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Background: Kenya introduced a monovalent rotavirus vaccine administered orally at 6 and 10 weeks of age into her National Immunization Program in July 2014. The study evaluated the long-term impact of the vaccine on hospitalization for all-cause and rotavirus-specific acute gastroenteritis (AGE) and strain epidemiology in Kenya., Methods: Data on all-cause and rotavirus-specific AGE and strain distribution were derived from an eleven-year hospital-based surveillance of AGE among children aged <5 years at Kiambu County Teaching and Referral Hospital (KCTRH) in Central Kenya between 2009 and 2020. Fecal samples were screened for group A rotavirus using ELISA and genotyped using multiplex semi-nested RT-PCR. Trends in all-cause and rotavirus-related AGE and strain distribution were compared between the pre-vaccine (July 2009-June 2014), early post-vaccine (July 2014-June 2016) and late post-vaccine (February 2019-October 2020) periods., Results: Rotavirus-specific AGE was detected at 27.5% (429/1546, 95% CI: 25.5-30.1%) in the pre-vaccine period; 13.8% (91/658, 95% CI: 11.3-16.6%) in the early post-vaccine period (July 2014-June 2016); and 12.0% (229/1916, 95% CI: 10.6-13.5%) in the late post-vaccine period (February 2019-October 2020). This amounted to a decline of 49.8% (95% CI: 34.6%-63.7%) in rotavirus-specific AGE in the early post-vaccine period and 53.4% (95% CI: 41.5-70.3%) in the late post-vaccine period when compared to the pre-vaccine period. All-cause AGE hospitalizations declined by 40.2% (95% CI: 30.8%-50.2%) and 75.3% (95% CI: 65.9-83.1%) in the early post-vaccine and late post-vaccine periods, respectively, when compared to the pre-vaccine period. G3P [8] was the predominant strain in the late post-vaccine period, replacing G1P[8] which had predominated in the pre-vaccine and early post-vaccine periods. Additionally, we detected considerable proportions of uncommon strains G3P[6] (4.8%) and G12P[6] (3.5%) in the post-vaccine era., Conclusion: Rotavirus vaccination has resulted in a significant decline in all-cause and rotavirus-specific AGE, and thus, provides strong evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunization. However, the shift in strain dominance and age distribution of rotavirus AGE in the post-vaccine era underscores the need for continued surveillance to assess any possible vaccine-induced selective pressure that could diminish the vaccine effectiveness over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Influenza vaccination is critical for children with sickle cell disease (SCD) due to risks of severe influenza infections. Despite declining influenza vaccination among children since the COVID-19 pandemic, less is known about influenza vaccine coverage among youth with SCD during this same period. We compared influenza vaccine uptake among youth with SCD seen by a SCD provider in clinic during the 2019-2020 and 2022-2023 influenza seasons and described infection characteristics. Overall, 85% (n = 220) of children received their influenza vaccine during 2019-2020 compared to 75% (n = 245) in 2022-2023 (p = 0.059). Participants seen during both seasons were more likely to shift from vaccinated in 2019-2020 to unvaccinated in 2022-2023 than vice versa (McNemar's OR = 3.0; p = 0.008). Among 66 documented infections, 25.8% resulted in hospitalization. We found high influenza vaccine uptake but those seen during both seasons were more likely to become unvaccinated. More research is needed to understand influenza vaccine decision-making in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23)., Methods: A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups., Results: Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74-2·20) and IPD (aHR 1·44; 95 %CI 1·41-1·46). In participants aged 64-74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75-2·33) and HP (aHR 1·46; 95 %CI 1·42-1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08-1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94-1·52)., Conclusions: No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NF and DH are currently in receipt of grant support from Seqirus UK Ltd. for the evaluation of influenza vaccines in the UK. NF and DH have previously received research-initiated and industry-initiated research grant support from GlaxoSmithKline (GSK) Biologicals for evaluation of rotavirus vaccination in the UK. DH has also received grants from GSK, Sanofi Pasteur, and Merck & Co (Kenilworth, New Jersey, USA) for rotavirus strain surveillance. KD, VD, LB, SA, NB and KF have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Respiratory syncytial virus (RSV) represents a high burden of disease in children and the primary cause of hospitalization, especially in children under 1 year old. In the Valencian Community (Spain), nirsevimab, a long-acting monoclonal antibody, was introduced for the RSV 2023-2024 season as a universal pre-exposure prophylaxis for high-risk children and those under 6 months old. This study examines its impact, coverage, and effectiveness. The campaign achieved 88.5 % coverage and 73.7 % of effectiveness. Analysis of over 27,000 susceptible children (over 24,000 immunized), showed that those immunized exhibited a threefold reduction in RSV incidence compared to non-immunized ones. To prevent one case, the number needed to immunize (NNI) was 63. Hospitalizations due to acute respiratory infections were almost two times lower in immunized children compared to non-immunized ones (0.9 % vs 1.6 %, respectively). These first results showcase the preliminary positive impact of this public health intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Luxembourg experienced major consecutive SARS-CoV-2 infection waves due to Omicron variants during 2022 while having achieved a high vaccination coverage in 2021. We investigated the risk factors associated to severe outcomes (i.e., hospitalisation, deaths) and estimated vaccine effectiveness (VE) as well as the role of immunity conferred by prior infections against severe outcomes in adults., Methods: We linked reported SARS-CoV-2 cases among residents aged ≥ 20 years with vaccination data and SARS-CoV-2 related hospitalisations and deaths. Cases were followed-up until day 14 for COVID-19 related hospital admission and up to day 28 for mortality after a positive test. We analysed the association between the vaccination status and severe forms using proportional Cox regression, adjusting for previous infection, age, sex and nursing homes residency. VE was measured as 1-adjusted hazard ratio of vaccinated vs unvaccinated individuals. The population preventable fraction was computed using the adjusted hazard ratio and the proportion of cases within the vaccination category., Results: Between December 2021, and March 2023, we recorded 187143 SARS-CoV-2 cases, 1728 (0.93%) hospitalizations and 611 (0.33%) deaths. The risk of severe outcomes increased with age, was higher among men and nursing home residents. Compared to unvaccinated adults, VE against hospitalization was 38.8% (95%CI: 28.1%-47.8%) for a complete primary cycle of vaccination, 62.1% (95%CI: 57.0%-66.7%) for one booster, and 71.6% (95%CI: 66.7%-76.2%) for two booster doses. VE against death was respectively 49.5% (95%CI: 30.8%-63.3%), 69.0% (95%CI: 61.2%-75.3%) and 76.2% (95%CI: 68.4%-82.2%). Previous infection was not associated with lower risk of hospitalisation or mortality. The vaccination lowered mortality by 55.8 % (95%CI: 46.3%-62.8%) and reduced hospital admissions by 49.1% (95%CI: 43.4%-54.4%)., Conclusions: Complete vaccination and booster but not previous infection were protective against hospitalization and death. The vaccination program in Luxembourg led to substantial reductions in SARS-CoV-2-related mortality and hospitalizations at the population level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Some patients with atrial fibrillation (AF), albeit less frequently, may regress from sustained to paroxysmal type. We sought to investigate how the regression of AF is associated with outcomes. Among the AF patients enrolled in the Fushimi AF Registry who were identified as having sustained AF at baseline, conversion of sustained to paroxysmal AF during follow-up was defined as AF regression. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death, myocardial infarction, ischemic stroke, systemic embolism, or hospitalization due to heart failure. Among 2,261 patients with sustained AF at baseline, AF regression was observed in 214 (9.5%) patients over a median follow-up period of 5.8 years (1.78% per patient-year). The annual incidence of MACE in patients with AF regression was significantly lower than those without (3.47% vs. 6.59% per patient-year, P < 0.001; adjusted hazard ratio [HR], 0.53, 95% confidence interval [CI], 0.38-0.72). Furthermore, AF regression was significantly associated with reduced risk of MACE during and after the regression period from sustained to paroxysmal forms (during regression period: adjusted HR, 0.45; 95% CI, 0.22-0.90; after regression period: adjusted HR, 0.43; 95% CI, 0.26-0.67). The incidence of MACE was comparable between spontaneous regression (35/178: 19.7%) and therapy-associated regression (either receiving catheter ablation or antiarrhythmic drugs before the regression) (7/36: 19.4%) (P=0.98). Regression of AF was associated with a lower incidence of adverse cardiovascular events. The risk of adverse events decreased significantly during the regression period and its reduction level persisted after regression. URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000005834., Competing Interests: Declaration of competing interest Dr. Akao received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare, and Daiichi Sankyo. All other authors have reported that they have no relationships relevant to the content of this paper to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bipolar disorder (BD) is associated with increased morbidity/mortality. Adverse outcome prediction might help with the management of patients with BD., Methods: We systematically reviewed the performance of machine learning (ML) studies in predicting adverse outcomes (relapse or recurrence, hospital admission, and suicide-related events) in patients with BD. Demographic, clinical, and neuroimaging-related poor outcome predictors were also reviewed. Three databases (PubMed, Scopus, and Web of Science) were explored from inception to July 2023., Results: Eighteen studies, accounting for >30,000 patients, were included. Support vector machine, decision trees, random forest, and logistic regression were the most frequently used ML algorithms. ML models' area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity ranged from 0.71 to 0.98, 72.7-92.8 %, and 59.0-95.2 % for relapse/recurrence prediction (4 studies (3 on relapses and 1 on recurrences). The corresponding values were 0.78-0.88, 21.4-100 %, and 77.0-99.7 % for hospital admissions (3 studies, 21,266 patients), and 0.71-0.99, 44.4-97.9 %, and 38.9-95.0 % for suicide-related events (10 studies, 5558 patients). Also, one study addressed a combination of the interest outcomes. Adverse outcome predictors included early onset BD, BD type I, comorbid psychiatric or substance use disorder, circadian rhythm disruption, hospitalization characteristics, and neuroimaging parameters, including increased dynamic amplitude of low-frequency fluctuation, decreased frontolimbic functional connectivity and aberrant dynamic functional connectivity in corticostriatal circuitry., Conclusions: ML models can predict adverse outcomes of BD with relatively acceptable performance measures. Future studies with larger samples and nested cross-validation validation should be conducted to reach more reliable results., Competing Interests: Declaration of competing interest There are no financial/personal relationships with any people or organizations that could inappropriately influence this study. There are no potential competing interests including employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Despite plausible behavioral and physiological pathways, limited evidence exists on how daily temperature variability is associated with acute mental health-related episodes., Objectives: We aimed to explore associations between daily temperature range (DTR) and mental health-related hospital visits using data of all hospital records in New York State during 1995-2014. We further examined factors that may modify these associations, including age, sex, hospital visit type and season., Methods: Using a case-crossover design with distributed lag non-linear DTR terms (0-6 days), we estimated associations between ZIP Code-level DTR and hospital visits for mood (4.6 million hospital visits), anxiety (2.4 million), adjustment (∼368,000), and schizophrenia disorders (∼211,000), controlling for daily mean temperature, via conditional logistic regression models. We assessed potential heterogeneity by age, sex, hospital visit type (in-patient vs. out-patient), and season (summer, winter, and transition seasons)., Results: For all included outcomes, we observed positive associations from period minimum DTR (0.1 °C) until 25th percentile (5.2 °C) and between mean DTR (7.7 °C) and 90th percentile (12.2 °C), beyond which we observed negative associations. For mood disorders, an increase in DTR from 0.1 °C to 12.2 °C was associated with a cumulative 16.0% increase (95% confidence interval [CI]: 12.8, 19.2%) in hospital visit rates. This increase was highest during transition seasons (32.5%; 95%CI: 26.4, 39.0%) compared with summer (10.7%; 95%CI: 4.8, 16.8%) and winter (-1.6%; 95%CI: -7.6, 4.7%). For adjustment and schizophrenia disorders, the strongest associations were seen among the youngest group (0-24 years) with almost no association in the oldest group (65+ years). We observed no evidence for modification by sex and hospital visit type., Discussion: Daily temperature variability was positively associated with mental health-related hospital visits within specific DTR ranges in New York State, after controlling for daily mean temperature. Given uncertainty on how climate change modifies temperature variability, additional research is crucial to comprehend the implications of these findings, particularly under different scenarios of future temperature variability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There is a considerable lack of epidemiological evidence on whether frailty, and frailty comorbid depression could increase the risk of infections in older adults. This study aimed to examine the prospective association between frailty, depression, and risk of infections., Methods: A total of 308,892 eligible participants were included. Linked hospital admission records (HES) were used to identify a primary or secondary diagnosis of depression, and infection. Frailty was assessed by Fried frailty phenotype indicators. Cox proportional hazard model was conducted to examine the associated risk between frailty, depression, comorbid frailty and depression and risk of incident infections. Results were stratified by age and gender., Results: During the follow-up, 74,749 (24.19 %) incident any infection cases were identified, the incidence density of any infection was 17.29/1000 person years. Frailty alone (HR = 1.38, 95 % CI: 1.33-1.43), depression alone (HR = 1.90, 95 % CI: 1.86-1.94), and comorbid frailty and depression (HR = 1.91, 95 % CI: 1.82-1.99) were associated with greater risks of any infections relative to participants with neither frailty nor depression. The associations between frailty alone, depression alone, comorbid frailty and depression, and any infections/most infection subtypes were significant for all age strata in both male and female., Limitations: Frailty phenotype was assessed through the adapted Fried criteria, based on a mix of self-reported and objective measurements., Conclusion: Frailty, depression, and comorbid frailty and depression were significantly associated with increased risk of incident infections., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: As climate change increases the frequency and intensity of extreme heat events, there is an urgent need to quantify the heat-related health burden. However, most past studies have focussed on a single health outcome (mainly mortality) or on specific heatwaves, thus providing limited knowledge of the total pressure heat exerts on health services., Objectives: This study aims to quantify the heat-related mortality and morbidity burden for five different health outcomes including all-cause mortality, hospitalizations, emergency department (ED) visits, ambulance transports and calls to a health hotline, using the province of Quebec (Canada) as a case study., Methods: A two-step statistical analysis was employed to estimate regional heat-health relationships using Distributed Lag Non-Linear Models (DLNM) and pooled estimates using a multivariate meta-regression. Heat burden was quantified by attributable fraction (AF) and attributable number (AN) for two temperature ranges: all heat (above the minimum mortality/morbidity temperature) and extreme heat (above the 95th percentile of temperature)., Results: Higher temperatures were associated with greater risk ratios for all health outcomes studied, but at different levels. Significant AF ranging from 2 to 3% for the all heat effect and 0.4-1.0% for extreme heat were found for all health outcomes, except for hospitalizations that had an AF of 0.1% for both heat exposures. The estimated burden of all heat (and extreme heat) every summer across the province was 470 (200) deaths, 225 (170) hospitalizations, 36 000 (6 200) ED visits, 7 200 (1 500) ambulance transports and 15 000 (3 300) calls to a health hotline, all figures significant., Discussion: This new knowledge on the total heat load will help public health authorities to target appropriate actions to reduce its burden now and in the future. The proposed state-of-the-art framework can easily be applied to other regions also experiencing the adverse effects of extreme heat., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Population screening for colorectal cancer (CRC) remains low, requiring alternative approaches for increasing participation. Opportunistic screening of hospitalized patients may aid in increasing uptake rates., Objective: To assess whether inpatients can be recruited for opportunistic CRC screening using fecal immunochemical testing (FIT)., Methods: Inpatient charts were prospectively reviewed for study eligibility on admission of patients to the medical wards of 3 hospitals in Winnipeg, Canada. Eligible patients were approached for participation and consent. Inoculated FIT specimen collection tubes were sent to the hospital laboratory for testing. Patients with positive FIT results received a follow-up colonoscopy., Results: In total, 1542 inpatient charts were screened for eligibility; 53 patients were identified for enrollment (51.9% were male; median age, 59 years), of whom 13 patients consented to participate but only 7 provided a stool specimen. One of those 7 patients had a positive FIT result. The overall screening rate was low, at 0.45%. The primary reason for exclusion of patients was age (outside of the range of 50-75 years), followed by patients having recent gastrointestinal bleeding and/or known intestinal diseases., Conclusions: Our data suggest that it is infeasible to recruit inpatients for opportunistic CRC screening in routine clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. 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.)

Background: Despite the severe impact of COVID-19 on cancer patients, data on COVID-19 outcomes in cancer patients from low- and middle-income countries is limited. We conducted a large study about the mortality rate of COVID-19 in cancer patients in Iran., Methods: We analyzed data from 1,079 cancer (average age: 58.2 years) and 5,514 non-cancer patients (average age: 57.2 years) who were admitted for COVID-19 in two referral hospitals between March 2019 and August 2021. Patients were followed up until death or 31st August 2021. Multiple logistic regression models estimated the odds ratio (OR) and 95% confidence intervals (CI) of factors associated with ICU admission and intubation. The Cox regression model estimated hazard ratios (HRs) and 95% CI of factors associated with hospital and post-discharge 60-day mortalities., Results: The cancer patients had higher ICU admission (OR = 1.65, 95% CI: 1.42-1.91; P-value 0.03) and intubation (OR = 3.13, 95% CI = 2.63-3.73, P-value < 0.001) than non-cancer patients. Moreover, hospital mortality was significantly higher in cancer patients than in non-cancer patients (HR = 2.12, 95% CI: 1.89-2.41, P-value < 0.001). HR for the post-discharge mortality was higher in these patients (HR = 2.79, 95% CI: 2.49-3.11, < 0.001). The hospital, comorbidities, low oxygen saturation, being on active treatment, and non-solid tumor were significantly associated with ICU admission (P-value < 0.05) in cancer patients, while only low oxygen saturation was associated with intubation. In addition, we found that old age, females, low oxygen saturation level, active treatment, and having a metastatic tumor were associated with death due to COVID-19 (P-value < 0.05). Only lung cancer patients had a significantly higher risk of death compared to other cancer types (HR = 1.50, 95% CI: 1.06-2.10, P-value = 0.02)., Conclusion: Cancer patients are at a higher risk of ICU admission, intubation, and death due to COVID-19 than non-cancer patients. Therefore, cancer patients who are infected with COVID-19 require intensive care in the hospital and active monitoring after their discharge from the hospital., (© 2024. The Author(s).)

Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes., Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them., Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not., Exposure: Various classes of oral antibiotics., Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group., Results: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital., Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

Objectives: To determine the prevalence of heart failure (HF) medication prescribing on discharge post-HF-related admission., Methods: A retrospective audit was conducted for 216 HF admissions over a period of 6 months; medication data from electronic records were collected for analysis., Key Findings: The prevalence of HF medication prescribing on discharge was: 32.9% (95% confidence interval: 26.6-39.6) renin-angiotensin-aldosterone system inhibitors, 10.6% (6.9-15.6) angiotensin receptor-neprilysin inhibitors, 31.5% (25.4-38.1) HF-specific beta-blockers, 42.6% (35.9-49.5) aldosterone receptor antagonists, and 11.6% (7.6-16.6) sodium-glucose cotransporter-2 inhibitors., Conclusion: HF medication prescribing remains relatively low despite the known benefits and recommendations listed in the guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. 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.)

Objective: To determine the effectiveness of nirmatrelvir/ritonavir and molnupiravir among vaccinated and unvaccinated non-hospitalized adults with COVID-19., Methods: Observational studies of nirmatrelvir/ritonavir or molnupiravir compared to no antiviral drug treatment for COVID-19 in non-hospitalized adults with data on vaccination status were included. We searched MEDLINE, EMBASE, Scopus, Web of Science, WHO COVID-19 Research Database and medRxiv for reports published between 1 January 2022 and 8 November 2023. The primary outcome was a composite of hospitalization or mortality up to 35 days after COVID-19 diagnosis. Risk of bias was assessed with ROBINS-I. Risk ratios (RR), hazard ratios (HR) and risk differences (RD) were separately estimated using random-effects models., Results: We included 30 cohort studies on adults treated with nirmatrelvir/ritonavir (n = 462 279) and molnupiravir (n = 48 008). Nirmatrelvir/ritonavir probably reduced the composite outcome (RR 0.62, 95%CI 0.55-0.70; I2 = 0%; moderate certainty) with no evidence of effect modification by vaccination status (RR Psubgroup = 0.47). In five studies, RD estimates against the composite outcome for nirmatrelvir/ritonavir were 1.21% (95%CI 0.57% to 1.84%) in vaccinated and 1.72% (95%CI 0.59% to 2.85%) in unvaccinated subgroups.Molnupiravir may slightly reduce the composite outcome (RR 0.75, 95%CI 0.67-0.85; I2 = 32%; low certainty). Evidence of effect modification by vaccination status was inconsistent among studies reporting different effect measures (RR Psubgroup = 0.78; HR Psubgroup = 0.08). In two studies, RD against the composite outcome for molnupiravir were -0.01% (95%CI -1.13% to 1.10%) in vaccinated and 1.73% (95%CI -2.08% to 5.53%) in unvaccinated subgroups., Conclusions: Among cohort studies of non-hospitalized adults with COVID-19, nirmatrelvir/ritonavir is effective against the composite outcome of severe COVID-19 independent of vaccination status. Further research and a reassessment of molnupiravir use among vaccinated adults are warranted., Registration: PROSPERO CRD42023429232., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Trachoma is the leading infectious cause of blindness worldwide. It is a neglected tropical disease caused by Chlamydia trachomatis. The objective of this study was to analyze the trachoma-associated morbidity and mortality in Brazil from 2000 to 2022. This ecological time-series study was based on secondary data on trachoma obtained from hospital admissions (trachoma as the primary or secondary cause) and death certificates (trachoma as the underlying or associated cause)., Methods: We calculated the sex- and age-standardized rates of hospital admissions and trachoma-specific mortality according to sociodemographic variables and analyzed the spatial distribution., Results: We identified 141/263,292,807 hospital admissions (primary cause: 83.0%) and 126/27,596,830 death certificates (associated cause: 91.3%) related to trachoma. Trachoma-related sequelae were reported in 8.5% of hospital admissions and 6.3% of death certificates. Trachoma was more common in males (hospital admissions and death certificates), people aged ≥70 years (hospital admissions and death certificates), those with brown skin (hospital admissions and death certificates), and those living in the North (hospital admissions) and Northeast (death certificates) regions of Brazil., Conclusions: Despite the relatively low rates of trachoma morbidity in Brazil, the associated mortality rates are of concern. The heterogeneous patterns of occurrence in the country in terms of population and territory reinforce the need to evaluate and monitor the available data, despite the low prevalence, in order to achieve and maintain the elimination targets in Brazil in the future.

Introduction: During 2020-2021 Australia maintained comparatively low rates of COVID-19 in the community and residential aged care facilities (RAC) due to stringent public health measures such as lockdowns. However, the public health measures implemented may have had unintended impacts on critical RAC resident health outcomes, such as falls, due to routine care disruptions and aged care resident isolation. We utilised a longitudinal data to assess the association between COVID-19 lockdowns and the rate of falls in RAC settings., Methods: A longitudinal cohort study was conduct using routinely collected data from 25 RAC facilities from one non-profit aged care provider in Sydney, Australia. The study included 2,996 long term residents between March 2019 and March 2021. The outcome measures were all falls, injurious falls, and falls assessed as requiring hospitalisation. Generalised estimating equations (GEE) were applied to determine the association between COVID-19 lockdown periods and fall-related outcomes while adjusting for confounders and seasonality., Results: During the study period 11,658 falls were recorded. Residents frequently experienced at least one fall during the study period (median: 1, interquartile range: 0-4). During Lockdown 1 (March-June 2020) the rate of all falls increased 32% (IRR 1.32, 95% CI 1.19-1.46, p < 0.01) and the rate of injurious falls increased by 28% (IRR 1.28, 95% CI 1.12-1.46, p < 0.01) compared to pre-pandemic rates. The rate of falls assessed as requiring hospitalisation remained unchanged during Lockdown 1 (IRR 1.07, 95% CI 0.86-1.32, p = 0.519). During Lockdown 2 (Dec 2020-Jan 2021) the rate of all falls, injurious falls, and falls assessed as requiring hospitalisation did not change significantly compared to pre-pandemic rates., Conclusion: These findings suggest that the consequences of stringent COVID-19 restrictions, as seen in Lockdown 1, produced changes in residents' care which contributed to more falls and associated harm. The subsequent lockdown, which were less restrictive and occurred after staff had gained experience, was associated with no significant increase in falls rate. The nature and extent of lockdowns implemented for infection control in RAC need to balance multiple potential adverse effects. Factors which facilitated resilience during this period require exploration in future research., (© 2024. The Author(s).)

Background: Studying the characteristics of hospitalized Coronavirus Disease 2019 (COVID-19) patients is vital for understanding the disease and preparing for future outbreaks. The aim of this study was to analyze and describe the clinical profiles and factors associated with mortality among COVID-19 patients admitted to Jimma Medical Center COVID-19 Treatment Center (JMC CTC) in Ethiopia., Methods: All confirmed COVID-19 patients admitted to JMC CTC between 17 April 2020 and 05 March 2022 were included in this study. Socio-demographic data, clinical information, and outcome variables were collected retrospectively from medical records and COVID-19 database at the hospital. Bivariable and multivariable analyses were performed to determine factors associated with COVID-19 severity and mortality. A P-value < 0.05 was considered statistically significant., Results: A total of 542 confirmed COVID-19 patients were admitted to JMC CTC, of which 322 (59.4%) were male. Their median age was 48 years (IQR 32-64). About 51% (n = 277) of them had severe COVID-19 upon admission. Patients with hypertension [AOR: 2.8 (95% CI: 1.02-7.7, p = 0.046)], diabetes [AOR: 8.8 (95% CI: 1.2-17.3, p = 0.039)], and underlying respiratory diseases [AOR: 18.8 (95% CI: 2.06-71.51, p = 0.009)] were more likely to present with severe COVID-19 cases. Overall, 129 (23.8%) died in the hospital. Death rate was higher among patients admitted with severe disease [AHR = 5.5 (3.07-9.9) p < 0.001)] and those with comorbidities such as hypertension [AHR = 3.5 (2.28-5.41), p < 0.001], underlying respiratory disease [AHR = 3.4 (1.97-5.94), p < 0.001], cardiovascular disease (CVDs) [AHR = 2.8 (1.73-4.55), p < 0.001], and kidney diseases [AHR = 3.7 (2.3-5.96), p < 0.001]., Conclusion: About half of COVID-19 cases admitted to the hospital had severe disease upon admission. Comorbidities such as hypertension, diabetes, and respiratory diseases were linked to severe illness. COVID-19 admissions were associated with high inpatient mortality, particularly among those with severe disease and comorbidities., (© 2024. The Author(s).)

Background: Acute ischaemic stroke (AIS) after percutaneous coronary intervention (PCI) is a rare, but debilitating, complication. However, contemporary data from real-world unselected patients are scarce., Aims: We aimed to explore the temporal trends, outcomes and variables associated with AIS as well as in-hospital all-cause mortality in a nationwide cohort., Methods: A retrospective analysis of healthcare records from 2006-2021 was implemented. Patients were stratified according to the occurrence of AIS in the setting of PCI. The temporal trends of AIS were analysed. A stepwise regression model was used to identify variables associated with AIS and in-hospital all-cause mortality., Results: A total of 4,910,430 PCIs were included for the current analysis. AIS occurred in 4,098 cases (0.08%). An incremental increase in the incidence of AIS after PCI from 0.03% to 0.14% per year was observed from 2006-2021. The strongest associations with AIS after PCI included carotid artery disease, medical history of stroke, atrial fibrillation, presentation with an ST-segment elevation myocardial infarction (STEMI) or non-STEMI and coronary thrombectomy. For patients with AIS, a higher in-hospital all-cause mortality (18.11% vs 3.29%; p<0.001) was documented. With regard to all-cause mortality, the strongest correlations in the stroke cohort were found for cardiogenic shock, dialysis and clinical presentation with a STEMI., Conclusions: In an unselected nationwide cohort of patients hospitalised for PCI, a gradual increase in AIS incidence was noted. We identified several variables associated with AIS as well as with in-hospital mortality. Hereby, clinicians might identify the patient population at risk for a peri-interventional AIS as well as those at risk for an adverse in-hospital outcome after PCI.

Background: Visual fields are important for postural stability and ability to manoeuvre around objects., Objective: Examine the association between visual field loss and falls requiring hospitalisation in adults aged 50 +., Methods: Older adults aged 50+ with and without visual field loss were identified using a fields database obtained from a cross-section of ophthalmologists' practices in Western Australia (WA). Data were linked to the Hospital Morbidity Data Collection and WA Hospital Mortality System to identify participants who experienced falls-related hospitalisations between 1990 and 2019. A generalised linear negative binomial regression model examined the association between falls requiring hospitalisation for those with and without field loss, based on the better eye mean deviation (mild: -2 to -6 dB, moderate: -6.01 dB to -12 dB, severe < -12.01 dB) in the most contemporaneous visual field test (3 years prior or if not available, 2 years after the fall), after adjusting for potential confounders., Results: A total of 31 021 unique individuals of whom 6054 (19.5%) experienced 11 818 falls requiring hospitalisation during a median observation time of 14.1 years. Only mean deviation index of <-12.01 dB (severe) was significantly associated with an increased rate of falls requiring hospitalisations by 14% (adjusted IRR 1.14, 95% CI 1.0-1.25) compared with no field loss, after adjusting for potential confounders. Other factors included age, with those aged 80+ having an increased rate (IRR 29.16, 95% CI 21.39-39.84), other comorbid conditions (IRR 1.49, 95% CI 1.38-1.60) and diabetes (IRR 1.25, 95% CI 1.14-1.37). Previous cataract surgery was associated with a decreased rate of falls that required hospitalisations by 13% (IRR 0.87, 95% CI 0.81-0.95) compared with those who did not have cataract surgery., Conclusion: The findings highlight the importance of continuous clinical monitoring of visual field loss and injury prevention strategies for older adults with visual field loss., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Emergency department observation units (EDOUs) are used to manage common pediatric illnesses and reduce the admission rate to the hospital. Most of these patients require a short duration of observation before a determination can be made whether they need to be admitted to the hospital or safely discharged home. The purpose of this study was to determine the characteristics of admissions from a pediatric EDOU for the top 10 diagnoses admitted to the unit. This will help standardize the disposition of such types of patients from the ED, hence improving the efficiency of the unit., Methods: We did a retrospective surveillance study of admitted patients from 0 to 18 years of age from the EDOU for the top 10 diagnoses. Descriptive data were reported using percentages and medians with interquartile ranges. Pearson χ 2 tests were used to determine significant differences ( P < 0.05) between the reason for admission and medical history., Results: In total, 520 patients were admitted from the EDOU during the study period. The median patient age was 3.39 years, with most being Hispanic and female. The top three primary diagnoses of all admitted patients were cellulitis and abscess, gastroenteritis, and bronchiolitis. Sixty-three percent of all admitted patients had secondary diagnoses. Most of these patients were admitted to the inpatient unit due to progression of the primary condition., Conclusions: The characteristics of admissions from the EDOU may help us to understand historical experience regarding diagnoses, timing, and indications of deterioration, resource utilization, and other metrics that resulted in transfers of EDOU patients to the intensive care unit/operating room/inpatient units.

Objective: Epicardial adipose tissue (EAT) quantity is associated with poor cardiovascular outcomes. However, the quality of EAT may be of incremental prognostic value. Cardiac magnetic resonance (CMR) is the gold standard for tissue characterization but has never been applied for EAT quality assessment. We aimed to investigate EAT quality measured on CMR T1 mapping as a predictor of poor outcomes in an all-comer cohort., Methods: We investigated the association of EAT area and EAT T1 times (EAT-T1) with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all-cause death., Results: A total of 966 participants were included (47.2% female; mean age: 58.4 years) in this prospective observational CMR registry. Mean EAT area and EAT-T1 were 7.3 cm 2 and 268 ms, respectively. On linear regression, EAT-T1 was not associated with markers of obesity, dyslipidemia, or comorbidities such as diabetes (p > 0.05 for all). During a follow-up of 57.7 months, a total of 280 (29.0%) events occurred. EAT-T1 was independently associated (adjusted hazard ratio per SD: 1.202; 95% CI: 1.022-1.413; p = 0.026) with the composite endpoint when adjusted for established clinical risk., Conclusions: EAT quality (as assessed via CMR T1 times), but not EAT quantity, is independently associated with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all-cause death., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Firearm injuries (FI) remain a significant cause of morbidity and mortality globally. Antibiotic use, supported by guideline recommendations for preventing post-injury infections in FI cases, encounters uncertainties regarding the selection of anti-microbial agents and associated outcomes. This study aimed to investigate the relationship between Injury Severity Scores (ISS) for FI cases presented to the emergency department., Methods: We empirically revised antimicrobial treatment protocols based on culture results and mortality rates. In the study, 164 firearm injury cases, admitted to the emergency department in 2022 and subsequently hospitalized in clinics and intensive care units (ICU), were evaluated. Cases included in the study were categorized into four groups based on ISS: mild, moderate, severe, and profound injury severity. The study compared the timing of hospital presentation following the injury, hospital length of stay, tissue or blood culture positivity, empirical treatment administered, antimicrobial revision based on culture results, need for ICU admission, mortality status, and ISS among the cases. Data were analyzed using IBM SPSS Statistics 22.0 (SPSS Inc., Chicago, IL). Variables in trauma patients were compared among various groups using Pearson Chi-Square tests. Binary logistic regression tests were performed to identify independent risk factors. A significance level of p<0.05 was considered statistically significant., Results: The study included 164 patients, all of whom were male. The mean age was calculated as 28.9±4.51 years. The average hospital length of stay was 25.54±21.81 days. Eighty-three patients (50.6%) required intensive care. Tissue cultures were obtained from 79 patients (48%). Bacterial growth was observed in 45 of these 79 patients (57%). The appropriate empirical antibiotic treatment rate, assessed among patients who received empirical treatment followed by culture-based antibiotic sensitivity testing, was 48.9%. It was observed that empirical antibiotic regimens were appropriate in 80% of cases in the mild group and 16.7% in the profound severe group (p=0.005). Our study compared the relationship between hospitalization duration and ISS groups. It was observed that hospitalization duration was significantly shorter in the mild group compared to the other groups (p=0.003, p=0.000, p=0.000). It was also observed that the need for ICU admission was higher in groups with higher ISS, indicating a correlation between higher ISS and increased ICU requirements (p=0.000)., Conclusion: In conclusion, for cases of firearm injuries, we believe empirical antimicrobial therapy should be initiated with narrow-spectrum agents such as beta-lactam + beta-lactamase inhibitor or third-generation cephalosporin + nitroimidazole in the mild group, considering the lack of Pseudomonal activity.

Background: An understanding of viral testing rates is crucial to accurately estimate the pathogen-specific hospitalisation burden. We aimed to estimate the patterns of testing for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus (PIV) and human metapneumovirus (hMPV) by geographical location, age and time in children <5 years old in Western Australia., Methods: We conducted a population-based cohort study of children born between 1 January 2010 and 31 December 2021, utilising linked administrative data incorporating birth and death records, hospitalisations and respiratory viral surveillance testing records from state-wide public pathology data. We examined within-hospital testing rates using survival analysis techniques and identified independent predictors of testing using binary logistic regression., Results: Our dataset included 46,553 laboratory tests for RSV, influenza, PIV, or hMPV from 355,021 children (52.5% male). Testing rates declined in the metropolitan region over the study period (RSV testing in infants: from 242.11/1000 child-years in 2012 to 155.47/1000 child-years in 2018) and increased thereafter. Conversely, rates increased in non-metropolitan areas (e.g., RSV in Goldfields: from 364.92 in 2012 to 504.37/1000 child-years in 2021). The strongest predictors of testing were age <12 months (adjusted odds ratio [aOR] = 2.25, 95% CI 2.20-2.31), preterm birth (<32 weeks: aOR = 2.90, 95% CI 2.76-3.05) and remote residence (aOR = 0.77, 95% CI 0.73-0.81)., Conclusion: These current testing rates highlight the potential underestimation of respiratory virus hospitalisations by routine surveillance and the need for estimation of the true burden of respiratory virus admissions., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Bronchiectasis carries a significant economic burden with high health care expenditures associated with frequent hospitalizations, physician visits, and treatments, including oral and intravenous antibiotics for repeated lung infections, airway-clearance therapy, and oxygen administration. Bronchiectasis exacerbations can contribute to this burden., Objective: To estimate US health care resource utilization (HCRU) and costs associated with bronchiectasis and with bronchiectasis exacerbations., Methods: This retrospective study used the 100% Medicare Fee-for-Service database (January 2014 to December 2020) to compare HCRU and costs among patients with bronchiectasis with those of patients without bronchiectasis (controls). For patients with bronchiectasis, the index date was a randomly selected bronchiectasis claim after more than 1 year of disease history and, for controls, a claim closest to their matched bronchiectasis patient's index date. All patients had continuous enrollment for at least 12 months pre-index (baseline) and at least 12 months post-index. Primary outcomes were all-cause, respiratory-related, and bronchiectasis-related HCRU and health care costs, which were presented by the overall sample and by segmented patient cohorts based on the number of exacerbations during baseline (0, 1, or ≥2)., Results: 92,529 patients with bronchiectasis (mean [SD] age, 76.7 [8.8] years; 72.3% female) and 92,529 matched controls qualified for the study. Compared with controls, patients with bronchiectasis presented greater mean (SD) all-cause physician visits (15.4 [10.0] vs 13.2 [9.7]; P < 0.001) and respiratory-related physician visits (5.2 [4.3] vs 1.9 [3.1]), pulmonologist visits (1.9 [2.2] vs 0.3 [1.0]), hospitalizations (0.4 [0.9] vs 0.3 [0.8]), emergency department visits (0.33 [1.0] vs 0.26 [1.0]), and total health care costs ($10,224 [$23,263] vs $6,704 [$19,593]). Respiratory-related HCRU was also greater in patients with more baseline exacerbations, with total health care costs of $8,506, $10,365, and $14,790 for patients with 0, 1, and at least 2 exacerbations, respectively ( P < 0.01)., Conclusions: This real-world study demonstrates the high disease burden associated with bronchiectasis and with exacerbations, highlighting the need to improve management and reduce exacerbations.

Respiratory syncytial virus is a major causative agent of lower respiratory tract infection in children, especially infants with substantial morbidity and mortality implications. The virus undergoes continuous evolution documented by accumulation of mutations in the glycoprotein gene necessitating vigilant surveillance to provide essential data to epidemiologists and researchers involved in development of vaccines. This study was aimed to perform molecular characterization of respiratory syncytial virus (RSV) among children ≤ 5 years admitted in hospital. In the current study we observed RSV-A (2019 (n = 95) and 2021 (n = 61) seasons) and RSV-B (2022 season (n = 68)). Phylogenetic analysis revealed all RSV-A strains (n = 47) to be GA.2.3.5 and RSV-B (n = 22) were classified as GB.5.0.5a. Selection pressure analysis identified one positive (P274L/V) and one negative site (P230T) in RSV-A, while in RSV-B there was only one negatively selected site (S295). This study spanning over three seasons contributes to RSV evolutionary dynamics in India emphasizing the importance of on-going surveillance to inform effective public health strategies and vaccine development efforts., (© 2024 Wiley Periodicals LLC.)

Background: The relationship of patient characteristics and social determinants of health (SDOH) with hospitalizations and costs in patients with major depressive disorder (MDD) has not been assessed using real-world data., Objective: To identify factors associated with higher hospitalizations and costs in patients with MDD., Methods: A retrospective observational study identified patients aged 18 years and older newly diagnosed with MDD between July 1, 2016, and December 31, 2018. SDOH were linked to patients at the "near-neighborhood" level. Multivariable models assessed association of patient characteristics with hospitalizations (incidence rate ratios [95% CI]) and costs (cost ratios [95% CI])., Results: Of 1,958,532 patients with MDD, 49.6% had Commercial and 50.4% Medicaid insurance; mean ages were similar (43.9; 43.4) with more female patients (67.6%; 70.5%). MDD patients with Commercial insurance had a mean household income of $75,044; 53.2% were married; 76.5% owned their home; 64.4% completed high school or less; and 2.8% had limited English-language proficiency (LEP). Patients covered by Medicaid had a household income of $46,708; 68.1% lived alone with 41.6% married; 54.6% owned their home; more than 4-in-5 patients (80.8%) completed high school or less, and 6.3% had LEP. Nearly one-third of Medicaid insured patients with MDD had at least 1 hospitalization (29.6%) with a mean length of stay 6.8 days; total health care costs were $21,467 annually. Commercially insured patients with MDD had 14.7% hospitalization rates with a length of stay of 5.9 days; total costs were $14,531. Multivariable models show female patients are less likely (Commercial 0.87; Medicaid 0.80; P < 0.05), and patients with more comorbidities are more likely to be hospitalized (Commercial 1.33; Medicaid 1.27; P < 0.05). All treatment classes relative to antidepressants only increased likelihood of hospitalizations-particularly antipsychotic+antianxiety use (Commercial 2.99; Medicaid 2.29)-and costs (Commercial 2.32; Medicaid 2.00) (all P < 0.05). Household income was inversely associated with hospitalizations for both insured populations. LEP reduced the likelihood of hospitalizations by more than 70% among Medicaid patients (0.27, P < 0.05) and was associated with higher costs for Commercial (2.01) but lower costs for Medicaid (0.37) ( P < 0.05). Living in areas with no shortage of mental health practitioners was associated with higher hospitalizations and costs., Conclusions: We identified patient characteristics associated with higher rates of hospitalizations and costs in patients with MDD in 2 insured populations. Female sex, higher comorbidities, and living in areas with no shortage of mental health practitioners were associated with higher hospitalizations and costs, whereas income was inversely associated with hospitalizations. The findings suggest disparities in access to care related to income, LEP, and availability of mental health practitioners that should be addressed to assure equitable care for patients with MDD.

This retrospective cohort study analyzed data from a Japanese health insurance database to assess the effectiveness of baloxavir (n = 4822) for preventing severe events compared with oseltamivir (n = 10,523) in patients with influenza B. The primary endpoint was hospitalization incidence (Days 2-14). The secondary endpoints included intravenous antibacterial drug use, pneumonia hospitalization, heart failure hospitalization, inhalational oxygen requirement, and use of other anti-influenza drugs. The hospitalization incidence was significantly lower with baloxavir (0.15% vs. 0.37%; risk ratio: 2.48, 95% confidence interval: 1.13-5.43). Pneumonia and additional anti-influenza therapy were also less frequent with baloxavir, thus supporting its use. Trial Registration: UMIN Clinical Trials Registry Study ID: UMIN000051382., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

We assessed the effect of rotavirus vaccination coverage on the number of inpatients with gastroenteritis of all ages in Japan. We identified patients admitted with all-cause gastroenteritis during 2011-2019 using data from the Diagnosis Procedure Combination system in Japan. We used generalized estimating equations with a Poisson distribution, using hospital codes as a cluster variable to estimate the impact of rotavirus vaccination coverage by prefecture on monthly numbers of inpatients with all-cause gastroenteritis. We analyzed 294,108 hospitalizations across 569 hospitals. Higher rotavirus vaccination coverage was associated with reduced gastroenteritis hospitalizations compared with the reference category of vaccination coverage <40% (e.g., for coverage >80%, adjusted incidence rate ratio was 0.87 [95% CI 0.83-0.90]). Our results show that achieving higher rotavirus vaccination coverage among infants could benefit the entire population by reducing overall hospitalizations for gastroenteritis for all age groups.

Background: Influenza represents a significant global health burden for individuals and society. This study assessed the burden of medically attended influenza at a tertiary medical center in Lebanon to describe the demographics, risk factors, and outcomes prior to the COVID-19 pandemic., Methods: This was a retrospective review of patients who tested positive for the influenza virus during three seasons between July 1, 2016 to June 30, 2019, at the American University of Beirut Medical Center., Results: A total of 2049 patients who tested positive for influenza were analyzed. Influenza A accounted for 79.6 % of cases, and influenza B for 19.7 %, with influenza activity starting in October/November and peaking in December/January. Older age above 65 years (AOR=3.584), obesity (AOR=2.183), and chronic conditions such as chronic lung diseases (AOR=1.832), and bacterial co-infection (AOR= 2.834) were found to be independent risk factors for developing complications. Viral co-infection increased the likelihood of death tenfold. Vaccinated patients had a shorter mean hospital stay duration and a lower intensive care unit admission rate., Conclusion: The burden of medically attended influenza at our tertiary medical center in Lebanon prior to the COVID-19 pandemic was high. Vaccination decreased the likelihood of complications leading to intensive care unit admission in patients at risk., Competing Interests: Declaration of Competing Interest All the authors declare that they have no established conflicting financial interests or personal relationships that may have influenced the research presented in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: A granular understanding of respiratory syncytial virus (RSV) burden in England is needed to prepare for new RSV prevention strategies. We estimated the rates of RSV hospital admissions before the age of 2 years in England and described baseline characteristics., Methods: A birth cohort of all infants born between March 1, 2015, and February 28, 2017 (n = 449,591) was established using Clinical Practice Research Datalink-Hospital Episode Statistics. Case cohorts included infants with admission for (1) RSV, (2) bronchiolitis, (3) any respiratory tract infection (RTI) <24 months and (4) RSV predicted by an algorithm <12 months. Baseline characteristics were described in the case and comparative cohorts (infants without corresponding admission). Cumulative incidence and admission rates were calculated. Multiple linear regression was used to estimate the proportion of RTI healthcare visits attributable to RSV., Results: The RSV-coded/RSV-predicted case cohorts were composed of 4813/12,694 infants (cumulative incidence: 1.1%/2.8%). Case cohort infants were more likely to have low birth weight, comorbidities and to be born during RSV season than comparative cohort infants, yet >77% were term-healthy infants and >54% were born before the RSV season. During the first year of life, 11.6 RSV-coded and 34.4 RSV-predicted hospitalizations occurred per 1000 person-years. Overall, >25% of unspecified lower RTI admissions were estimated to be due to RSV., Conclusions: In England, 1 in 91 infants had an RSV-coded admission, likely underestimated by ~3-fold. Most infants were term-healthy infants born before the RSV season. To decrease the total burden of RSV at the population level, immunization programs need to protect all infants., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: In June 2022, French health authorities issued a universal recommendation for routine administration and reimbursement of rotavirus vaccines in infants. Given this recent recommendation by French health authorities, we sought to understand the public health impact of a universal rotavirus vaccination strategy compared with no vaccination., Materials and Methods: A deterministic, age-structured, nonlinear dynamic transmission model, accounting for herd immunity, was developed. We considered 3 vaccination coverage scenarios: high (95%), medium (75%) and low (55%). Model parameter values were based on published modeling and epidemiological literature. Model outcomes included rotavirus gastroenteritis (RVGE) cases and healthcare resource utilization due to RVGE (hospitalizations, general practitioner or emergency department visits), as well as the number needed to vaccinate to prevent 1 RVGE case (mild or severe) and 1 RVGE-related hospitalization. Model calibration and analyses were conducted using Mathematica 11.3., Results: Over 5 years following implementation, RVGE cases for children under 5 years are estimated to be reduced by 84% under a high vaccination coverage scenario, by 72% under a medium vaccination coverage scenario and by 47% under a low vaccination coverage scenario. Across all scenarios, the number needed to vaccinate to avert 1 RVGE case and hospitalization varied between 1.86-2.04 and 24.15-27.44, respectively., Conclusions: Rotavirus vaccination with high vaccination coverage in France is expected to substantially reduce the number of RVGE cases and associated healthcare resource utilization., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Current pediatric pressure injury (PI) prevention measures are based on risk factors related to PI development in adults. Children offer a unique concern for PI development because their bodies are still developing, and their skin responds differently to external pressure., Objective: To explore risk factors for the development of full-thickness PIs in children aged 21 weeks' gestation to 21 years., Methods: This retrospective, observational, correlational study included 799 hospitalized children who developed a PI. The pediatric and adult PI risk factors used in the study were identified from the International Pressure Ulcer Prevention and Treatment Guideline. A stepwise multivariate logistic regression model was used., Results: Multivariate analyses revealed that risk factors for predicting a full-thickness PI varied by age. For children aged 38 weeks to 12 months, risk factors included tissue perfusion and oxygenation: generalized edema, conditions of the OR, and nutrition deficits. For children aged 1 to 7 years, fragile skin status was a risk factor. For youth aged 8 to 21 years, the two risk factors were tissue perfusion and oxygenation: decreased oxygenation and extracorporeal membrane oxygenation. Across the total sample, extracorporeal membrane oxygenation, tissue perfusion and oxygenation: decreased oxygenation and malnutrition were risk factors for predicting a full-thickness PI., Conclusions: Full-thickness PI risk factors differ among the ages of pediatric patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Afghanistan introduced monovalent rotavirus vaccine (Rotarix) into its national immunisation schedule in January, 2018. While post-licensure studies have shown substantial declines in rotavirus gastroenteritis cases and deaths globally, there is little evidence of rotavirus vaccine effectiveness and impact from low-income countries in Asia. We aimed to evaluate the effectiveness of the Rotarix vaccine and the impact of Rotarix vaccine on rotavirus gastroenteritis hospitalisations (ie, hospital admissions) among children younger than 5 years in Afghanistan., Methods: We used a test-negative case-control design embedded in an active sentinel surveillance platform to evaluate vaccine effectiveness. Children born on or after Jan 1, 2018, who had documentation of their rotavirus vaccination status and who were admitted for acute gastroenteritis at one of four sentinel hospitals from May, 2018 to December, 2021 were eligible to be included. We used an unconditional logistic regression model to estimate vaccine effectiveness and 95% CIs for a complete series of doses compared with no rotavirus vaccine doses among patients admitted with acute gastroenteritis. Vaccine effectiveness against hospitalisation was calculated as (1 - [odds of being vaccinated in cases] / [odds of being vaccinated in controls]) × 100%. We compared pre-vaccine (2013-15) and post-vaccine (2019-21) surveillance data from two sites to calculate vaccine impact., Findings: The vaccine effectiveness analysis included 1172 cases and 2173 controls. Approximately 2108 (63·0%) of 3345 cases and controls were male, 1237 (37·0%) were female, and 2171 (65·0%) were aged 6-11 months. Two doses of Rotarix were 45% (95% CI 22-62) effective against rotavirus hospitalisation in children aged 6-59 months, adjusting for age, severity, admission year, and rotavirus season. Rotavirus positivity decreased from 51% pre-vaccine to 39% post-vaccine, resulting in a 39% adjusted reduction in rotavirus positivity among children younger than 5 years admitted with acute gastroenteritis., Interpretation: Rotarix showed moderate effectiveness in preventing rotavirus gastroenteritis hospitalisations, consistent with findings in other low-income countries. These findings support the continued administration of the rotavirus vaccine in Afghanistan., Funding: Gavi, the Vaccine Alliance., Translation: For the Dari translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Significant age and sex differences have been reported at each stage of the stroke pathway, from risk factors to outcomes. However, there is some uncertainty in previous studies with regard to the role of potential confounders and selection bias. Therefore, using German nationwide administrative data, we aimed to determine the magnitude and direction of trends in age- or sex-specific differences with respect to admission rates, risk factors, and acute treatments of ischemic and hemorrhagic stroke., Methods: We obtained and analyzed data from the Research Data Centres of the Federal Statistical Office for the years 2010 to 2020 with regard to all acute stroke hospitalizations, risk factors, treatments, and in-hospital mortality, stratified by sex and stroke subtype. This database provides a complete national-level census of stroke hospitalizations combined with population census counts. All hospitalized patients ≥15 years with an acute stroke (diagnosis code: I60-64) were included in the analysis., Results: Over the 11-year study period, there were 3 375 157 stroke events; 51.2% (n=1 728 954) occurred in men. There were higher rates of stroke admissions in men compared with women for both ischemic (378.1 versus 346.7/100 000 population) and hemorrhagic subtypes (75.6 versus 65.5/100 000 population) across all age groups. The incidence of ischemic stroke admissions peaked in 2016 among women (354.0/100 000 population) and in 2017 among men (395.8/100 000 population), followed by a consistent decline from 2018 onward. There was a recent decline in hemorrhagic stroke admissions observed for both sexes, reaching its nadir in 2020 (68.9/100 000 for men; 59.5/100 000 for women). Female sex was associated with in-hospital mortality for both ischemic (adjusted odds ratio, 1.11 [1.09-1.12]; P <0.001) and hemorrhagic stroke (adjusted odds ratio, 1.18 [95% CI, 1.16-1.20]; P <0.001)., Conclusions: Despite improvements in stroke prevention and treatment pathways in the past decade, sex-specific differences remain with regard to hospitalization rates, risk factors, and mortality. Better understanding the mechanisms for these differences may allow us to develop a sex-stratified approach to stroke care., Competing Interests: Dr Reinecke reports personal fees from Daiichi, MedUpdate, DiaPlan, NeoVasc, NovoNordisk, StreamedUp, and Corvia; grants and personal fees from Pluristem; and grants from BMS/Pfizer, Bard, and Biotronik; all outside the submitted work. Dr Anderson reports grants from the US National Institutes of Health and the American Heart Association. Dr Engelbertz has received travel support from Abbott outside the submitted work. Dr Rothwell has in the past provided consultancy services for Abbott Vascular, Bayer, Bristol-Myers Squibb, and Sanofi US Services. Dr Koeppe has received research funding from Stryker, outside the submitted work. The other author reports no conflicts.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness, with severe outcomes in older adults. Information on the prevalence, hospitalization rate, and impact on the health-related quality of life (HRQoL) of RSV in older adults with acute respiratory infections (ARI) in outpatient settings in Japan is limited., Methods: This multi-center epidemiological study included outpatients aged ≥60 years presenting with ARI between August 2021 and February 2023. Nasal and throat swabs were collected and tested by reverse transcription polymerase chain reaction (RT-PCR). The prevalence of RT-PCR-confirmed RSV (cRSV)-ARI, cRSV-lower respiratory tract disease (LRTD), and other respiratory viruses was calculated by season, region, age group, and RSV subtype. HRQoL was assessed via patient-reported outcomes., Results: The study included 923 ARI episodes (cRSV-ARI: N = 24; non-cRSV-ARI: N = 899). In years 1 and 2 (August 2021-July 2022 and August 2022-February 2023), the prevalence of cRSV-ARI was 2.5% and 2.8%, respectively. There was a predominance of RSV-B and RSV-A subtypes in years 1 and 2, respectively. In years 1 and 2 combined, 37.5% of cRSV-ARI cases had lower respiratory tract infection; all cRSV-LRTD cases occurred in those aged 60-74 years. RSV-ARI cases reported throat, chest, and respiratory symptoms, leading to impaired functioning and HRQoL., Conclusions: During the observed study period, RSV was circulating among older adults in Japan. RSV was a leading cause of ARI and LRTD. More data are needed to fully clarify the burden of RSV among older adults in Japan., Competing Interests: Declaration of Competing interest Eliazar Sabater Cabrera has been employed by and has held financial equities in GSK; Daniel Molnar was employed by and held financial equities in GSK during the conduct of the study and preparation of the manuscript; Silvia Damaso has been employed by and has held financial equities in GSK; Jean-Yves Pirçon has been employed by and has held financial equities in GSK; Maria Moitinho de Almeida has been employed by and has held financial equities in GSK; Victor Preckler Moreno was employed by and held financial equities in GSK when the study was conducted; Taizo Matsuki was employed by and held financial equities in GSK when the study was conducted, and is currently employed by MSD; Hiroshi Takahashi received funding from GSK to conduct this study; Daisuke Himeji received funding from GSK to conduct this study. Yasushi Fukushima received funding from GSK to conduct this study. These authors declare no other financial or non-financial relationships and activities. Hiroyuki Ohbayashi declares no financial or non-financial relationships and activities and no conflicts of interest; Takayuki Sakurai declares no financial or non-financial relationships and activities and no conflicts of interest; Arihiro Kiyosue declares no financial or non-financial relationships and activities and no conflicts of interest., (Copyright © 2024 [Author/Employing Institution]. Published by Elsevier B.V. All rights reserved.)

Objective: We described patterns and trends in ED use among adults with epilepsy in the United States., Methods: Utilizing inpatient and ED discharge data from seven states, we conducted a cross-sectional analysis to identify adult ED visits diagnosed with epilepsy or seizures from 2010 to 2019. Using ED visit counts and estimates of state-level epilepsy prevalence, we calculated ED visit rates overall and by payer, condition, and year., Results: Our data captured 304,935 ED visits with epilepsy as a primary or secondary diagnosis in 2019. Across the seven states, visit rates ranged between 366 and 726 per 1000 and were higher than rates for adults without epilepsy in all states but one. ED visit rates were highest among Medicare and Medicaid beneficiaries (vs commercial or self-pay). Adults with epilepsy were more likely to be admitted as inpatients. Visits for nervous system disorders were 6.3-8.2 times higher among people with epilepsy, and visits for mental health conditions were 1.2-2.6 times higher. Increases in ED visit rates from 2010 to 2019 among people with epilepsy exceeded increases among adults without by 6.0-27.3 percentage points., Conclusion: Adults with epilepsy visit the ED frequently and visit rates have been increasing over time. These results underscore the importance of identifying factors contributing to ED use and designing tailored interventions to improve ambulatory care quality., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Upper gastrointestinal bleeding (GIB) in patients has been well-characterized in liver cirrhosis but studies on lower GIB are limited. The clinical characteristics, management and outcomes in patients with and without liver cirrhosis was compared to determine the overall features of GIB in patients with liver cirrhosis compared with non-cirrhotics., Methods: A retrospective study on cirrhotics hospitalized for GIB 2010-2021, matched with control group of non-cirrhotics (1:4) for upper vs. lower GIB. Patients with overt bleeding leading to hospitalization were included., Results: Overall, 396 patients had cirrhosis, 267 (67%) men, median age 62, alcoholic etiology 177/396 (45%), median MELD 12 (range 6-32). Overall 102 cirrhotics had GIB, matched with 391 non-cirrhotics. Overall 87 (85%) cirrhotic patients had upper and 15% lower GIB. Compared to non-cirrhotics, the cause of GIB was more commonly acute variceal bleeding (AVB) (42% vs. 1%), hemorrhoids 40% vs. 6% ( p  = 0.002), less commonly gastric ulcer 13% vs. 31% ( p  < 0.001), duodenal ulcer 9% vs. 29% ( p  < 0.001), 5% of cirrhotics used NSAIDs vs. 26% of controls ( p  < 0.001). Rebleeding occurred in 14% of cirrhotics vs. 3% in controls ( p  < 0.001). Only one cirrhotic patient (1%) died from GIB vs. 0.8% of controls within 45 days. Overall mortality 45 days after hospitalization was 10% in cirrhotics vs. 5% in controls ( p  < 0.001)., Conclusions: Bleeding from gastric and duodenal ulcers were less common in cirrhotics than in controls. Bleeding from hemorrhoids was more common in cirrhotics. Mortality due to GIB was low in both groups but overall mortality was significantly higher in cirrhotics.

Objectives: To describe and compare healthcare resource utilization (HRU) among advanced therapy-naïve and advanced therapy-experienced patients with ulcerative colitis (UC) initiating ustekinumab or vedolizumab in the United States., Methods: Claims data from IQVIA PharMetrics Plus de-identified database (01/01/2015-06/30/2022) were used to identify adult patients with UC initiating ustekinumab or vedolizumab (index date) after 10/21/2019. Baseline characteristics were balanced using inverse probability of treatment weighting. All-cause and UC-related HRU (number of inpatient admissions, inpatient days, emergency department visits, and outpatient visits) were described during the post-index period, and Poisson regression models were used to evaluate associations between index therapy and HRU outcomes. Analyses were performed separately among advanced therapy-naïve or advanced therapy-experienced patients., Results: A total of 444 (ustekinumab) and 1,917 (vedolizumab) advanced therapy-naïve patients, and 647 (ustekinumab) and 1,152 (vedolizumab) advanced therapy-experienced patients were identified. In advanced therapy-naïve patients, higher rates of UC-related inpatient days (rate ratio [95% confidence interval] = 1.84 [1.15, 3.58]; p  = 0.004), emergency department visits (1.39 [1.01, 2.17]; p  = 0.044), and outpatient visits (1.81 [1.61, 2.04]; p  < 0.001) were observed among patients initiating vedolizumab relative to ustekinumab. In advanced therapy-experienced patients, higher rates of UC-related inpatient admissions (1.47 [1.06, 2.12]; p  = 0.012), inpatient days (2.18 (1.44, 3.71); p  < 0.001), and outpatient visits (1.50 (1.19, 1.82); p  < 0.001) were observed among patients initiating vedolizumab relative to ustekinumab. Results were similar when all-cause HRU was examined., Conclusions: Among patients with UC with and without advanced therapy experience, higher rates of all-cause and UC-related HRU were observed among those treated with vedolizumab relative to ustekinumab.

Objective: Hospitalized children are a potentially underimmunized population. We sought to determine the proportion of patients admitted to our pediatric medicine inpatient units who are underimmunized or unimmunized and to identify barriers to immunization faced by families of children admitted to hospital., Methods: We conducted a prospective study of children aged 2 months to 18 years admitted to our pediatric medicine inpatient units between July 2021 and October 2022. Immunization and demographic data were collected from electronic medical charts. Immunization status of each child was categorized as up-to-date if they had received all eligible vaccine doses in accordance with the provincial immunization schedule. Caregivers completed a survey on barriers to immunizations; results were compared between caregivers of children whose vaccines were up-to-date and those who were not., Results: Hospitalized children were missing more doses of the preschool vaccines than the general population based on published provincial data. Only 142 of 244 (58.2%) of study patients were up-to-date on all their immunizations. Caregivers of children whose immunizations were not up-to-date reported significantly more barriers to vaccination in all survey categories: access to shots, concerns about shots, and importance of shots., Conclusions: There is a disparity in immunization status between children admitted to hospital in a Canadian setting compared with national targets and community immunization rates. Caregivers of underimmunized hospitalized children cited significantly more barriers to immunization when compared with hospitalized children who are up-to-date. Pursuing a hospital-based immunization strategy could lead to improved immunization status for hospitalized children., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning., Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study., Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20)., Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19., Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research., Competing Interests: Declaration of interests AHa is co-director and owner of H2CD, and owner and director of Future Cognition, which support online studies and develop custom cognitive assessment software, respectively. PJHe is director and CEO of H2CD. JDC declares grants from AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Gilead Sciences, and Genentech; and consulting fees from AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Gilead Sciences, Chiesi, Zambon, and Genentech. L-PH declares grants to their institution from UK Research and Innovation (UKRI), Regenerative Medicine Platform, Celgene, British Lung Foundation, and Oxford Boehringer Ingleheim; the author is on the advisory board for the CATALYST trial and acts as chair of the Respiratory Translational Research Collaboration. AHo declares a grant to their institution from UKRI and the UK National Institute for Health Research (NIHR) to complete this work, funding from NIHR Manchester Clinical Research Facility to support study delivery, and personal funding from NIHR Manchester Biomedical Research Centre (BRC). AHo declares institutional payments to support grant-funded research from NIHR, UK Medical Research Council (MRC), Cystic Fibrosis Trust, Cystic Fibrosis Foundation, North West Lung Centre Charity, and Moulton Trust; consulting fees from Mylan Pharmaceuticals for advisory board participation; and payment from Vertex Pharmaceuticals for educational presentation, participation on a clinical trials advisory board, and writing of a review article. AHo's non-paid roles include chair of the Cystic Fibrosis Clinical Trials Accelerator Program, deputy chair of the NIHR Respiratory Translational Research Collaboration, and director of a university spin-out company (Mi-trial). BR declares payments from the British Heart Foundation Oxford Centre of Research Excellence, NIHR Oxford BRC, and UKRI for grants and contracts; and consulting fees from Axcella Therapeutics. ASh, ASi, and MM declare a grant to their institution from UKRI and NIHR to complete this work. ASh declares unremunerated participation on the AstraZeneca Thrombotic Thrombocytopenic Taskforce and Scottish and UK Governments COVID-19 advisory groups. LH-W declares a grant from NIHR unrelated to the submitted work; acting as independent chair of the NIHR Health Technology Assessment Committee for Colour COPD trial; and membership of the American Thoracic Society Pulmonary Rehabilitation Assembly Web and Planning Committees. NIL declares acting as director of research at the Intensive Care Society UK. CEB declares a grant to their institution from UKRI and NIHR to complete this work; the author reports grants from GSK, AstraZeneca, Sanofi, Boehringer Ingelheim, Chiesi, Novartis, Roche, Genentech, Mologic, and 4DPharma; and consultancy fees paid to their institution from GSK, AstraZeneca, Sanofi, Boehringer Ingelheim, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, and Teva. LVW declares research funding unrelated to the submitted work from GSK and Orion; consulting fees unrelated to the submitted work from Galapagos; a Wellcome Conference speaker honorarium; travel support from Genentech; advisory board participation for Galapagos; and an associate editor role for the European Respiratory Journal. RAE declares a grant to their institution from UKRI and NIHR to complete this work; the author declares speaker fees from Boehringer Ingelheim and unpaid roles as European Respiratory Society Assembly 01·02 Pulmonary Rehabilitation secretary and with the American Thoracic Society Pulmonary Rehabilitation Assembly programme committee. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are increasingly being used among hospitalized patients. Our objective was to assess the risk of diabetic ketoacidosis (DKA) among hospitalized patients receiving an SGLT-2i., Research Design and Methods: We conducted a multicentre cohort study of patients hospitalized at 19 hospitals. We included patients over 18 years of age who received an SGLT-2i or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in hospital. The primary outcome was the risk of DKA during their hospitalization., Results: 61,517 patients received a DPP-4i and 11,061 received an SGLT-2i. The risk of inpatient DKA was 0.07 % (N = 41 events) among adults who received a DPP-4i and 0.18 % (N = 20 events) among adults who received an SGLT-2i; adjusted odds ratio of 3.30 (95 % CI: 1.85-5.72)., Conclusions: In hospitalized patients, the absolute risk of DKA was 0.2 %, which corresponded to a three-fold higher relative risk., Competing Interests: Declaration of competing interest MF was a consultant for ProofDx, a start-up company creating point of care diagnostic tests for COVID-19 using CRISPR. MF is an advisor for SIGNAL1, a start-up company deploying machine learned models to improve inpatient care. MF has been paid for medicolegal cases unrelated to the content of this study. FR is a provincial clinical lead for quality improvement at Ontario Health (as a part-time salaried employee). This research was undertaken, in part, with funding from the Canada Research Chairs Program. AV is a part-time employee of Ontario Health and is supported by the Temerty Professorship of AI Research and Education in Medicine at the University of Toronto., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: ESO is supported by a US National Institutes of Health grant (R01AG057725). All other authors declare no competing interests.

Objectives: Small for gestational age (SGA) singletons are at increased risk for neurodevelopmental abnormalities. Scarce data exist regarding the long-term implications of SGA in twins. We opted to study the association between SGA of one twin and long-term neurologic related morbidity in dichorionic diamniotic twins., Study Design: A population-based retrospective cohort study including consecutive dichorionic diamniotic twins, born between the years 1991 and 2021 at a tertiary medical center was conducted. Total and subtypes of neurologic related pediatric hospitalizations among SGA versus non-SGA twins were compared. A Kaplan-Meier survival curve was used to compare the cumulative neurologic morbidity incidence, and a Cox proportional hazards model was constructed to adjust for confounders., Results: The study population included 4222 newborns; 180 (4.3%) were SGA. Rate of long-term neurologic related hospitalizations was comparable between the two groups (8.7 vs. 8.0%, p = 0.755; Kaplan-Meier survival curve Log-rank p = 0.652). Using a Cox proportional hazards model, controlling for gender and birth order, no association was found between SGA and the risk for subsequent neurologic pediatric morbidity of the offspring (Adjusted HR = 1.0, 95% CI 0.6-1.8, p = 0.973)., Conclusions: SGA is not associated with an increased risk for long-term pediatric neurologic morbidity in dichorionic diamniotic twins., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In the U.S., overdose deaths and substance treatment admissions related to methamphetamine are rising. This study aims to measure and compare U.S. temporal trends in methamphetamine-involved psychiatric hospitalizations., Methods: We conducted a population-based, trend analysis of U.S. psychiatric hospitalizations and calculated quarterly (Q) rates per 100,000 population of substance-involved psychiatric hospitalizations. We assessed U.S. regional quarterly percentage hospitalization rate changes using Joinpoint regression., Results: From Q4 2015-Q4 2019, there were 963,202 psychiatric hospitalizations, 50,223 (5.2 %) involved methamphetamine and 102,877 (10.7 %) involved opioids and/or cocaine without methamphetamine. Methamphetamine-involved psychiatric hospitalization rates increased by 68.0 %, psychiatric hospitalizations rates involving opioid and/or cocaine without methamphetamine decreased by 22 %, while nonsubstance-involved psychiatric hospitalizations rates remained unchanged. The largest significant increases in methamphetamine-involved psychiatric hospitalization rates were among people >61 years old, males, and Midwesterners. Methamphetamine-involved psychiatric hospitalization rates doubled among Black patients. The largest average percent increase among methamphetamine-involved psychiatric hospitalizations was 10.2 % from Q4 2015-Q2 2017 in the Midwest., Conclusion and Relevance: Most psychiatric hospitalizations did not involve substances. Methamphetamine-involved psychiatric hospitalizations greatly increased while opioid-involved psychiatric hospitalizations decreased, but involved more total encounters. Greater access to harm reduction services, contingency management programs, and mental health services is urgently needed., Competing Interests: Declaration of Competing Interest None of the authors have conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic has had several phases with varying characteristics. We aimed to compare severity outcomes in different phases in a population with limited bias from risk factors., Methods: In a nationwide observational study of all unvaccinated first-time COVID-19 test positive individuals in Sweden aged 18-64 years without comorbidity, from week 45 of 2020 to week 5 of 2022, variant periods with certain variants constituting ≥ 92 % of all whole genome-sequenced cases nationwide, were compared regarding hospitalisation (with main discharge code of COVID-19), severe illness (use of high-flow nasal oxygen or admission to intensive care unit), and death due to COVID-19. Logistic regression was used to estimate odds ratios (ORs) for comparison of these outcomes between variant periods, using adjustments for variant period, age, sex, country of birth, place of residence, income, and education., Findings: The study included 789,133 individuals, including 15,145 hospitalised individuals. Among all individuals, the adjusted ORs for hospitalisation were 1.7 for the Alpha period vs the Pre-variant period (week 45-52 2020), 1.8 for the Delta period vs the Alpha period, and 0.1 for the Omicron period vs the Delta period (all comparisons significant). Among hospitalised individuals, the adjusted ORs for severe illness were 1.4 for the Alpha period vs the Pre-variant period, 1.7 for the Delta period vs the Alpha period, and 0.5 for the Omicron period vs the Delta period (all comparisons significant), and the adjusted ORs for death were 1.1 for the Alpha period vs the Pre-variant period (non-significant), 1.8 for the Delta period vs the Alpha period (significant), and 0.1 for the Omicron period vs the Delta period (non-significant)., Interpretation: In this population with limited bias from risk factors, vaccination, and previous infection, disease severity increased from the pre-variant to the Delta period and then decreased with the Omicron period, among all individuals and among hospitalised individuals. These severity outcome differences should be considered when the pandemic is evaluated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: This article aims to characterise hospital admissions involving opioid toxicity across South Australia to guide future implementation and evaluation of risk mitigation strategies., Methods: International Classification of Diseases, 10th Edition codes (T40.0-T40.4) were used to identify admissions involving pre-hospital opioid toxicity in public hospitals across South Australia from 1 June 2017 to 30 August 2020. Demographic and episode of care data were extracted and summarised using descriptive statistics. Admission cost estimates were calculated using Independent Hospital Pricing Authority data., Results: A total of 2046 cases met the criteria for inclusion; over half (56%) were female and median age on admission was 44 years (interquartile range 27 years). Where opioid toxicity was the primary diagnosis, 70% of admissions did not specify the responsible opioid and 23% were related to heroin use. One-fifth of admissions occurred outside of metropolitan Adelaide. Individuals living in an area of relative socio-economic disadvantage were over-represented. Over half of admissions required a stay >24 h; 19% were admitted for ≥5 days, 22% required intensive care and ~10% required mechanical ventilation. The total estimated cost of admissions involving opioid toxicity in South Australia over the 3-year period was $18,230,546.50, equating to $5.6 million per annum., Discussions and Conclusions: These findings highlight the significant personal, fiscal, and systemic impacts of opioid toxicity-related hospital admissions in South Australia and provide a baseline to evaluate the effectiveness of initiatives to reduce opioid-related harm, including real-time prescription monitoring and take-home naloxone supply., (© 2024 Australasian Professional Society on Alcohol and other Drugs.)

Background: People with immune-mediated inflammatory disease are at increased risk of pneumococcal pneumonia. The effectiveness of pneumococcal vaccination in people with immune-mediated inflammatory diseases has not been evaluated. We investigated the effectiveness of pneumococcal vaccination in preventing morbidity and mortality associated with pneumonia in patients with immune-mediated inflammatory diseases., Methods: In this matched case-control study, we used primary-care electronic health record data from the Clinical Practice Research Datalink Gold database in the UK, with linked hospitalisation and mortality data. Adults with incident common immune-mediated inflammatory diseases diagnosed between April 1, 1997, and Dec 31, 2019, were followed up from the first diagnosis date to the occurrence of an outcome or date of last follow-up. Cases (ie, those with an outcome of interest) were age-matched and sex-matched to up to ten contemporaneous controls by use of incidence density sampling. Outcomes were hospitalisation due to pneumonia, death due to pneumonia, or primary-care consultation for lower respiratory tract infection requiring antibiotics. We defined hospital admission for pneumonia using hospital discharge diagnoses, death due to pneumonia using death certification data, and lower respiratory tract infection as present when primary-care consultation and antibiotic prescription occurred on the same date. We used multivariable, unconditional, logistical regression and constructed three models to examine the association between pneumococcal vaccination as an exposure and each of the three outcomes., Findings: The first nested case-control analysis included 12 360 patients (7326 [59·3%] women and 5034 [40·7%] men): 1884 (15·2%) who were hospitalised due to pneumonia and 10 476 (84·8%) who were not admitted to hospital due to pneumonia. The second analysis included 5321 patients (3112 [58·5%] women and 2209 [41·5%] men): 781 (14·7%) who died due to pneumonia and 4540 (85·3%) who were alive on the index date. The third analysis included 54 530 patients (33 605 [61·6%] women and 20 925 [38·4%] men): 10 549 (19·3%) with lower respiratory tract infection treated with antibiotics and 43 981 (80·7%) without infection. In the multivariable analysis, pneumococcal vaccination was negatively associated with hospitalisation due to pneumonia (adjusted odds ratio 0·70 [95% CI 0·60-0·81]), death due to pneumonia (0·60 [0·48-0·76]), and lower respiratory tract infection treated with antibiotics (0·76 [0·72-0·80])., Interpretation: Pneumococcal vaccination is associated with protection against hospitalisation and death due to pneumonia in patients with immune-mediated inflammatory diseases, without apparent residual confounding. However, residual unmeasured confounding cannot be fully excluded in observational research, which includes nested case-control studies. These findings should also be corroborated with data from other countries, given that this study used UK-based data., Funding: National Institute for Health and Care Research., Competing Interests: Declaration of interests AA reports personal fees from UpToDate (royalty), Cadilla Pharmaceuticals (lecture fees), and Limbic (consulting), unrelated to this work. CDM is Director of the National Institute for Health and Care Research (NIHR) School for Primary Care Research. Keele University has received research funding for CDM from the NIHR and the Medical Research Council. JSNV-T was seconded to the UK Department of Health and Social Care from October, 2017, to March, 2022. He performed a one-off consultancy for MSD, which manufactures PPV23, in May, 2023. All other authors declare no competing interests. The views expressed in this manuscript are those of its authors and not necessarily those of the NIHR, the Department of Health and Social Care, or any other entity mentioned above., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Importance: Medications for opioid use disorder (MOUD) are highly effective, but only 22% of individuals in the US with opioid use disorder receive them. Hospitalization potentially provides an opportunity to initiate MOUD and link patients to ongoing treatment., Objective: To study the effectiveness of interprofessional hospital addiction consultation services in increasing MOUD treatment initiation and engagement., Design, Setting, and Participants: This pragmatic stepped-wedge cluster randomized implementation and effectiveness (hybrid type 1) trial was conducted in 6 public hospitals in New York, New York, and included 2315 adults with hospitalizations identified in Medicaid claims data between October 2017 and January 2021. Data analysis was conducted in December 2023. Hospitals were randomized to an intervention start date, and outcomes were compared during treatment as usual (TAU) and intervention conditions. Bayesian analysis accounted for the clustering of patients within hospitals and open cohort nature of the study. The addiction consultation service intervention was compared with TAU using posterior probabilities of model parameters from hierarchical logistic regression models that were adjusted for age, sex, and study period. Eligible participants had an admission or discharge diagnosis of opioid use disorder or opioid poisoning/adverse effects, were hospitalized at least 1 night in a medical/surgical inpatient unit, and were not receiving MOUD before hospitalization., Interventions: Hospitals implemented an addiction consultation service that provided inpatient specialty care for substance use disorders. Consultation teams comprised a medical clinician, social worker or addiction counselor, and peer counselor., Main Outcomes and Measures: The dual primary outcomes were (1) MOUD treatment initiation during the first 14 days after hospital discharge and (2) MOUD engagement for the 30 days following initiation., Results: Of 2315 adults, 628 (27.1%) were female, and the mean (SD) age was 47.0 (12.4) years. Initiation of MOUD was 11.0% in the Consult for Addiction Treatment and Care in Hospitals (CATCH) program vs 6.7% in TAU, engagement was 7.4% vs 5.3%, respectively, and continuation for 6 months was 3.2% vs 2.4%. Patients hospitalized during CATCH had 7.96 times higher odds of initiating MOUD (log-odds ratio, 2.07; 95% credible interval, 0.51-4.00) and 6.90 times higher odds of MOUD engagement (log-odds ratio, 1.93; 95% credible interval, 0.09-4.18)., Conclusions: This randomized clinical trial found that interprofessional addiction consultation services significantly increased postdischarge MOUD initiation and engagement among patients with opioid use disorder. However, the observed rates of MOUD initiation and engagement were still low; further efforts are still needed to improve hospital-based and community-based services for MOUD treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT03611335.