Investigating Patient Use and Experience of Online Appointment Booking in Primary Care: Mixed Methods Study.

BACKGROUND: Online appointment booking is a commonly used tool in several industries. There is limited evidence about the benefits and challenges of using online appointment booking in health care settings. Potential benefits include convenience and the ability to track appointments, although some groups of patients may find it harder to engage with online appointment booking. We sought to understand how patients in England used and experienced online appointment booking. OBJECTIVE: This study aims to describe and compare the characteristics of patients in relation to their use of online appointment booking in general practice and investigate patients' views regarding online appointment booking arrangements. METHODS: This was a mixed methods study set in English general practice comprising a retrospective analysis of the General Practice Patient Survey (GPPS) and semistructured interviews with patients. Data used in the retrospective analysis comprised responses to the 2018 and 2019 GPPS analyzed using mixed-effects logistic regression. Semistructured interviews with purposively sampled patients from 11 general practices in England explored experiences of and views on online appointment booking. Framework analysis was used to allow for comparison with the findings of the retrospective analysis. RESULTS: The retrospective analysis included 1,327,693 GPPS responders (2018-2019 combined). We conducted 43 interviews with patients with a variety of experiences and awareness of online appointment booking; of these 43 patients, 6 (14%) were from ethnic minority groups. In the retrospective analysis, more patients were aware that online appointment booking was available (581,224/1,288,341, 45.11%) than had experience using it (203,184/1,301,694, 15.61%). There were deprivation gradients for awareness and use and a substantial decline in both awareness and use in patients aged >75 years. For interview participants, age and life stage were factors influencing experiences and perceptions, working patients valued convenience, and older patients preferred to use the telephone. Patients with long-term conditions were more aware of (odds ratio [OR] 1.43, 95% CI 1.41-1.44) and more likely to use (OR 1.65, 95% CI 1.63-1.67) online appointment booking. Interview participants with long-term conditions described online appointment booking as useful for routine nonurgent appointments. Patients in deprived areas were clustered in practices with low awareness and use of online appointment booking among GPPS respondents (OR for use 0.65, 95% CI 0.64-0.67). Other key findings included the influence of the availability of appointments online and differences in the registration process for accessing online booking. CONCLUSIONS: Whether and how patients engage with online appointment booking is influenced by the practice with which they are registered, whether they live with long-term conditions, and their deprivation status. These factors should be considered in designing and implementing online appointment booking and have implications for patient engagement with the wider range of online services offered in general practice.

THE CLASSIFICATION OF HIATAL SHAPES AND ITS USE AS A MARKER FOR COMPLEXITY, OPERATIVE INTERVENTIONS, AND RECURRENCE.

BACKGROUND: Diaphragmatic reconstruction is a vital, but challenging component of hiatal hernia and anti-reflux surgery. Results are optimized by minimizing axial tension along the esophagus, assessed with intra-abdominal length, and radial tension across the hiatus, which has not been standardized. We categorized hiatal openings into four shapes, as a surrogate for radial tension, to correlate their association with operative interventions and recurrence. METHODS: We retrospectively reviewed all primary hiatal hernias (≥3cm) repaired at a single center between 2010-2020. Patients with intra-operative hiatal photos with at least one year of follow up were included. The hiatal openings were classified into four shapes: slit, inverted teardrop, "D", and oval and ordered in this manner of hypothesized increased complexity and tension. RESULTS: A total of 239 patients were studied, with 113 (47%) having a recurrence. Age (p<0.001), proportion of paraesophageal hernias (p<0.001), hernia axial length (p<0.001), and hiatal width (p<0.001) all increased as shape progressed from slit to inverted teardrop to 'D" to oval. Mesh (p=0.003) and relaxing incisions (p<0.001) were more commonly employed in more advanced shapes, "D" and ovals. However, recurrence (p=0.88) did not correlate with hiatal shape. CONCLUSION: Four different hiatal shapes are commonly seen during hernia repair. These shapes represent a spectrum of hernia chronicity and complexity necessitating increased use of operative measures but not correlating with recurrence. While failing to be a direct marker for recurrence risk, hiatal shape may serve as an intra-operative tool to inform surgeons of the potential need for additional hiatal interventions.

EBV T-cell immunotherapy generated by peptide selection has enhanced effector functionality compared to LCL stimulation.

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific T cells is an effective treatment for relapsed or refractory EBV-induced post-transplant lymphoproliferative disorders (PTLD) with overall survival rates of up to 69%. EBV-specific T cells have been conventionally made by repeated stimulation with EBV-transformed lymphoblastoid cell lines (LCL), which act as antigen-presenting cells. However, this process is expensive, takes many months, and has practical risks associated with live virus. We have developed a peptide-based, virus-free, serum-free closed system to manufacture a bank of virus-specific T cells (VST) for clinical use. We compared these with standard LCL-derived VST using comprehensive characterization and potency assays to determine differences that might influence clinical benefits. Multi-parameter flow cytometry revealed that peptide-derived VST had an expanded central memory population and less exhaustion marker expression than LCL-derived VST. A quantitative HLA-matched allogeneic cytotoxicity assay demonstrated similar specific killing of EBV-infected targets, though peptide-derived EBV T cells had a significantly higher expression of antiviral cytokines and degranulation markers after antigen recall. High-throughput T cell receptor-beta (TCRß) sequencing demonstrated oligoclonal repertoires, with more matches to known EBV-binding complementary determining region 3 (CDR3) sequences in peptide-derived EBV T cells. Peptide-derived products showed broader and enhanced specificities to EBV nuclear antigens (EBNAs) in both CD8 and CD4 compartments, which may improve the targeting of highly expressed latency antigens in PTLD. Importantly, peptide-based isolation and expansion allows rapid manufacture and significantly increased product yield over conventional LCL-based approaches.

Sarm1-Dependent Metabolic Reprogramming of Schwann Cells Following Nerve Injury.

Schwann cells (SCs) transition into a repair phenotype after peripheral nerve injury, which is crucial for supporting axon regeneration. However, the early SC injury response preceding the repair state remains poorly understood. Here, we demonstrate that Sarm1, a key regulator of axon degeneration, is expressed in SCs and has a critical role in the early SC injury response. Leveraging the fact that Sarm1 deletion impairs the SC transition to the repair state, we used single-nucleus RNA sequencing to compare the transcriptional responses of wild-type and Sarm1 knockout SCs 24 hours after nerve injury. Remarkably, Sarm1-deficient SCs, unlike wild-type SCs, showed increased expression of genes involved in oxidative phosphorylation and the TCA cycle. These findings were functionally validated, revealing that Sarm1 knockout SCs displayed increased mitochondrial respiration in response to injury. Intriguingly, Sarm1 knockout SCs also exhibited enhanced axon protection compared to wild-type SCs in an in vitro model of axon degeneration. We propose that Sarm1 gates the transition of SCs from a protective, oxidative phosphorylation-dependent state (which we term Protection Associated Schwann Cells or PASCs) to a glycolytic, pro-regenerative repair phenotype after injury. Our findings challenge the prevailing view of Sarm1 as an exclusively axon-autonomous regulator of degeneration and reveal a paradigm shift in understanding the role of Sarm1 in the SC injury response, with broad implications for the treatment of peripheral neuropathies and neurodegenerative diseases.

Trace mineral concentrations in Canadian beef calves at weaning.

Objective: To describe the copper and selenium statuses of beef calves at weaning. Animal: Calves (n = 1998) were sampled from 106 Canadian cow-calf herds in the fall of 2021. Procedure: Serum samples from calves were tested for copper, selenium, and molybdenum concentrations. Results: Although the percentages of calves classified as selenium deficient (< 0.025 ppm) were relatively low (0.5% western Canada, 3% eastern Canada), 53% of calves from western Canada and 77% of calves from eastern Canada were classified as having less than adequate selenium concentrations (< 0.08 ppm). Copper deficiency (< 0.5 ppm) was common in calves from both western (17%) and eastern (14%) Canada. High molybdenum concentrations (> 0.10 ppm) were identified in 6% of calves from western Canada and 7% of calves from eastern Canada. Conclusion: Selenium concentrations were higher in calves from western Canada than from those in eastern Canada (P < 0.001). Copper and molybdenum concentrations were not significantly different between western and eastern Canada. Less-than-adequate serum copper was the most common deficiency identified in Canadian beef calves at weaning. Clinical relevance: Trace minerals are important for immune system function in calves at weaning. Selenium concentrations in calves at weaning were lower than in cows from the same herds collected at pregnancy testing 2 y earlier. Copper deficiency was also identified, though less frequently than for mature cows. Supplementation programs for calves should be customized based on testing and recognize both regional and age differences in risk.

Concentrations d'oligo-éléments minéraux chez les veaux de boucherie canadiens au sevrage. Objectif: Décrire les statuts en cuivre et en sélénium des veaux de boucherie au sevrage. Animal: Des veaux (n = 1998) ont été échantillonnés dans 106 troupeaux de type vache-veau canadiens à l'automne 2021. Procédure: Des échantillons de sérum de veaux ont été testés pour déterminer les concentrations de cuivre, de sélénium et de molybdène. Résultats: Même si les pourcentages de veaux classés comme déficients en sélénium (< 0,025 ppm) étaient relativement faibles (0,5 % dans l'ouest du Canada, 3 % dans l'est du Canada), 53 % des veaux de l'ouest du Canada et 77 % des veaux de l'est du Canada étaient classés comme ayant moins des concentrations de sélénium moins qu'adéquates (< 0,08 ppm). Une carence en cuivre (< 0,5 ppm) était courante chez les veaux de l'ouest (17 %) et de l'est (14 %) du Canada. Des concentrations élevées de molybdène (> 0,10 ppm) ont été identifiées chez 6 % des veaux de l'ouest du Canada et 7 % des veaux de l'est du Canada. Conclusion: Les concentrations de sélénium étaient plus élevées chez les veaux de l'ouest du Canada que chez ceux de l'est du Canada (P < 0,001). Les concentrations de cuivre et de molybdène n'étaient pas significativement différentes entre l'ouest et l'est du Canada. Un taux de cuivre sérique nettement insuffisamment était la carence la plus courante identifiée chez les veaux de boucherie canadiens au sevrage. Pertinence clinique: Les oligo-éléments sont importants pour le fonctionnement du système immunitaire des veaux au sevrage. Les concentrations de sélénium chez les veaux au sevrage étaient inférieures à celles des vaches des mêmes troupeaux collectées lors des tests de gestation deux ans plus tôt. Des carences en cuivre ont également été identifiées, quoique moins fréquemment que chez les vaches matures. Les programmes de supplémentation pour les veaux doivent être personnalisés en fonction des tests et reconnaître les différences de risque selon la région et l'âge.(Traduit par Dr Serge Messier).

Identification of genetic markers of resistance to macrolide class antibiotics in Mannheimia haemolytica isolates from a Saskatchewan feedlot.

Mannheimia haemolytica is a major contributor to bovine respiratory disease (BRD), which causes substantial economic losses to the beef industry, and there is an urgent need for rapid and accurate diagnostic tests to provide evidence for treatment decisions and support antimicrobial stewardship. Diagnostic sequencing can provide information about antimicrobial resistance genes in M. haemolytica more rapidly than conventional diagnostics. Realizing the full potential of diagnostic sequencing requires a comprehensive understanding of the genetic markers of antimicrobial resistance. We identified genetic markers of resistance in M. haemolytica to macrolide class antibiotics commonly used for control of BRD. Genome sequences were determined for 99 M. haemolytica isolates with six different susceptibility phenotypes collected over 2 years from a feedlot in Saskatchewan, Canada. Known macrolide resistance genes estT, msr(E), and mph(E) were identified in most resistant isolates within predicted integrative and conjugative elements (ICEs). ICE sequences lacking antibiotic resistance genes were detected in 10 of 47 susceptible isolates. No resistance-associated polymorphisms were detected in ribosomal RNA genes, although previously unreported mutations in the L22 and L23 ribosomal proteins were identified in 12 and 27 resistant isolates, respectively. Pangenome analysis led to the identification of 79 genes associated with resistance to gamithromycin, of which 95% (75 of 79) had no functional annotation. Most of the observed phenotypic resistance was explained by previously identified antibiotic resistance genes, although resistance to the macrolides gamithromycin and tulathromycin was not explained in 39 of 47 isolates, demonstrating the need for continued surveillance for novel determinants of macrolide resistance.IMPORTANCEBovine respiratory disease is the costliest disease of beef cattle in North America and the most common reason for injectable antibiotic use in beef cattle. Metagenomic sequencing offers the potential to make economically significant reductions in turnaround time for diagnostic information for evidence-based selection of antibiotics for use in the feedlot. The success of diagnostic sequencing depends on a comprehensive catalog of antimicrobial resistance genes and other genome features associated with reduced susceptibility. We analyzed the genome sequences of isolates of Mannheimia haemolytica, a major bovine respiratory disease pathogen, and identified both previously known and novel genes associated with reduced susceptibility to macrolide class antimicrobials. These findings reinforce the need for ongoing surveillance for markers of antimicrobial resistance to support improved diagnostics and antimicrobial stewardship.

Supporting patients with a mental health diagnosis to use online services in primary care. A qualitative interview study.

Objective: The increase in reliance on online services for general practice has the potential to increase inequalities within some populations. Patients with a mental health condition are one such group. Digital facilitation is defined as a range of processes, procedures, and people, which seek to support NHS patients in using online services. This study aimed to examine the views and experiences of digital facilitation in primary care amongst patients living with a mental health condition. Methods: Semi-structured interviews were conducted with patients living with a mental health condition, recruited from general practices across England participating in the Di-Facto study. Thematic analysis was conducted on interview transcripts. Results: Interviews were conducted with ten participants with a mental health condition, recruited from five general practices. Three themes were identified: (1) familiarity with online services; (2) experiences of those using online services; (3) the need for digital facilitation. The need for digital facilitation was identified in the registration for online services, and in trusting online services. Conclusions: Online services offer convenience for patients, but registration for the use of such services remains a potential area of difficulty. Participants had difficulties with registering for online services and had concerns about trust in using them. Support offered by general practices in using online services needs to be varied and adaptable to meet the needs of individual patients.

Comparison of postweaning bovine respiratory disease treatment rates between non-vaccinated control beef calves and calves variably primed and boosted using commercially available bovine coronavirus vaccines.

Objective: Bovine respiratory disease (BRD) and overall postweaning treatment rates were compared among 3 groups of calves either differentially primed and boosted with commercially available bovine coronavirus (BCoV) vaccine or not vaccinated against BCoV. Animals: Commercial heifer and steer beef calves born in April and May 2022. Procedure: In June 2022, calves were randomly enrolled into 3 treatment groups. Those in 2 groups [V1 (n = 160) and V2 (n = 160)] were administered a mucosal priming dose of 1 of 2 commercial BCoV vaccines; those in the 3rd group [CTL (n = 151)] were unvaccinated against BCoV. The V1 and V2 groups were boosted by intramuscular injection pre-weaning with the same vaccine used for priming. Weaning occurred 3 wk after the last preweaning processing day. Ranch staff used a BRD case definition provided by their herd veterinarian to identify, treat, and record treatments for 45 d post-weaning. Results: Postweaning BRD treatment rates for V1, V2, and CTL were 7%, 9%, and 14%, respectively. The CTL calves had 2.2× greater odds of receiving treatment for BRD than V1 calves. There were no differences in odds of treatment between CTL and V2 calves or V1 and V2 calves. Conclusion: In a herd with previously diagnosed BCoV BRD cases, prime-boost vaccination of calves is associated with a difference in odds of BRD treatment post-weaning compared to not vaccinating calves against BCoV. Clinical relevance: Prime-boost vaccination with commercial BCoV vaccine may be an important management tool for herds with known BCoV BRD outbreaks.

Comparaison des taux de traitement des maladies respiratoires bovines après le sevrage entre des veaux de boucherie témoins non vaccinés et des veaux vaccinés amorce-rappel de manière variable à l'aide de vaccins contre le coronavirus bovin commercialement disponibles. Objectif: La maladie respiratoire bovine (BRD) et les taux globaux de traitement post-sevrage ont été comparés parmi 3 groupes de veaux soit vaccinés de manière différentielle et avec un rappel avec le vaccin contre le coronavirus bovin (BCoV) disponible commercialement, soit non vaccinés contre le BCoV. Animaux: Génisses et veaux de boucherie commerciaux nés en avril et mai 2022. Procédure: En juin 2022, les veaux ont été randomisés lors du recrutement dans 3 groupes de traitement. Ceux des 2 groupes [V1 (n = 160) et V2 (n = 160)] ont reçu une dose d'amorce par voie muqueuse de l'un des deux vaccins commerciaux BCoV; ceux du 3ème groupe [CTL (n = 151)] n'étaient pas vaccinés contre le BCoV. Les groupes V1 et V2 ont eu un rappel par injection intramusculaire avant le sevrage avec le même vaccin que celui utilisé pour l'amorçage. Le sevrage a eu lieu 3 semaines après le dernier jour de conditionnement pré-sevrage. Le personnel du ranch a utilisé une définition de cas de BRD fournie par le vétérinaire de leur troupeau pour identifier, traiter et enregistrer les traitements pendant 45 jours après le sevrage. Résultats: Les taux de traitement BRD post-sevrage pour V1, V2 et CTL étaient respectivement de 7 %, 9 % et 14 %. Les veaux CTL avaient 2,2 fois plus de chances de recevoir un traitement contre la BRD que les veaux V1. Il n'y avait aucune différence dans les probabilités de traitement entre les veaux CTL et V2 ou entre les veaux V1 et V2. Conclusion: Dans un troupeau avec des cas de BRD causés par le BCoV déjà diagnostiqués, la vaccination amorce-rappel des veaux est associée à une différence de probabilité de traitement par le BRD après le sevrage par rapport à la nonvaccination des veaux contre le BCoV. Pertinence clinique: La vaccination amorce-rappel avec le vaccin commercial BCoV peut être un outil de gestion important pour les troupeaux présentant des foyers connus de BCoV BRD.(Traduit par Dr Serge Messier).

Molecular organization of autonomic, respiratory, and spinally-projecting neurons in the mouse ventrolateral medulla.

The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control, serving as a significant source of synaptic input to the spinal cord. Experimental studies have shown that gene expression in individual VLM neurons is predictive of their function. However, the molecular and cellular organization of the VLM has remained uncertain. This study aimed to create a comprehensive dataset of VLM cells using single-cell RNA sequencing in male and female mice. The dataset was enriched with targeted sequencing of spinally-projecting and adrenergic/noradrenergic VLM neurons. Based on differentially expressed genes, the resulting dataset of 114,805 VLM cells identifies 23 subtypes of neurons, excluding those in the inferior olive, and 5 subtypes of astrocytes. Spinally-projecting neurons were found to be abundant in 7 subtypes of neurons, which were validated through in-situ hybridization. These subtypes included adrenergic/noradrenergic neurons, serotonergic neurons, and neurons expressing gene markers associated with pre-motor neurons in the ventromedial medulla. Further analysis of adrenergic/noradrenergic neurons and serotonergic neurons identified 9 and 6 subtypes, respectively, within each class of monoaminergic neurons. Marker genes that identify the neural network responsible for breathing were concentrated in 2 subtypes of neurons, delineated from each other by markers for excitatory and inhibitory neurons. These datasets are available for public download and for analysis with a user-friendly interface. Collectively, this study provides a fine-scale molecular identification of cells in the VLM, forming the foundation for a better understanding of the VLM's role in vital functions and motor control.Significance statement The ventrolateral medulla (VLM) is an anatomically complex region of the brain that plays a crucial role in regulating vital functions, including autonomic and respiratory control, sleep-wake behaviors, cranial motor functions, and locomotion. This study comprehensively classifies VLM cell types and neuronal subtypes based on their molecular and anatomical features, by leveraging single-nuclei RNA sequencing, RNA fluorescence in situ hybridization, and axonal tract tracing. We present a dataset comprising 114,805 single-nuclei transcriptomes that identifies and validates the precise molecular characteristics of neurons involved in autonomic and motor systems functions. This publicly-available dataset offers new opportunities for comprehensive experimental studies to dissect the central organization of vital homeostatic functions and body movement.

Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial.

Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Effects of aerobic and resistance exercise for 9 months on serum free light chains in type 2 diabetes.

Background and aims: Serum polyclonal free light chains (FLCs) levels are associated with overall survival in the general population, reflecting their utility as a biomarker of underlying immune activation and inflammation. Regular exercise is known to ameliorate low-grade inflammation in chronic diseases such as type 2 diabetes; however, the effects of different exercise training modalities on FLCs in adults with type 2 diabetes is unknown. This study investigated the effects of 9-month of aerobic, resistance or combined supervised exercise on serum FLCs in 164 patients with type 2 diabetes (age 58 ± 8 years; 63% female). Methods: 164 participants from the Health Benefits of Aerobic and Resistance Training in individuals with type 2 diabetes trial (HART-D) were randomly assigned to no exercise (n = 27), aerobic exercise alone (n = 41), resistance exercise alone (n = 49), or a combination of aerobic and resistance exercise (n = 47). Fasting serum samples were collected before and after completion of the intervention to quantify changes in kappa and lambda FLCs, and serum creatinine, using commercially-available ELISAs. Results: At baseline, combined kappa and lambda FLCs (FLC sum; calculated as kappa + lambda FLCs) were positively correlated with high-sensitive C-reactive protein (hs-CRP) (r = 0.237, p < 0.05) and fat mass (r = 0.162, p < 0.05), and negatively associated with aerobic fitness (r = -0.238, p < 0.05). While non-exercise controls exhibited an increase in FLCs over the 9-month study, exercise training blunted this increase (Δ FLC sum control arm: 3.25 ± 5.07 mg∙L-1 vs. all exercise arms: -0.252 ± 6.60 mg∙L-1, p < 0.05), regardless of exercise modality. Conclusion: Serum FLCs were associated with physical fitness and body composition in patients with type 2 diabetes. 9-month of exercise training prevented the accumulation of FLCs, regardless of exercise modality. Unlike hs-CRP-which did not change during the trial-serum FLCs may serve as a more sensitive biomarker of chronic low-grade inflammation in this population.

The hidden work of general practitioners: An ethnography.

High quality primary care is a foundational element of effective health services. Internationally, primary care physicians (general practitioners (GPs), family doctors) are experiencing significant workload pressures. How non-patient-facing work contributes to these pressures and what constitutes this work is poorly understood and often unrecognised and undervalued by patients, policy makers, and even clinicians engaged in it. This paper examines non-patient-facing work ethnographically, informed by practice theory, the Listening Guide, and empirical ethics. Ethnographic observations (104 h), in-depth interviews (n = 16; 8 with GPs and 8 with other primary care staff) and reflexive workshops were conducted in two general practices in England. Our analysis shows that 'hidden work' was integral to direct patient care, involving diverse clinical practices such as: interpreting test results; crafting referrals; and accepting interruptions from clinical colleagues. We suggest the term 'hidden care work' more accurately reflects the care-ful nature of this work, which was laden with ambiguity and clinical uncertainty. Completing hidden care work outside of expected working hours was normalised, creating feelings of inefficiency, and exacerbating workload pressure. Pushing tasks forward into an imagined future (when conditions might allow its completion) commonly led to overspill into GPs' own time. GPs experienced tension between their desire to provide safe, continuous, 'caring' care and the desire to work a manageable day, in a context of increasing demand and burgeoning complexity.

Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER.

PURPOSE: Evaluate long-term efficacy and safety of elamipretide during the open-label extension (OLE) of the TAZPOWER trial in individuals with Barth syndrome (BTHS). METHODS: TAZPOWER was a 28-week randomized, double-blind, and placebo-controlled trial followed by a 168-week OLE. Patients entering the OLE continued elamipretide 40 mg subcutaneous daily. OLE primary endpoints were safety and tolerability; secondary endpoints included change from baseline in the 6-minute walk test (6MWT) and BarTH Syndrome Symptom Assessment (BTHS-SA) Total Fatigue score. Muscle strength, physician- and patient-assessed outcomes, echocardiographic parameters, and biomarkers, including cardiolipin (CL) and monolysocardiolipin (MLCL), were assessed. RESULTS: Ten patients entered the OLE; 8 reached the week 168 visit. Elamipretide was well tolerated, with injection-site reactions being the most common adverse events. Significant improvements from OLE baseline on 6MWT occurred at all OLE time points (cumulative 96.1 m of improvement [week 168, P = .003]). Mean BTHS-SA Total Fatigue scores were below baseline (improved) at all OLE time points. Three-dimensional (3D) left ventricular stroke, end-diastolic, and end-systolic volumes improved, showing significant trends for improvement from baseline to week 168. MLCL/CL values showed improvement, correlating to important clinical outcomes. CONCLUSION: Elamipretide was associated with sustained long-term tolerability and efficacy, with improvements in functional assessments and cardiac function in BTHS.

The Canadian Cow-Calf Surveillance Network - productivity and health summary 2018 to 2022.

Cow-calf surveillance data provide critical information about changing herd demographics, productivity, health, and management as well as the opportunity to investigate the impact of differing management practices. A national cow-calf network was established to collect baseline information on herd health, production performance measures, and management. Questionnaires were used to collect information on herd attributes as well as data for the calving season, breeding, pregnancy testing, and weaning for herds from across Canada. From 2018 to 2022, a total of 565 calving record questionnaires, representing 110,658 calving female records from 171 herds were returned, along with 543 herd breeding to weaning questionnaires. Suggested benchmark values based on the 25th percentiles from Western and Eastern Canada were determined to be <5% for non-pregnancy, <2% for calf death from birth to 24 h, and < 2% for calf death from 24 h to weaning. Herds from Eastern Canada were more likely to report any assistance at calving (p < 0.001) than herds from Western Canada. Participating herds from the east had longer breeding (p < 0.001) and calving (p < 0.001) seasons than those from the west and were also more likely to use artificial insemination or embryo transfer (p < 0.001). Timing of calving season and use of large pastures for calving were not associated with mortality at birth. Herds that started calving before April were more likely to have calves die before 30 d than those that started calving later; however, this difference was not observed between 30 d and weaning. Herds that started to calve earlier were also more likely to report treating more calves for bovine respiratory disease, diarrhea, and navel or joint infections as well as to calf deaths from respiratory disease. Calves from herds in the east were more likely to be treated or die from diarrhea than from the west. Females from herds that started calving later were less likely to be pregnant. The unique longitudinal productivity and health data resulting from this network established a national baseline to address region-specific needs for knowledge translation and solutions to enhance productivity and support sustainability.

Variation in Pen-Level Prevalence of BRD Bacterial Pathogens and Antimicrobial Resistance Following Feedlot Arrival in Beef Calves.

Antimicrobials are crucial for treating bovine respiratory disease (BRD) in beef feedlots. Evidence is needed to support antimicrobial use (AMU) decisions, particularly in the early part of the feeding period when BRD risk is highest. The study objective was to describe changes in prevalence and antimicrobial susceptibility of BRD bacterial pathogens at feedlot processing (1 day on feed (1DOF)), 12 days later (13DOF), and for a subset at 36DOF following metaphylactic antimicrobial treatment. Mixed-origin steer calves (n = 1599) from Western Canada were managed as 16 pens of 100 calves, receiving either tulathromycin (n = 1199) or oxytetracycline (n = 400) at arrival. Deep nasopharyngeal swabs collected at all time points underwent culture and antimicrobial susceptibility testing (AST). Variability in the pen-level prevalence of bacteria and antimicrobial susceptibility profiles were observed over time, between years, and metaphylaxis options. Susceptibility to most antimicrobials was high, but resistance increased from 1DOF to 13DOF, especially for tetracyclines and macrolides. Simulation results suggested that sampling 20 to 30 calves per pen of 200 reflected the relative pen-level prevalence of the culture and AST outcomes of interest. Pen-level assessment of antimicrobial resistance early in the feeding period can inform the evaluation of AMU protocols and surveillance efforts and support antimicrobial stewardship in animal agriculture.

Locality is the strongest predictor of expert performance in image-based differentiation of bacterial and fungal corneal ulcers from India.

PURPOSE: This study sought to identify the sources of differential performance and misclassification error among local (Indian) and external (non-Indian) corneal specialists in identifying bacterial and fungal keratitis based on corneal photography. METHODS: This study is a secondary analysis of survey data assessing the ability of corneal specialists to identify acute bacterial versus fungal keratitis by using corneal photography. One-hundred images of 100 eyes from 100 patients with acute bacterial or fungal keratitis in South India were previously presented to an international cohort of cornea specialists for interpretation over the span of April to July 2021. Each expert provided a predicted probability that the ulcer was either bacterial or fungal. Using these data, we performed multivariable linear regression to identify factors predictive of expert performance, accounting for primary practice location and surrogate measures to infer local fungal ulcer prevalence, including locality, latitude, and dew point. In addition, Brier score decomposition was used to determine experts' reliability ("calibration") and resolution ("boldness") and were compared between local (Indian) and external (non-Indian) experts. RESULTS: Sixty-six experts from 16 countries participated. Indian practice location was the only independently significant predictor of performance in multivariable linear regression. Resolution among Indian experts was significantly better (0.08) than among non-Indian experts (0.01; P < 0.001), indicating greater confidence in their predictions. There was no significant difference in reliability between the two groups ( P = 0.40). CONCLUSION: Local cornea experts outperformed their international counterparts independent of regional variability in tropical risk factors for fungal keratitis. This may be explained by regional characteristics of infectious ulcers with which local corneal specialists are familiar.