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Alterations in decision-making are considered core to anorexia nervosa (AN) phenomenology and may maintain illness through maladaptive choice behavior. This systematic review (n = 77) aimed to extend prior reviews beyond standard neuropsychological batteries by incorporating novel value-based choice tasks and computational methods. We organize findings across key factors, including: 1) illness state, 2) developmental stage, and 3) AN subtype, and highlight available neuroimaging findings. Differences in decision-making appear consistent during illness, including in weight-restored samples, but not in recovery and not in all domains. Differences are not consistently present in adolescence, although punishment sensitivity may be heightened; AN subtypes are not consistently distinguishable. Overall, decision-making varies by context and is influenced by reward/punishment processing, risk/uncertainty, and flexibility/control. Utilization of computational modeling methods, possibly increasing precision, highlight that, although raw behavior may not differ at recovery, latent decision-making processes appear impacted. Clinical interventions may benefit from consideration of context when working to shape choice behavior and from consideration of latent decision-making processes that influence how choices are made., Competing Interests: Declaration of Competing Interest We have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: In England, group B streptococci (GBS; Streptococcus agalactiae) are considered universally susceptible to penicillin. Reports from Africa, Asia, North America and a few European countries have described GBS isolates with penicillin MICs above the epidemiological cut-off (0.125 mg/L). Our aim was to characterize a penicillin-resistant GBS (PRGBS) isolate recovered in 2016 from a patient treated with long-term antimicrobials in the UK., Methods: Antibiotic susceptibility of a referred isolate from a discharging sinus overlying a chronic prosthetic joint infection was determined using gradient strip testing for seven antibiotics. Illumina short read sequencing was carried out using a HiSeq 2500 platform to determine MLST, capsular type, to detect mutations in the pbp genes, and to compare the isolate with contemporaneous GBS isolates circulating in the UK., Results: The GBS isolate belonged to capsular type Ia and MLST 144. We observed resistance to penicillin (MIC = 1 mg/L) and tetracycline (32 mg/L) with susceptibility to linezolid (1 mg/L), erythromycin (0.064 mg/L), clindamycin (0.064 mg/L), teicoplanin (0.064 mg/L) and vancomycin (0.25 mg/L). Deduced amino acid sequences revealed substitutions and non-synonymous changes in PBP2x and PBP2b. Genomic analysis of contemporaneous cases (n = 34) from across the UK identified single nucleotide polymorphism (SNP) variation ranged from 153-6596 SNPs., Conclusions: We confirm the first identification of a PRGBS isolate amongst referrals to the UK's national reference laboratory. Substitutions in pbp1a, pbp2a, pbp2x and pbp2b were identified that likely developed in the face of long-term beta-lactam antibiotic use., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objective: To describe an ultrasound-guided suprazygomatic approach to the trigeminal nerve block in cat cadavers., Study Design: Prospective descriptive study., Animals: Ten feline cadaver heads., Methods: A 25:75 methylene blue-iopamidol mixture (0.1 mL cm -1 cranium length) was injected into 10 cadaver heads using an ultrasound-guided suprazygomatic approach. A computed tomography (CT) scan was performed to identify contrast presence at the orbital fissure, foramen rotundum and ovale, followed by anatomical dissection to identify staining of the pterygopalatine fossa (PPF), extraconal retrobulbar area, mandibular and maxillary nerves. Descriptive statistics were used to summarize results., Results: A total of 20 injections were performed. Of these, 1/20 misinjection occurred and excluded from further reporting. The volume of injectate was 0.9 (0.9-1.1) mL [median (range)]. Staining of the PPF, extraconal space, maxillary and mandibular nerves over more than 6 mm was achieved in 19/19 (100%), 18/19 (95%), 17/19 (89%) and 19/19 (100%) of injections, respectively. CT showed presence of contrast within 5 mm of the orbital fissure, foramen rotundum and ovale in 18/19 (95%), 19/19 (100%) and 19/19 (100%) of the injections, respectively. No intracranial migration was observed., Conclusions and Clinical Relevance: This cadaver study illustrates that the suprazygomatic ultrasound-guided trigeminal nerve injection technique can successfully stain the PPF, retrobulbar cone extraconally, mandibular and maxillary nerves. Consequently, this technique has the potential to be used in vivo in cats to desensitize areas innervated by the trigeminal nerve., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: Bivalent original/BA.4-5 and monovalent XBB.1.5 mRNA boosters were offered to UK healthcare workers (HCWs) in the autumn of 2023. We aimed to estimate booster vaccine effectiveness (VE) and post-infection immunity among the SIREN HCW cohort over the subsequent 6-month period of XBB.1.5 and JN.1 variant circulation., Methods: Between October 2023 to March 2024, 2867 SIREN study participants tested fortnightly for SARS-CoV-2 and completed symptoms questionnaires. We used multi-state models, adjusted for vaccination, prior infection, and demographic covariates, to estimate protection against mild/asymptomatic and moderate SARS-CoV-2 infection., Results: Half of the participants (1422) received a booster during October 2023 (280 bivalent, 1142 monovalent), and 536 (19%) had a PCR-confirmed infection over the study period. Bivalent booster VE was 15.1% (-55.4 to 53.6%) at 0-2 months and 4.2% (-46.4 to 37.3%) at 2-4 months post-vaccination. Monovalent booster VE was 44.2% (95% CI 21.7 to 60.3%) at 0-2 months, and 24.1% (-0.7 to 42.9%) at 2-4 months. VE was greater against moderate infection than against mild/asymptomatic infection, but neither booster showed evidence of protection after 4 months. Controlling for vaccination, compared to an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection., Conclusions: Monovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations that target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among HCWs., Competing Interests: Declaration of Competing Interest All authors have completed the ICJME uniform disclosure form at: https://www.icmje.org/disclosure-of-interest/ and declare: CSB and SH report grant funding from the NIHR HPRU; CSB reports participation in an ad-hoc one-off market research advisory on a variety of infection topics; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Ketamine is increasingly being utilized in the management of acute pain in the emergency department (ED), including for older adults, a population at increased risk of adverse effects from medications. We aimed to compare the safety and analgesic effects of high-dose (≥0.3mg/kg) to low-dose (<0.3mg/kg) intravenous (IV) ketamine among older ED patients., Methods: Multi-center, retrospective cohort study of adults ≥60years who received IV ketamine for pain between 2018 and 2021. The primary outcome was pain improvement as measured by the Numerical Rating Scale (NRS) pain score within 60min after administration. Secondary outcomes included adverse effects (early discontinuation, nausea, rescue benzodiazepines and intubation) and the need for rescue analgesia. Linear regression was used to assess the association between the change in NRS pain scores and dose after adjusting for baseline pain, requiring an additional dose of ketamine, and receiving an opioid., Results: A total of 130 older adults received ketamine as an analgesic (37 high-dose, 93 low-dose). Median age was 69.2years, 52 % were women, 40 % had a history of substance use disorder. Prior to ketamine, 76 % received alternate analgesics and 23 % antiemetics. Baseline mean pain score was lower in the high-dose group (6.7 vs. 8.3, difference -1.7 [95 % CI -2.6 to -0.7], p = 0.013). Change in NRS pain scores were similar between the high-dose and low-dose groups (-2.4 [95 % CI -3.6 to -1.3] vs -1.6 [95 % CI -2.2 to -0.9], p = 0.27). After adjustment for baseline pain score, the high-dose group had a larger reduction in pain scores (-1.3 [95 % CI -2.6 to -0.1], p = 0.042) and percent change of pain (-23.8 % [95 % CI -42.1 % to -5.4 %], p = 0.012). There was no significant difference in rates of rescue analgesia (35.1 % vs. 44.1 %, p = 0.35) or early discontinuation (29.7 % vs. 32.3 %, p = 0.78). Rates of adverse effects were similar., Conclusion: High-dose and low-dose ketamine reduced pain scores in older adults. High-dose ketamine led to a greater reduction in pain scores, and there was no observed difference in adverse effects or the need for rescue analgesia. One-third needed discontinuation of ketamine in both groups., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Propofol is one of the first-line sedative-hypnotic agents for critically ill adults requiring mechanical ventilation. While propofol can elevate triglyceride levels, and the latter is a risk factor for pancreatitis, the association between propofol and acute pancreatitis is unclear., Objectives: To determine the clinical impact and potential associations between propofol infusion, hypertriglyceridemia and acute pancreatitis., Methods: This is an observational multicenter study of adults (≥18 years old) admitted to an intensive care unit. requiring mechanical ventilation and receiving continuous propofol infusion for at least 24 hours. The primary outcomes were the frequency of hypertriglyceridemia and acute pancreatitis. Further analyses were done to determine the clinical impact of elevated triglyceride levels (i.e. sedation changes) and risk factors for pancreatitis development., Measurements and Main Results: Of 11,828 patients included, 33.2% (N=3922) had triglyceride levels measured, of whom 21.7% (N=851) had hypertriglyceridemia at 4.5 (SD 6.8) days after propofol initiation. Of those still requiring sedation, 70.4% (N=576/818) received alternative sedatives following hypertriglyceridemia. Pancreatitis occurred in 1.2% (N=47/3922) and was more frequent in those with hypertriglyceridemia (3.2%, 27/851 versus 0.7%, 20/3071; P<0.001). Following adjustment for potential confounding variables, each 100 mg/dL increase in triglyceride levels was associated with an 11% increase in risk of pancreatitis. Propofol dose was not associated with pancreatitis development., Conclusions: Acute pancreatitis is uncommon in patients receiving propofol infusion, and occurs over a wide range of triglyceride levels, indicating a multifactorial pathophysiology. Hypertriglyceridemia frequently prompts the use of alternative sedatives. Further study is needed to determine how to best monitor and treat hypertriglyceridemia in critically ill patients receiving propofol infusion.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no conflicts of interest to declare. Provenance and peer review: Commissioned; externally peer reviewed.

Objective: Transgender and gender-diverse (TGD) individuals have a gender identity or expression that differs from the sex assigned to them at birth. They are an underserved population who experience health care inequities. Our primary objective was to identify if there are treatment differences between TGD and cisgender lesbian/gay/bisexual/queer (LGBQ) or heterosexual individuals presenting with abdominal pain to the emergency department (ED)., Methods: Retrospective observational cohort study of patients ≥12 years of age presenting to 21 EDs within a health care system with a chief complaint of abdominal pain between 2018 and 2022. TGD patients were matched 1:1:1:1 to cisgender LGBQ women and men and cisgender heterosexual women and men, respectively. Propensity score matching covariates included age, ED site, mental health history, and gastrointestinal history. The primary outcome was pain assessment within 60 min of arrival. The secondary outcome was analgesics administered in the ED., Results: We identified 300 TGD patients, of whom 300 TGD patients were successfully matched for a total cohort of 1300 patients. The median (IQR) age was 25 (20-32) years and most patients were treated in a community ED (58.2%). There was no difference between groups in pain assessment within 60 min of arrival (59.0% TGD vs. 63.2% non TGD, p = 0.19). There were no differences in the number of times pain was assessed (median [IQR] 2 [1-3] vs. 2 [1-4], p = 0.31) or the severity of pain between groups (5.5 [4-7] vs. 6 [4-7], p = 0.11). TGD patients were more likely to receive nonsteroidal anti-inflammatory drugs (32.0% vs. 24.9%, p = 0.015) and less likely to receive opioids than non-TGD patients (24.7% vs. 36.9%, p = <0.001). TGD and nonbinary patients, along with LGBQ cisgender women (24.7%) and heterosexual cisgender women (34%), were less likely to receive opioids than LGBQ cisgender men (54%) and heterosexual cisgender men (42.3%, p < 0.01)., Conclusion: There was no difference in frequency of pain assessment, regardless of gender identity or sexual orientation. More cisgender men, compared to TGD and cisgender women, received opioids for their pain., (© 2024 Society for Academic Emergency Medicine.)

Introduction: Following SARS-CoV-2 infection, some patients experience a range of long-lasting symptoms, with a specific burden on their lives and ability to work., Aim: We describe the prevalence and impact of persistent symptoms pre-/post-vaccination in SIREN study participants., Methods: A cross-sectional study of SARS-CoV-2 positive participants was carried out within SIREN, a frequently tested UK healthcare worker cohort with vaccination and demographic data available. Participants with a SARS-CoV-2 positive PCR or anti-SARS-CoV-2 sample between 01 March 2020 and 31 September 2022 were asked via a questionnaire about symptoms and days absent from work following infection. Responses were excluded if infection dates were inconsistent with study records or missing key data. Symptom type/duration and whether infection occurred pre-/post-vaccination and during which variant period were described. Logistic regression was used to estimate factors associated with persistent symptoms (>12 weeks), adjusting for vaccination and demographic factors. The median days absent from work were also determined., Results: Of 16,599 invitations, 6677 participants responded, and 5053 were included in the analysis. The prevalence of persistent symptoms (symptoms lasting over 12 weeks) differed by infection episode; highest for first infections (32.7%; 1557/4767) compared to second (21.6%; 214/991) and third infections (21.6%; 16/74). Most frequently reported symptoms were fatigue, tiredness, shortness of breath and difficulty concentrating. A higher prevalence of persistent symptoms was reported during the Wild-type variant period compared to the other variant periods (52.9% Wild-type vs. 20.7% Omicron, for any symptom reported during their first infection). Overall, persistent symptoms were higher among unvaccinated participants (unvaccinated 38.1% vs vaccinated 22.0%). Multivariable analysis showed that participants were less likely to report persistent symptoms in infections occurring after vaccination compared to those with an infection before vaccination in the Alpha/Delta and Omicron periods (Alpha/Delta: adjusted Odds Ratio (aOR) 0.66, CI 95% 0.51-0.87, p = aOR 0.07, CI 95% 0.01-0.65, p = 0.02). About half of participants reported that their persistent symptoms impacted their day-to-day (51.8%) and work-related (42.1%) activities 'a little', and 24.0% and 14.4% reported that the impact was 'A lot'. 8.9% reported they had reduced their working hours, and 13.9% had changed their working pattern., Discussion: Persistent symptoms were frequent in our cohort, and there was a reduction in symptom duration in those with multiple infection episodes during later variant periods and post-vaccination. The impact of persistent symptoms resulting in reducing working hours or adjusting working patterns has important implications for workforce resilience. UK healthcare workers were highly exposed during the pandemic, demonstrating a significant burden., 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., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Local adaptation may facilitate range expansion during invasions, but the mechanisms promoting destructive invasions remain unclear. Cheatgrass ( Bromus tectorum ), native to Eurasia and Africa, has invaded globally, with particularly severe impacts in western North America. We sequenced 307 genotypes and conducted controlled experiments. We found that diverse lineages invaded North America, where long-distance gene flow is common. Ancestry and phenotypic clines in the native range predicted those in the invaded range, indicating pre-adapted genotypes colonized different regions. Common gardens showed directional selection on flowering time that reversed between warm and cold sites, potentially maintaining clines. In the Great Basin, genomic predictions of strong local adaptation identified sites where cheatgrass is most dominant. Preventing new introductions that may fuel adaptation is critical for managing ongoing invasions., Competing Interests: Competing interests: Authors declare that they have no competing interests.

Purpose: This study evaluated the impact of obesity on cardiometabolic risk factors (CRF) interrelationships and predictive efficiency of CVD development in older African (AA) and European Americans (EA)., Design: A comparative research design evaluated CRF risk profile differences between participant groups., Setting: Seven neighborhoods in a southern US city., Subjects: A sample of 179 older AA (n = 128) and EA (n = 51) adults., Measures: Non-fasting blood samples were evaluated for lipids and lipoproteins, glycosylated hemoglobin, systolic -(SBP) and diastolic blood pressure (DBP), body mass index (BMI), body fat percentage (BF%) and physical function., Analysis: Data were analysis with descriptive statistics, t-tests, and correlations., Results: AA were heavier than EA although all had above average age-appropriate fitness. Means and relationships between CRF and other variables were different ( P < .05) based on race. Both AA (41.3 + 5.8) and EA (38.6 + 6.4) BF% were CRF risks. Holding BMI constant, CRF were generally not related, and the relationships were different for AA and EA. AA had a range of 13.0 to 27.2% more favorable values for cholesterol, HDL-C, and triglyceride. EA had favorable A1c (EA 5.8 vs AA 6.2%) values., Conclusions: A limitation of this report is the small sample size. Although further research is warranted, these findings suggest population specific CRF selections would improve CVD prediction in AA., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Outcomes after pediatric liver transplantation are generally excellent, but the limited avavailability of suitable, size-matched liver allografts remains a significant barrier. Machine perfusion technology has emerged as a promising approach to expand the donor pool, enabling the use of less ideal whole liver grafts, such as livers donated after circulatory death, and enhancing the execution of split liver transplantation., Methods: This review examines the application of machine perfusion in pediatric liver transplantation, focusing on two primary techniques: hypothermic oxygentaed perfusion and normothermic machine perfusion. These methods optimize storage, resuscitation, and assessment of liver grafts before transplantation, potentially expanding the range of usable donor organs., Results: The use of machine perfusion allows for the consideration of suboptimal donor livers and facilitates split liver transplantation, both of which could increase organ availability for pediatric patients. Implementation of machine perfusion could also help reduce waiting list mortality by enabling the safe use of a broader spectrum of donor organs., Conclusions: Adoption of machine perfusion in pediatric liver transplantation will require collaborative, multidisciplinary efforts across transplant centers. By fostering cooperative learning and sharing resources. the integration of machine perfusion into clinical practice has the potential to reduce mortality among children awaiting liver transplantation., (© 2024 Wiley Periodicals LLC.)

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods : In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aimed to examine the associations between detailed maternal nativity (DMN) and two labor and delivery (L&D) characteristics among US-born, Latin American and Caribbean-born, and SSA-born Black women in the US. L&D characteristics included the place of delivery (i.e., hospital, birthing center, or home) and the method of delivery (i.e., vaginal or cesarean)., Methods: Using Natality data, the authors examined the associations between detailed maternal nativity (DMN) and two L&D characteristics among US-born, Latin American and Caribbean-born, and SSA-born Black women in the USA who had a live delivery between 2016 and 2020 (N = 2,041,880). The main predictor was DMN (i.e., maternal country of birth) and the outcomes of interest were the place of delivery and the method of delivery. Associations were evaluated using multivariate multinominal and multivariate logistic regression models., Results: Findings indicated that foreign-born Black women overall had decreased odds of delivering in birthing centers or at home, except for Ghanaian-born women who had increased odds of having an unintended home delivery. All Latin American and Caribbean-born and most SSA-born women had increased odds of delivering via cesarean., Conclusions: The findings underscore the importance of considering DMN in exploring L&D characteristics. Specifically, increased odds of cesarean delivery among Latin American and Caribbean-born women highlight a potential area for interventions. Further research is warranted to understand the underlying factors driving the observed differences and the diverse needs of the growing population of foreign-born Black women in the US, and to develop effective strategies to promote equitable and optimal birthing experiences for all., (© 2024. W. Montague Cobb-NMA Health Institute.)

Objectives: Inappropriate prescribing of antibiotics is a key driver of antimicrobial resistance. This study aimed to describe urine sampling rates and antibiotic prescribing for patients with lower urinary tract infections (UTIs) in English general practice., Design: A retrospective population-based study using administrative data., Setting: IQVIA Medical Research Database (IMRD) data from general practices in England, 2015-2022., Participants: Patients who have consulted with an uncomplicated UTI in England general practices captured in the IMRD., Outcome Measures: Trends in UTI episodes (episodes were defined as UTI diagnosis codes occurring within 14 days of each other), testing and antibiotic prescribing on the same day as initial UTI consultation were assessed from January 2015 to December 2022. Associations, using univariate and multivariate logistic regressions, were examined between consultation and demographic factors on the odds of a urine test., Results: There were 743 350 UTI episodes; 50.8% had a urine test. Testing rates fluctuated with an upward trend and large decline in 2020. Same-day UTI antibiotic prescribing occurred in 78.2% of episodes. In multivariate modelling, factors found to decrease odds of a urine test included age ≥85 years (0.83, 95% CI 0.82 to 0.84), consultation type (remote vs face to face, 0.45, 95% CI 0.45 to 0.46), episodes in London compared with the South (0.74, 95% CI 0.72 to 0.75) and increasing practice size (0.77, 95% CI 0.76 to 0.78). Odds of urine tests increased in males (OR 1.11, 95% CI 1.10 to 1.13), for those episodes without a same-day UTI antibiotic (1.10, 95% CI 1.04 to 1.16) for episodes for those with higher deprivation status (Indices of Multiple Deprivation 8 vs 1, 1.51, 95% CI 1.48 to 1.54). Compared with 2015, 2016-2019 saw increased odds of testing while 2020 and 2021 saw decreases, with 2022 showing increased odds., Conclusion: Urine testing for UTI in general practice in England showed an upward trend, with same-day antibiotic prescribing remaining consistent, suggesting greater alignment to national guidelines. The COVID-19 pandemic impacted testing rates, though as of 2022, they began to recover., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Since November 2023, the absolute number of attendances at emergency departments for pneumonia among children aged 5-14 years in England have been above expected levels for the time of year. This increased signal peaked during March 2024 but then persisted into early summer 2024 despite decreases in prevalence of seasonal respiratory pathogens. Record linkage between emergency department and laboratory databases points to this unusual activity being driven largely by Mycoplasma pneumoniae .

Purpose: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality., Methods: Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models., Results: 108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time., Conclusion: Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy., (© 2024. The Author(s).)

Competing Interests: Declaration of Competing Interest None of the authors declare a competing interest.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2023. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the collective group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 6 guidelines, and 5 meta-analyses covering topics including guideline releases and updates on rapid sequence intubation in the critically ill, managing cardiac arrest or life-threatening toxicity due to poisoning, and management of major bleeding following trauma. Also discussed are ongoing controversies surrounding fluid resuscitation, time and treatment modalities for ischemic stroke, steroid use in community-acquired pneumonia, targeted blood product administration, and much more., Competing Interests: Declaration of competing interest There are two authors who declare potential competing interests. Caitlin Brown has receiving funding from Alexion/Astra Zeneca and Brian Gilbert consults and has received speakers fees from Haemonetics. All other authors have nothing to disclose relevant to this article., (Copyright © 2024. Published by Elsevier Inc.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Rapid sequence intubation (RSI) is a common emergency department (ED) procedure with an associated complication of postintubation hypotension (PIH). It has not been clearly established whether the selection and dose of induction agent affect risk of PIH. The objective of this study was to determine the incidence of PIH in patients receiving full-dose compared to reduced-dose induction agent for RSI in the ED., Methods: This was a health system-wide, retrospective cohort study comparing incidence of PIH based on the induction medication and dose given for RSI in the ED. Patients were included if they underwent RSI from July 1, 2018, through December 31, 2020, were 18 years of age or older, and received etomidate or ketamine. A reduced dose was defined as a ketamine dose of 1.25 mg/kg or less and an etomidate dose of 0.2 mg/kg or less., Results: A total of 909 patients were included in the final analysis, with most receiving etomidate (n = 764; 84%) and a smaller number receiving ketamine (n = 145; 16%). Patients who received ketamine had a higher mean pre-intubation shock index (full dose, 1.08; reduced dose, 1.04) than those who received etomidate (full dose, 0.89; reduced dose, 0.92) (P ≤ 0.001). Reduced doses of induction agent were observed for 107 patients receiving etomidate (14.0%) and 60 patients receiving ketamine (41.4%). Patients who received full-dose ketamine for induction had the highest rate of PIH (n = 31; 36.5%), and the difference was statistically significant compared to patients receiving reduced-dose ketamine (16.7%; P = 0.021) and full-dose etomidate (22.8%; P = 0.010)., Conclusion: We observed that full-dose ketamine was associated with the highest rate of PIH; however, this group had the poorest baseline hemodynamics, confounding interpretation. Our results do not support broad use of a reduced-dose induction agent., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.

Background: People who inject drugs (PWID) are at increased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB), but little is known about clinical outcomes of CA-SAB in PWID compared with the wider population of patients with CA-SAB., Methods: Three national datasets were linked to provide clinical and mortality data on patients hospitalized with CA-SAB in England between 1 January 2017 and 31 December 2020. PWID were identified using the International Classification of Diseases, Tenth Revision code for "mental health and behavioral disorder due to opioid use" (F11). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for associations of PWID with 30-day all-cause mortality and 90-day hospital readmission., Results: In 10 045 cases of CA-SAB, 1612 (16.0%) were PWID. Overall, 796 (7.9%) patients died within 30 days of CA-SAB admission and 1189 (11.8%) patients were readmitted to hospital within 90 days of CA-SAB. In those without infective endocarditis, there was strong evidence of lower odds of mortality among PWID compared with non-PWID (aOR, 0.47 [95% confidence interval {CI}: .33-.68]; P < .001), whereas there was no association in CA-SAB case fatality with endocarditis (aOR, 1.40 [95% CI: .87-2.25]; P = .163). PWID were less likely to be readmitted within 90 days of CA-SAB (aOR, 0.79 [95% CI: .65-.95]; P = .011)., Conclusions: In this large cohort study of patients with CA-SAB in England, PWID had lower odds of death in the absence of endocarditis and lower odds of readmission within 90 days compared to non-PWID patients. This study highlights the overrepresentation of PWID among patients with CA-SAB nationally., Competing Interests: Potential conflicts of interest. All authors declare that they have no commercial or other association that might pose a conflict of interest. S. M. C. reports stock options in AstraZeneca. C. S. B reports ad hoc one-off market research advisory conducted anonymously via market research companies with no direct communication nor any knowledge of any pharmaceutical companies or products (one has related to S. aureus within the past 36 months, on avpre-surgical nasal S. aureus decolonization protocol). All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1 UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1 global strains, invasive M1 UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1 UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1 UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1 UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1 UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks., (© 2024. The Author(s).)

Background: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing., Objectives: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics., Methods: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy., Results: Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07-0.83)., Conclusions: In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens., Design: Multicenter retrospective observational study., Setting: Tertiary care hospital and 15 community and academic centers of a large healthcare system., Patients: Hospitalized patients with PE treated with systemic alteplase., Interventions: None., Measurements and Main Results: Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively ( p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting., Conclusions: In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications., Competing Interests: Dr. Tierney received funding from the American College of Physicians and the Society of Hospital Medicine. Dr. Brown received funding from Alexion, Astra Zeneca, and Trevena Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris . This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris . A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.

Introduction: Inconsistencies of reports contributes to the underreporting of Alzheimer's disease (AD) on death certificates. Whether underreporting exists within South Carolina has not been studied., Methods: We conducted a prospective, population-based study on a cohort of persons ( N  = 78,534) previously diagnosed with AD and died between 2014-2019. We linked vital records with the South Carolina Alzheimer's Disease and Related Dementias Registry to investigate their cause of death and survival rates. Descriptive analyses calculated frequencies of demographic and health-related characteristics. Turnbull's method estimated the survival probabilities for different subgroups of patients. Hazard ratios were computed from the Cox proportional hazards model, adjusting for the following confounding variables of age at diagnosis, education level, gender, and race., Results: The top immediate cause of death was Alzheimer's disease among all racial groups, except for Native American/American Indian. More females (60.3%) were affected by AD compared to males (39.7%). There is a 25% probability of survival, beyond 5 years, after AD diagnosis. Black/African American AD patients have the smallest risk of all-cause mortality across all racial/ethnic groups (HR 0.87; 95% CI, 0.85-0.89). Individuals with lower education had a lower likelihood of mortality., Conclusion: Although AD was not underreported in the state of South Carolina further research is needed to develop protocols around classification of deaths among those diagnosed with dementia and comorbidities, including cardiovascular disease, to ensure dementia is properly reported as we move to prevent and treat Alzheimer's disease by 2025 and beyond., Competing Interests: The 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 © 2024 Brown, Ning, Money, Alford, Pan, Miller and Lohman.)

Objective: To evaluate severe complications and mortality over years of independent practice among general surgeons., Background: Despite concerns that newly graduated general surgeons may be unprepared for independent practice, it is unclear whether patient outcomes differ between early and later career surgeons., Methods: We used Medicare claims for patients discharged between July 1, 2007 and December 31, 2019 to evaluate 30-day severe complications and mortality for 26 operations defined as core procedures by the American Board of Surgery. Generalized additive mixed models were used to assess the association between surgeon years in practice and 30-day outcomes while adjusting for differences in patient, hospital, and surgeon characteristics., Results: The cohort included 1,329,358 operations performed by 14,399 surgeons. In generalized mixed models, the relative risk (RR) of mortality was higher among surgeons in their first year of practice compared with surgeons in their 15th year of practice [5.5% (95% CI: 4.1%-7.3%) vs 4.7% (95% CI: 3.5%-6.3%), RR: 1.17 (95% CI: 1.11-1.22)]. Similarly, the RR of severe complications was higher among surgeons in their first year of practice compared with surgeons in their 15th year of practice [7.5% (95% CI: 6.6%-8.5%) versus 6.9% (95% CI: 6.1%-7.9%), RR: 1.08 (95% CI: 1.03-1.14)]. When stratified by individual operation, 21 operations had a significantly higher RR of mortality and all 26 operations had a significantly higher RR of severe complications in the first compared with the 15th year of practice., Conclusions: Among general surgeons performing common operations, rates of mortality and severe complications were higher among newly graduated surgeons compared with later career surgeons., Competing Interests: R.A.H. receives unrelated funding from the Blue Cross Blue Shield of Michigan Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK108740-05). A.E.T. receives unrelated funding from the Ruth L Kirschstein Institutional National Service Award administered by the National Institutes of Health. C.S.B. receives unrelated funding from the Ruth L. Kirschstein Postdoctoral Research Fellowship Award administered by the National Institute on Drug Abuse (F32-DA050416). A.M.R. receives unrelated funding from the NIH and AHRQ. B.M. receives funding from the NIH. J.B.D. receives grant funding from the NIH, AHRQ, Blue Cross Blue Shield of Michigan Foundation, and is a cofounder of ArborMetrix, Inc. B.C.G received funding for this work from the Agency for Healthcare Research and Quality (AHRQ; 5K08HS027653-02) and receives unrelated funding from the National Board of Medical Examiners (NBME) Edward J. Stemmler M.D. Medical Education Research Fund, the American Board of Medical Specialties, the American Board of Family Medicine, and the Accreditation Council for Graduate Medical Education (ACGME). The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate if pharmacological treatment with prednisone and L-N-acetylcysteine (STE + NAC) influence functional hearing preservation in cochlear implant (CI) surgery., Study Designs: Preimplantation and postimplantation longitudinal case-control study., Setting: Tertiary referral center., Patients: Pediatric and adult recipients of CI with preimplantation functional hearing defined as an average of air-conducted thresholds at 125, 250, and 500 Hz (low-frequency pure-tone average [LFPTA]) <80 dB., Interventions: Preimplantation and postimplantation audiometry. Weight-adjusted oral prednisone and L-N-acetylcysteine starting 2 days before surgery (Miami cocktail). Prednisone was continued for 3 days and L-N-acetylcysteine for 12 days after surgery, respectively. Cochlear implantation with conventional length electrodes., Main Outcome Measures: Proportion of patients with LFPTA <80 dB, and LFPTA change at 1-year postimplantation., Results: All 61 patients received intratympanic and intravenous dexamethasone intraoperatively, with 41 patients receiving STE + NAC and 20 patients not receiving STE + NAC. At 1-year postimplantation, the proportion of functional hearing preservation was 83% in the STE + NAC group compared with 55% of subjects who did not receive STE + NAC ( p = 0.0302). The median LFPTA change for STE + NAC-treated and not treated subjects was 8.33 dB (mean, 13.82 ± 17.4 dB) and 18.34 dB (mean, 26.5 ± 23.4 dB), respectively ( p = 0.0401, Wilcoxon rank test). Perioperative STE + NAC treatment resulted in 10 dB of LFPTA better hearing than when not receiving this treatment. Better low-frequency preimplantation hearing thresholds were predictive of postimplantation functional hearing. No serious side effects were reported., Conclusion: Perioperative STE + NAC, "The Miami Cocktail," was safe and superior to intraoperative steroids alone in functional hearing preservation 1-year after cochlear implantation., Competing Interests: Disclosures: Dr. Eshraghi is a consultant and received funding from MED-EL corporation. Dr. Holcomb is a consultant and received research funding from Cochlear Corp. and MED-EL and is a consultant for Advanced Bionics. Other authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2024, Otology & Neurotology, Inc.)

Purpose: The preferred vasopressor in post-cardiac arrest shock has not been established with robust clinical outcomes data. Our goal was to perform a systematic review and meta-analysis comparing rates of in-hospital mortality, refractory shock, and hemodynamic parameters in post-cardiac arrest patients who received either norepinephrine or epinephrine as primary vasopressor support., Methods: We conducted a search of PubMed, Cochrane Library, and CINAHL from 2000 to 2022. Included studies were prospective, retrospective, or published abstracts comparing norepinephrine and epinephrine in adults with post-cardiac arrest shock or with cardiogenic shock and extractable post-cardiac arrest data. The primary outcome of interest was in-hospital mortality. Other outcomes included incidence of arrhythmias or refractory shock., Results: The database search returned 2646 studies. Two studies involving 853 participants were included in the systematic review. The proposed meta-analysis was deferred due to low yield. Crude incidence of in-hospital mortality was numerically higher in the epinephrine group compared with norepinephrine in both studies, but only statistically significant in one. Risk of bias was moderate to severe for in-hospital mortality. Additional outcomes were reported differently between studies, minimizing direct comparison., Conclusion: The vasopressor with the best mortality and hemodynamic outcomes in post-cardiac arrest shock remains unclear. Randomized studies are crucial to remedy this., Competing Interests: Declaration of Competing Interest The following authors report no conflict of interest: CL, CC, NA, LR. The following authors received funding by Spero Therapeutics-provided unrestricted research grant via its Investigator Initiated Research Program: BF, MR, GS. GS reports participating in an advisory board meeting for Hema Biologics in 2022 regarding blood factor products. CB reports grant funding from Alexion/Astra Zeneca Rare Disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Acute ischemic stroke is a neurologic emergency, requiring rapid recognition and treatment with intravenous thrombolysis. Since the publication of the 2019 American Heart Association/American Stroke Association Guidelines that recommend tenecteplase as an alternative agent, several centers across the United States are transitioning from alteplase to tenecteplase as the agent of choice for thrombolysis in acute ischemic stroke., Methods: Our health system transitioned to tenecteplase for the treatment of acute ischemic stroke in 2021 due to increasing evidence for efficacy and potential for improved door-to-needle time. Herein we describe our experience and provide guidance for other institutions to implement this change., Conclusion: Emergency nurses are vital to the care of acute ischemic stroke patients. There are several pharmacologic and logistical differences between alteplase and tenecteplase for this indication. This paper outlines these key differences., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Objective: Reward and punishment sensitivity are known to be altered in anorexia nervosa (AN). Most research has examined these constructs separately although motivated behavior is influenced by considering both the potential for reward and risk of punishment. The present study sought to compare the relative balance of reward and punishment sensitivity in AN versus healthy controls (HCs) and examine whether motivational bias is associated with AN symptoms and treatment outcomes., Methods: Adolescents and adults with AN (n = 262) in a partial hospitalization program completed the Eating Disorders Examination Questionnaire (EDE-Q), Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales, and Sensitivity to Punishment/Sensitivity to Reward Questionnaire (SPSRQ) at admission and discharge. HCs (HC; n = 90) completed the BIS/BAS and SPSRQ. Motivational Bias Scores were calculated to reflect the dominance of reward versus punishment sensitivity., Results: Individuals with AN demonstrated significantly greater bias toward punishment sensitivity than HC. In AN, a bias toward punishment was associated with higher EDE-Q Global score at admission. Change in motivational bias during treatment predicted EDE-Q Global scores, but not BMI, at discharge, with greater increases in reward sensitivity or greater decreases in punishment sensitivity during treatment predicting lower eating pathology. Similar findings were observed using the BIS/BAS and SPSRQ., Discussion: Change in motivational bias during treatment is associated with improved outcomes in AN. However, it appears that much of the change in motivational bias can be attributed to changes in punishment sensitivity, rather than reward sensitivity. Future research should examine the mechanisms underlying punishment sensitivity decreases during treatment., Public Significance: Sensitivity to reward and punishment may be important treatment targets for individuals with anorexia nervosa (AN). To date, most research has considered reward and punishment sensitivity separately, rather than examining their relationship to each other. We found that the balance of reward and punishment sensitivity (i.e., motivational bias) differs between healthy controls and those with AN and that this bias is associated with eating disorder symptoms and treatment outcome., (© 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion., Design: Retrospective cohort study., Setting: A large multi-site health system with hospitals across the United States., Patients: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC., Interventions: None., Measurements and Main Results: Between May 5 th , 2018, to January 31 st , 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71-2.20) or multivariable analysis (OR 1.34, 95% CI 0.68-2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37-16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74-12.18, p < 0.001)., Conclusion: There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC., Competing Interests: Declaration of Competing Interest All authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Sepsis is a serious and life-threatening condition caused by a dysregulated immune response to an infection. Recent guidance issued in the UK gave recommendations around recognition and antibiotic treatment of sepsis, but did not consider factors relating to health inequalities. The aim of this study was to summarise the literature investigating associations between health inequalities and sepsis., Methods: Searches were conducted in Embase for peer-reviewed articles published since 2010 that included sepsis in combination with one of the following five areas: socioeconomic status, race/ethnicity, community factors, medical needs and pregnancy/maternity., Results: Five searches identified 1,402 studies, with 50 unique studies included in the review after screening (13 sociodemographic, 14 race/ethnicity, 3 community, 3 care/medical needs and 20 pregnancy/maternity; 3 papers examined multiple health inequalities). Most of the studies were conducted in the USA (31/50), with only four studies using UK data (all pregnancy related). Socioeconomic factors associated with increased sepsis incidence included lower socioeconomic status, unemployment and lower education level, although findings were not consistent across studies. For ethnicity, mixed results were reported. Living in a medically underserved area or being resident in a nursing home increased risk of sepsis. Mortality rates after sepsis were found to be higher in people living in rural areas or in those discharged to skilled nursing facilities while associations with ethnicity were mixed. Complications during delivery, caesarean-section delivery, increased deprivation and black and other ethnic minority race were associated with post-partum sepsis., Conclusion: There are clear correlations between sepsis morbidity and mortality and the presence of factors associated with health inequalities. To inform local guidance and drive public health measures, there is a need for studies conducted across more diverse setting and countries., (© 2024. The Author(s).)

Objective: Staphylococcus capitis , a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day mortality for the detection of S. capitis versus other CoNS species., Methods: In this retrospective case-control study, we included hospitalised infants with any CoNS species detected from a normally sterile body site up to 90 days of age. We linked English laboratory reports from the Second Generation Surveillance System database, mortality data from the Personal Demographics Service, and neonatal unit admissions from the National Neonatal Research Database. In primary analysis, multivariable logistic regression was used, with two co-primary outcomes: survival to discharge and death within 30 days of positive specimen date. Sensitivity analyses using multiply imputed datasets followed., Results: We identified 16 636 CoNS episodes relating to 13 745 infants. CoNS episodes were highest among infants born extremely preterm (22-27 weeks) and with extremely low birth weight (400-999 g). In primary analysis, there were no differences in survival to discharge (p=0.71) or 30-day mortality (p=0.77) between CoNS species. In sensitivity analyses, there were no differences in outcomes between infection with four of the most common CoNS species ( Staphylococcus epidermidis, S. capitis , Staphylococcus haemolyticus and Staphylococcus warneri ) but the remaining CoNS species were at higher risk of adverse outcomes when treated in aggregate., Conclusion: Infants with S. capitis detected from sterile site samples did not experience significant differences in either survival to discharge or 30-day mortality compared with infants with detection of other common CoNS species., Competing Interests: Competing interests: YW is an Imperial Institutional Strategic Support Fund Springboard Research Fellow, funded by the Wellcome Trust and Imperial College London. YW, AD and CSB are affiliated with the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London in partnership with the UK Health Security Agency (formerly Public Health England), in collaboration with Imperial Healthcare Partners, University of Cambridge and University of Warwick., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting., Design: Retrospective cohort study., Setting: Academic medical center in Minnesota., Patients: Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours., Interventions: None., Measurements: Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected., Main Results: Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1-4.5) and ICU length of stay of 4.9 days (3-8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1-0.3) and 30 hours (15.1-51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33-96%), while 64% (37-91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients., Conclusions: Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy., Competing Interests: The authors have no disclosures or conflicts of interest relevant to this work., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Candida auris is a globally emerged fungal pathogen causing nosocomial invasive infections. Here, we use cutting-edge genomic approaches to elucidate the temporal and geographic epidemiology of drug-resistant C. auris within the UK. We analysed a representative sample of over 200 isolates from multiple UK hospitals to assess the number and timings of C. auris introductions and infer subsequent patterns of inter- and intra-hospital transmission of azole drug-resistant isolates. We identify at least one introduction from Clade I and two from Clade III into the UK, and observe temporal and geographical evidence for multiple transmission events of antifungal drug resistant isolates between hospitals and identified local within-hospital patient-to-patient transmission events. Our study confirms outbreaks of drug-resistant C. auris are linked and that transmission amongst patients occurs, explaining local hospital outbreaks, and demonstrating a need for improved epidemiological surveillance of C. auris to protect patients and healthcare services., Competing Interests: Competing interestsJ.R. and A.A. have received honoraria from Gilead Sciences., (© The Author(s) 2024.)

Postcraniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of postcraniotomy patients, as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Nonsteroidal anti-inflammatory drugs (NSAIDs) present as a potential solution due to their nonaddictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. The degree to which NSAIDs alter platelet function and bleeding time to a clinically relevant manner has remained controversial, although several well-designed studies concluded that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for postintracranial neurosurgical procedure pain management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Third doses of COVID-19 vaccines were widely deployed following the primary vaccine course waning and the emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2), by primary series vaccination type. Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021t o 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (3rd dose) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). The relative VE of 3rd dose (heterologous BNT162b2) was greater for primary course ChAdOX1 recipients, with VE 0-2 months post-3rd dose over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with the potential emergence of immune-escape variants and the importance of continued monitoring., Competing Interests: Declaration of Competing Interest We declare no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers., Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated., Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI -11.4 to 27.8) and 1.7% (95% CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection., Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern., Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others., Competing Interests: We declare no competing interests. DCr reports participation on steering groups for the SIREN Scotland trial and TAVI UK trial and is a trustee of the Medical Schools Council of the UK. DDA reports attendance and travel expenses for MRC board/panel meetings and is a member of the Scientific Pandemic Influenza Advisory Committee, the steering group for SIREN Scotland; the MRC Infection Immunity board, the MRC Population Health Science Group, the MRC Better Methods for Better Research Panel, and the Joint Biosecurity Centre/UKHSA Data Science Advisory Board. CSB and SH report grant funding from the NIHR HPRU. CSB reports participation in an ad-hoc one-off market research advisory on a variety of infection topics., (Crown Copyright © 2023 Published by Elsevier Ltd.)

Background: National Health Service (NHS) guidance for acute respiratory tract infections (RTIs) advocates self-care, encourages utilization of local pharmacies and recommends consulting general practitioners (GPs) primarily for the vulnerable or those with persistent symptoms. Coronavirus disease 2019 exerted substantial strain on the English NHS, affecting public access to primary care services., Methods: For 3 years, public surveys assessed RTI incidences in the previous 12 months and associated health-seeking behaviours. Telephone surveys of 1676 respondents across England were conducted in March 2021 and 1663 respondents in March 2022. Findings were compared with a face-to-face baseline survey of 2022 respondents from March 2020. Key demographics were representative of the population., Results: In 2021, the proportion of respondents who reported an RTI (51%) significantly declined from 2020 (70%, P < 0.05), then returned to pre-pandemic rates in 2022 (67%). Respondents reported more proactive symptom management in both 2021 and 2022 from 2020: there were greater reports of seeking over-the-counter treatments (55%, 55% vs. 35%, P < 0.05) and use of alternative remedies (38%, 38% vs. 21%, P < 0.05). 2022 observed a reduction in those who reported consulting their GP for their most recent RTI (15%) compared to 2021 (25%, P < 0.05) and 2020 (23%), which was not accounted for through greater consultation rates with other healthcare services., Conclusions: Public health bodies should consider how pandemic-related changes may have facilitated increased self-care for self-limiting infections such as RTIs. Resources and support must include safety-netting advice to safeguard against unintentional consequences of increased self-care., (© Crown copyright 2023.)

Objective: To determine whether the gender of clinicians making antimicrobial stewardship recommendations has an impact on intervention acceptance rate., Design: A retrospective, multivariable analysis of antimicrobial stewardship prospective audit and feedback outcomes., Setting: A multisite healthcare system including Mayo Clinic Rochester (MN), Mayo Clinic Arizona, Mayo Clinic Florida and 17 health-system hospital sites, where prospective audit and feedback is performed and documented within an electronic tool embedded in the medical record., Participants: The study included 143 Mayo Clinic clinicians (84 cisfemales and 59 cismales)., Methods: Outcomes were analyzed from July 1, 2017, to June 30, 2022, for intervention rates, communication methods, and intervention acceptance by clinician gender, profession, patient age, and intensive care unit (ICU) status of patient., Results: Of 81,927 rules, 71,729 rules met study inclusion. There were 18,175 (25%) rules associated with an intervention. Most of the rules were reviewed by pharmacists (86.2%) and stewardship staff (85.5%). Of 10,363 interventions with an outcome documented, 8,829 (85.2%) were accepted and 1,534 (14.8%) were rejected. Female clinicians had 6,782 (86.5%) of 7,843 interventions accepted, and male clinicians had 2,047 (81.2%) of 2,520 interventions accepted ( P = .19). Female patients had more interventions than male patients (female vs male: 25.9% vs 24.9%; OR, 1.04; 95% CI, 1.02-1.08; P = .001). Patients in the ICU had a significantly lower intervention acceptance rate (ICU vs non-ICU: 78.2% vs 86.7%; OR, 0.56; 95% CI, 0.45-0.7; P < .001)., Conclusions: Female and male clinicians were equally effective at prospective audit and feedback in a multisite antimicrobial stewardship program. Patients in the ICU were less likely to have stewardship interventions accepted.

Objectives: A global outbreak of mpox (monkeypox) has been ongoing since 2022, with most cases in the UK detected in gay, bisexual and other men who have sex with men (GBMSM). Asymptomatic and pauci-symptomatic mpox infection has been reported outside of the UK. We aimed to investigate whether mpox could be detected in specimens from GBMSM in England who were attending sexual health services (SHSs) for asymptomatic sexually transmitted infection screening., Methods: Anonymised, residual clinical specimens from GBMSM undertaking routine asymptomatic screening for gonorrhoea ( Neisseria gonorrhoeae (NG)) and chlamydia ( Chlamydia trachomatis (CT)) infection were tested for the presence of mpox virus. Specimens were collected between 1 August and 7 October 2022 from three SHSs in high-mpox incidence areas in England. Testing was performed using a dual-clade, mpox virus-specific real-time PCR., Results: During the collection period, 2927 clinical specimens (951 pharyngeal swabs, 1022 urine specimens and 954 rectal swabs) were obtained from 1159 GBMSM. Mpox virus was detected in four specimens from two participants who attended the same SHS at different times (the first during the week 8-12 of August, the second during the week 19-23 of September). One participant was positive in the urine specimen only, while the other tested positive at all three sites., Conclusions: A very low prevalence (2 of 1159, 0.17%) of mpox infection was detected in GBMSM attending SHS in England for asymptomatic NG/CT screening, suggesting that undetected infection in this population was unlikely to be a main driver of transmission. Confirmed mpox cases in the UK declined from over 1100 per month in June and July to 764 cumulatively during the collection period. These data give reassurance that the observed reduction in cases during the collection period was not due to undetected infection or changes in presentation among SHS attendees. Currently, there is insufficient evidence to support routine testing of asymptomatic GBMSM for mpox infection in England., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic saw unprecedented resources and funds driven into research for the development, and subsequent rapid distribution, of vaccines, diagnostics and directly acting antivirals (DAAs). DAAs have undeniably prevented progression and life-threatening conditions in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are concerns of antimicrobial resistance (AMR), antiviral resistance specifically, for DAAs. To preserve activity of DAAs for COVID-19 therapy, as well as detect possible mutations conferring resistance, antimicrobial stewardship and surveillance were rapidly implemented in England. This paper expands on the ubiquitous ongoing public health activities carried out in England, including epidemiologic, virologic and genomic surveillance, to support the stewardship of DAAs and assess the deployment, safety, effectiveness and resistance potential of these novel and repurposed therapeutics., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)