negative meanings to an HIV cure. Partners expressed concern about each other's health and potentially caring for a sick partner and emphasized the importance of safety when participating in an HIV cure trial. They identified the need for partner protection measures during analytical treatment interruptions (ATIs) as an ethical imperative. Participants recounted experiences of HIV stigma due to being in HIV serodifferent relationships and viewed ATIs as leading to a detectable viral load, which could limit sexual expression, complicate disclosure decision making, and worsen HIV-related stigma. Our study's main contribution is to inform efforts to meaningfully engage diverse HIV serodifferent partners in HIV cure research in the United States. Our data suggest people with HIV make decisions to participate in research based on close ones in their life and underscore the critical importance of acknowledging relationship dynamics in decisions to participate in research.

Nearly half of new HIV cases in the United States are among youth. Little is known about the willingness of young adults living with HIV (YLWH) to participate in HIV cure-related research. In 2021, we recruited 271 YLWH aged 18-29 for an online survey. We asked questions about willingness to participate in HIV cure research, perceived risks and benefits, acceptable trade-offs, and perceptions on analytical treatment interruptions. We conducted descriptive analyses to summarize data and bivariate analyses to explore correlations by demographics. Most respondents (mean age = 26) identified as men (86%) and Black Americans (69%). YLWH expressed high willingness to consider participating in cell- and gene-based approaches (75%) and immune-based approaches (71%). Approximately 45% would be willing to let their viral load become detectable for a period of time during an HIV cure study, 27% would not be willing, and 28% did not know. The social risk most likely to deter participation was the possibility of transmitting HIV to sex partners while off HIV medications (65% of respondents would be deterred a great deal or a lot). Compared to the 25-29 age group (n = 192), the 18-24 age group (n = 79) was more likely to indicate that having to disclose HIV status would matter a great deal in considering participation in HIV cure research (38% vs. 21%, p = .003). Inclusion and engagement of YLWH are critical for advancing novel HIV curative agents. Our article concludes with possible considerations for engaging YLWH in HIV cure research. Physical, clinical, and social risks will need to be kept to a minimum, and research teams will need to proactively mitigate the possibility of transmitting HIV to sex partners while off HIV medications.