Virtual Support for Bereaved Parents: Acceptability, Feasibility, and Preliminary Efficacy of HOPE Group

Background Bereaved parents demonstrate increased risk for long-term psychological problems and poorer overall quality of life. Bereavement support programs can promote improved coping and are positively received by parents but remain underutilized. Virtual programs may help address barriers to accessing bereavement resources, such as families’ physical distance to the hospital and trauma reactions when exposed to a setting where the child received care. The objective of this quality improvement study is to examine caregivers’ bereavement experiences and perspectives on HOPE Group, a virtual group program for bereaved caregivers administered by the palliative care team at Nemours Children\u27s Hospital, Delaware

A Method for Setting Northern Bobwhite Population and Habitat Objectives for Large Landscape Partnerships

Population and habitat objectives are the foundation for many conservation actions. Often objectives set at one scale are difficult to translate to larger or smaller scales. Three bird habitat Joint Ventures, Gulf Coast, Oaks & Prairies, and Rio Grande, working cooperatively with the Gulf Coast Prairie Landscape Conservation Cooperative, have a common objective to stabilize northern bobwhite (Colinus virginianus) populations in four Bird Conservation Regions. We cooperatively developed a method using the North American Breeding Bird Survey trend for several scenarios with different time horizons (10-, 20-, 30-year, or longer), the spring home range size, and the per acre cost of habitat management actions, to set spring population and habitat objectives and projected costs. The spring population objectives can easily be converted to fall population objectives using the percent summer gain. We provide an example of how three Joint Ventures could use this methodology to set bobwhite objectives within their geographies and then scale those objectives up to the next larger geography, a Landscape Conservation Cooperative geography. This methodology can be used by other multi-state partnerships (e.g., Joint Ventures and Landscape Conservation Cooperatives) across the bobwhite range to provide the bobwhite conservation community meaningful objectives at regional and national scales

High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Improved Prognostic Stratification With the New World Health Organization 2019 Classification A Validation Study From a Single-Institution Retrospective Analysis

Objectives: There is a pressing need to develop clinical management pathways for grade 3 (G3) gastroenteropancreatic neuroendocrine neoplasms (GEP NEN). Methods: We performed a retrospective study on patients with metastatic G3 GEP NEN. The relationship between baseline characteristics and progression-free survival and overall survival was analyzed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Results: We included 142 patients (74 well-differentiated neuroendocrine tumors [WDNETs], 68 poorly differentiated neuroendocrine carcinomas [PDNECs]). Patients with WDNET had prolonged survival compared with PDNEC (median, 24 vs 15 months, P = 0.0001), which persisted in both pancreatic and nonpancreatic cohorts. Well-differentiated morphology, Ki-67 <50% and positive somatostatin receptor imaging were independently associated with prolonged survival. Of the subgroup treated with first-line platinum-based chemotherapy, response rates were favorable (partial response, 47%; stable disease, 30%); there was no significant difference in response rates nor progression-free survival between WDNET and PDNEC despite significantly prolonged overall survival in the WDNET cohort. Conclusions: Our study corroborates the knowledge of 2 prognostically distinct subgroups within the World Health Organization 2019 G3 GEP NEN population, observed in both pancreatic and nonpancreatic gastrointestinal cohorts. Definitive management pathways are needed to reflect the differences between G3 WDNET and PDNEC

Predicting selection for antimicrobial resistance in UK wastewater and aquatic environments: ciprofloxacin poses a significant risk

Antimicrobial resistance (AMR) is a threat to human and animal health, with the environment increasingly recognised as playing an important role in AMR evolution, dissemination, and transmission. Antibiotics can select for AMR at very low concentrations, similar to those in the environment, yet their release into the environment, e.g., from wastewater treatment plants, is not currently regulated. Understanding the selection risk antibiotics pose in wastewater and receiving waters is key to understanding if environmental regulation of antibiotics is required. We investigated the risk of selection occurring in UK wastewater and receiving waters by determining where measured environmental concentration data (n = 8187) for four antibiotics (ciprofloxacin, azithromycin, clarithromycin, and erythromycin) collected in England and Wales 2015–2018 (sites n = 67) exceeded selective concentration thresholds derived from complex microbial community evolution experiments undertaken previously. We show that selection for AMR by ciprofloxacin is likely to have occurred routinely in England and Wales wastewater during the 2015–2018 period, with some seasonal and regional trends. Wastewater treatment reduces the selection risk posed by ciprofloxacin significantly, but not completely, and predicted risk in surface waters remains high in several cases. Conversely, the potential risks posed by the macrolides (azithromycin, clarithromycin, and erythromycin) were lower than those posed by ciprofloxacin. Our data demonstrate further action is needed to prevent selection for AMR in wastewater, with environmental quality standards for some antibiotics required in the future, and that selection risk is not solely a concern in low/middle income countries

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Burnout in frontline ambulance workers

This thesis focusses on the issue of burnout in frontline ambulance workers. The first chapter presents a systematic review of quantitative research conducted with frontline ambulance workers, using the Maslach Burnout Inventory to identify the prevalence of burnout and factors associated with it. Fifteen papers were included in the review. A wide range of factors were identified and organised into five overarching concepts. Four of these were understood to be potential predictors of burnout: job demands, job resources, personal resources and individual factors. One factor group represented outcomes of burnout. The majority of studies used correlational analysis however, thus causality could not be asserted. Prevalence rates of burnout were estimated based on six of the studies included in the review, but could not be established definitively due to differences across studies in the use of the Maslach Burnout Inventory. The review raised further questions about the methodology typically used to assess burnout in ambulance workers. Chapter two presents a quantitative research study focused on the relationship between workplace violence, coping styles and burnout in frontline ambulance workers. Participants were recruited from four National Health Service Ambulance Trusts and their responses to questionnaire measures were compared. The findings revealed high levels of workplace violence and burnout symptomology. Dysfunctional coping styles mediated the relationship between workplace violence and both the emotional exhaustion and depersonalisation aspects of burnout. Findings were inconclusive regarding the utility of problem-focused and emotion-focused coping in the violence-burnout relationship. Results are discussed, and clinical and research implications are identified. The third chapter is the author’s reflective account of conducting this research. The reflection presents an evaluation of the author’s identity as both a researcher and clinician and the conflicts that arose during the research process. The relative strengths of different research methodologies are considered as part of this chapter

Osteoclast inhibitors to prevent bone metastases in men with high-risk, non-metastatic prostate cancer: A systematic review and meta-analysis

<div><p>Background</p><p>In advanced prostate cancer, osteoclast inhibitors prevent and palliate skeletal related events associated with bone metastases. However, it is uncertain whether they play a disease-modifying role earlier in the course of the disease.</p><p>Methods</p><p>Medline, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and ASCO conference proceedings were searched for randomized controlled trials that compared osteoclast inhibitors with placebo and/or standard of care (SOC) in patients with high-risk, non-metastatic prostate cancer. The primary outcome measure was incidence of new bone metastases; secondary outcomes included overall survival (OS), prostate cancer specific survival, mortality unrelated to prostate cancer, toxicity and health related quality of life outcomes. Results are presented as relative risk (RR) with 95% confidence intervals (CI).</p><p>Results</p><p>Six randomized controlled trials (5947 participants) were included, five evaluating bisphosphonates and one denosumab. Overall, there was no difference in incidence of bone metastases between participants treated with osteoclast inhibitors versus placebo/SOC (RR 1.09, 95%CI 0.84–1.41, p = 0.51) however significant heterogeneity was observed between studies. The denosumab trial was the largest and only positive trial amongst the included studies (RR 0.83, 95%CI 0.73–0.95, p = 0.007). No significant difference was observed in OS (RR 0.99 95% CI 0.89–1.10, p = 0.84) nor prostate cancer specific survival (RR 1.12 95%CI 0.93–1.36, p = 0.24). Most studies reported increased rates of osteonecrosis of the jaw (5% or less) and hypocalcemia (2% or less) with osteoclast inhibitors.</p><p>Conclusions</p><p>While there is limited evidence that bisphosphonates alter the natural history of high-risk, non-metastatic prostate cancer, denosumab delays onset of bone metastases in this patient population. Neither class of osteoclast inhibitor demonstrated an impact on survival outcomes. Future trials with better defined patient selection and a robust definition for high risk disease is critical.</p></div

Forest plot for incidence of new bone metastases.

<p>Abbreviations: ITAS, intermediate term androgen suppression; STAS, short term androgen suppression; ZA, zoledronic acid.</p

Forest plot for prostate cancer specific survival.

<p>Abbreviations: ITAS, intermediate term androgen suppression; STAS, short term androgen suppression; ZA, zoledronic acid.</p

Participant characteristics denoting metastasis risk.

<p>Participant characteristics denoting metastasis risk.</p