Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC): a randomised controlled trial.

BACKGROUND: No randomised controlled trials have yet reported on the effectiveness of molnupiravir on longer term outcomes for COVID-19. The PANORAMIC trial found molnupiravir reduced time to recovery in acute COVID-19 over 28 days. We aimed to report the effect of molnupiravir treatment for COVID-19 on wellbeing, severe and persistent symptoms, new infections, health care and social service use, medication use, and time off work at 3 months and 6 months post-randomisation. METHODS: This study is a follow-up to the main analysis, which was based on the first 28 days of follow-up and has been previously reported. For this multicentre, primary care, open-label, multi-arm, prospective randomised controlled trial conducted in the UK, participants were eligible if aged at least 50 years, or at least 18 years with a comorbidity, and unwell 5 days or less with confirmed COVID-19 in the community. Participants were randomly assigned to the usual care group or molnupiravir group plus usual care (800 mg twice a day for 5 days), which was stratified by age (<50 years or ≥50 years) and vaccination status (at least one dose: yes or no). The primary outcome was hospitalisation or death (or both) at 28 days; all longer term outcomes were considered to be secondary outcomes and included self-reported ratings of wellness (on a scale of 0-10), experiencing any symptom (fever, cough, shortness of breath, fatigue, muscle ache, nausea and vomiting, diarrhoea, loss of smell or taste, headache, dizziness, abdominal pain, and generally feeling unwell) rated as severe (moderately bad or major problem) or persistent, any health and social care use, health-related quality of life (measured by the EQ-5D-5L), time off work or school, new infections, and hospitalisation. FINDINGS: Between Dec 8, 2021, and April 27, 2022, 25 783 participants were randomly assigned to the molnupiravir plus usual care group (n=12 821) or usual care group (n=12 962). Long-term follow-up data were available for 23 008 (89·2%) of 25 784 participants with 11 778 (91·9%) of 12 821 participants in the molnupiravir plus usual care group and 11 230 (86·6%) of 12 963 in the usual care group. 22 806 (99·1%) of 23 008 had at least one previous dose of a SARS-CoV-2 vaccine. Any severe (3 months: adjusted risk difference -1·6% [-2·6% to -0·6%]; probability superiority [p(sup)]>0·99; number needed to treat [NNT] 62·5; 6 months: -1·9% [-2·9% to -0·9%]; p(sup)>0·99, NNT 52·6) or persistent symptoms (3 months: adjusted risk difference -2·1% [-2·9% to -1·5%]; p(sup)>0·99; NNT 47·6; 6 months: -2·5% [-3·3% to -1·6%]; p(sup)>0·99; NNT 40) were reduced in severity, and health-related quality of life (measured by the EQ-5D-5L) improved in the molnupiravir plus usual care group at 3 months and 6 months (3 months: adjusted mean difference 1·08 [0·65 to 1·53]; p(sup)>0·99; 6 months: 1·09 [0·63 to 1·55]; p(sup)>0·99). Ratings of wellness (3 months: adjusted mean difference 0·15 (0·11 to 0·19); p(sup)>0·99; 6 months: 0·12 (0·07 to 0·16); p(sup)>0·99), experiencing any more severe symptom (3 months; adjusted risk difference -1·6% [-2·6% to -0·6%]; p(sup)=0·99; 6 months: -1·9% [-2·9% to -0·9%]; p(sup)>0·99), and health-care use (3 months: adjusted risk difference -1·4% [-2·3% to -0·4%]; p(sup)>0·99; NNT 71·4; 6 months: -0·5% [-1·5% to 0·4%]; p(sup)>0·99; NNT 200) had high probabilities of superiority with molnupiravir treatment. There were significant differences in persistence of any symptom (910 [8·9%] of 10 190 vs 1027 [11%] of 9332, NNT 67) at 6 months, and reported time off work at 3 months (2017 [17·9%] of 11 274 vs 2385 [22·4%] of 10 628) and 6 months (460 [4·4%] of 10 562 vs 527 [5·4%] of 9846; NNT 100). There were no differences in hospitalisations at long-term follow-up. INTERPRETATION: In a vaccinated population, people treated with molnupiravir for acute COVID-19 felt better, experienced fewer and less severe COVID-19 associated symptoms, accessed health care less often, and took less time off work at 6 months. However, the absolute differences in this open-label design are small with high numbers needed to treat. FUNDING: UK Research and Innovation and National Institute for Health and Care Research.

Characterizing medication safety incidents in surgical patients: a retrospective cross-sectional analysis of incident reports.

Background: Medication-related safety incidents (MSIs) are among the most frequent contributors to preventable harm in hospital patients. There is a paucity of research that explores the factors that contribute to MSIs across the departments of high-risk specialties such as surgery. Objectives: To characterize MSIs involving surgical patients across two secondary care sites at a University Health Board. Design: Retrospective cross-sectional convergent analysis of anonymous MSI reports extracted from the risk management system between 1st January 2017 and 31st October 2020 was undertaken. Methods: Incident reports contained categorical data pertaining to the type and nature of the incident as well as free-text reporter accounts. Categorical data were analyzed quantitatively, undergoing descriptive analysis using IBM SPSS Statistics © software (Version 26.0.01; 2019). Content analysis of free-text responses was undertaken using the Organizational Accident Causation model as the underpinning theoretical framework. Results: Of a total of 670 incidents, most MSIs did not result in harm (n = 495, 73.9%). Most MSIs occurred during administration (n = 439, 65.5%). Half of the incidents (n = 335, 50%) were related to one of three medication types: opioids, antimicrobials, and antithrombotic agents. Communication failures were the most frequent error-producing condition (n = 39, 5.8%) and drug omission was the most frequent active failure (n = 156, 23.3%). Conclusion: To the knowledge of the authors, this is the first study in the United Kingdom that reports the medications most frequently involved in MSI reports for surgical patients. Staff in the surgical setting should be informed of the high frequency of incidents involving opioids, antimicrobials, heparin, and other antithrombotic agents as they appear in half of MSI reports in the surgical setting. Further research should explore administration error reduction strategies as well as tools to improve communication between staff to mitigate the risk of medicines-related harm associated with key medications.

Introduction: Errors with medications not only often happen in hospitals but also have the potential to cause great harm to patients. They can occur at any time, from prescribing a patient the correct dose of medication to finally administering them the correct medication. Reducing the risk of errors is particularly crucial for surgical patients, where medication-related safety incidents can complicate the safety of surgical procedures. This study looked at the types of medication incidents reported by staff for patients who were having surgery. Methods: We reviewed the incident reports involving medications for patients on surgical wards and in theatres, as reported by staff. These included reports from between 1st January 2017 and 31st October 2020 from two university hospitals in Wales. Results: A total of 670 incidents were reported by staff, most of which did not result in any harm (n = 495, 73.9%). Half of the incidents that were reported involved at least one of three types of medications: opioids, antimicrobials and blood thinning medication. Communication failures were attributed to be the most common factor leading to errors occurring, whilst a failure to give the medication was the most common error reported. Conclusion: Staff that are working with patients on surgical wards and in theatres should be alerted to the high frequency of incidents involving opioids, antimicrobials and blood thinning medication. Moreover, strategies that improve staff communication should be employed to avoid medication-related safety incidents.

Types of medicines-related errors occurring in patients undergoing surgery.

The diagnostic and prognostic utility of oxidative stress circulatory biomarkers in traumatic brain injury patients: a systematic review.

OBJECTIVE: The objective of this review is to qualitatively appraise the available literature to evaluate the efficacy of circulatory systemic oxidative stress markers (OSMx) in determining the diagnosis and outcome of TBI. METHODS: A systematic review was conducted of PubMed/Medline, Embase and Google Scholar databases per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for studies which employed serum or plasma OSMx analysis for diagnostic or prognostic purposes in patients with TBI. RESULTS: Eight studies were included. There were 654 patients across the eight studies, of which 518 (79.2%) patients had sustained a TBI. The heterogeneity between studies in terms of OSMxs analyzed ultimately made collective analysis inappropriate. Nevertheless, several studies highlighted the potential role of circulatory OSMx levels in determining the diagnosis (presence and severity) and prognosis (functional outcome and mortality) of TBI. CONCLUSION: The care for patients with TBI remains a complex clinical challenge with a high morbidity and mortality profile. Evidenced by this review, circulatory OSMxs appear to have the potential to supplement current diagnostic measures, in addition to identifying new treatment strategies and monitoring recovery. Despite early promise, the evidence for such markers remains in its infancy and robust prospective studies are needed.

Arachnoid Cysts in Athletes with Sports-Related Concussion: A Case Series and Literature Review.

BACKGROUND: Arachnoid cysts (AC) are associated with a risk of rupture or haemorrhage following head impact and pose a potential predisposing factor for significant complications of sport-related concussion. Despite a recognised association between ACs and intracranial haemorrhage/cyst rupture, the risk profile of participating in contact sports with AC is not well defined. We report a retrospective case series of players presenting to the Birmingham Sports Concussion Clinic between 2017 and 2023 and underwent MRI head, with a comprehensive review of the prior literature. RESULTS: 432 athletes underwent MRI of which 11 were identified to have AC (middle fossa n = 8; posterior fossa n = 2, intraventricular n = 1). Average maximal diameter was 4.1 ± 1.2 cm. 64% had a protracted recovery (≥ 3 months). 9% experienced an AC specific complication (cyst rupture, complete neurological recovery, maximal diameter 6.5 cm, Galassi II, 4 previous concussions). 91% of patients (mean maximal diameter 3.9 ± 1.0 cm) experienced no complications despite multiple previous accumulated sports-related concussions (mean 3.3, range 1-9). Case studies from the literature are summarised (n = 63), with 98% reporting complications, none of which resulted in adverse or unfavourable neurological outcomes. Across prospective and retrospective cohort studies, 1.5% had a structural injury, and (where outcome was reported) all had a favourable outcome. CONCLUSIONS: AC is an incidental finding in athletes, with the majority in our cohort having sustained serial concussions without AC complication. The single complication within this cohort occurred in the largest AC, and AC size is proposed as a tentative factor associated with increased risk of contact sports participation. Complications of AC appear to be a rare occurrence. This case series and review has not identified evidence to suggest that participation in sports with AC is of significant risk, though individualised assessment and discussion of the potential risks of contact sports participation should be offered.

The effects of alternate-day fasting on sleep and physical activity in poor sleeping adults: A randomized control trial.

Utilizing a randomized control design, 42 healthy adults (22.5 ± 2.8 years) participated in alternate-day modified fasting over a 12-day treatment period. Assessments of sleep included sleep time, efficiency, latency and wake after sleep onset, and assessments of physical activity included steps, energy expenditure, sedentary time, time spent in light physical activity and time spent in moderate-to-vigorous activity. Additional measurements included body composition and mood. The alternate-day modified fasting group consumed 25.8% ± 0.3% fewer calories compared with the control group (p = 0.03). There were no differences between groups for change in body mass index (p = 0.87), total fat mass (p = 0.91) or total lean mass (p = 0.88). Daily energy expenditure did not differ between groups (p = 0.11). On fast days, participants spent 34.5 ± 12.7 more minutes sedentary (p = 0.01), took 1100 ± 362 fewer steps (p < 0.01), and engaged in 27.2 ± 8.4 fewer minutes of moderate-to-vigorous physical activity (p = 0.00) compared with non-fasting days. Sleep duration, efficiency, latency or wake after sleep onset were not different between conditions (p = 0.92, p = 0.10, p = 0.09 and p = 0.66, respectively). We conclude that alternate-day modified fasting does not alter sleep time, efficiency, latency or wake after sleep onset in people reporting poor sleep quality, and does not alter overall physical activity. Although average daily physical activity is not altered, fasting in this manner does tend to result in more sedentary time and less physical activity with compensation on non-fasting days.

MulTI-domain self-management in older People wiTh OstEoarthritis and multi-morbidities: protocol for the TIPTOE randomised controlled trial.

BACKGROUND: Four out of five people living with osteoarthritis (OA) also suffer with at least one other long-term health condition. The complex interaction between OA and multiple long-term conditions (MLTCs) can result in difficulties with self-care, restricted mobility, pain, anxiety, depression and reduced quality of life. The aim of the MulTI-domain Self-management in Older People wiTh OstEoarthritis and Multi-Morbidities (TIPTOE) trial is to evaluate the clinical and cost-effectiveness of the Living Well self-management support intervention, co-designed with people living with OA, integrated into usual care, in comparison to usual care alone. METHODS: TIPTOE is a multi-centre, two-arm, individually randomised controlled trial where 824 individuals over 65 years old with knee and/or hip joint pain from their OA affected joint and at least one other long-term health condition will be randomised to receive either the Living Well Self-Management support intervention or usual care. Eligible participants can self-refer onto the trial via a website or be referred via NHS services across Wales and England. Those randomised to receive the Living Well support intervention will be offered up to six one-to-one coaching sessions with a TIPTOE-trained healthcare practitioner and a co-designed book. Participants will be encouraged to nominate a support person to assist them throughout the study. All participants will complete a series of self-reported outcome measures at baseline and 6- and 12-month follow-up. The primary outcome is symptoms and quality of life as assessed by the Musculoskeletal Health Questionnaire (MSK-HQ). Routine data will be used to evaluate health resource use. A mixed methods process evaluation will be conducted alongside the trial to inform future implementation should the TIPTOE intervention be found both clinically and cost-effective. An embedded 'Study Within A Project' (SWAP) will explore and address barriers to the inclusion of under-served patient groups (e.g. oldest old, low socioeconomic groups, ethnic groups). DISCUSSION: TIPTOE will evaluate the clinical and cost-effectiveness of a co-designed, living well personalised self-management support intervention for older individuals with knee and/or hip OA and MLTCs. The trial has been designed to maximise inclusivity and access. TRIAL REGISTRATION: ISRCTN 16024745 . Registered on October 16, 2023.

Safety-netting advice documentation out-of-hours: a retrospective cohort from 2013 to 2020.

BACKGROUND: Providing safety-netting advice (SNA) in out-of-hours primary care is a recognised standard of safe care but it is not known how frequently this occurs in practice. AIM: Assess the frequency and type of SNA documented in out-of-hours primary care and explore factors associated with its presence. DESIGN AND SETTING: Retrospective cohort using the Birmingham Out-of-hours General Practice Research Database. METHOD: A stratified sample of 30 adult consultation records per month from July 2013 to February 2020 were assessed using a safety-netting coding tool. Associations were tested using linear and logistic regression. RESULTS: The overall frequency of SNA per consultation was 78.0%, increasing from 75.7% (2014) to 81.5% (2019). The proportion of specific SNA and the average number of symptoms patients were told to look out for increased with time. The most common symptom to look out for was if the patients' condition worsened followed by if their symptoms persisted, but only one in five consultations included a time-frame to reconsult for persistent symptoms. SNA was more frequently documented in face-to-face treatment-centre encounters compared to telephone-consultations (Odds Ratio [OR]=1.77, p=0.02), for possible infections (OR=1.53, p=0.006), and less frequently for mental (vs. physical) health consultations (OR=0.33, p=0.002) and where follow-up was planned (OR=0.34, p<0.001). CONCLUSION: The frequency of SNA documented in OOH was higher than previously reported during in-hours care. Over time, the frequency of SNA and proportion that contained specific advice increased, however this study highlights potential consultations where SNA could be improved, such as mental health and telephone consultations.

Improving health system responses when patients are harmed: a protocol for a multistage mixed-methods study.

INTRODUCTION: At least 10% of hospital admissions in high-income countries, including Australia, are associated with patient safety incidents, which contribute to patient harm ('adverse events'). When a patient is seriously harmed, an investigation or review is undertaken to reduce the risk of further incidents occurring. Despite 20 years of investigations into adverse events in healthcare, few evaluations provide evidence of their quality and effectiveness in reducing preventable harm.This study aims to develop consistent, informed and robust best practice guidance, at state and national levels, that will improve the response, learning and health system improvements arising from adverse events. METHODS AND ANALYSIS: The setting will be healthcare organisations in Australian public health systems in the states of New South Wales, Queensland, Victoria and the Australian Capital Territory. We will apply a multistage mixed-methods research design with evaluation and in-situ feasibility testing. This will include literature reviews (stage 1), an assessment of the quality of 300 adverse event investigation reports from participating hospitals (stage 2), and a policy/procedure document review from participating hospitals (stage 3) as well as focus groups and interviews on perspectives and experiences of investigations with healthcare staff and consumers (stage 4). After triangulating results from stages 1-4, we will then codesign tools and guidance for the conduct of investigations with staff and consumers (stage 5) and conduct feasibility testing on the guidance (stage 6). Participants will include healthcare safety systems policymakers and staff (n=120-255) who commission, undertake or review investigations and consumers (n=20-32) who have been impacted by adverse events. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Northern Sydney Local Health District Human Research Ethics Committee (2023/ETH02007 and 2023/ETH02341).The research findings will be incorporated into best practice guidance, published in international and national journals and disseminated through conferences.

Are equine-assisted services beneficial for military veterans with post-traumatic stress disorder? A systematic review and meta-analysis.

BACKGROUND: Equine-assisted services (EAS) involves the use of horses within therapy, learning or horsemanship sessions and has been used with military veterans suffering from post-traumatic stress disorder (PTSD). This study systematically reviewed existing research on the use of EAS in the treatment of PTSD in military veterans and evaluated its effectiveness. METHODS: A systematic review was performed, in May 2023, with searches and data extraction carried out from three separate databases (PubMed, JSTOR and Science Direct) related to testing the effect of EAS on PTSD outcomes in veterans. A risk of bias assessment of included studies was conducted and meta-analysis of outcomes performed when two or more studies reported the same outcomes. Other effects of EAS on veterans' health were also discussed. RESULTS: A total of 13 studies were identified based on our inclusion and exclusion criteria with 11 originating from the US and the remaining two from Australia and Israel. There were 344 participants amongst all of the studies with a mean age of 47 years and a male:female ratio of 19:6. Eight out of the 13 studies reported PTSD scores, as measured by either PTSD Checklist for DSM-5 (PCL-5) or PCL-Veteran/-Military versions (PCL-V/-M), and results suggested a reduction in PTSD score after EAS treatment of 22.6%. A meta-analysis confirmed that EAS favored a significantly lower PTSD score after treatment, with a mean difference of 12.46, 95% CI [9.03,15.88], p < 0.00001. However, only one study had low risk of bias whilst all the rest of the studies had some concerns to high risk of bias. CONCLUSIONS: EAS appeared to have a positive influence on PTSD symptoms in military veterans, significantly reducing PTSD severity scores. Other benefits of EAS may be peer support, social integration, learning new skills and bonding. However, the results of this systematic review must be interpreted with caution as almost all of the studies were of low quality. Therefore, further rigorous research is required with larger participants to be able to draw conclusions about the benefits of EAS on PTSD severity.

Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation.

Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.

Recommendations from evaluating the implementation of the 'GP Daffodil Standards' to support the provision of palliative and end-of-life care in primary care: a mixed-methods study.

BACKGROUND: The 'GP Daffodil Standards for Advanced Serious Illness and End of Life Care' was launched by the Royal College of General Practitioners and Marie Curie in 2019 to support improvement of end-of-life care activity in primary care. AIM: To undertake and independent evaluation of the implementation of the Daffodil Standards. METHOD: A multi-method evaluation, informed by Normalisation Process Theory. An online survey with GPs in the UK (Phase 1) and semi-structured interviews with a sub-sample of survey responders (Phase 2) were used to map end-of-life activities and understand the use of the standards. Illustrative case studies of good practice were used to outline recommendations to improve and sustain the implementation of the standards (Phase 3). Data were analysed both quantitatively (Phase 1: descriptive statistics) and qualitatively (Phases 2 and 3: framework analysis). RESULTS: For the Phase 1 survey (n = 82) and Phase 2 semi-structured interviews (n = 8), results demonstrated the motivation to undertake end-of-life care activities and active use of the standards. GPs find it difficult to take this further because of limitations in resources and capacity. There is the indication that a misperception exists for both the purpose and role of the standards. For Phase 3, two case studies are complete, providing more in-depth practical insights into the planning, use, and implementation of the standards. All data collection stopped in December 2023. CONCLUSION: Final results were reported and best practice shared, along with recommendations to sustain the ongoing implementation of the Daffodil Standards.

Anatomic Total Shoulder Arthroplasty Outcomes Were Not Negatively Affected by the COVID-19 Pandemic.

Objective To investigate whether patients undergoing anatomic total shoulder arthroplasty (ATSA) between January and March 2020 experienced different postoperative outcomes than patients in 2019. We hypothesized that patients in 2020 would have less access to physical therapy (PT) and experience different postoperative outcomes. Methods Records from patients who received ATSA between January 1st, 2019, and March 17th, 2019, and January 1st, 2020, to March 17th, 2020, were analyzed. Patient data, including demographic information, range of motion (ROM), strength, and PT was collected and compared between the two groups. The 2020 patients were contacted by phone during October 2022 and patient-reported metrics were gathered. Results The present study identified 24 patients in 2019 and 27 patients in 2020 who underwent ATSA during the specified time frame and had a minimum 1-year follow-up. Patients in 2019 experienced improvements in forward elevation (FE) ROM (125.4° to 146.7°; p = 0.008), external rotation (ER; 33.0° to 47.7°; p < 0.001), and internal rotation (IR; S1 to L4; p = 0.019). Patients in 2020 also experienced significant improvements in FE (120.2° to 141.1°; p = 0.009), ER (32.9° to 42.0°; p = 0.037), and IR (S1 to L3; p = 0.002). Patients in 2020 terminated PT earlier (2019: 125.8 days; 2020: 91.1 days; p = 0.046) and completed fewer sessions (2019: 21.4 sessions; 2020: 13.1 sessions; p = 0.003). At the final follow-up, patients in 2020 reported an average Visual Analogue Scale (VAS) pain score of 1.67 ± 1.1. Conclusion Despite decreased PT, patients who underwent ATSA in 2020 had significant improvements in ROM and strength and were comparable to patients in 2019.

Anatomic Total Shoulder Arthroplasty Outcomes Were Not Negatively Affected by the COVID-19 Pandemic / Os desfechos da artroplastia anatômica total do ombro não foram afetados negativamente pela pandemia de Covid-19

Abstract Objective To investigate whether patients undergoing anatomic total shoulder arthroplasty (ATSA) between January and March 2020 experienced different postoperative outcomes than patients in 2019. We hypothesized that patients in 2020 would have less access to physical therapy (PT) and experience different postoperative outcomes. Methods Records from patients who received ATSA between January 1st, 2019, and March 17th, 2019, and January 1st, 2020, to March 17th, 2020, were analyzed. Patient data, including demographic information, range of motion (ROM), strength, and PT was collected and compared between the two groups. The 2020 patients were contacted by phone during October 2022 and patient-reported metrics were gathered. Results The present study identified 24 patients in 2019 and 27 patients in 2020 who underwent ATSA during the specified time frame and had a minimum 1-year follow-up. Patients in 2019 experienced improvements in forward elevation (FE) ROM (125.4° to 146.7°; p = 0.008), external rotation (ER; 33.0° to 47.7°; p < 0.001), and internal rotation (IR; S1 to L4; p = 0.019). Patients in 2020 also experienced significant improvements in FE (120.2° to 141.1°; p = 0.009), ER (32.9° to 42.0°; p = 0.037), and IR (S1 to L3; p = 0.002). Patients in 2020 terminated PT earlier (2019: 125.8 days; 2020: 91.1 days; p = 0.046) and completed fewer sessions (2019: 21.4 sessions; 2020: 13.1 sessions; p = 0.003). At the final follow-up, patients in 2020 reported an average Visual Analogue Scale (VAS) pain score of 1.67 ± 1.1. Conclusion Despite decreased PT, patients who underwent ATSA in 2020 had significant improvements in ROM and strength and were comparable to patients in 2019.

Resumo Objetivo Investigar se os pacientes submetidos à artroplastia total anatômica do ombro (ATAO) entre janeiro e março de 2020 tiveram resultados pós-operatórios diferentes dos pacientes operados em 2019. Nossa hipótese é a de que os pacientes de 2020 teriam menos acesso à fisioterapia (FT) e apresentariam desfechos pós-opera-tórios diferentes. Métodos Foram analisados os prontuários de pacientes submetidos à ATAO de 1° de janeiro de 2019 a 17 de março de 2019 e de 1° de janeiro de 2020 a 17 de março de 2020. Os dados dos pacientes, incluindo informações demográficas, amplitude de movimento (ADM), força e FT foram coletados e comparados entre os dois grupos. Os pacientes de 2020 foram contatados por telefone durante outubro de 2022, e as métricas relatadas por eles pacientes foram coletadas. Resultados Este estudo identificou 24 pacientes em 2019 e 27 pacientes em 2020 que foram submetidos à ATAO durante o período especificado e tiveram acompanhamento mínimo de 1 ano. Os pacientes em 2019 apresentaram melhoras na ADM de elevação anterior (EA; 125,4° a 146,7°; p = 0,008), rotação externa (RE; 33,0° a 47,7°; p < 0,001) e rotação interna (RI; S1 a L4; p = 0,019). Os pacientes em 2020 também apresentaram melhoras significativas de EA (120,2° a 141,1°; p = 0,009), RE (32,9° a 42,0°; p = 0,037) e RI (S1 a L3; p = 0,002). Os pacientes de 2020 terminaram a FT mais cedo (2019: 125,8 dias; 2020: 91,1 dias; p = 0,046) e fizeram menos sessões (2019: 21,4 sessões; 2020: 13,1 sessões; p = 0,003). No acompanhamento final, os pacientes de 2020 relataram uma pontuação média de dor na Escala Visual Analógica (EVA) de 1,67 ± 1,1. Conclusão Apesar da menor realização de FT, os pacientes submetidos à ATAO em 2020 apresentaram melhoras significativas na ADM e na força e foram comparáveis aos pacientes de 2019.

Sensitive bispecific chimeric T cell receptors for cancer therapy.

The expression of a synthetic chimeric antigen receptor (CAR) to redirect antigen specificity of T cells is transforming the treatment of hematological malignancies and autoimmune diseases [1-7]. In cancer, durable efficacy is frequently limited by the escape of tumors that express low levels or lack the target antigen [8-12]. These clinical results emphasize the need for immune receptors that combine high sensitivity and multispecificity to improve outcomes. Current mono- and bispecific CARs do not faithfully recapitulate T cell receptor (TCR) function and require high antigen levels on tumor cells for recognition [13-17]. Here, we describe a novel synthetic chimeric TCR (ChTCR) that exhibits superior antigen sensitivity and is readily adapted for bispecific targeting. Bispecific ChTCRs mimic TCR structure, form classical immune synapses, and exhibit TCR-like proximal signaling. T cells expressing Bi-ChTCRs more effectively eliminated tumors with heterogeneous antigen expression in vivo compared to T cells expressing optimized bispecific CARs. The Bi-ChTCR architecture is resilient and can be designed to target multiple B cell lineage and multiple myeloma antigens. Our findings identify a broadly applicable approach for engineering T cells to target hematologic malignancies with heterogeneous antigen expression, thereby overcoming the most frequent mechanism of relapse after current CAR T therapies.

Validated medication deprescribing instruments for patients with palliative care needs: a systematic review / Instrumentos validados de desprescripción de medicamentos para los pacientes que reciben cuidados paliativos: una revisión sistemática

Objectives: Patients with life-limiting illnesses are prone to unnecessary polypharmacy. Deprescribing tools may contribute to minimizing negative outcomes. Thus, the aims of the study were to identify validated instruments for deprescribing inappropriate medications for patients with palliative care needs and to assess the impact on clinical, humanistic, and economic outcomes. Methods: A systematic review was conducted in LILACS, PUBMED, EMBASE, COCHRANE, and WEB OF SCIENCE databases (until May 2021). A manual search was performed in the references of enrolled articles. The screening, eligibility, extraction, and bias risk assessment were carried out by 2 independent researchers. Experimental and observational studies were eligible for inclusion. Results: Out of the 5791 studies retrieved, after excluding duplicates (n = 1050), conducting title/abstract screening (n = 4741), and full reading (n = 41), only 1 study met the inclusion criteria. In this included study, a randomized controlled trial was conducted, which showed a high level of bias risk overall. Adults 75 years or older (n = 130) with limited life expectancy and polypharmacy were allocated to 2 groups [intervention arm (deprescribing); and control arm (usual care)]. Deprescribing was performed with the aid of the STOPPFrail tool. The mean number of inappropriate medications and monthly medication costs were significantly lower in the intervention arm. No statistically significant differences were found in terms of unscheduled hospital presentations, falls, fractures, mortality, and quality of life. Conclusions: Despite the availability of several instruments to support deprescribing in patients with palliative care needs, only 1 of them has undergone validation and robust assessment for effectiveness in clinical practice. The STOPPFrail tool appears to reduce the number of inappropriate medications for older people with limited life expectancy (and probably palliative care needs)...(AU)

Objetivo: Los pacientes con enfermedades terminales son propensos a la polifarmacia innecesaria. Las herramientas de desprescripción pueden contribuir a minimizar los resultados negativos. Por lo tanto, los objetivos del estudio fueron identificar instrumentos validados para la desprescripción de medicamentos inapropiados en pacientes con necesidades de cuidados paliativos y evaluar el impacto en los resultados clínicos, humanísticos y económicos. Métodos: Se realizó una revisión sistemática en las bases de datos LILACS, PUBMED, EMBASE, COCHRANE y WEB OF SCIENCE (hasta mayo de 2021). Se realizó una búsqueda manual en las referencias de los artículos incluidos. La selección, elegibilidad, extracción y evaluación del riesgo de sesgo se llevaron a cabo por dos investigadores independientes. Se aceptó la inclusión de estudios observacionales y experimentales. Resultados: De los 5791 estudios recuperados, después de excluir duplicados (n = 1050), realizar la selección de títulos/resúmenes (n = 4741) y la lectura completa (n = 41), solo un estudio cumplió con los criterios de inclusión. En este estudio incluido, se realizó un ensayo controlado aleatorizado, que mostró un alto nivel de riesgo de sesgo en general. A los adultos de 75 años o más (n = 130) con esperanza de vida limitada y polifarmacia se les asignaron dos grupos [grupo de intervención (desprescripción) y grupo de control (atención habitual)]. Se realizó la desprescripción con la ayuda de la herramienta STOPPFrail. El número promedio de medicamentos inapropiados y los costos mensuales de los medicamentos fueron significativamente más bajos en el grupo de intervención. No se encontraron diferencias estadísticamente significativas en términos de presentaciones hospitalarias no programadas, caídas, fracturas, mortalidad y calidad de vida. Conclusiones: A pesar de la disponibilidad de varias herramientas para apoyar la deprescripción en pacientes con necesidades de cuidados paliativos...(AU)

Instrumentos validados de desprescripción de medicamentos para los pacientes que reciben cuidados paliativos: una revisión sistemática / Validated medication deprescribing instruments for patients with palliative care needs: a systematic review

Objectives: Patients with life-limiting illnesses are prone to unnecessary polypharmacy. Deprescribing tools may contribute to minimizing negative outcomes. Thus, the aims of the study were to identify validated instruments for deprescribing inappropriate medications for patients with palliative care needs and to assess the impact on clinical, humanistic, and economic outcomes. Methods: A systematic review was conducted in LILACS, PUBMED, EMBASE, COCHRANE, and WEB OF SCIENCE databases (until May 2021). A manual search was performed in the references of enrolled articles. The screening, eligibility, extraction, and bias risk assessment were carried out by 2 independent researchers. Experimental and observational studies were eligible for inclusion. Results: Out of the 5791 studies retrieved, after excluding duplicates (n = 1050), conducting title/abstract screening (n = 4741), and full reading (n = 41), only 1 study met the inclusion criteria. In this included study, a randomized controlled trial was conducted, which showed a high level of bias risk overall. Adults 75 years or older (n = 130) with limited life expectancy and polypharmacy were allocated to 2 groups [intervention arm (deprescribing); and control arm (usual care)]. Deprescribing was performed with the aid of the STOPPFrail tool. The mean number of inappropriate medications and monthly medication costs were significantly lower in the intervention arm. No statistically significant differences were found in terms of unscheduled hospital presentations, falls, fractures, mortality, and quality of life. Conclusions: Despite the availability of several instruments to support deprescribing in patients with palliative care needs, only 1 of them has undergone validation and robust assessment for effectiveness in clinical practice. The STOPPFrail tool appears to reduce the number of inappropriate medications for older people with limited life expectancy (and probably palliative care needs)...(AU)

Objetivo: Los pacientes con enfermedades terminales son propensos a la polifarmacia innecesaria. Las herramientas de desprescripción pueden contribuir a minimizar los resultados negativos. Por lo tanto, los objetivos del estudio fueron identificar instrumentos validados para la desprescripción de medicamentos inapropiados en pacientes con necesidades de cuidados paliativos y evaluar el impacto en los resultados clínicos, humanísticos y económicos. Métodos: Se realizó una revisión sistemática en las bases de datos LILACS, PUBMED, EMBASE, COCHRANE y WEB OF SCIENCE (hasta mayo de 2021). Se realizó una búsqueda manual en las referencias de los artículos incluidos. La selección, elegibilidad, extracción y evaluación del riesgo de sesgo se llevaron a cabo por dos investigadores independientes. Se aceptó la inclusión de estudios observacionales y experimentales. Resultados: De los 5791 estudios recuperados, después de excluir duplicados (n = 1050), realizar la selección de títulos/resúmenes (n = 4741) y la lectura completa (n = 41), solo un estudio cumplió con los criterios de inclusión. En este estudio incluido, se realizó un ensayo controlado aleatorizado, que mostró un alto nivel de riesgo de sesgo en general. A los adultos de 75 años o más (n = 130) con esperanza de vida limitada y polifarmacia se les asignaron dos grupos [grupo de intervención (desprescripción) y grupo de control (atención habitual)]. Se realizó la desprescripción con la ayuda de la herramienta STOPPFrail. El número promedio de medicamentos inapropiados y los costos mensuales de los medicamentos fueron significativamente más bajos en el grupo de intervención. No se encontraron diferencias estadísticamente significativas en términos de presentaciones hospitalarias no programadas, caídas, fracturas, mortalidad y calidad de vida. Conclusiones: A pesar de la disponibilidad de varias herramientas para apoyar la deprescripción en pacientes con necesidades de cuidados paliativos...(AU)

Evaluation of different models of general practitioners working in or alongside emergency departments: a mixed-methods realist evaluation.

Background: Emergency healthcare services are under intense pressure to meet increasing patient demands. Many patients presenting to emergency departments could be managed by general practitioners in general practitioner-emergency department service models. Objectives: To evaluate the effectiveness, safety, patient experience and system implications of the different general practitioner-emergency department models. Design: Mixed-methods realist evaluation. Methods: Phase 1 (2017-8), to understand current practice: rapid realist literature review, national survey and follow-up key informant interviews, national stakeholder event and safety data analysis. Phase 2 (2018-21), to collect and analyse qualitative (observations, interviews) and quantitative data (time series analysis); cost-consequences analysis of routine data; and case site data for 'marker condition' analysis from a purposive sample of 13 case sites in England and Wales. Phase 3 (2021-2), to conduct mixed-methods analysis for programme theory and toolkit development. Results: General practitioners commonly work in emergency departments, but delivery models vary widely in terms of the scope of the general practitioner role and the scale of the general practitioner service. We developed a taxonomy to describe general practitioner-emergency department service models (Integrated with the emergency department service, Parallel within the emergency department, Outside the emergency department on the hospital site) and present a programme theory as principal output of the study to describe how these service models were observed to operate. Routine data were of variable quality, limiting our analysis. Time series analysis demonstrated trends across intervention sites for: increased time spent in the emergency department; increased emergency department attendances and reattendances; and mixed results for hospital admissions. Evidence on patient experience was limited but broadly supportive; we identified department-level processes to optimise the safety of general practitioner-emergency department models. Limitations: The quality, heterogeneity and extent of routine emergency department data collection during the study period limited the conclusions. Recruitment was limited by criteria for case sites (time series requirements) and individual patients (with 'marker conditions'). Pandemic and other pressures limited data collection for marker condition analysis. Data collected and analysed were pre pandemic; new approaches such as 'telephone first' and their relevance to our findings remains unexplored. Conclusion: Findings suggest that general practitioner-emergency department service models do not meet the aim of reducing the overall emergency department waiting times and improving patient flow with limited evidence of cost savings. Qualitative data indicated that general practitioners were often valued as members of the wider emergency department team. We have developed a toolkit, based on our findings, to provide guidance for implementing and delivering general practitioner-emergency department services. Future work: The emergency care data set has since been introduced across England to help standardise data collection to facilitate further research. We would advocate the systematic capture of patient experience measures and patient-reported outcome measures as part of routine care. More could be done to support the development of the general practitioner in emergency department role, including a core set of competencies and governance structure, to reflect the different general practitioner-emergency department models and to evaluate the effectiveness and cost effectiveness to guide future policy. Study registration: This study is registered as PROSPERO CRD42017069741. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/145/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 10. See the NIHR Funding and Awards website for further award information.

Hospital emergency departments are under huge pressure. Patients are waiting many hours to be seen, some with problems that general practitioners could deal with. To reduce waiting times and improve patient care, arrangements have been put in place for general practitioners to work in or alongside emergency departments (general practitioner­emergency department models). We studied the different ways of working to find out what works well, how and for whom. We brought together a lot of information. We reviewed existing evidence, sent out surveys to 184 emergency departments, spent time in the emergency departments observing how they operated and interviewing 106 staff in 13 hospitals and 24 patients who visited those emergency departments. We also looked at statistical information recorded by hospitals. Two public contributors were involved from the beginning, and we held two stakeholder events to ensure the relevance of our research to professionals and patients. Getting reliable figures to compare the various general practitioner­emergency department set-ups (inside, parallel to or outside the emergency department) was difficult. Our findings suggest that over time more people are coming to emergency departments and overall waiting times did not generally improve due to general practitioner­emergency department models. Evidence that general practitioners might admit fewer patients to hospital was mixed, with limited findings of cost savings. Patients were generally supportive of the care they received, although we could not speak to as many patients as we planned. The skills and experience of general practitioners were often valued as members of the wider emergency department team. We identified how the care provided was kept safe with: strong leaders, good communication between different types of staff, highly trained and experienced nurses responsible for streaming and specific training for general practitioners on how they were expected to work. We have produced a guide to help professionals develop and improve general practitioner­emergency department services and we have written easy-to-read summaries of all the articles we published.

Programme theories to describe how different general practitioner service models work in different contexts in or alongside emergency departments (GP-ED): realist evaluation.

BACKGROUND: Addressing increasing patient demand and improving ED patient flow is a key ambition for NHS England. Delivering general practitioner (GP) services in or alongside EDs (GP-ED) was advocated in 2017 for this reason, supported by £100 million (US$130 million) of capital funding. Current evidence shows no overall improvement in addressing demand and reducing waiting times, but considerable variation in how different service models operate, subject to local context. METHODS: We conducted mixed-methods analysis using inductive and deductive approaches for qualitative (observations, interviews) and quantitative data (time series analyses of attendances, reattendances, hospital admissions, length of stay) based on previous research using a purposive sample of 13 GP-ED service models (3 inside-integrated, 4 inside-parallel service, 3 outside-onsite and 3 with no GPs) in England and Wales. We used realist methodology to understand the relationship between contexts, mechanisms and outcomes to develop programme theories about how and why different GP-ED service models work. RESULTS: GP-ED service models are complex, with variation in scope and scale of the service, influenced by individual, departmental and external factors. Quantitative data were of variable quality: overall, no reduction in attendances and waiting times, a mixed picture for hospital admissions and length of hospital stay. Our programme theories describe how the GP-ED service models operate: inside the ED, integrated with patient flow and general ED demand, with a wider GP role than usual primary care; outside the ED, addressing primary care demand with an experienced streaming nurse facilitating the 'right patients' are streamed to the GP; or within the ED as a parallel service with most variability in the level of integration and GP role. CONCLUSION: GP-ED services are complex . Our programme theories inform recommendations on how services could be modified in particular contexts to address local demand, or whether alternative healthcare services should be considered.

Lateral Femoral Condyle Allograft in the Treatment of Elbow Capitellar Avascular Necrosis: A Case Report.

CASE: A 27-year-old woman developed capitellar osteonecrosis after long-term corticosteroid use to treat non-Hodgkin lymphoma. She underwent an osteochondral reconstruction using a lateral femoral condyle (LFC) allograft. This graft was selected because it has a similar radius of curvature to the capitellum. The patient had osseous integration, painless, near full range of motion of her elbow 6 months postoperatively and good shoulder function 1.0 year postoperatively. CONCLUSION: The LFC allograft should be considered a viable option in treating capitellar osteonecrosis.

Improving appropriate use of intravenous albumin: results of a single-centre audit and multifaceted intervention.

BACKGROUND: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence. AIM: To reduce unnecessary transfusion of albumin. INTERVENTIONS: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage. IMPLEMENTATION AND EVALUATION: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures. RESULTS: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period. CONCLUSION: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin.