Search

Background: Exercise has been demonstrated to result in improvements in physical function, cognition, and quality of life in People with Parkinson's (PwP) but its adoption is variable., Objectives: To investigate exercise preferences, levels, influencing factors among a diverse Parkinson's disease (PD) population, to understand exercise adoption patterns and plan informed interventions., Methods: A cross-sectional survey collected data through online platforms and paper-based methods. The Exercise Index (ExI) calculated exercise level based on frequency and duration., Results: Of 2976 PwP, 40.6% exercised regularly, 38.3% occasionally, and 21.2% did not exercise. The overall mean ExI was 18.99 ± 12.37. Factors associated with high exercise levels included exercising in groups (ExI 24-26), weightlifting (ExI 27 (highest)), using muscle-building equipment (ExI 25-26), and exercising at home following an app (ExI 26). A positive trend between ExI and varied exercise groups, locations, types, and equipment was observed. No expected benefit from exercise achieved the lowest ExI (8). Having at least two exercise-promoting factors, a bachelor's degree or higher, receiving exercise advice at initial visits, and aged ≤40 years at PD onset were strong predictors of exercise (adjust OR = 7.814; 6.981; 4.170; 3.565). Falls and "other" most troublesome PD symptoms were negative predictors (aOR = 0.359; 0.466). Barriers to exercise did not predict the odds of exercise., Conclusions: The study shows that PwP's exercise behavior is influenced by their exercise belief, age at PD onset, doctor's advice at initial visits, education level, symptoms, and exercise-promoting factors. High exercise levels were associated with certain types of exercises and exercising in groups., (© 2024 International Parkinson and Movement Disorder Society.)

A 57-year-old woman with good past health was admitted to the accident and emergency department at an outside hospital for sudden onset chest pain. Electrocardiogram revealed ST-segment elevation at inferior leads.

It remains unknown whether frailty status confers an increased risk of readmission in patients with rheumatoid arthritis (RA). From the 2018 Nationwide Readmissions Database (NRD), we identified adult patients (age ≥ 18 years) admitted with a diagnosis of RA between January to June 2018. Utilizing validated Hospital Frailty Score, patients' frailty risk score was calculated at the time of index admission and categorized into frail (score ≥ 5) and non-frail (score < 5) groups. Our primary outcomes of interest were (1) 180- day readmission rate (2) inpatient mortality; secondary outcomes included prolonged length of stay, LOS (LOS ≥ 7 days), and costs of hospitalization. Multivariable Cox proportional hazard analysis was performed to evaluate the independent effect of frailty adjusting for confounding variables. 133,187 patients met inclusion criteria, with mean age 67.7 years, of whom 64,131 (48.1%) patients were categorized as frail. The rate of readmission was significantly higher in the frail (56.60%) compared to the non-frail group (30.61%). At index hospitalization, frail patients also had significantly higher inpatient mortality compared to non-frail patients (3.36% vs 0.39%, p < 0.005), longer LOS (26.24% vs 7.82%, p < 0.005). On multivariate analysis frailty was independently associated with a 9% increased risk of readmission (adjusted hazard ratio, 1.09; 95% confidence interval, 1.08 - 1.11). People with RA who are frail have higher rates of readmission than those who are not frail. These findings are crucial in identifying at-risk patients with RA and in discharge planning after hospitalization. Key Points • People with RA who are frail have higher rates of readmission than those who are not frail. • Frail RA patients are also at higher risk of hospitalization-related adverse outcomes, including inpatient mortality and longer hospital stay. • Sepsis is the most common cause for readmission identified in frail patients with RA. • These findings suggest that frailty may be a useful metric in identifying patients with RA at an increased risk of adverse health outcomes., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Chronic pain has an enormous impact on the quality of life of billions of patients, families, and caregivers worldwide. Current therapies do not adequately address pain for most patients. A basic understanding of the conserved genetic framework controlling pain may help us develop better, non-addictive pain therapies. Here, we identify new conserved and druggable analgesic targets using the tissue-specific functional genomic screening of candidate "pain" genes in fly. From these efforts, we describe 23 new pain genes for further consideration. This included Acsl, a fatty acid-metabolizing enzyme, and mammalian orthologs involved in arachidonic acid metabolism. The Acsl knockdown and mutant larvae showed delayed nocifensive responses to localized and global noxious heat. Mechanistically, the Acsl knockdown reduced dendritic branching of nociceptive neurons. Surprisingly, the pain phenotype in these animals could be rescued through dietary intervention with vitamin B5, highlighting the interplay between genetics, metabolism, and nutrient environment to establish sensory perception thresholds. Together, our functional genomic screening within the sensory nociceptor has identified new nociception genes that provide a better understanding of pain biology and can help guide the development of new painkillers., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Competing Interests: RNS Lui has served as an advisory board member for Gilead Sciences and speaker for GenieBiome; he also holds equity in Pfizer. As an editor of the journal, RNS Lui was not involved in the peer review process. LLY Mak has served as a speaker for Roche. HLY Chan is an advisor for Aligos, GlaxoSmithKline, Roche, Vaccitech, and Virion Therapeutics; a speaker for Echosens, Gilead Sciences, Roche, and Viatris; and a data management board member for Aligos, Arbutus, Roche, Vaccitech, and Zhimeng Therapeutics. MF Yuen has served as an advisor/consultant for and/or received grant/research support from AbbVie, Aligos, AiCuris, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol Myers Squibb, ClearB Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Roche, Silverback Therapeutics, Sysmex Corporation, Tune Therapeutics, Vir Biotechnology, and Visirna Therapeutics. GLH Wong has served as an advisory board member for AstraZeneca, Gilead Sciences, and Janssen, as well as a speaker for Abbott, AbbVie, Ascletis, Bristol Myers Squibb, Echosens, Gilead Sciences, Janssen, and Roche; she has also received a research grant from Gilead Sciences. Other authors have disclosed no conflicts of interest.

Objective: The objective of this study was to evaluate the association between frailty status and risk of readmissions, inpatient death, and cost of admission among patients with systemic lupus erythematosus (SLE)., Methods: We conducted a retrospective cohort study using the National Readmissions Database. Using International Statistical Classification of Diseases, Tenth Revision codes, we identified individuals >18 years of age who had a primary or secondary diagnosis of SLE and were hospitalized between January and June 2018. Using the validated claims-based Hospital Frailty Risk Score, we categorized individuals as frail (score ≥ 5) or nonfrail (score < 5) at the time of index hospitalization. Our primary outcome was readmission rates post discharge from index hospitalization. Secondary outcomes were rates of inpatient mortality and the total cost of hospitalizations. Cox proportional hazard models were used to estimate the association between frailty and risk of readmissions, with adjustment for age, sex, insurance type, household income, and Elixhauser Comorbidity Index score., Results: A total of 39,738 patients with SLE met eligibility criteria. Over a median follow-up of eight months, frail patients with SLE (n = 18,385) had higher Elixhauser Comorbidity Index scores and longer length of stay compared to nonfrail patients with SLE (n = 21,353). Frail patients with SLE had higher readmission rates, a higher proportion of prolonged hospitalizations, and higher costs per hospitalization. Frailty was independently associated with a 10% higher risk of readmission after adjustment for covariates., Conclusion: Among hospitalized adults with SLE, presence of frailty was associated with higher readmission and inpatient mortality rates. Our results highlight that frailty status can help risk stratify patients with SLE at increased risk for readmissions and other adverse health outcomes., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The overuse and misuse of tetracycline (TCs) antibiotics, including tetracycline (TTC), oxytetracycline (OTC), doxycycline (DC), and chlortetracycline (CTC), pose a serious threat to human health. However, current rapid sensing platforms for tetracyclines can only quantify the total amount of TCs mixture, lacking real-time identification of individual components. To address this challenge, we integrated a deep learning strategy with fluorescence and colorimetry-based multi-mode logic gates in our self-designed smartphone-integrated toolbox for the real-time identification of natural TCs. Our ratiometric fluorescent probe (CD-Au NCs@ZIF-8) encapsulated carbon dots and Au NCs in ZIF-8 to prevent false negative or positive results. Additionally, our independently developed WeChat app enabled linear quantification of the four natural TCs using the fluorescence channels. The colorimetric channels were also utilized as outputs of logic gates to achieve real-time identification of the four individual natural tetracyclines. We anticipate this strategy could provide a new perspective for effective control of antibiotics., 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 © 2023. Published by Elsevier Ltd.)

To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms.Adults with and without long COVID were recruited from the general community in Greater Vancouver, Canada. The cohort was divided into those with pulmonary long COVID (PLC), which was defined as persons with new or worsening respiratory symptoms following at least one year from their initial acute SARS-CoV-2 infection (N=9); and control subjects defined as SARS-CoV-2 infected persons whose acute respiratory symptoms had fully resolved or individuals who had no history of acute COVID-19 (N=9). These participants underwent bronchoscopy from which a single cell suspension was created from bronchial brush samples and then sequenced.A total of 56 906 cells were recovered for the downstream analysis, with 34 840 cells belonging to the PLC group, which strikingly showed a unique cluster of neutrophils in the PLC group (p<0.05). Ingenuity Pathway Analysis revealed that the neutrophil degranulation pathway was enriched across epithelial cell clusters. Differential gene expression analysis between the PLC and control groups demonstrated upregulation of inflammatory chemokines and epithelial barrier dysfunction across epithelial cell clusters, as well as over-expression of mucin genes across secretory cell clusters.In conclusion, a single-cell transcriptomic landscape of the small airways suggest that neutrophils may play a significant role in mediating the chronic small airway inflammation driving pulmonary symptoms of long COVID., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Patients with benign upper gastrointestinal (UGI) conditions such as achalasia, gastroparesis and refractory gastroesophageal reflux disease often suffer from debilitating symptoms. These conditions can be complex and challenging to diagnose and treat, making them well suited for discussion within a multidisciplinary meeting (MDM). There is, however, a paucity of data describing the value of a benign UGI MDM. The aim of this study was to assess the impact of our unit's benign UGI MDM service and its outcomes. This was a retrospective analysis of prospectively collected data for all consecutive patients reviewed in the monthly benign UGI MDM between July 2021 and February 2024. The primary outcome was the incidence that MDM review changed clinical treatment. Secondary outcomes included change in diagnosis, additional investigations and referrals to subspecialists. A total of 104 patients met inclusion criteria. A total of 73 (70.2%) patients had a change in their overall management following MDM review; 25 (24.0%), 31 (29.8%) and 48 (46.2%) patients had changes in pharmacological, endoscopic and surgical interventions respectively. Most changes in pharmacological and endoscopic intervention involved treatment escalation, whereas most changes in surgical intervention involved treatment de-escalation. A total of 84 (80.8%) patients had a documented diagnosis post-MDM with 44 (42.3%) having a change in their pre-MDM diagnosis. 50 (48.1%) patients had additional investigation/s requested and 49 (47.1%) had additional referral pathway/s recommended. Over two thirds of patients had at least one aspect of their management plan changed following MDM review. These changes occurred across pharmacological, endoscopic, and surgical interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Mass Casualty Incidents (MCIs) involving high-speed passenger ferries (HSPFs) may result in the dual-wave phenomenon, in which the emergency department (ED) is overwhelmed by an initial wave of minor injuries, followed by a second wave of more seriously injured victims. This study aimed to characterize the time pattern of ED presentation of victims in such accidents in Hong Kong., Methods: All HSPF MCIs from 2005 to 2015 were reviewed retrospectively, with the time interval from accident to ED registration determined for each victim. Multivariable linear regression was used to identify independent factors associated with the time of ED presentation after the accidents., Results: Eight MCIs involving 492 victims were identified. Victims with an Injury Severity Score (ISS) ≥ 9 had a significantly shorter median time interval compared to those with minor injuries. An ISS ≥ 9 and evacuation by emergency service vessels were associated with a shorter delay in ED arrival, whereas ship sinking, accident at nighttime, and a longer linear distance between the accident and receiving ED were associated with a longer delay., Conclusion: The dual-wave phenomenon was not present in HSPF MCIs. Early communication is the key to ensure early resource mobilisation and a well-timed response.

Substituted 5-hydroxy γ-pyrones have shown promise as covalent inhibitor leads against cysteine proteases and transcription factors, but their hydrolytic instability has hindered optimization efforts. Previous mechanistic proposals have suggested that these molecules function as Michael acceptor prodrugs, releasing a leaving group to generate an o -quinone methide-like structure. Addition to this electrophile of either water or an active site cysteine was purported to lead to inhibitor hydrolysis or enzyme inhibition, respectively. Through the use of kinetic nuclear magnetic resonance experiments, Hammett analysis, kinetic isotope effect studies, and density functional theory calculations, our findings suggest that enzyme inhibition and hydrolysis proceed by distinct pathways and are differentially influenced by substituent electronics. This mechanistic revision helps enable a more rational optimization for this class of promising compounds.

Animal morphology is influenced by several factors, including gonadal development and gametogenesis. Although their effects are well documented in male/female differentiation, much less is known about same-sex effects, such as those caused by their mode of reproduction. Here, using geometric morphometric analyses, we compare two groups of all-female triploid hybrid fish Chrosomus eos × eos-neogaeus, that differ only by their sexual and asexual reproductive strategies. We demonstrate that morphological differences arise from factors inherently associated with their mode of reproduction, with results replicated in two distinct lineages and in natural and common garden environments. Such differences provide additional insight about the costs and benefits of both reproductive strategies, which have mostly been of a demographic, population genetic, or genetic nature. In particular, these findings have important implications for the ecology of asexual organisms and contribute to the study of sex evolution by adding complexity to the paradox of sex theory., (© 2024. The Author(s).)

Recent advances in federated learning (FL) have brought large-scale collaborative machine learning opportunities for massively distributed clients with performance and data privacy guarantees. However, most current works focus on the interest of the central controller in FL and overlook the interests of the FL clients. This may result in unfair treatment of clients, which discourages them from actively participating in the learning process and damages the sustainability of the FL ecosystem. Therefore, the topic of ensuring fairness in FL is attracting a great deal of research interest. In recent years, diverse fairness-aware FL (FAFL) approaches have been proposed in an effort to achieve fairness in FL from different perspectives. However, there is no comprehensive survey that helps readers gain insight into this interdisciplinary field. This article aims to provide such a survey. By examining the fundamental and simplifying assumptions, as well as the notions of fairness adopted by the existing literature in this field, we propose a taxonomy of FAFL approaches covering major steps in FL, including client selection, optimization, contribution evaluation, and incentive distribution. In addition, we discuss the main metrics for experimentally evaluating the performance of FAFL approaches and suggest promising future research directions toward FAFL.

ChAdOx1-S is a viral vector vaccine developed by AstraZeneca. We aimed to assess the effectiveness of 1 and 2 doses of the ChAdOx1-S vaccine in reducing COVID-19-related in-hospital mortality in individuals with schizophrenia. This is a retrospective cohort study using a nationwide hospital database in Brazil. Individuals diagnosed with COVID-19 and schizophrenia were included in the study. The exposures were 0, 1, and 2 doses of ChAdOx1-S. The outcome of mortality was measured in hazard ratios (HR), calculated using multivariable Cox regression models. The study included 1,929 positive cases of COVID-19 in schizophrenia patients. After adjusting for age, socioeconomic factors, and comorbidities, we observed a significant 55% decrease in the hazard of mortality in the 2-dose vaccination group (HR 0.45, 95% CI: 0.310-0.652) compared to the unvaccinated. Surprisingly, our results did not show any significant reduction in the hazard of mortality in the 1 dose vaccination group (HR 1.278, 95% CI: 0.910-1.795). The effectiveness of two doses of ChAdOx1-S in individuals with schizophrenia aligns with findings from studies on the general population. That one dose was insignificant. Overall, these findings are important for informing public health decisions - prioritizing individuals with schizophrenia for vaccinations and managing acceptance of vaccines.

Cancer is a global health challenge, with changing demographics and lifestyle factors producing an increasing burden worldwide. Screening advancements are enabling earlier diagnoses, but current cancer immunotherapies only induce remission in a small proportion of patients and come at a high cost. Cancer vaccines may offer a solution to these challenges, but they have been mired by poor results in past decades. Greater understanding of tumor biology, coupled with the success of vaccine technologies during the COVID-19 pandemic, has reinvigorated cancer vaccine development. With the first signs of efficacy being reported, cancer vaccines may be beginning to fulfill their potential. Solid tumors, however, present different hurdles than infectious diseases. Combining insights from previous cancer vaccine clinical development and contemporary knowledge of tumor immunology, we ask: who are the 'right' patients, what are the 'right' targets, and which are the 'right' modalities to maximize the chances of cancer vaccine success?

Longitudinal physical activity monitoring is a novel and promising objective outcome measure for patients with degenerative spine disorder (DSD) that currently lacks established standards for data collection and interpretation. Here, we monitored 100 patients with DSD with the Apple Watch to establish the optimal duration and pattern of step count monitoring needed to estimate their weekly physical activity before their elective surgery. Participants were predominantly female (65.3%), had an average age of 61.5 years, and showed consistent step counts between preoperative days, as well as across weekends and weekdays. Intraclass correlations (ICC) analysis showed that a step count average over 2 days achieved an ICC of 0.92 when compared to a 7-day average before surgery, while 4 days were required for a similar agreement of 0.93 with a 14-day average. Sequential linear regression demonstrated that incorporating additional preoperative days improved the model's ability to predict 7- and 14-days step count averages. We conclude that, while daily preoperative step counts remain relatively stable, longer activity monitoring is necessary to account for the variance in step count over an increasing time frame, and the full extent of data fluctuation may only become apparent with long-term trend analysis., (© 2024. The Author(s).)

Chronic kidney disease (CKD) imposes a significant burden on healthcare systems worldwide, and diabetes is a major risk factor for CKD. There is currently no consensus in Hong Kong regarding the prioritisation of early identification and intervention for CKD. A comprehensive and Hong Kong-specific diabetes and CKD treatment guideline is also lacking. A multidisciplinary group of experts discussed issues surrounding the current management of CKD and reviewed evidence in the context of local experience to support recommendations. The experts used a modified Delphi approach to finalise recommendations. Consensus was regarded as ≥75% acceptability among all expert panel members. The panel members finalised 14 CKD-focused consensus statements addressing disease definition, screening, disease monitoring, lifestyle management, and treatment strategies. The recommendations provided are relevant to the Hong Kong healthcare setting and can be used as a guide by physicians across various specialties to facilitate the appropriate management of CKD., Competing Interests: RCW Ma has received research funding from AstraZeneca, Bayer, Merck Sharp & Dohme, Novo Nordisk, Pfizer, Roche Diagnostics, and Tricida Inc for carrying out clinical trials or studies, and from AstraZeneca, Bayer, Boehringer Ingelheim, and Merck for speaker honoraria or consultancy on advisory boards. All proceeds have been donated to The Chinese University of Hong Kong to support diabetes research. CC Szeto receives research support from AstraZeneca, Boehringer Ingelheim, and Otsuka Pharmaceutical. KCB Tan has participated in advisory boards and speakers bureaus for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and Sanofi. MCS Wong is an advisory committee member for Pfizer; an external expert for GlaxoSmithKline Limited, a member of the advisory board of AstraZeneca, and an honorary advisor of GenieBiome Limited. He was paid consultancy fees for providing research advice and delivering talks. Also, as an editor of the journal, he was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

The existence and function of Lgr5 + cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5 + populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5 + cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5 + cells to the adult muscle layer. Embryonic Lgr5 + epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5 + stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5 + stem/progenitor cell pool., (© 2024. The Author(s).)

Introduction: Extensive trauma, commonly seen in wounded military Service Members, often leads to a severe sterile inflammation termed systemic inflammatory response syndrome (SIRS), which can progress to multiple organ dysfunction syndrome (MODS) and death. MODS is a serious threat to wounded Service Members, historically causing 10% of all deaths in trauma admissions at a forward deployed combat hospital. The importance of this problem will be exacerbated in large-scale combat operations, in which evacuation will be delayed and care of complex injuries at lower echelons of care may be prolonged. The main goal of this study was to optimize an existing mouse model of lethal SIRS/MODS as a therapeutic screening platform for the evaluation of immunomodulatory drugs., Materials and Methods: Male C57BL/6 mice were euthanized, and the bones and muscles were collected and blended into a paste termed tissue-bone matrix (TBX). The TBX at 12.5%-20% relative to body weight of each recipient mouse was implanted into subcutaneous pouches created on the dorsum of anesthetized animals. Mice were observed for clinical scores for up to 48 hours postimplantation and euthanized at the preset point of moribundity. To test effects of anesthetics on TBX-induced mortality, animals received isoflurane or ketamine/xylazine (K/X). In a separate set of studies, mice received TBX followed by intraperitoneal injection with 20 mg/kg or 40 mg/kg Eritoran or a placebo carrier. All Eritoran studies were performed in a blinded fashion., Results: We observed that K/X anesthesia significantly increased the lethality of the implanted TBX in comparison to inhaled anesthetics. Although all the mice anesthetized with isoflurane and implanted with 12.5% TBX survived for 24 hours, 60% of mice anesthetized with K/X were moribund by 24 hours postimplantation. To mimic more closely the timing of lethal SIRS/MODS following polytrauma in human patients, we extended observation to 48 hours. We performed TBX dose-response studies and found that as low as 15%, 17.5%, and 20% TBX caused moribundity/mortality in 50%, 80%, and 100% mice, respectively, over a 48-hour time period. With 17.5% TBX, we tested if moribundity/mortality could be rescued by anti-inflammatory drug Eritoran, a toll-like receptor 4 antagonist. Neither 20 mg/kg nor 40 mg/kg doses of Eritoran were found to be effective in this model., Conclusions: We optimized a TBX mouse model of SIRS/MODS for the purpose of evaluating novel therapeutic interventions to prevent trauma-related pathophysiologies in wounded Service Members. Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Study Design/setting: Prospective cohort study., Objective: To use a commercial wearable device to measure real-life, continuous physical activity in patients with CS and to establish age-adjusted and sex-adjusted standardized scores., Summary of Background Data: Patients with cervical spondylosis (CS) often present with pain or neurologic deficits that result in functional limitations and inactivity. However, little is known regarding the influence of CS on the patient's real-life physical activity., Methods: This study included 100 English-speaking adult patients with cervical degenerative diseases undergoing elective spine surgery at Stanford University who owned iPhones. Patients undergoing surgery for spine infections, trauma, tumors, or lumbar degenerative disease were excluded. Activity two weeks before surgery was expressed as raw daily step counts. Standardized z-scores were calculated based on age-specific and sex-specific values of a control population. Responses to patient-reported outcome measures (PROMs) surveys assessed convergent validity. Functional impairment was categorized based on predetermined z-score cut-off values., Results: Thirty CS with a mean (±SD) age of 56.0 (±13.4) y wore an Apple Watch for ≥8 hours/day in 87.1% of the days. The mean watch wear time was 15.7 (±4.2) hours/day, and the mean daily step count was 6400 (±3792). There was no significant difference in activity between 13 patients (43%) with myelopathy and 17 (57%) without myelopathy. Test-retest reliability between wearable step count measurements was excellent (ICC β=0.95). Physical activity showed a moderate positive correlation with 36-Item Short Form Survey Physical Component Summary, EuroQol-5-dimension visual analog scale, and Patient-Reported Outcomes Measurement Information System Physical Function Subscale. Activity performance was classified into categories of "no impairment" [step count=9640 (±2,412)], "mild impairment" [6054(±816)], "moderate impairment" [3,481 (±752)], and "severe impairment" [1,619 (±240)]., Conclusion: CS patients' physical activity is significantly lower than the general population or the frequently stated goals of 7000 to 10,000 steps/day. Standardized, continuous wearable physical activity monitoring in CS is a reliable, valid, and normalized outcome tool that may help characterize functional impairment before and after spinal interventions., Competing Interests: N.M. and C.Z. are consultants for Stryker. C.Z. is also a consultant for Amgen and 7D Surgical. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: All authors have disclosed no conflicts of interest.

Species with widespread distributions play a crucial role in our understanding of climate change impacts on population structure. In marine species, population structure is often governed by both high connectivity potential and selection across strong environmental gradients. Despite the complexity of factors influencing marine populations, studying species with broad distribution can provide valuable insights into the relative importance of these factors and the consequences of climate-induced alterations across environmental gradients. We used the northern shrimp Pandalus borealis and its wide latitudinal distribution to identify current drivers of population structure and predict the species' vulnerability to climate change. A total of 1514 individuals sampled across 24° latitude were genotyped at high geographic (54 stations) and genetic (14,331 SNPs) resolutions to assess genetic variation and environmental correlations. Four populations were identified in addition to finer substructure associated with local adaptation. Geographic patterns of neutral population structure reflected predominant oceanographic currents, while a significant proportion of the genetic variation was associated with gradients in salinity and temperature. Adaptive landscapes generated using climate projections suggest a larger genomic offset in the southern extent of the P. borealis range, where shrimp had the largest adaptive standing genetic variation. Our genomic results combined with recent observations point to further deterioration in southern regions and an impending vulnerable status in the regions at higher latitudes for P. borealis. They also provide rare insights into the drivers of population structure and climatic vulnerability of a widespread meroplanktonic species, which is crucial to understanding future challenges associated with invertebrates essential to ecosystem functioning., (© 2024 His Majesty the King in Right of Canada and The Authors. Molecular Ecology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Fisheries and Oceans Canada.)

Background and Objective: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). The objective of this study is to investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR., Methods: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤ 3cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate., Key Findings and Limitations: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1- yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups., Conclusions and Clinical Implications: In patients with NMIBC of ≤ 3cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR. The study results support ERBT as the first-line surgical treatment for patients with bladder tumours of≤ 3cm., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS)., Methods: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS., Results: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically., Conclusions: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.

Stressful events are inherently emotional. As a result, the ability to regulate emotions is critical in responding effectively to stressors. Differential abilities in the management of stress appear very early in life, compelling a need to better understand factors that may shape the capacity for emotion regulation (ER). Variations in both biologic and behavioural characteristics are thought to influence individual differences in ER development. We sought to determine the differential contributions of temperament and heart rate variability (HRV; an indicator of autonomic nervous system function) to infant resting state emotionality and emotional reactivity in response to a stressor at 6 months of age. Participants included 108 mother-infant dyads. Mothers completed a measure of infant temperament at 6 months postnatal. Mother and infant also participated in a standardized stressor (the Repeated Still Face Paradigm) at that time. Electrocardiographic data were acquired from the infant during a baseline resting state and throughout the stressor. Fast Fourier Transformation was used to analyse the high frequency (HF) domain of HRV, a measure of parasympathetic nervous system activity. Infant ER was measured via standardized coding of emotional distress behaviours from video-records at baseline and throughout the stressor. Severity of mothers' depressive symptoms was included as a covariate in analyses. Results of linear regression indicate that neither temperament nor HRV were associated significantly with an infant's emotional resting state, although a small effect size was found for the relationship between infant negative affectivity and greater emotional distress (β = 0.23, p = 0.08) prior to the stressor. Higher HF-HRV (suggesting parasympathetic dominance) was related to greater emotional distress in response to the stressor (β = 0.34, p = 0.009). This greater emotional reactivity may reflect a more robust capacity to mount an emotional response to the stressor when infants encounter it from a bedrock of parasympathetic activation. Findings may inform eventual markers for assessment of ER in infancy and areas for intervention to enhance infant management of emotions, especially during stressful events., (© 2024 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

Introduction: Human immunodeficiency virus (HIV)-associated tuberculosis (TB) remains an important health challenge worldwide. Although TB prevalence has decreased in the general population, there is limited information regarding temporal trends in the incidence of HIV-associated TB in Hong Kong. There are also insufficient data regarding changes in clinical manifestation patterns among HIV-associated TB patients over time. This study aimed to describe temporal trends in the epidemiology and clinical manifestations of HIV-associated TB in Hong Kong., Methods: We retrospectively reviewed data regarding HIV-associated TB patients that were reported to the TB-HIV Registry of the Department of Health during the period 2007 to 2020. Trends of TB as a primary acquired immunodeficiency syndrome (AIDS)-defining illness, as well as changes in demographic features and clinical manifestations of HIV-associated TB during this period were examined using Cochran-Armitage trend test., Results: A decreasing trend was observed in the proportion of all reported cases of AIDS in which TB was a primary AIDS-defining illness during the study period. The proportions of female patients and patients with extrapulmonary involvement significantly increased, whereas the proportions of ever-smokers and patients with sputum smear positivity significantly decreased during the same period. A decreasing trend was observed in the proportion of patients with pulmonary TB in which the lower zone was the predominant site of lung parenchymal lesions. Among patients with a diagnosis of HIV infection before TB, an increasing trend was observed in the proportion of patients receiving antiretroviral therapy., Conclusion: Important temporal changes were observed in the epidemiology and clinical manifestations of HIV-associated TB. These results highlight the need for continued surveillance regarding the patterns of demographic features and clinical manifestations to inform policymakers when planning control strategies for HIV-associated TB., Competing Interests: All authors have disclosed no conflicts of interest.

Overactive bladder (OAB) is a common urological disease with a high prevalence in older adult populations. Antimuscarinic drugs have been the most common treatment for OAB for more than a decade, but their anticholinergic side-effects and potential impact on cognitive function among older patients are usually underestimated. This consensus aimed to provide practical recommendations concerning OAB management, with a particular emphasis on older patients. A joint consensus panel was formed by representatives of the Hong Kong Urological Association and the Hong Kong Geriatrics Society. Literature searches regarding OAB and its management were performed in PubMed and Ovid. Several working meetings were held to present and discuss available evidence, develop consensus statements, and vote for the statements. A modified Delphi method was used in this consensus process. To address questions regarding various aspects of OAB, 29 consensus statements were proposed covering the following areas: diagnosis, initial assessment, non-pharmacological treatments, considerations before administration of pharmacological treatments, various pharmacological treatments, combination therapy, and surgical treatment. Twenty-five consensus statements were accepted., Competing Interests: All authors have disclosed no conflicts of interest.

Aims: Currently, there is limited data on prognostic indicators after insertion of percutaneous ventricular assist device (PVAD) in the treatment of cardiogenic shock (CS). This study evaluated the prognostic role of cardiac power output (CPO) ratio, defined as CPO at 24 h divided by early CPO (30 min to 2 h), in CS patients after PVAD., Methods and Results: Consecutive CS patients from the QEH-PVAD Registry were followed up for survival at 90 days after PVAD. Among 121 consecutive patients, 98 underwent right heart catheterization after PVAD, with CPO ratio available in 68 patients. The CPO ratio and 24-h CPO, but not the early CPO post PVAD, were significantly associated with 90-day survival, with corresponding area under curve in ROC analysis of 0.816, 0.740, and 0.469, respectively. In multivariate analysis, only the CPO ratio and lactate level at 24 h remained as independent survival predictors. The CPO ratio was not associated with age, sex, and body size. Patients with lower CPO ratio had significantly lower coronary perfusion pressure, worse right heart indices, and higher pulmonary vascular resistance. A lower CPO ratio was also significantly associated with mechanical ventilation and higher creatine kinase levels in myocardial infarction patients., Conclusion: In post-PVAD patients, the CPO ratio outperformed the absolute CPO values and other haemodynamic metrics in predicting survival at 90 days. Such a proportional change of CPO over time, likely reflecting native heart function recovery, may help to guide management of CS patients post-PVAD., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Over the past decade, the adoption of virtual wards has surged. Virtual wards aim to prevent unnecessary hospital admissions, expedite home discharge, and enhance patient satisfaction, which are particularly beneficial for the older adult population who faces risks associated with hospitalization. Consequently, substantial investments are being made in virtual rehabilitation wards (VRWs), despite evidence of varying levels of success in their implementation. However, the facilitators and barriers experienced by virtual ward staff for the rapid implementation of these innovative care models remain poorly understood., Objective: This paper presents insights from hospital staff working on an Australian VRW in response to the growing demand for programs aimed at preventing hospital admissions. We explore staff's perspectives on the facilitators and barriers of the VRW, shedding light on service setup and delivery., Methods: Qualitative interviews were conducted with 21 VRW staff using the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework. The analysis of data was performed using framework analysis and the 7 domains of the NASSS framework., Results: The results were mapped onto the 7 domains of the NASSS framework. (1) Condition: Managing certain conditions, especially those involving comorbidities and sociocultural factors, can be challenging. (2) Technology: The VRW demonstrated suitability for technologically engaged patients without cognitive impairment, offering advantages in clinical decision-making through remote monitoring and video calls. However, interoperability issues and equipment malfunctions caused staff frustration, highlighting the importance of promptly addressing technical challenges. (3) Value proposition: The VRW empowered patients to choose their care location, extending access to care for rural communities and enabling home-based treatment for older adults. (4) Adopters and (5) organizations: Despite these benefits, the cultural shift from in-person to remote treatment introduced uncertainties in workflows, professional responsibilities, resource allocation, and intake processes. (6) Wider system and (7) embedding: As the service continues to develop to address gaps in hospital capacity, it is imperative to prioritize ongoing adaptation. This includes refining the process of smoothly transferring patients back to the hospital, addressing technical aspects, ensuring seamless continuity of care, and thoughtfully considering how the burden of care may shift to patients and their families., Conclusions: In this qualitative study exploring health care staff's experience of an innovative VRW, we identified several drivers and challenges to implementation and acceptability. The findings have implications for future services considering implementing VRWs for older adults in terms of service setup and delivery. Future work will focus on assessing patient and carer experiences of the VRW., (© Leanne Greene, Miia Rahja, Kate Laver, Vun Vun Wong, Chris Leung, Maria Crotty. Originally published in JMIR Aging (https://aging.jmir.org).)

Spontaneous coronary artery dissection (SCAD) is a rare condition in which there is coronary dissection that is not due to atherosclerosis or iatrogenic causes. It is more common in young women and is associated with risk factors such as the peripartum period and connective tissue disorders. We present five unique cases of SCAD to illustrate the variety of presentations and clinical management. The youngest and oldest patients in our series were 34 and 63 years old, respectively. The majority of our patients (60%) were of African American ethnicity. Two of the patients in the case series developed a new-onset congestive heart failure, and one patient had an iatrogenic complication after intervention. The majority of the patients were treated with conservative medical management (60%), while the others were treated with primary percutaneous coronary intervention (PCI). SCAD is a rare but life-threatening disease that may have varying presentations and precipitating risk factors. As demonstrated in our case series, SCAD may present atypically, and clinicians should maintain a high degree of suspicion in a relevant presentation. Treatment of SCAD may involve conservative management, primary PCI, or coronary artery bypass grafting (CABG) depending on the case. Clinicians may also have to address complications from SCAD, such as cardiomyopathy, that may arise., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jnani et al.)

Background: Double barrelled uro-colostomy (DBUC) is an alternative to traditional ileal conduit (IC) and separate colostomy in patients requiring simultaneous urinary and faecal diversion for reconstruction in pelvic exenteration surgery (PES)., Methods: This cohort study evaluated short- and long-term morbidity and mortality associated with DBUC formation in 20 consecutive adult patients undergoing PES in an Australian Complex Pelvic Surgical Unit. Data were obtained from a prospective database., Results: Mean age 59 years (range 27-76 years). PES was performed for malignant disease in 18 patients (curative intent in 17). Mean operative duration 11.8 h (range 7-17 h). Mean follow-up duration 29.1 months (range 2.6-90.1 months). Early DBUC-related complications occurred in four patients (20.0%): urinary tract infection (UTI)/urosepsis (n = 4) and early ureteric stenosis requiring intervention (n = 1). Late DBUC-related complications occurred in five patients (25.0%): recurrent UTI/urosepsis (n = 4), chronic kidney disease (n = 4), ureteric stenosis (n = 2) and parastomal hernia (n = 4). No mortality occurred secondary to a DBUC complication., Conclusion: DBUC is a safe reconstructive option with acceptable morbidity profile in patients requiring simultaneous urinary and faecal diversion., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Documentation of clinical encounters continues to be a challenge to implement in practice and there is a lack of literature on documentation best practices in pharmacy. In order to inform documentation practices at an academic pharmacy clinic, a quality assurance (QA) initiative was implemented at the UBC Pharmacists Clinic (the Clinic). The goal of this QA initiative was to determine what facilitators and barriers to documentation existed for Clinic pharmacists and improve the efficiency of consultation note writing. Phase 1 conducted an online survey to assess each pharmacist's documentation practice at baseline. Phase 2 implemented new interventions that could advance these skills. There were five main interventions introduced: 1) revised consultation note templates, 2) a documentation "checklist", 3) a documentation "decision tree", 4) a clinical documentation guide and 5) a documentation peer-feedback workshop. During Phase 3, pharmacists re-answered the same survey questions 10 months later. This allowed for a direct comparison of documentation practices and skills before and after the interventions. After the interventions, pharmacists reduced the time to complete their notes by nearly 14 min. The revised note structure resulted in an increased uptake of template use from 37% to 100%. Furthermore, prior to the interventions, the majority of pharmacists ranked writing consultation notes as the most burdensome aspect of their daily workflow. Afterwards, the perceived level of burden reduced significantly. These findings can be used to inform how students are taught documentation and improve the quality of documentation by pharmacists in team-based or primary care settings., (© Individual authors.)

People with Parkinson's disease with motor fluctuations can be treated by continuous subcutaneous apomorphine infusion (CSAI) to reduce their symptoms. Nonetheless, factors are lacking to predict patients' quality-of-life amelioration after CSAI. This pilot study aimed to evaluate associations between personality dimensions and quality-of-life improvement after 6 months of CSAI. Thirty-nine people with Parkinson's disease awaiting CSAI were included. Linear regression models between 'Temperament and Character Inventory' personality dimensions at baseline and percentage of change in Parkinson's Disease Questionnaire-39 scores after 6 months of CSAI were realized ( n = 35). The Temperament and Character Inventory was also compared between patients awaiting CSAI and patients awaiting deep brain stimulation of the sub-thalamic nucleus ( n = 39 from the PREDI-STIM study). Higher reward dependence scores were associated with a better quality-of-life outcome after 6 months of CSAI, while self-directedness scores were associated with a better quality of life before CSAI (as opposed to harm avoidance, reward dependence and self-transcendence scores associated with a worse quality of life). Moreover, people with Parkinson's disease awaiting deep brain stimulation of the sub-thalamic nucleus had similar Temperament and Character Inventory dimensions compared to patients awaiting CSAI. People with Parkinson's disease with higher reward dependence scores at baseline had the best quality-of-life improvement after 6 months of CSAI. This finding could be used to better prepare and accompany people with Parkinson's disease during CSAI establishment. Moreover, this result could serve as an orientation factor to second-line treatments., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Rationale: Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments. Objectives: To apply a segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma. Methods: In each of 19 bronchopulmonary segments in CT lung scans from 199 patients with asthma, AT was categorized as present if lung attenuation was less than -856 Hounsfield units at expiration in ⩾15% of the lung area. The resulting AT segment score (0-19) was related to patient outcomes. Measurements and Main Results: AT varied at the lung segment level and tended to persist at the patient and lung segment levels over 3 years. Patients with widespread AT (⩾10 segments) had more severe asthma ( P  < 0.05). The mean (±SD) AT segment score in patients with a body mass index ⩾30 kg/m 2 was lower than in patients with a body mass index <30 kg/m 2 (3.5 ± 4.6 vs. 5.5 ± 6.3; P  = 0.008), and the frequency of AT in lower lobe segments in obese patients was less than in upper and middle lobe segments (35% vs. 46%; P  = 0.001). The AT segment score in patients with sputum eosinophils ⩾2% was higher than in patients without sputum eosinophilia (7.0 ± 6.1 vs. 3.3 ± 4.9; P  < 0.0001). Lung segments with AT more frequently had airway mucus plugging than lung segments without AT (48% vs. 18%; P  ⩽ 0.0001). Conclusions: In patients with asthma, air trapping is more severe in those with airway eosinophilia and mucus plugging, whereas those who are obese have less severe trapping because their lower lobe segments are spared.

Background: The COVID-19 pandemic has not only caused tremendous loss of life and health but has also greatly disrupted the world economy. The impact of this disruption has been especially harsh in urban settings of developing countries. We estimated the impact of the pandemic on the occurrence of food insecurity in a cohort of women living in Mexico City, and the socioeconomic characteristics associated with food insecurity severity., Methods: We analyzed data longitudinally from 685 women in the Mexico City-based ELEMENT cohort. Food insecurity at the household level was gathered using the Latin American and Caribbean Food Security Scale and measured in-person during 2015 to 2019 before the pandemic and by telephone during 2020-2021, in the midst of the pandemic. Fluctuations in the average of food insecurity as a function of calendar time were modeled using kernel-weighted local polynomial regression. Fixed and random-effects ordinal logistic regression models of food insecurity were fitted, with timing of data collection (pre-pandemic vs. during pandemic) as the main predictor., Results: Food insecurity (at any level) increased from 41.6% during the pre-pandemic period to 53.8% in the pandemic stage. This increase was higher in the combined severe-moderate food insecurity levels: from 1.6% pre-pandemic to 16.8% during the pandemic. The odds of severe food insecurity were 3.4 times higher during the pandemic relative to pre-pandemic levels (p<0.01). Socioeconomic status quintile (Q) was significantly related to food insecurity (Q2 OR = 0.35 p<0.1, Q3 OR = 0.48 p = 0.014, Q4 OR = 0.24 p<0.01, and Q5 OR = 0.17 p<0.01), as well as lack of access to social security (OR = 1.69, p = 0.01), and schooling (OR = 0.37, p<0.01)., Conclusions: Food insecurity increased in Mexico City households in the ELEMENT cohort as a result of the COVID-19 pandemic. These results contribute to the body of evidence suggesting that governments should implement well-designed, focalized programs in the context of economic crisis such as the one caused by COVID-19 to prevent families from the expected adverse health and well-being consequences associated to food insecurity, especially for the most vulnerable., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bautista-Arredondo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To evaluate the efficacy and safety of CHM in the prevention of COVID-19 infection and treatment for COVID-19 related symptoms., Design: Prospective open-label randomized controlled trial., Setting: Participants' home in Hong Kong., Participants: Participants who had household close contact with COVID-19-infected family members., Interventions: Close contacts were stratified into 4 groups (cohort A, B, C, D) based on symptoms and infection status and were randomized in 4:1 ratio to receive CHM granules (9g/sachet, two times daily) or blank control for 7 days with 2 weeks of follow-up., Main Outcome Measures: The primary outcome measure was the rate of positive nucleic acid tests. Secondary outcomes were the proportion of developed COVID-19 related symptoms and adverse events during the whole 3-week study period. Subgroup analysis was used to evaluate demographic factors associated with positive infection rates., Results: A total of 2163 contacts were enrolled and randomly assigned to the CHM group (1720 contacts) and blank control (443 contacts) group. During the 21 days, the rate of PCR-positive cases in cohort A was markedly lower in the CHM group (3.6%) compared to the control group (7.0%) ( P =0.036). Overall, the rate of infection in the CHM group was significantly lower than that in the control group (10.69% vs . 6.03%; RR 0.56, 95% CI 0.39-0.82) after 7-day treatment. No serious adverse events were reported during the medication period., Conclusion: The preliminary findings indicate that CHM may be effective and safe in preventing COVID-19. Future double-blind, randomized controlled trials and long-term follow-up are needed to fully evaluate the efficacy of CHM in a larger contact population., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05269511., Competing Interests: The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Du, Lam, Leung, Li, Lyu, Yuen, Cheung, Lam, Bian and Zhong.)

Introduction: Chronic obstructive pulmonary disease (COPD) accounts for 545 million people living with chronic respiratory disorders and is the third leading cause of morbidity and mortality around the world. COPD is a progressive disease, characterized by episodes of acute worsening of symptoms such as cough, dyspnea, and sputum production., Areas Covered: Airway inflammation is a prominent feature of COPD. Chronic airway inflammation results in airway structural remodeling and emphysema. Persistent airway inflammation is a treatable trait of COPD and plays a significant role in disease development and progression. In this review, the authors summarize the current and emerging biomarkers that reveal the heterogeneity of airway inflammation subtypes, clinical outcomes, and therapeutic response in COPD., Expert Opinion: Airway inflammation can be broadly categorized as eosinophilic (type 2 inflammation) and non-eosinophilic (non-type 2 inflammation) in COPD. Currently, blood eosinophil counts are incorporated in clinical practice guidelines to identify COPD patients who are at a higher risk of exacerbations and lung function decline, and who are likely to respond to inhaled corticosteroids. As new therapeutics are being developed for the chronic management of COPD, it is essential to identify biomarkers that will predict treatment response.

Influenza in dogs holds considerable public health significance due to their close companionship with humans, yet several facets of this phenomenon remain largely unexplored. This study undertook a systematic review and meta-analysis of observational studies to gauge the global seroprevalence of influenza in dogs. We also assessed whether pet dogs exhibited a higher seroprevalence of influenza compared to non-pet dogs, explored seasonal variations in seroprevalence, scrutinised the design and reporting standards of existing studies, and elucidated the geographical distribution of canine influenza virus (cIV). A comprehensive analysis of 97 studies spanning 27 countries revealed that seroprevalence of various influenza strains in dogs consistently registered below 10% and exhibited relative stability over the past decade. Significantly, we noted that seroprevalence of human influenza virus was notably higher in pet dogs compared to their non-pet counterparts, whereas seroprevalence of other influenza strains remained relatively uniform among both categories of dogs. Seasonal variations in seroprevalence of cIV were not observed. In summary, our findings indicated the global circulation of cIV strains H3N2 and H3N8, with other strains primarily confined to China. Given the lack of reported cases of the transmission of cIV from dogs to humans, our findings suggest a higher risk of reverse zoonosis than zoonosis. Finally, we strongly advocate for standardised reporting guidelines to underpin future canine influenza research endeavours., (© 2024 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.)

Introduction: Limited evidence exists on management recommendations for neonates born to SARS-CoV-2-positive mothers. This study looked at transmission risk of neonates presenting for primary care in a large regional health system within New York during the early months of the COVID-19 pandemic., Methods: This was a prospective, observational study of newborns born to SARS-CoV-2-positive mothers presenting at any of the 19 Northwell Health-Cohen Children's Medical Center primary care practices who underwent another oropharyngeal/nasopharyngeal swab for detection of SARS-CoV-2 by day of life (DOL) 14., Results: Among 293 newborns born to SARS-CoV-2-positive mothers who were negative at birth, 222 were retested at DOL 14, corresponding to times with different predominant strains. Of these, seven tested positive but had no symptoms., Conclusion: The overall low transmission rates and absence of symptomatic infection support the safety of direct breastfeeding after hospital discharge with appropriate hand and breast hygiene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Jan, Katz, Fagan, Santos, Beachy, Steinway, Chen, Tsouristakis, Mancenido, Leung, Moore, Wilson, Lin, Harte, Katzow and Rubin.)

The determination of metabolic stability is critical for drug discovery programs, allowing for the optimization of chemical entities and compound prioritization. As such, it is common to perform high-volume in vitro metabolic stability experiments early in the lead optimization process to understand metabolic liabilities. Additional metabolite identification experiments are subsequently performed for a more comprehensive understanding of the metabolic clearance routes to aid medicinal chemists in the structural design of compounds. Collectively, these experiments require extensive sample preparation and a substantial amount of time and resources. To overcome the challenges, a high-throughput integrated assay for simultaneous hepatocyte metabolic stability assessment and metabolite profiling was developed. This assay platform consists of four parts: 1) an automated liquid-handling system for sample preparation and incubation, 2) a liquid chromatography and high-resolution mass spectrometry-based system to simultaneously monitor the parent compound depletion and metabolite formation, 3) an automated data analysis and report system for hepatic clearance assessment; and 4) streamlined autobatch processing for software-based metabolite profiling. The assay platform was evaluated using eight control compounds with various metabolic rates and biotransformation routes in hepatocytes across three species. Multiple sample preparation and data analysis steps were evaluated and validated for accuracy, repeatability, and metabolite coverage. The combined utility of an automated liquid-handling instrument, a high-resolution mass spectrometer, and multiple streamlined data processing software improves the process of these highly demanding screening assays and allows for simultaneous determination of metabolic stability and metabolite profiles for more efficient lead optimization during early drug discovery. SIGNIFICANCE STATEMENT: Metabolic stability assessment and metabolite profiling are pivotal in drug discovery to fully comprehend metabolic liabilities for chemical entity optimization and lead selection. Process of these assays can be repetitive and resource demanding. Here, we developed an integrated hepatocyte stability assay that combines automation, high-resolution mass spectrometers, and batch-processing software to improve and combine the workflow of these assays. The integrated approach allows simultaneous metabolic stability assessment and metabolite profiling, significantly accelerating screening and lead optimization in a resource-effective manner., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Effectively identifying deteriorated patients is vital to the development and validation of automated systems designed to predict clinical deterioration. Existing outcome measures used for this purpose have significant limitations. Published criteria for admission to high acuity inpatient areas may represent markers of patient deterioration and could inform the development of alternate outcome measures., Objectives: In this scoping review, we aimed to characterise published criteria for admission of adult inpatients to high acuity inpatient areas including intensive care units. A secondary aim was to identify variables that are extractable from electronic health records (EHRs)., Data Sources: Electronic databases PubMed and ProQuest EBook Central were searched to identify papers published from 1999 to date of search. We included publications which described prescriptive criteria for admission of adult inpatients to a clinical area with a higher level of care than a general hospital ward., Charting Methods: Data was extracted from each publication using a standardised data-charting form. Admission criteria characteristics were summarised and cross-tabulated for each criterion by population group., Results: Five domains were identified: diagnosis-based criteria, clinical parameter criteria, organ-support criteria, organ-monitoring criteria and patient baseline criteria. Six clinical parameter-based criteria and five needs-based criteria were frequently proposed and represent variables extractable from EHRs. Thresholds for objective clinical parameter criteria varied across publications, and by disease subgroup, and universal cut-offs for criteria could not be elucidated., Conclusions: This study identified multiple criteria which may represent markers of deterioration. Many of the criteria are extractable from the EHR, making them potential candidates for future automated systems. Variability in admission criteria and associated thresholds across the literature suggests clinical deterioration is a heterogeneous phenomenon which may resist being defined as a single entity via a consensus-driven process., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2024.)

Hepatitis B Virus (HBV) is a major driver of infectious disease mortality. Curative therapies are needed and ideally should induce CD8 T cell-mediated clearance of infected hepatocytes plus anti-hepatitis B surface antigen (HBsAg) antibodies (anti-HBs) to neutralize residual virus. We developed a novel therapeutic vaccine using non-replicating arenavirus vectors. Antigens were screened for genotype conservation and magnitude and genotype reactivity of T cell response, then cloned into Pichinde virus (PICV) vectors (recombinant PICV, GS-2829) and lymphocytic choriomeningitis virus (LCMV) vectors (replication-incompetent, GS-6779). Alternating immunizations with GS-2829 and GS-6779 induced high-magnitude HBV T cell responses, and high anti-HBs titers. Dose schedule optimization in macaques achieved strong polyfunctional CD8 T cell responses against core, HBsAg, and polymerase and high titer anti-HBs. In AAV-HBV mice, GS-2829 and GS-6779 were efficacious in animals with low pre-treatment serum HBsAg. Based on these results, GS-2829 and GS-6779 could become a central component of cure regimens., Competing Interests: Potential conflicts of interest . M. M., S. D., T. G., R. C., C. L., A. T., J. P., S. P. F., and S. B. are or were employees of Gilead Sciences. S. S., S. A. E., D. D., H. L., and K. O. are employees of Hookipa Pharma. M. D. R. has financial relationships with CaroGen Corporation, received royalties from a Yale University patent, and received research funding from Gilead Sciences. Al; other authors reported no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background and Objectives: Degenerative thoracolumbar disorders (DTDs) typically cause pain and functional impairment. However, little is known regarding the DTD impact on patient's real-life physical activity. The objective of this study is to validate a wearable measure of physical activity monitoring in patients with DTD and to create gender- and sex-specific performance thresholds that are standardized to the mean of a control population., Methods: A commercially available smartwatch (Apple Watch) was used to monitor preoperative physical activity in patients undergoing surgery for DTD. Mean preoperative physical activity 2 weeks before the scheduled surgery was expressed as raw step count. Standardized z-scores were referenced to age- and sex-specific values of a control population from a large public database. Step counts were assessed for convergent validity with established patient-reported outcome measures, and impairment in activity was stratified into performance groups based on z-score cutoff values., Results: Sixty-five patients (62% female) with a mean (±SD) age of 63.8 (±12.8) years had a mean preoperative daily step count of 5556 (±3978). Physical activity showed significant correlation with patient-reported outcome measures, including Oswestry disability index (r = -0.26, 95% CI: -0.47-0.01), 36-Item Short Form Survey Physical Component Summary score (r = 0.30, 95% CI: 0.06-0.51), and Patient-Reported Outcomes Measurement Information System Physical Function (r = 0.49, 95% CI: 0.27-0.65). "No," "Mild," "moderate," and "severe impairment" in activity performance were defined as corresponding z-scores of >0, 0 to -0.99, -1 to -1.99, and ≤-2, accounting for 22%, 34%, 40%, and 5% of the study population. Each one-step category increase in activity impairment resulted in increased subjective disability as measured by the Oswestry Disability Index, 36-Item Short Form Survey Physical Component Summary, and Patient-Reported Outcomes Measurement Information System Physical Function (all P -values <.05)., Conclusion: We establish the first wearable objective measure of real-life physical activity for patients with DTD, with the first age- and sex-adjusted standard scores to enable clinicians and researchers to set treatment goals and directly compare activity levels between individual patients with DTD and normal controls., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

The KRAS G12D mutation was believed to be locked in a GTP-bound form, rendering it fully active. However, recent studies have indicated that the presence of mutant KRAS alone is insufficient; it requires additional activation through inflammatory stimuli to effectively drive the development of pancreatic ductal adenocarcinoma (PDAC). It remains unclear to what extent RAS activation occurs during the development of PDAC in the context of inflammation. Here, in a mouse model with the concurrent expression of Kras G12D/+ and inflammation mediator IKK2 in pancreatic acinar cells, we showed that, compared to KRAS G12D alone, the cooperative interaction between KRAS G12D and IKK2 rapidly elevated both the protein level and activity of KRAS G12D and NRAS in a short term. This high level was sustained throughout the rest phase of PDAC development. These results suggest that inflammation not only rapidly augments the activity but also the protein abundance, leading to an enhanced total amount of GTP-bound RAS (KRAS G12D and NRAS) in the early stage. Notably, while KRAS G12D could be further activated by IKK2, not all KRAS G12D proteins were in the GTP-bound state. Overall, our findings suggest that although KRAS G12D is not fully active in the context of inflammation, concurrent increases in both the protein level and activity of KRAS G12D as well as NRAS at the early stage by inflammation contribute to the rise in total GTP-bound RAS., 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 B.V. All rights reserved.)

Background: Oseltamivir is a low-cost antiviral agent that could support or complement treatment of COVID-19. This study assessed whether oseltamivir is effective in reducing COVID-19-related mortality., Methods: This retrospective cohort study evaluated real-world data from a nationwide database of hospitalisation due to severe acute respiratory syndrome in Brazil. Propensity score matching was used to mimic a randomised controlled trial with 'oseltamivir' and 'no antivirals at all' as the intervention and control groups, respectively., Results: A total of 21 480 and 268 486 patients admitted between February 2020 and January 2023 were included in the intervention and control groups, respectively. After matching, the odds ratio (OR) for death was 0.901 (95% confidence interval [CI] 0.873-0.930). The OR (95% CI) for death in patients who were admitted to the ICU, and on non-invasive or invasive ventilation was 0.868 (0.821-0.917), 0.935 (0.893-0.980), and 0.883 (0.814-0.958), respectively., Conclusions: Overall, the use of oseltamivir was associated with an attributable risk reduction of 2.50% (95% CI 1.77-3.29). Similar results were observed in patients who were admitted to the ICU, and on non-invasive or invasive ventilation. Oseltamivir is a low-cost potential antiviral treatment for COVID-19., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: University attendance represents a transition period for students that often coincides with the emergence of mental health and substance use challenges. Digital interventions have been identified as a promising means of supporting students due to their scalability, adaptability, and acceptability. Minder is a mental health and substance use mobile app that was codeveloped with university students., Objective: This study aims to examine the effectiveness of the Minder mobile app in improving mental health and substance use outcomes in a general population of university students., Methods: A 2-arm, parallel-assignment, single-blinded, 30-day randomized controlled trial was used to evaluate Minder using intention-to-treat analysis. In total, 1489 participants were recruited and randomly assigned to the intervention (n=743, 49.9%) or waitlist control (n=746, 50.1%) condition. The Minder app delivers evidence-based content through an automated chatbot and connects participants with services and university social groups. Participants are also assigned a trained peer coach to support them. The primary outcomes were measured through in-app self-assessments and included changes in general anxiety symptomology, depressive symptomology, and alcohol consumption risk measured using the 7-item General Anxiety Disorder scale, 9-item Patient Health Questionnaire, and US Alcohol Use Disorders Identification Test-Consumption Scale, respectively, from baseline to 30-day follow-up. Secondary outcomes included measures related to changes in the frequency of substance use (cannabis, alcohol, opioids, and nonmedical stimulants) and mental well-being. Generalized linear mixed-effects models were used to examine each outcome., Results: In total, 79.3% (589/743) of participants in the intervention group and 83% (619/746) of participants in the control group completed the follow-up survey. The intervention group had significantly greater average reductions in anxiety symptoms measured using the 7-item General Anxiety Disorder scale (adjusted group mean difference=-0.85, 95% CI -1.27 to -0.42; P<.001; Cohen d=-0.17) and depressive symptoms measured using the 9-item Patient Health Questionnaire (adjusted group mean difference=-0.63, 95% CI -1.08 to -0.17; P=.007; Cohen d=-0.11). A reduction in the US Alcohol Use Disorders Identification Test-Consumption Scale score among intervention participants was also observed, but it was not significant (P=.23). Statistically significant differences in favor of the intervention group were found for mental well-being and reductions in the frequency of cannabis use and typical number of drinks consumed. A total of 77.1% (573/743) of participants in the intervention group accessed at least 1 app component during the study period., Conclusions: In a general population sample of university students, the Minder app was effective in reducing symptoms of anxiety and depression, with provisional support for increasing mental well-being and reducing the frequency of cannabis and alcohol use. These findings highlight the potential ability of e-tools focused on prevention and early intervention to be integrated into existing university systems to support students' needs., Trial Registration: ClinicalTrials.gov NCT05606601; https://clinicaltrials.gov/ct2/show/NCT05606601., International Registered Report Identifier (irrid): RR2-10.2196/49364., (©Melissa Vereschagin, Angel Y Wang, Chris G Richardson, Hui Xie, Richard J Munthali, Kristen L Hudec, Calista Leung, Katharine D Wojcik, Lonna Munro, Priyanka Halli, Ronald C Kessler, Daniel V Vigo. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.03.2024.)