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Annual vaccination against seasonal influenza viruses is recommended for certain individuals that have a high risk for complications resulting from infection with these viruses. Recently it was recommended in a number of countries including the USA to vaccinate all healthy children between 6 and 59 months of age as well. However, vaccination of immunologically naïve subjects against seasonal influenza may prevent the induction of heterosubtypic immunity against potentially pandemic strains of an alternative subtype, otherwise induced by infection with the seasonal strains. Here we show in a mouse model that the induction of protective heterosubtypic immunity by infection with a human A/ H3N2 influenza virus is prevented by effective vaccination against the A/H3N2 strain. Consequently, vaccinated mice were no longer protected against a lethal infection with an avian A/H5N1 influenza virus. As a result H3N2-vaccinated mice continued to loose body weight after A/H5N1 infection, had 100-fold higher lung virus titers on day 7 post infection and more severe histopathological changes than mice that were not protected by vaccination against A/H3N2 influenza. The lack of protection correlated with reduced virus-specific CD8+ T cell responses after A/H5N1 virus challenge infection. These findings may have implications for the general recommendation to vaccinate all healthy children against seasonal influenza in the light of the current pandemic threat caused by highly pathogenic avian A/H5N1 influenza viruses. [ABSTRACT FROM AUTHOR]

Determines whether ganglioside GM1-like epitopes in campylobacter are specific to O sero-types associated with Guillain-Barre syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis. Collection of isolates in the United States using a cholera toxin-binding assay; Percentage of isolates positive for the GM1-like epitope; Exposure of humans to strains exhibiting GM1-like mimicry.

Objectives: The autogenous arteriovenous access for chronic hemodialysis is recommended over the prosthetic access because of its longer lifespan. However, more than half of the United States dialysis patients receive a prosthetic access. We conducted a systematic review to summarize the best available evidence comparing the two accesses types in terms of patient-important outcomes. Methods: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and SCOPUS) and included randomized controlled trials and controlled cohort studies. We pooled data for each outcome using a random effects model to estimate the relative risk (RR) and its associated 95% confidence interval (CI). We estimated inconsistency caused by true differences between studies using the I2 statistic. Results: Eighty-three studies, of which 80 were nonrandomized, met eligibility criteria. Compared with the prosthetic access, the autogenous access was associated with a significant reduction in the risk of death (RR, 0.76; 95% CI, 0.67-0.86; I2 = 48%, 27 studies) and access infection (RR, 0.18; 95% CI, 0.11-0.31; I2 = 93%, 43 studies), and a nonsignificant reduction in the risk of postoperative complications (hematoma, bleeding, pseudoaneurysm and steal syndrome, RR 0.73; 95% CI, 0.48-1.16; I2 = 65%, 31 studies) and length of hospitalization (pooled weighted mean difference –3.8 days; 95% CI, –7.8 to 0.2; P = .06). The autogenous access also had better primary and secondary patency at 12 and 36 months. Conclusion: Low-quality evidence from inconsistent studies with limited protection against bias shows that autogenous access for chronic hemodialysis is superior to prosthetic access. [Copyright &y& Elsevier]

Aims: Reliable national estimates for the incidence and prevalence of immunoglobulin A nephropathy (IgAN) in the United States (U.S.) are needed. We performed a national survey with pathologists and used insurance claims data to estimate IgAN frequency nationwide., Materials and Methods: An online survey with pathologists was conducted between November and December 2021 to obtain data on the number and types of biopsies evaluated and the proportion with IgAN confirmed. Biopsy data were extrapolated to two different claims databases to estimate incidence and prevalence. Results were validated against a separate dataset of electronic health records., Results: A total of 43 pathologists from across U.S. regions reported evaluating a mean of 169 kidney biopsies (standard deviation 179.1) in the past 12 months. Of the 7,267 total biopsies evaluated, 632 (8.7%) were IgAN. Based on the respective claims databases, annual incidence rates of 2.1 and 2.2 per 100,000 and prevalence rates of 59.9 and 62.7 per 100,000 were estimated. Results from the validation dataset were similar, with an incidence of 1.9 per 100,000 and prevalence of 54.2 per 100,000., Conclusion: This study estimated incidence and prevalence of IgAN. Extrapolating the findings to the U.S. population for 2021, total prevalence was 198,887 - 208,184 persons.

Background and Purpose: This study was undertaken to compare the sensitivity and specificity of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria for multifocal motor neuropathy (MMN) with those of the American Association of Electrodiagnostic Medicine (AAEM)., Methods: Sensitivity and specificity of the two sets of criteria were retrospectively evaluated in 53 patients with MMN and 280 controls with axonal peripheral neuropathy, inflammatory demyelinating polyneuropathy, or amyotrophic lateral sclerosis. Comparison of the utility of nerve conduction studies with different numbers of nerves examined was also assessed., Results: The 2010 EFNS/PNS criteria had a sensitivity of 47% for definite MMN and 57% for probable/definite MMN, whereas the AAEM criteria had a sensitivity of 28% for definite MMN and 53% for probable/definite MMN. The sensitivity of the AAEM criteria was higher when utilizing area compared to amplitude reduction to define conduction block. Using supportive criteria, the sensitivity of the 2010 EFNS/PNS criteria for probable/definite MMN increased to 64%, and an additional 36% patients fulfilled the criteria (possible MMN). Specificity values for definite and probable/definite MMN were slightly higher with the AAEM criteria (100%) compared to the EFNS/PNS criteria (98.5% and 97%). Extended nerve conduction studies yielded slightly increased diagnostic sensitivity for both sets of criteria without significantly affecting specificity., Conclusions: In our patient populations, the 2010 EFNS/PNS criteria demonstrated higher sensitivity but slightly lower specificity compared to the AAEM criteria. Extended nerve conduction studies are advised to achieve slightly higher sensitivity while maintaining very high specificity., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Chikungunya virus infection can lead to long-term debilitating symptoms. A precursor phase 3 clinical study showed high seroprotection (defined as a 50% plaque reduction of chikungunya virus-specific neutralising antibodies on a micro plaque reduction neutralisation test [μPRNT] titre of ≥150 in baseline seronegative participants) up to 6 months after a single vaccination of the chikungunya virus vaccine VLA1553 (Valneva Austria, Vienna, Austria) and a good safety profile. Here we report antibody persistence and safety up to 2 years., Methods: In this single-arm, multicentre, phase 3b study, we recruited participants from the precursor phase 3 trial from professional vaccine trial sites in the USA. Participants (aged ≥18 years) were eligible if they had completed the previous study and received VLA1553. Chikungunya virus-specific neutralising antibodies were evaluated at 28 days, 6 months, and 1 year and 2 years after vaccination. The primary outcome was the proportion of seroprotected participants (ie, μPRNT 50 titre of ≥150) at 1 and 2 years, assessed in all eligible participants who had at least one post-vaccination immunogenicity sample available, overall and by age group at the time of vaccination (18-64 years and ≥65 years). Adverse events of special interest at the time of transition from the previous study to the current study (ie, at 6 months) and serious adverse events during the current study were recorded (ie, between 6 months and 2 years). All analyses were descriptive. This study is registered with ClinicalTrials.gov, NCT04838444, and immunogenicity follow-up is ongoing., Findings: In the precursor study, participants were screened between Sept 17, 2020, and April 10, 2021; data cutoff for this analysis was March 31, 2023. Of 2724 participants in the precursor study who received one dose of VLA1553, 363 participants were analysed in this study (310 [85%] aged 18-64 years and 53 [15%] aged ≥65 years at enrolment in the precursor study; mean age 47·7 years [SD 14·2], 207 [57%] of 363 participants were female, 156 [43%] were male, 280 [77%] were White, and 314 [87%] were not Hispanic or Latino). Strong seroprotection was observed at 1 year (98·9% [356 of 360 assessable participants; 97·2-99·7]) and 2 years (96·8% [306 of 316; 94·3-98·5]) after vaccination, and was very similar between those aged 18-64 years (at 1 year: 98·7% [303 of 307; 96·7-99·6]; at 2 years: 96·6% [256 of 265; 93·7-98·4]) and those aged 65 years and older (at 1 year: 100% [53 of 53; 93·3-100]; at 2 years: 98·0% [50 of 51; 89·6-100]) at each timepoint. No adverse events of special interest were ongoing at the time of transition. Ten serious adverse events occurred in nine (2%) participants between the 6-month and 2-year timepoints, including one death (due to drug overdose) that was determined to not be related to VLA1553., Interpretation: After a single VLA1553 vaccination, chikungunya virus-neutralising antibodies above the threshold considered to be protective persisted up to 2 years and there were no long-term serious adverse events related to vaccination. VLA1553 is an efficient and safe intervention that offers high seroprotection against chikungunya virus infection, a virus likely to spread globally with an urgent demand for long-lasting prophylaxis., Funding: Valneva Austria, Coalition for Epidemic Preparedness Innovation, and EU Horizon 2020., Competing Interests: Declaration of interests All authors (except RMa) are current or former Valneva employees and all except SH and ST own stock or have share options, or both, in Valneva. NW, SH, and ST are previous employees of Valneva. NW is a current employee of the Coalition for Epidemic Preparedness Innovation and is an inventor in a patent (US 20220313810 A1; single shot chikungunya virus vaccine) relevant to the work. RH is an inventor in a patent (WO2021/028407 A1; single shot chikungunya virus vaccine) relevant to the work. RMa is consultant of Valneva and received payments for medical writing support on other projects and is an inventor in a patent relevant to the work (patent application number PCT/EP2024/056050 [immunogenic chikungunya compositions for administration to immunocompromised patients] filed at the European Patent Office, The Hague, Netherlands)., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: High-risk pregnancies and birth defects are often greater within communities of color where resources for a healthy pregnancy are generally lacking. Infant and maternal mortality, preterm birth, and instances of increased developmental and physical defects are related to environmental exposures (e.g., pesticides, lead in water, wildfire smoke), dietary additives, and lack of access to adequate healthcare. More frequently people of color and other under-served groups, are affected by historical inequality and unconscious bias. Compounding these disparities, research into these issues and efforts to address them are poorly supported., Methods: The speakers in this symposium presented evidence for health disparities within communities of color to foster research aimed at identifying toxic levels of potentially hazardous dietary chemicals, or exposures in the pediatric population can focus on addressing the current inadequacy of translating scientific findings into enforceable policies., Results: The disparities discussed within this symposium highlighted key areas in desperate need of policy reform. In the United States, regulatory exposure levels have been established for lead exposures but frequently exceed these limits without mitigation. Neural tube defects can be prevented by a simple dietary solution such as fortification of staple foods with folic acid. Recent literature on gender as a social determinant of health has determined women suffer more negative health consequences due to social attitudes., Conclusions: Ultimately, this symposium provided an understanding of the experience of disadvantaged and marginalized persons during pregnancy, illustrated the disparities that exist in reproductive health, and described the need to address and prevent them., (© 2024 Wiley Periodicals LLC.)

Importance: The World Health Organization has called for eliminating cervical cancer as a public health problem. Accurate and up-to-date estimates of population-based cervical cancer incidence are essential for monitoring progress toward elimination and informing local cancer control strategies, but these estimates are lacking for the US-Affiliated Pacific Islands (USAPI)., Objective: To calculate age-standardized incidence rates for cervical cancer in the 6 USAPI and compare these rates with rates in the US (50 states and the District of Columbia)., Design, Setting, and Participants: This cross-sectional study used population-based data from the Pacific Regional Central Cancer Registry for women aged 20 years or older who were diagnosed with invasive cervical cancer from January 1, 2007, to December 31, 2020. The registry comprises data on all cervical cancers from the USAPI, which include 3 US territories (American Samoa, Commonwealth of the Northern Mariana Islands, and Guam) and 3 freely associated states (Federated States of Micronesia [FSM], Republic of the Marshall Islands [RMI], and Republic of Palau). Data were analyzed from July 10, 2023, to November 28, 2023., Main Outcomes and Measures: The main outcome was age-standardized cervical cancer incidence rates, stratified by age, stage, and histologic code for the USAPI using population estimates from 3 different sources (US Census Bureau International Database, United Nations Population Division, and Pacific Data Hub). Rate ratios were calculated to compare incidence rates between the USAPI and the US., Results: From 2007 to 2020, 409 cases of cervical cancer were diagnosed in the USAPI (median age at diagnosis, 46.0 years [25th-75th percentile, 39.0-55.0 years]), with an age-standardized incidence rate ranging from 21.7 (95% CI, 19.6-23.9) to 22.1 (95% CI, 20.0-24.4) per 100 000 women, depending on the population estimate. Incidence rates were highest in RMI, ranging from 58.1 (95% CI, 48.0-69.7) to 83.4 (95% CI, 68.3-101.0) per 100 000 women, followed by FSM, ranging from 28.7 (95% CI, 23.4-34.9) to 29.8 (95% CI, 24.3-36.3) per 100 000 women. Compared with the US, incidence rates were highest in RMI (rate ratio, 5.7 [95% CI, 4.7-6.8] to 8.2 [95% CI, 6.7-9.9]) and FSM (rate ratio; 2.8; 95% CI, 2.3-3.4). Of all cases in the USAPI, 213 (68.2%) were diagnosed at a late stage., Conclusions and Relevance: In this cross-sectional study, cervical cancer remained a major public health issue in some USAPI, with RMI reporting the highest incidence rates. The findings suggest that improvements in human papillomavirus vaccination and cancer screening coverage through efforts tailored to the unique geographic, sociocultural, economic, and health care landscape of the USAPI may reduce the burden of cervical cancer.

Catheter-based angiography is an essential procedure for the diagnosis and treatment of vascular complications in patients. Since cerebral and coronary angiography are similar techniques that utilize the same access sites and general principles, the associated risks overlap and should be identified to help direct patient care. The purpose of this study was to determine complication rates in a combined cohort of cerebral and coronary angiography patients, as well as conduct a comparative analysis of coronary and cerebral angiography complications. The National Inpatient Sample was queried from 2008 to 2014 to identify patients who underwent coronary or cerebral angiography. After assessment of baseline characteristics, complication rates, and disposition in the combined cohort, propensity matching was utilized to create sub-cohorts of coronary and cerebral angiography patients based on demographics and comorbidities. Comparative analysis of procedural complications and disposition was then performed. A total of 3,763,651 hospitalizations were included in our study cohort (3,505,715 coronary angiographies and 257,936 cerebral angiographies). The median age was 62.9 years, with females being 46.42%. The most prevalent comorbidities in the overall cohort were hypertension (69.92%), coronary artery disease (69.48%), smoking (35.64%), and diabetes mellitus (35.13%). Propensity matching demonstrated that the cerebral angiography cohort had lower rates of acute and unspecified renal failure (5.4% vs 9.2%, OR 0.57, 95% CI, 0.53-0.61, P < 0.001), hemorrhage/hematoma formation (0.8% vs 1.3%, OR 0.63, 95% CI, 0.54-0.73, P < 0.001), and equivalent rates of retroperitoneum hematoma formation (0.03% vs 0.04%, OR 1.49, 95% CI, 0.76-2.90, P = 0.247) and arterial embolism/thrombus formation (0.3% vs 0.3%, OR 1.01, 95% CI, 0.81-1.27, P = 0.900). Our study showed both cerebral and coronary angiography have generally low rates of procedural complications. Matched cohort analysis demonstrated that cerebral angiography patients are at no greater risk for complications than coronary angiography patients., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Incidence rates of Lyme borreliosis, a tickborne disease attributed to infection by Borrelia species, are increasing, and limitations to existing treatments potentiate the possibility of severe outcomes. Nevertheless, there are no licensed vaccines for Lyme borreliosis prevention in humans. This study investigated the immunogenicity and safety of a booster dose of VLA15, an investigational outer surface protein A (OspA)-based Lyme borreliosis vaccine that has previously shown safety and immunogenicity when administered as a primary vaccination series, following a primary VLA15 vaccination series., Methods: We report the results of the booster phase of a randomised, observer-blinded, placebo-controlled, multicentre, phase 2 study that enrolled healthy adults aged 18-65 years from five US clinical study centres to receive 135 μg or 180 μg VLA15 or placebo at months 0, 2, and 6 in the main study phase. Participants who received 180 μg VLA15 in the main study phase and did not have relevant protocol deviations were eligible for the booster phase (months 18-30). Participants were randomly reassigned (2:1) to receive an intramuscular injection of a VLA15 booster or placebo 1 year after the completion of primary vaccination (month 18) via a randomisation list generated by an unmasked statistician with a block size of six. Individuals involved in data safety monitoring, rerandomisation, vaccine handling, and vaccine accountability were unmasked; the study sponsor and statisticians were only unmasked after analysis of data up to 1 month after booster administration. All other individuals remained masked throughout the booster phase. The outcomes for the booster phase were the immunogenicity (evaluated in the booster per-protocol population) and safety (evaluated for all participants who received the booster) of the booster dose up to month 30. The study is registered at ClinicalTrials.gov (NCT03970733) and is completed., Findings: Between Feb 4 and March 23, 2021, 58 participants (28 men and 30 women) were screened, randomly assigned, and received VLA15 (n=39) or placebo (n=19). One participant in the placebo group was lost to follow-up. The IgG geometric mean titres for each OspA serotype (serotypes 1-6) in the VLA15 group peaked at 1 month after the booster dose (1277·0 U/mL [95% CI 861·8-1892·3] to 2194·5 U/mL [1566·8-3073·7] vs 23·6 U/mL [18·1-30·8] to 36·8 U/mL [26·4-51·3] in the placebo group [p<0·0001 for all serotypes]), remained elevated at month 24 (137·4 U/mL [95·8-196·9] to 265·8 U/mL [202·9-348·2] vs 22·3 U/mL [17·7-28·0] to 29·1 U/mL [20·8-40·6] in the placebo group; p<0·0001 for all serotypes), and declined by month 30 (54·1 U/mL [38·6-75·7] to 101·6 U/mL [77·6-133·1] vs 21·9 U/mL [18·0-26·6] to 24·9 U/mL [19·0-32·6] in the placebo group; p<0·0001 for all serotypes except serotype 1 [p=0·0006]). Solicited local adverse events were reported more frequently in the VLA15 group (35 [92%, 95% CI 79-97] of 38 participants) than the placebo group (six [32%, 15-54] of 19 participants; p<0·0001) after booster vaccination. There was no significant difference in the frequency of solicited systemic adverse events between groups (20 [59%, 42-74] of 34 participants in the VLA15 group vs six [38%, 18-61] of 16 participants in the placebo group). Related unsolicited adverse events (none severe) were reported by two (5%, 1-17) of 39 participants in the VLA15 group and none (0%, 0-17) of 19 participants in the placebo group. There were no severe solicited local or systemic adverse events or deaths during the study., Interpretation: A booster dose of VLA15 is safe and induces substantial anamnestic immune responses against all six OspA serotypes. As with previously investigated OspA-based Lyme borreliosis vaccines, waning immune responses were observed with VLA15, and annual boosters might therefore be required., Funding: Valneva., Competing Interests: Declaration of interests SKG, MS, KD, LW, VK, MO, RH, WB, SE-L, and NB are current or former employees of Valneva and may hold stock or stock options. AK, JL-S, and UD are paid consultants for Valneva., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Breast cancer is the most common cancer diagnosed among women globally and in the United States (US); however, its incidence in the six US-Affiliated Pacific Islands (USAPI) remains less characterized., Methods: We analyzed data from a population-based cancer registry using different population estimates to calculate incidence rates for breast cancer among women aged >20 years in the USAPI. Rate ratios and 95 % confidence intervals (CI) were calculated to compare incidence rates between the USAPI and the US (50 states and the District of Columbia)., Results: From 2007-2020, 1118 new cases of breast cancer were diagnosed in the USAPI, with 66.3 % (n = 741) of cases reported in Guam. Age-standardized incidence rates ranged from 66.4 to 68.7 per 100,000 women in USAPI and 101.1-110.5 per 100,000 women in Guam. Compared to the US, incidence rates were lower in USAPI, with rate ratios ranging from 0.38 (95 % CI: 0.36, 0.40) to 0.39 (95 % CI: 0.37, 0.42). The proportion of late-stage cancer was significantly higher in the USAPI (48.7 %) than in the US (34.0 %), particularly in the Federated States of Micronesia (78.7 %) and Palau (73.1 %)., Conclusions: Breast cancer incidence rates were lower in the USAPI than in the US; however, late-stage diagnoses were disproportionately higher. Low incidence and late-stage cancers may signal challenges in screening, cancer surveillance, and health care access and resources. Expanding access to timely breast cancer screening, diagnosis, and treatment could reduce the proportion of late-stage cancers and improve survival in the USAPI., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest related to the content of this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Due to the nursing faculty shortage, expert clinical nurses are working as novice clinical instructors (CIs). Orientation is needed to prepare these nurses to teach; however, lack of evidence-based guidelines for orientation programs can lead to variability among institutions., Purpose: The purpose of this study was to describe clinical nursing faculty orientation practices in the United States., Methods: A descriptive convergent mixed methods design was used., Results: One hundred thirteen CIs participated. Of these, 70.8% were not provided with a formal orientation to their role. Duration, modality, and content varied widely among orientations. Four themes were derived from the qualitative data: Administrative Requirements, Transition to Clinical Educator, Mentorship, and Resilience., Conclusions: Clinical faculty orientation practices vary widely in the United States. Evidence-based guidelines are needed to streamline orientations to provide CIs with the requisite knowledge and skills to support clinical students., Competing Interests: The authors declare no conflicts of interest or relevant funding., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Rising Lyme borreliosis incidence rates, potential for severe outcomes, and limitations in accurate and timely diagnosis for treatment initiation suggest the need for a preventive vaccine; however, no vaccine is currently available for human use. We performed two studies in adults to optimise the dose level and vaccination schedule for VLA15, an investigational Lyme borreliosis vaccine targeting outer surface protein A (OspA) serotypes 1-6, which are associated with the most common pathogenic Borrelia species in Europe and North America., Methods: Both randomised, observer-blind, placebo-controlled, multicentre phase 2 studies included participants aged 18-65 years without recent history of Lyme borreliosis or tick bites. Study one was conducted at nine clinical research and study centre sites in the USA (n=6), Germany (n=2), and Belgium (n=1); study two was conducted at five of the study one US sites. Based on a randomisation list created by an unmasked statistician for each study, participants were randomly assigned via an electronic case report form randomisation module to receive 90 μg (study one only), 135 μg, or 180 μg VLA15 or placebo by intramuscular injection at months 0, 1, and 2 (study one) or 0, 2, and 6 (study two). Study one began with a run-in phase to confirm safety, after which the Data Safety Monitoring Board recommended the removal of the 90 μg group and continuation of the study. In the study one run-in phase, randomisation was stratified by study site, whereas in the study one main phase and in study two, randomisation was stratified by study site, age group, and baseline B burgdorferi (sensu lato) serostatus. All individuals were masked, other than staff involved in randomisation, vaccine preparation or administration, or safety data monitoring. The primary endpoint for both studies was OspA-specific IgG geometric mean titres (GMTs) at 1 month after the third vaccination and was evaluated in the per-protocol population. Safety endpoints were evaluated in the safety population: all participants who received at least one vaccination. Both studies are registered at ClinicalTrials.gov (study one NCT03769194 and study two NCT03970733) and are completed., Findings: For study one, 573 participants were screened and randomly assigned to treatment groups between Dec 21, 2018, and Sept, 26, 2019. For study two, 248 participants were screened and randomly assigned between June 26 and Sept 3, 2019. In study one, 29 participants were assigned to receive 90 μg VLA15, 215 to 135 μg, 205 to 180 μg, and 124 to placebo. In study two, 97 participants were assigned to receive 135 μg VLA15, 100 to 180 μg, and 51 to placebo. At 1 month after the third vaccination (ie, month 3), OspA-specific IgG GMTs in study one ranged from 74·3 (serotype 1; 95% CI 46·4-119·0) to 267·4 units per mL (serotype 3; 194·8-367·1) for 90 μg VLA15, 101·9 (serotype 1; 87·1-119·4) to 283·2 units per mL (serotype 3; 248·2-323·1) for 135 μg, and 115·8 (serotype 1; 98·8-135·7) to 308·6 units per mL (serotype 3; 266·8-356·8) for 180 μg. In study two, ranges at 1 month after the third vaccination (ie, month 7) were 278·5 (serotype 1; 214·9-361·0) to 545·2 units per mL (serotype 2; 431·8-688·4) for 135 μg VLA15 and 274·7 (serotype 1; 209·4-360·4) to 596·8 units per mL (serotype 3; 471·9-754·8) for 180 μg. Relative to placebo, the VLA15 groups had more frequent reports of solicited local adverse events (study one: 94%, 95% CI 91-96 vs 26%, 19-34; study two: 96%, 93-98 vs 35%, 24-49 after any vaccination) and solicited systemic adverse events (study one: 69%, 65-73 vs 43%, 34-52; study two: 74%, 67-80 vs 51%, 38-64); most were mild or moderate. In study one, unsolicited adverse events were reported by 52% (48-57) of participants in the VLA15 groups and 52% (43-60) of those in the placebo groups; for study two these were 65% (58-71) and 69% (55-80), respectively. Percentages of participants reporting serious unsolicited adverse events (study one: 2%, 1-4; study two: 4%, 2-7) and adverse events of special interest (study one: 1%, 0-2; study two: 1%, 0-3) were low across all groups. A single severe, possibly related unsolicited adverse event was reported (worsening of pre-existing ventricular extrasystoles, which resolved after change of relevant concomitant medication); no related serious adverse events or deaths were reported., Interpretation: VLA15 was safe, well tolerated, and elicited robust antibody responses to all six OspA serotypes. These findings support further clinical development of VLA15 using the 180 μg dose and 0-2-6-month schedule, which was associated with the greatest immune responses., Funding: Valneva., Competing Interests: Declaration of interests NB, LW, VK, MO, NW, RH, MS, KD, SE-L, and WB are current or former employees of Valneva and may hold stock or stock options. UD, AK, and JL-S are paid consultants for Valneva., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: The present study examined how activity engagement mediates the association between personality and cognition., Methods: Participants were middle-aged and older adults (Age range: 24-93 years; N  > 16,000) from the Midlife in the United States Study, the Health and Retirement Study, the English Longitudinal Study of Ageing, and the Wisconsin Longitudinal Study of Aging. In each sample, personality traits and demographic factors were assessed at baseline, engagement in cognitive, physical, and social activities was assessed in a second wave, and cognition was measured in a third wave, 8 to 20 years later., Results: Random-effect meta-analyses indicated that lower neuroticism and higher extraversion, openness, and conscientiousness were prospectively associated with better cognition. Most of these associations were partly mediated by greater engagement in physical and cognitive activities but not social activities. Physical activity accounted for 7% (neuroticism) to 50% (extraversion) and cognitive activity accounted for 14% (neuroticism) to 45% (extraversion) of the association with cognition., Conclusion: The present study provides replicable evidence that physical and cognitive activities partly mediate the prospective association between personality traits and cognitive functioning.

The U.S.-affiliated Pacific Islands (USAPI) have higher cervical cancer incidence and mortality rates and lower screening coverage compared with the United States. This is likely because of economic, geographical, health care delivery, and cultural barriers for women living in these resource-constrained, isolated regions. The most recent U.S. and World Health Organization cervical cancer screening guidelines recommended primary human papillomavirus (HPV) testing as one screening option or the preferred screening modality. Primary HPV screening-based strategies offer several advantages over current screening methods in the USAPI. However, adoption of this newer screening modality has been slow in the United States and not yet incorporated into USAPI screening programs. The U.S. Centers for Disease Control and Prevention and partners initiated the Pacific Against Cervical Cancer (PACe) project in 2019 to evaluate the feasibility, acceptability, and cost-effectiveness of primary HPV testing-based strategies in Guam and in Yap, Federated States of Micronesia. This report provides an overview of the PACe project and outlines the approaches we took in implementing primary HPV testing as a new cervical cancer screening strategy (including the option of self-sampling in Yap), encompassing four core components: (1) community engagement and education, (2) medical and laboratory capacity building, (3) health information and system improvement, and (4) modeling and cost-effectiveness analysis. The PACe project provides examples of systematic implementation and resource appropriate technologies to the USAPI, with broader implications for never screened and under-screened populations in the United States and Pacific as they face similar barriers to accessing cervical cancer screening services.

Few studies have investigated paternal characteristics in relationship with adverse pregnancy outcomes, and results are inconsistent. The purpose of this study was to review studies examining associations between characteristics of Black fathers and adverse pregnancy outcomes in the United States. A systematic narrative synthesis was conducted of research studies examining paternal characteristics of Black fathers in association with adverse pregnancy outcomes: preterm birth, hypertensive disorders of pregnancy, gestational diabetes, spontaneous abortion, and maternal mortality. Seven databases (Academic Search Premier, CINHAL, CENTRAL, ClinicalTrials.gov, Embase, PubMed, and Web of Science) were searched for original research articles from inception to February 2023. Articles were excluded if they (a) were in a language other than English, (b) did not describe original research, (c) included a geographic region outside of the United States, (d) did not include adverse maternal outcomes as a study outcome, (e) did not describe race of fathers in the study sample, and (f) did not describe a paternal characteristic of Black fathers. The search resulted in 210 articles. Six studies were included in the final review; five studies examined associations between paternal characteristics of Black fathers and preterm birth, finding significantly increased odds of preterm birth among births with Black fathers. Among births with non-Hispanic Black paternity, the odds of hypertensive disorders of pregnancy were reduced or not significantly associated. Researchers should continue to explore paternal factors that influence pregnancy outcomes in racial/ethnic-specific models to identify optimal intervention strategies to improve disparities in maternal and child health outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Telemedicine use in prenatal care has greatly expanded without substantial research. Optimizing user experiences can increase telemedicine's utilization to support care access. The purpose of this study was to explore patient and provider experiences using telemedicine for routine prenatal care during the COVID-19 pandemic, identifying factors affecting its utilization and satisfaction., Methods: In this mixed methods study, online surveys and semi-structured interviews with pregnant and postpartum patients and perinatal providers across the United States were used to explore experiences with telemedicine and prenatal care during the COVID-19 pandemic. Data were collected from July to December 2021. Survey findings were analyzed using descriptive and inferential statistics, and interviews were thematically coded and analyzed, followed by mixed methods analysis., Results: Results of 946 surveys (750 patients and 196 providers) and 30 interviews (15 patients and 15 providers) met inclusion for analysis. Telemedicine was utilized by 42% of patients and 72% of perinatal provider participants. The primary reason patients did not use telemedicine was because it was not offered. Patients and providers who did not use telemedicine expressed the following main concerns with virtual care: uncertainty about care quality, particularly when blood pressure and the fetal heart rate were not assessed, and potential challenges with developing trusting patient-provider relationships. Patients and providers who used telemedicine rated their experience as mild to moderate satisfaction across the 6 Telehealth Usability Questionnaire domains. Satisfaction scores were not dependent on whether physical examination components were included in virtual visits., Discussion: Providing patients with the choice to use telemedicine as needed or combined with in-person visits for routine prenatal care may increase care utilization. Although not directly linked with satisfaction, interest in using telemedicine would likely increase for patients and providers concerned with care quality if blood pressure and fetal heart rate are assessed during virtual visits., (© 2024 by the American College of Nurse‐Midwives.)

The present study sought to analyze malpractice cases related to gender affirming surgery to provide information to physicians as it may serve to minimize the risk of malpractice suits. The Westlaw and Lexis Nexis databases were queried for jury verdicts and settlements related to gender affirming surgery malpractice lawsuits. A total of 26 cases were identified between 1970 and 2020, five of which were determined relevant on further review. Motives included adverse surgical and medical outcomes, and failure to treat. All cases were decided in favor of the defendant and resulted in $0 compensatory damages., Competing Interests: Conflict of Interest This study did not receive any funding and none of the authors have no conflicts of interest to disclose. None of the authors has a financial interest in any of the products, devices, or drugs., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.

The integration of pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations with artificial intelligence/machine learning algorithms is one of the most attractive areas of the pharmacometric research. These hybrid techniques are currently under investigation to perform several tasks, among which precision dosing. In this scenario, this paper presents and evaluates a new framework embedding PK-PD models into a reinforcement learning (RL) algorithm, Q-learning (QL), to personalize pharmacological treatment. Each patient is represented with a set of PK-PD parameters and has a personal QL agent which optimizes the individual treatment. In the training phase, leveraging PK-PD simulations, the QL agent assesses different actions, defined consistently with the clinical knowledge to consider only plausible dose-adjustments, in order to find the optimal rules. The proposed framework was evaluated to optimize the erdafitinib treatment in patients with metastatic urothelial carcinoma. This drug was approved by the US Food and Drug Administration (FDA) with a dose-adaptive protocol based on monitoring the levels of serum phosphate, which represent a biomarker of both treatment efficacy and toxicity. To evaluate the flexibility of the methodology, a heterogeneous virtual population of 141 patients was generated using an erdafitinib population PK (PopPK)-PD literature model. For each patient, treatment response was simulated by using both QL-optimized protocol and the clinical one. QL agents outperform the approved dose-adaptive rules, increasing more than 10% the efficacy and the safety of treatment at each end point. Results confirm the great potentialities of the integration of PopPK-PD models and RL algorithms to optimize precision dosing tasks., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Background: Trauma is common in the United States, increases risk of long-term adverse health effects, and individuals who experience it often find seeking medical care difficult. Trauma-informed care (TIC) builds trust and fosters healing relationships between clinicians and patients; however medical education has lacked consistent training in TIC. Using recently published competencies for undergraduate medical education (UME), this manuscript provides curricular examples across 8 domains to assist faculty in developing educational content., Methods: The authors identified published curricula for each of the 8 competency domains using a published search strategy and publicly available database. Inclusion criteria were published works focused on UME in the United States; abstracts and curricula not focused on UME were excluded. The authors used a consensus-based process to review 15 eligible curricula for mapping with the competencies., Results: Of 15 published UME curricula, 11 met criteria and exemplify each of the 8 UME competency domains. Most of the available curricula fall into the Knowledge for Practice and Patient Care domains. Most were offered in the first 2 years of medical school., Conclusion: Competency-based medical education for TIC is new, and most current educational offerings are foundational in nature. Additional innovation is needed in the competency domains of Professionalism, Systems-Based Practice, Interprofessional Collaboration, and Personal/Professional Development. This manuscript offers a set of curricular examples that can be used to aid efforts at implementing TIC competencies in UME; future work must focus on improving assessment methods and developmental sequencing as more students are exposed to TIC principles., Competing Interests: Conflicts of InterestNone declared

Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcomes. Here, we mimicked IGF-1 deficiency of preterm newborns in mice by perinatal administration of an IGF-1 receptor antagonist. This resulted in sex-biased brain microstructural, functional, and behavioral alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioral tests. Pharmacological enhancement of GABAergic tonic inhibition by the U.S. Food and Drug Administration-approved drug ganaxolone rescued functional/behavioral alterations in mice. Establishing an unprecedented mouse model of prematurity, our work dissects the mechanisms at the core of abnormal behaviors and identifies a readily translatable therapeutic strategy for preterm brain disorders.

Objective: Despite the increasing representation of females in neurosurgical training, the fraction of female to male neurosurgeons decreases dramatically as faculty rank (Assistant, Associate, or Full Professor) increases. To assess this discrepancy, we quantified self-reported time-to-promotion trajectories for female and male neurosurgeons holding academic appointments., Methods: In this cross-sectional institutional review board (IRB)-approved study, 147 female and 84 male neurosurgeons currently holding faculty positions in the US were contacted via email and invited to complete an anonymous, standardized survey. Respondents provided the calendar year of postgraduate training completion, promotion to different faculty ranks, geographic region of current practice (Western, Midwest, Southern, Northeast), and practice subspecialty., Results: The response rate was 44.2% for females and 59.5% for males, with 114 participants included (65 female, 49 male). On average, female neurosurgeons required 25% longer to become an Associate Professor (P = 0.017), 34% longer to become a Full Professor (P = 0.004), 37% longer for promotion from Assistant to Associate Professor (P < 0.001), and 32% longer from Assistant to Full Professor (P = 0.012). Promotion timelines did not vary by region or specialty among male and female cohorts. Linear regressions revealed that female neurosurgeons with more recent training completion experienced shorter time-to-promotion to Associate and Full Professor compared to females of earlier generations (P = 0.005 and 0.001, respectively), while male timelines remained stable., Conclusions: This study identifies a significant delay in time-to-promotion for female neurosurgeons compared to their male counterparts. Investigation and standardization of promotion timelines are necessary to ensure meaningful representation gains from the increased number of women entering neurosurgical training., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Attachment of polyethylene glycol (PEG) chains is a common, well-studied, and Food and Drug Administration-approved method to address the pharmacokinetic challenges of therapeutic proteins. Occasionally, PEGylation impairs the activity of pharmacodynamics (PD). To overcome this problem, disease-relevant cleavable linkers between the polymer and the therapeutic protein can unleash full PD by de-PEGylating the protein at its target site. In this study, we engineered a matrix metalloproteinase (MMP)-responsive fibroblast growth factor 2 (FGF-2) mutant that was site-specifically extended with a PEG polymer chain. Using bioinspired strategies, the bioconjugate was designed to release the native protein at the desired structure/environment with preservation of the proliferative capacity in vitro on NIH3T3 cells. In vivo, hepatic exposure was diminished but not its renal distribution over time compared to unconjugated FGF-2. By releasing the growth factor from the PEG polymer in response to MMP cleavage, restored FGF-2 may enter hard-to-reach tissues and activate cell surface receptors or nuclear targets.

Aim: To assess treatment patterns and outcomes in patients with non-del(5q) lower-risk myelodysplastic syndromes. Methods: Patient medical records were reviewed in the USA, Canada (CAN), UK and the EU. Results: Analysis included 119 patients in the USA/CAN (median age, 61.5 years) and 245 patients in the UK/EU (median age, 67.3 years). Most patients received erythropoiesis-stimulating agents (ESAs) as first-line (1L) therapy (USA/CAN: 89.0%; UK/EU: 90.2%). A substantial proportion of 1L erythropoiesis-stimulating agent-treated patients were transfusion dependent before 1L (USA/CAN: 37.1%; UK/EU: 51.2%); a small percentage of these patients achieved transfusion independence during 1L therapy (USA/CAN: 2.8%; UK/EU: 14.4%). Conclusion: These findings highlight an unmet need for more effective treatments among patients with non-del(5q) lower-risk myelodysplastic syndromes.

ABSTRACT Unstable housing among persons diagnosed with HIV (PDWH) has been consistently linked to poor HIV-related care engagement. We examined the relationship between enrollment in a supportive housing program and health care utilization (use of outpatient services, emergency department (ED) visits, and hospitalizations) for a group of unstably housed, Medicaid and Health Homes (HH)-enrolled PDWH in New York State. We analyzed monthly longitudinal data consisting of linked supportive housing data, HH data, and Medicaid claims from New York State (excluding New York City) between 2012 and 2017 using time series models. Participants who had at least six consecutive months of supportive housing at month t had 20% higher odds of using an outpatient service, 19% lower odds of visiting the ED, and 24% lower odds of being hospitalized compared to those with less than six consecutive months of supportive housing after adjusting for covariates. Supportive housing may promote better medical management by increasing outpatient visits among chronically homeless PDWH.

Background Context: Anterior cervical discectomy and fusion (ACDF) is a commonly-performed and generally well-tolerated procedure used to treat cervical disc herniation. Rarely, patients require discharge to inpatient rehab, leading to inconvenience for the patient and increased healthcare expenditure for the medical system., Purpose: The objective of this study was to create an accurate and practical predictive model for, as well as delineate associated factors with, rehab discharge following elective ACDF., Study Design: This was a retrospective, single-center, cohort study., Patient Sample: Patients who underwent ACDF between 2012 and 2022 were included. Those with confounding diagnoses or who underwent concurrent, staged, or nonelective procedures were excluded., Outcome Measures: Primary outcomes for this study included measurements of accuracy for predicting rehab discharge. Secondary outcomes included associations of variables with rehab discharge., Methods: Current Procedural Terminology codes identified patients. Charts were reviewed to obtain additional demographic and clinical characteristics on which an initial univariate analysis was performed. Two logistic regression and two machine learning models were trained and evaluated on the data using cross-validation. A multimodel logistic regression was implemented to analyze independent variable associations with rehab discharge., Results: A total of 466 patients were included in the study. The logistic regression model with minimum corrected Akaike information criterion score performed best overall, with the highest values for area under the receiver operating characteristic curve (0.83), Youden's J statistic (0.71), balanced accuracy (85.7%), sensitivity (90.3%), and positive predictive value (38.5%). Rehab discharge was associated with a modified frailty index of 2 (p=.007), lack of home support (p=.002), and having Medicare or Medicaid insurance (p=.007) after correction for multiple hypotheses., Conclusions: Nonmedical social determinants of health, such as having public insurance or a lack of support at home, may play a role in rehab discharge following elective ACDF. In combination with the modified frailty index and other variables, these factors can be used to predict rehab discharge with high accuracy, improving the patient experience and reducing healthcare costs., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Indigenous people experience health disparities, including higher rates of substance use disorders (SUDs). Digital therapeutics are a growing platform for treatment services and have the potential to expand access to culturally responsive interventions for Indigenous people. As one of the first randomized controlled trials for SUDs for American Indian and Alaska Native (AI/AN) adults, the aim of this study was to pilot test the efficacy of a culturally tailored intervention among urban Indigenous adults., Methods: The study used a randomized controlled parallel design of 12 weeks of treatment-as-usual (TAU) (n = 26) versus TAU + Therapeutic Education System-Native Version (TES-NAV) (n = 27) with follow-up assessments at end of treatment and week 24 in an urban outpatient addiction treatment program for Native American adults. TAU consisted of individual/group counseling and cultural activities. The TES-NAV arm comprised TAU + 26 self-directed culturally tailored digital skills-based modules grounded in the community reinforcement approach with contingency management for abstinence and module completion. Primary outcome was longest consecutive weeks of abstinence from drugs and heavy drinking measured using self-report (Timeline Followback) and urine alcohol and drug toxicology screen during 12 weeks of treatment. Secondary outcomes were percent days abstinence during and posttreatment, coping strategies, social connectedness, and substance use and sexual risk behaviors., Results: The study enrolled fifty-three (52.8 % male) AI/AN adults seeking treatment for a SUD. Although the study did not detect a benefit of TAU+TES-NAV over TAU on the primary outcome (Median = 2 consecutive weeks of abstinence for both arms) at end of treatment (treatment effect: Z = -0.78, p = 0.437), TAU+TES-NAV participants did demonstrate significantly greater percent days of abstinence at the week 24 follow-up (69.3 % versus 49.0 % for TAU; t = 2.08, p = 0.045) and significantly greater change in social connectedness mean score, baseline to week 12 (Z = -2.66, p = 0.011), compared to TAU. The study detected no differences between treatment arms for coping strategies or risk behaviors., Conclusion: The addition of TES-NAV to TAU did not significantly improve consecutive weeks of abstinence from drugs or heavy drinking; however, several secondary findings suggest promise for a culturally tailored digital therapeutic SUD intervention among urban Indigenous people., Clinical Trials: GOV REGISTRATION: #NCT03363256., Competing Interests: Declaration of competing interest Dr. Venner provides training and consultation in evidence-based treatments for fee. Dr. Venner has a conflict-of-interest management plan at her academic institution. Dr. Marsch is affiliated with the company that developed the Therapeutic Education System, the company that deploys reSET®, as well as Click Therapeutics and Square2 Systems. These relationships are extensively managed by her academic institution. The remaining authors have no competing interests to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Molluscum contagiosum (MC) is characterized by skin lesions containing the highly contagious molluscum contagiosum poxvirus (MCV). MCV primarily infects children, with one US Food and Drug Administration (FDA)-approved drug-device treatment in use but no approved medications. Assessing antivirals is hindered by the inability of MCV to replicate in vitro. Here, we use vaccinia virus as a surrogate to provide evidence of the anti-poxvirus properties of berdazimer sodium, a new chemical entity, and the active substance in berdazimer gel, 10.3%, a nitric oxide-releasing topical in phase 3 development for the treatment of MC. We show that berdazimer sodium reduced poxvirus replication and, through a novel methodology, demonstrate that cells infected with drug-treated MCV virions have reduced early gene expression. Specifically, this is accomplished by studying the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB)-blocking protein MC160 as an example of an early gene. The results provide a plausible unique antiviral mechanism of action supporting increased MCV resolution observed in patients treated with berdazimer gel, 10.3% and describe a novel methodology that overcomes limitations in investigating MCV response in vitro to a potential new MC topical medication.

Background & Aims: Although histology is considered the gold standard for diagnosis of alcohol-associated hepatitis (AH), it is not required for entry into therapeutic studies if patients meet National Institute on Alcohol Abuse and Alcoholism (NIAAA) consensus criteria for probable AH. Our aim was to assess the diagnostic accuracy of NIAAA criteria against liver biopsy and to explore new criteria to enhance diagnostic accuracy for AH., Methods: A total of 268 consecutive patients with alcohol-related liver disease with liver biopsy were prospectively included: 210 and 58 in the derivation and validation cohorts, respectively. NIAAA criteria and histological diagnosis of alcoholic steatohepatitis (ASH) were independently reviewed by clinical investigators and pathologists from Hospital Clínic and Mayo Clinic. Using biopsy-proven ASH as gold standard we determined diagnostic capability of NIAAA criteria and proposed the new improved criteria., Results: In the derivation cohort, diagnostic accuracy of NIAAA for AH was modest (72%) due to low sensitivity (63%). Subjects who did not meet NIAAA with ASH at liver biopsy had lower 1-year survival compared with subjects without ASH (70% vs 90%; P < .001). NIAAAm-CRP criteria, created by adding C-reactive protein and modifying the variables of the original NIAAA, had higher sensitivity (70%), accuracy (78%), and specificity (83%). Accuracy was also higher in a sensitivity analysis in severe AH (74% vs 65%). In the validation cohort, NIAAAm-CRP and NIAAA criteria had a sensitivity of 56% vs 52% and an accuracy of 76% vs 69%, respectively., Conclusion: NIAAA criteria are suboptimal for the diagnosis of AH. The proposed NIAAAm-CRP criteria may improve accuracy for noninvasive diagnosis of AH in patients with alcohol-related liver disease., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options., Methods: Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe. Alterations were considered non-SoC when mapped at either OncoKB level 3, regardless of tDNA/ctDNA origin, or at OncoKB levels 1/2, provided they were undetectable in matched tDNA, and had not been exploited in previous therapy lines., Results: Altogether, actionable alterations were detected in 54/124 (43.5%) MTB patients, but only in 39 cases (31%) were these alterations (25 from tDNA, 14 from ctDNA) actionable/unexploited, e.g. they had not resulted in the assignment of pre-MTB treatments. Interestingly, actionable and actionable/unexploited alterations both decreased (37.5% and 22.7% respectively) in a subset of 88 MTB patients profiled by tDNA-only, but increased considerably (77.7% and 66.7%) in 18 distinct patients undergoing combined tDNA/ctDNA testing, approaching the potential treatment opportunities (76.9%) in 147 treatment-naïve patients undergoing routine tDNA profiling for the first time. Non-SoC therapy was MTB-recommended to all 39 patients with actionable/unexploited alterations, but only 22 (56%) accessed the applicable drug, mainly due to clinical deterioration, lengthy drug-gathering procedures, and geographical distance from recruiting clinical trials. Partial response and stable disease were recorded in 8 and 7 of 19 evaluable patients, respectively. The time to progression (TTP) ratio (MTB-recommended treatment vs last pre-MTB treatment) exceeded the conventional Von Hoff 1.3 cut-off in 9/19 cases, high absolute TTP and Von Hoff values coinciding in 3 cases. Retrospectively, 8 patients receiving post-MTB treatment(s) as per physician's choice were noted to have a much longer overall survival from MTB accrual than 11 patients who had received no further treatment (35.09 vs 6.67 months, p = 0.006)., Conclusions: MTB-recommended/non-SoC treatments are effective, including those assigned by ctDNA-only alterations. However, real-world MTBs may inadvertently recruit patients electively susceptible to diverse and/or multiple treatments., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: In recent years, the role of intravenous thrombolysis (IVT) before endovascular stroke treatment (EVT) has been discussed intensively. Whether the discussion was accompanied by changing rates of bridging IVT is unknown., Methods: Data were extracted from the prospectively maintained German Stroke Registry, including patients treated with EVT at one of 28 stroke centers in Germany between 2016 and 2021. Primary outcome parameters were the rate of bridging IVT (a) in the entire registry cohort and (b) in patients without formal contraindications to IVT (i.e. recent oral anticoagulants, time window ⩾4.5 h, extensive early ischemic changes) adjusted for demographic and clinical confounders., Results: 10,162 patients (52.8% women, median age 77 years, median National Institutes of Health Stroke Scale score 14) were analyzed. In the entire cohort, the rate of bridging IVT decreased from 63.8% in 2016 to 43.6% in 2021 (average absolute annual decrease 3.1%, 95% CI 2.4%-3.8%), while the proportion of patients with at least one formal contraindication increased by only 1.2% annually (95% CI 0.6%-1.9%). Among 5460 patients without record of formal contraindications, the rate of bridging IVT decreased from 75.5% in 2016 to 63.2% in 2021 and was significantly associated with admission date in a multivariable model (average absolute annual decrease 1.4%, 95% CI 0.6%-2.2%). Clinical factors associated with lower odds of bridging IVT included diabetes mellitus, carotid-T-occlusion, dual antiplatelet therapy, and direct admission to a thrombectomy center., Conclusion: We observed a substantial decline in bridging IVT rates independent of demographic confounders and not explained by an increase in contraindications. This observation deserves further exploration in independent populations.

With the current crisis related to the diffusion of fentanyl and other novel opioids in several countries and populations, new and effective approaches are needed to better elucidate the phenomenon. In this context, hair testing offers a unique perspective in the investigation of drug consumption, producing useful information in terms of exposure to psychoactive substances. In this research, we applied targeted ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analytical methods to detect novel synthetic and prescription opioids and other common controlled psychoactive drugs in the keratin matrix. A total of 120 hair samples were analyzed from the United States (US) and Italy, segmented when longer than 6 cm, and then analyzed. In the 60 samples (83 segments in total) analyzed from a purposive sample of data collected in the US, fentanyl was detected in 14 cases (16.9%), with no detection of nitazens or brorphine. We also detected fentanyl metabolites, despropionyl-p-fluorofentanyl, and prescription opioids. In the 60 samples collected in Italy (91 segments in total), ketamine was the most prevalent compound detected (in 41 cases; 45.1%), with ketamine demonstrating a strong correlation with detection of amphetamines and MDMA, likely due to co-use of these substances in recreational contexts. Several common drugs were also detected but no exposure to fentanyl or its analogs were detected. Results of this retrospective exploration of drug use add to increasing evidence that hair testing can serve as a useful adjunct to epidemiology studies that seek to determine biologically confirmed use and exposure in high-risk populations., (© 2023 The Authors. Journal of Forensic Sciences published by Wiley Periodicals LLC on behalf of American Academy of Forensic Sciences.)

Background: A significant portion of individuals in the United States and worldwide experience diseases related to or driven by diet. As research surrounding user-centered design and the microbiome grows, movement of the spectrum of translational science from bench to bedside for improvement of human health through nutrition becomes more accessible. In this literature survey, we examined recent literature examining informatics research at the interface of nutrition and the microbiome., Objectives: The objective of this survey was to synthesize recent literature describing how technology is being applied to understand health at the interface of nutrition and the microbiome focusing on the perspective of the consumer., Methods: A survey of the literature published between January 1, 2021 and October 10, 2022 was performed using the PubMed database and resulting literature was evaluated against inclusion and exclusion criteria., Results: A total of 139 papers were retrieved and evaluated against inclusion and exclusion criteria. After evaluation, 45 papers were reviewed in depth revealing four major themes: (1) microbiome and diet, (2) usability,(3) reproducibility and rigor, and (4) precision medicine and precision nutrition., Conclusions: A review of the relationships between current literature on technology, nutrition and the microbiome, and self-management of dietary patterns was performed. Major themes that emerged from this survey revealed exciting new horizons for consumer management of diet and disease, as well as progress towards elucidating the relationship between diet, the microbiome, and health outcomes. The survey revealed continuing interest in the study of diet-related disease and the microbiome and acknowledgement of needs for data re-use, sharing, and unbiased and rigorous measurement of the microbiome. The literature also showed trends toward enhancing the usability of digital interventions to support consumer health and home management, and consensus building around how precision medicine and precision nutrition may be applied in the future to improve human health outcomes and prevent diet-related disease., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (IMIA and Thieme. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: A large literature has examined a broad range of factors associated with increased risk of stroke. Few studies, however, have examined the association between personality and stroke. The present study adopted a systematic approach using a multi-cohort design to examine the associations between 5-Factor Model personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and incident stroke using data from 6 large longitudinal samples of adults., Methods: Participants (age range: 16-104 years old, N=58 105) were from the MIDUS (Midlife in the United States) Study, the HRS (Health and Retirement Study), The US (Understanding Society) study, the WLS (Wisconsin Longitudinal Study), the NHATS (National Health and Aging Trends Study), and the LISS (Longitudinal Internet Studies for the Social Sciences). Personality traits, demographic factors, clinical and behavioral risk factors were assessed at baseline; stroke incidence was tracked over 7 to 20 years follow-up., Results: Meta-analyses indicated that higher neuroticism was related to a higher risk of incident stroke (hazard ratio, 1.15 [95% CI, 1.10-1.20]; P <0.001), whereas higher conscientiousness was protective (HR, 0.89 [95% CI, 0.85-0.93]; P <0.001). Additional meta-analyses indicated that BMI, diabetes, blood pressure, physical inactivity, and smoking as additional covariates partially accounted for these associations. Extraversion, openness, and agreeableness were unrelated to stroke incidence., Conclusions: Similar to other cardiovascular and neurological conditions, higher neuroticism is a risk factor for stroke incidence, whereas higher conscientiousness is a protective factor., Competing Interests: Disclosures Drs Terracciano and Sutin report at National Institute on Aging.

Purpose: To assess the oral health status of children with Down syndrome (DS) in the United States and evaluate the oral health needs of families with DS. Methods: Among 320 parents who consented to participate, 260 (81.2 percent) surveys were completed. A survey was distributed through the National Down Syndrome Society to parents of children with DS up to age 21 years, which asked questions about children's general and oral health. Results: Parents who reported that their children had difficulty rinsing and spitting were more likely to report their child's overall general health as poor (P<0.05). Parents' frequency of daily toothbrushing was similar to their children's toothbrushing habits (P<0.05). Conclusions: Dysphagia for children with Down syndrome may negatively impact oral health in addition to general health. Encouraging parental involvement in oral care for children with DS may lower their risk for oral disease. Continued support is needed to ensure dental school education includes training for the treatment and management of patients with DS.

A multidisciplinary team is needed to optimally care for infants with congenital heart disease (CHD). Different compositions of teams trained in cardiology, critical care, cardiothoracic surgery, anesthesia, and neonatology have been identified as being primarily responsible for perioperative care of this high-risk population in dedicated cardiac intensive care units (CICUs). Although the specific role of cardiac intensivists has become more well defined over the past two decades, the responsibilities of neonatologists remain highly variable in the CICU with neonatologists providing care along with a unique spectrum of primary, shared, or consultative care. The neonatologist can function as the primary physician and assume all or share responsibility with the cardiac intensivists for the management of infants with CHD. A neonatologist can provide care as a secondary consultant physician in a supportive role for the primary CICU team. Additionally, neonates with CHD can be mixed with older children in a CICU, cohorted in a dedicated space within the CICU or placed in a stand-alone infant CICU without older children. Although variations exist between centers on which model of care is deployed and the location within a CICU, characterization of current practice patterns represents the initial step required to determine optimal best practices to improve the quality of care for neonates with cardiac disease. In this manuscript, we present four models utilized in the United States in which the neonatologist provides neonatal-cardiac-focused care in a dedicated CICU. We also outline the different permutations of location where neonates can be cared for in dedicated pediatric/infant CICUs.

Deleterious variants in collagen genes are the most common cause of hereditary connective tissue disorders (HCTD). Adaptations of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria are still lacking. A multidisciplinary team was set up for developing specifications of the ACMG/AMP criteria for COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL11A1, COL11A2 and COL12A1, associated with various forms of HCTD featuring joint hypermobility, which is becoming one of the most common reasons of referral for molecular testing in this field. Such specifications were validated against 209 variants, and resulted effective for classifying as pathogenic and likely pathogenic null alleles without downgrading of the PVS1 level of strength and recurrent Glycine substitutions. Adaptations of selected criteria reduced uncertainties on private Glycine substitutions, intronic variants predicted to affect the splicing, and null alleles with a downgraded PVS1 level of strength. Segregation and multigene panel sequencing data mitigated uncertainties on non-Glycine substitutions by the attribution of one or more benignity criteria. These specifications may improve the clinical utility of molecular testing in HCTD by reducing the number of variants with neutral/conflicting interpretations. Close interactions between laboratory and clinicians are crucial to estimate the a priori utility of molecular test and to improve medical reports., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To identify trends, costs, and predictors in the use of different surgical procedures for post-radical prostatectomy incontinence (PPI)., Materials and Methods: We identified 21,589 men who were diagnosed with localized prostate cancer (PCa) and treated with radical prostatectomy (RP) from 2003 to 2017. The primary outcome was the incontinence procedure performances. Optum's de-identified Clinformatics ® Data Mart Database was queried to define the cohort of interest. The average costs of the different incontinence procedures were obtained and compared. Also, demographic, and clinical predictors of incontinence surgery were evaluated by multivariable regression analysis., Results: Of the 21,589 men with localized PCa treated with RP, 740 (3.43%) underwent at least one incontinence procedure during a median of 5 years of follow-up. In total, there were 844 unique incontinence procedures. Male slings were the most common procedure (47.5%), had an intermediate cost compared to the other treatment options, and was the first-choice treatment for the majority of patients (50%). The use of an artificial urinary sphincter (AUS) was the second most common (35.3%), but also was the most expensive treatment and was first-choice-treatment for 32.3% of patients. On multivariable analysis, metabolic syndrome related disorders, adjuvant/salvage radiation therapy as well as a history of neurological comorbidities were independently associated with an increased likelihood of incontinence surgery., Conclusions: The receipt of male slings increased and then subsequently decreased, while AUS utilization was stable, and the use of urethral bulking agents was uncommon. From a cost standpoint, AUS was the most expensive option. Finally, patient's comorbidity history and RP related factors were found to influence the choice for primary or subsequent PPI interventions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial., Aim: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System., Method: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19., Results: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time., Conclusion: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Lung cancer is the leading cause of cancer deaths in the world. Surgery is the most potentially curative therapeutic option for patients with early-stage non-small cell lung cancer (NSCLC). The five-year survival for these patients remains poor and variable, depending on the stage of disease at diagnosis, and the risk of recurrence following tumor resection is high. During the last 20 years, there has been a modest improvement in the therapeutic strategies for resectable NSCLC. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, have become the cornerstone for the treatment of metastatic NSCLC patients. Recently, their clinical development has been shifted in the neoadjuvant and adjuvant settings where they have demonstrated remarkable efficacy, leading to improved clinical outcomes. Based on the positive results from phase III trials, ICIs have become a therapeutic option in neoadjuvant and adjuvant settings. On October 2021 the Food and Drug Administration (FDA) approved atezolizumab as an adjuvant treatment following surgery and platinum-based chemotherapy for patients with NSCLC whose tumors express PD-L1 ≥ 1%. In March 2022, nivolumab in combination with platinum-doublet chemotherapy was approved for adult patients with resectable NSCLC in the neoadjuvant setting. The current review provides an updated overview of the clinical trials exploring the role of immunotherapy in patients with early-stage NSCLC, focusing on the biological rationale for their use in the perioperative setting. We will also discuss the role of potential predictive biomarkers to personalize therapy and optimize the incorporation of immunotherapy into the multimodality management of stage I-III NSCLC.

Prostate cancer (PCa) is one of the most common cancers in European males. Although therapeutic approaches have changed in recent years, and several new drugs have been approved by the Food and Drug Administration (FDA), androgen deprivation therapy (ADT) remains the standard of care. Currently, PCa represents a clinical and economic burden due to the development of resistance to ADT, paving the way to cancer progression, metastasis, and to long-term side effects induced by ADT and radio-chemotherapeutic regimens. In light of this, a growing number of studies are focusing on the tumor microenvironment (TME) because of its role in supporting tumor growth. Cancer-associated fibroblasts (CAFs) have a central function in the TME because they communicate with prostate cancer cells, altering their metabolism and sensitivity to drugs; hence, targeted therapy against the TME, and, in particular, CAFs, could represent an alternative therapeutic approach to defeat therapy resistance in PCa. In this review, we focus on different CAF origins, subsets, and functions to highlight their potential in future therapeutic strategies for prostate cancer.

Objective: The present study examined the association between Five Factor Model personality traits and lung function and dyspnea., Methods: Participants were middle aged and older adults aged 34-103 years old (N > 25,000) from the Midlife in the United States Study (MIDUS), the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the National Health and Aging Trends Survey (NHATS), and the Wisconsin Longitudinal Study graduate (WLSG) and sibling (WLSS) samples. Data on peak expiratory flow (PEF), dyspnea, personality traits, smoking, physical activity, body mass index (BMI), emotional/psychiatric problems, and demographic factors were obtained in each sample., Results: A meta-analysis indicated that higher neuroticism was related to lower PEF, higher risk of PEF less than 80% of predicted value, and higher risk of dyspnea. In contrast, higher extraversion and conscientiousness were associated with higher PEF, lower likelihood of PEF lower than 80% of the predicted value, and lower risk of dyspnea. Higher openness was related to higher PEF and lower risk of PEF less than 80%, whereas agreeableness was related to higher PEF and lower risk of dyspnea. Smoking, physical activity, BMI and emotional/psychiatric problems partially accounted for these associations. There was little evidence that lung disease moderated the association between personality and PEF and dyspnea., Conclusions: Across cohorts, this study found replicable evidence that personality is associated with lung function and associated symptomatology., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To assess the compliance of "integrated" continuous glucose monitoring (CGM) systems with U.S. Food and Drug Administration requirements, the calculation of confidence intervals (CIs) on agreement rates (ARs), that is, the percentage of CGM measurements lying within a certain deviation of a comparator method, is stipulated. However, despite the existence of numerous approaches that could yield different results, a specific procedure for calculating CIs is not described anywhere. This report, therefore, proposes a suitable statistical procedure to allow transparency and comparability between CGM systems. Three existing methods were applied to six data sets from different CGM performance studies. The results indicate that a bootstrap-based method that accounts for the clustered structure of CGM data is reliable and robust. We thus recommend its use for the estimation of CIs of ARs. A software implementation of the proposed method is freely available (https://github.com/IfDTUlm/CGM&#95;Performance&#95;Assessment).

Objectives: To describe cancer screening characteristics and better understand individual-, environmental-, and organizational-level barriers of sexual and gender minority (SGM) populations.&nbsp., Sample & Setting: This study was conducted using a combined sample from the Behavioral Risk Factor Surveillance System (BRFSS) national dataset from 2014 and 2016., Methods & Variables: Chi-square tests for independence and logistic regression analysis tests were performed to determine whether relationships existed between SGM status and demographics., Results: Black respondents or those who reported their race as other, were female, had some college or technical school or more, and had healthcare coverage were less likely to present for cancer screening. SGM respondents who were in good or better health; were unmarried; were aged 18-44 years or 45-55 years; or were Asian, Native American, or Hawaiian, or reported their race as other, had higher odds of screening for cancer., Implications for Nursing: Disparities in cancer screening among SGM populations are not well documented. These findings will inform structured education and preventative interventions to improve screening participation among SGM populations.

Objective: To examine the trends in first and last authorship of women within clinical retina research over the last 25 years., Design: Cross-sectional study., Participants: First and last author names were retrieved from original articles published between January 1, 1995, and January 1, 2021, in the American Journal of Ophthalmology, JAMA Ophthalmology (Archives of Ophthalmology), Ophthalmology, and Retina., Methods: The medical subject heading major term "retina" was used in PubMed to filter publications specific to the field of retina. Publications by single authors and collaborative study groups and those classified as comments, letters, and editorials were excluded. First and last author names were obtained, and Gender API was used to assign sex. Names were crosschecked with the American Society of Retina Specialists (ASRS) directory for United States-based authors., Main Outcome Measures: The proportion of male and female first and last authors throughout the study period and the association between first and last authorship gender were assessed., Results: A total of 4142 articles were included. The percentage of women in first and last authorship positions significantly increased from 23% to 37.7% and 14.2% to 24.6%, respectively, over 25 years (P < 0.001 and P < 0.001, respectively). When the last authors were women, 32.5% of the first authors were women, and when the last authors were men, 27.1% of the first authors were women (P = 0.002). Based on the ASRS 2020 directory, 17% of practicing retina specialists in the United States were women in 2020. For publications in 2020, 28.2% of the first authors and 22.3% of the last authors of retina publications from the United States were women (P < 0.001 and P < 0.001, respectively)., Conclusions: Although a disparity in authorship persists in the subspecialties of ophthalmology, this data suggest that retina is a field where the gap is improving. Mentorship by senior female authors is associated with a higher proportion of female first authors., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: Postpartum mood disorders are associated with adverse outcomes for newborns and mothers and may require urgent evaluation. The emergency department is often a healthcare entry point, but factors associated with these emergency department visits are unknown., Methods: A longitudinal retrospective analysis using the Nationwide Emergency Department Sample to assess national estimates of emergency department visits by women ages 15-49 with primary diagnosis of a postpartum mood disorder between 2006 and 2016. Emergency department visit rates for postpartum mood disorders per 100,000 live births were calculated., Results: Emergency department visits related to postpartum mood disorders remained stable from 2006 to 2016 (5153 to 5390 respectively). Two-thirds of visits were by patients younger than 30. Approximately half of visits for postpartum mood disorders were funded by Medicaid (42.4-56.7%) compared to 27.4-41.2% funded by Medicaid for all other age-matched women. Of postpartum mood disorder visits 30.3% were by women from the lowest income quartile. The highest rate of emergency department visits occurred in the youngest patients (ages 15-19: 231 visits versus ages 35-49: 105 visits). Postpartum mood disorder admissions were higher than those for age-matched women with all other diagnoses (19.8% vs. 6.5%)., Discussion: The high rate of women that are young and with public insurance visiting the emergency department for postpartum mood disorders demonstrates an increased risk for these disorders in these populations and an opportunity for targeted intervention by policymakers and providers. Higher admission rates for postpartum mood disorders compared to all other diagnoses reveals a chance to optimize outpatient screening and treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma. Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions. Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients. Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients.[Box: see text]Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .