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Abstract Background High-throughput screening using RNAi is a powerful gene discovery method but is often complicated by false positive and false negative results. Whereas false positive results associated with RNAi reagents has been a matter of extensive study, the issue of false negatives has received less attention. Results We performed a meta-analysis of several genome-wide, cell-based Drosophila RNAi screens, together with a more focused RNAi screen, and conclude that the rate of false negative results is at least 8%. Further, we demonstrate how knowledge of the cell transcriptome can be used to resolve ambiguous results and how the number of false negative results can be reduced by using multiple, independently-tested RNAi reagents per gene. Conclusions RNAi reagents that target the same gene do not always yield consistent results due to false positives and weak or ineffective reagents. False positive results can be partially minimized by filtering with transcriptome data. RNAi libraries with multiple reagents per gene also reduce false positive and false negative outcomes when inconsistent results are disambiguated carefully.

Thrombocytopenia is common in pregnancy and is diverse in etiology. Immune thrombocytopenic purpura (ITP) may affect both mother and the newborn. Gestational (incidental) thrombocytopenia in an otherwise fit woman, at term is the most frequent type of thrombocytopenia and poses no clinical consequences for mother or infant. We report six women who presented with severe thrombocytopenia during pregnancy. Five were treated in late pregnancy, either with intravenous immunoglobulin (IVIg), or IVIg followed by steroids. There was no response, and four received a platelet transfusion during delivery. The platelet counts in all the infants were normal and the maternal thrombocytopenia resolved spontaneously after delivery in all cases. Our observations suggest that this is a group of patients with a severe form of gestational thrombocytopenia. The severe form of gestational thrombocytopenia appears to be rare, and recognition is important, as it may recur in subsequent pregnancies and does not require any therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: General practice faces pressures because of increased demand and a shortage of GPs. Paramedics in general practice (PGPs) increasingly contribute to managing minor illnesses, conducting home visits, and providing urgent consultations., Aim: To explore the impact of paramedic consultations on patient-reported experience, safe management, and NHS costs., Design and Setting: Prospective cohort study comparing PGP with GP consultations at 34 GP sites in England., Method: Eligible participants had a consultation with a PGP (25 PGP sites) or GP (nine non-PGP sites) between May 2022 and February 2023. Questionnaires were provided after the initial consultation and 30 days later. Questionnaires assessed patient experience, outcomes, and perceived safety (PCOQ and PREOS PC), quality of life (EQ-5D-5L), and healthcare use., Results: Of 715 participants recruited, 489 completed the 30-day questionnaire. No evidence was found that PGP consultations resulted in greater improvement/deterioration in patient-reported health and wellbeing (-0.03, 95% confidence interval [CI] = -0.09 to 0.04); confidence in health provision (-0.05, 95% CI = -0.15 to 0.05); health knowledge (0.05, 95% CI = -0.04 to 0.15); or confidence in the health plan (-0.06, 95% CI = -0.11 to -0.01) over the 30-day period. However, the PGP group reported lower confidence in health provision (mean 4.0 versus 4.5; P <0.001), poorer perceptions of practice engagement in safety promotion (median 75 versus 88; P <0.001), and more communication problems with staff (17% versus 8%; P <0.001) immediately after the initial consultation. Patients receiving PGP consultations reported fewer GP appointments during the 30-day period; however, savings to the NHS were offset by higher use of other healthcare professionals., Conclusion: Well-designed training and supervision are needed to ensure PGPs have the right knowledge and can clearly convey healthcare plans to patients. While PGPs may reduce GP workload pressure, they do not necessarily reduce NHS costs., (© The Authors.)

Purpose of Review: This review aims to provide a comprehensive analysis of the nonoperative management of Gartland Type II fractures in pediatric patients., Recent Findings: Supracondylar humeral fractures (SCF) are one of the most common traumatic fractures in pediatric populations, characterized as transverse fractures at the distal humerus between the medial and lateral columns. Early studies strongly opposed closed reduction and casting as an acceptable treatment modality for Gartland type II fractures as an early case series showed high rates of complications; however, more recent studies have suggested better outcomes. The optimal management of Gartland Type II supracondylar fractures has yet to be fully elucidated. This review highlights the indications, complications, and outcomes of nonoperative Gartland Type II supracondylar humeral fracture management. Additionally, it demonstrates the need for further research to inform guidelines on managing this condition., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Examination of the host-associated microbiome in wildlife can provide critical insights into the eco-evolutionary factors driving species diversification and response to disease. This is particularly relevant for isolated populations lacking genomic variation, a phenomenon that is increasingly common as human activities create habitat 'islands' for wildlife. Here, we characterised the gut and otic microbial communities of one such species: Channel Island foxes (Urocyon littoralis). The gut microbiome provided evidence of phylosymbiosis by reflecting the host phylogeny, geographic proximity, history of island colonisation and contemporary ecological differences, whereas the otic microbiome primarily reflected geography and disease. Santa Catalina Island foxes are uniquely predisposed to ceruminous gland tumours following infection with Otodectes cynotis ear mites, while San Clemente and San Nicolas Island foxes exhibit ear mite infections without evidence of tumours. Comparative analyses of otic microbiomes revealed that mite-infected Santa Catalina and San Clemente Island foxes exhibited reduced bacterial diversity, skewed abundance towards the opportunistic pathogen Staphylococcus pseudintermedius and disrupted microbial community networks. However, Santa Catalina Island foxes uniquely harboured Fusobacterium and Prevotella bacteria as potential keystone taxa. These bacteria have previously been associated with colorectal cancer and may predispose Santa Catalina Island foxes to an elevated cancer risk. In contrast, mite-infected San Nicolas Island foxes maintained high bacterial diversity and robust microbial community networks, suggesting that they harbour more resilient microbiomes. Considered together, our results highlight the diverse eco-evolutionary factors influencing commensal microbial communities and their hosts and underscore how the microbiome can contribute to disease outcomes., (© 2024 John Wiley & Sons Ltd.)

Background: The final year of life is often associated with increasing health complexities and use of health services. This frequently includes admission to an acute hospital which may or may not convey overall benefit. This uncertainty makes decisions regarding admission complex for clinicians. There is evidence of much variation in approaches to admission., Aims: To explore how Primary Care clinicians approach hospitalisation decisions for people in the final year of life., Design: Systematic literature review and narrative synthesis., Data Sources: We searched the following databases from inception to April 2023: CINAHL, Cochrane Library, Embase, MedLine, PsychInfo and Web of Science followed by reference and forward citation reviews of included records., Results: A total of 18 studies were included: 14 qualitative, 3 quantitative and 1 mixed methods study. As most of the results were qualitative, we performed a thematic analysis with narrative synthesis. Six key themes were identified: navigating the views of other stakeholders; clinician attributes; clinician interpretation of events; the perceived adequacy of the current setting and the alternatives; system factors and continuity of care., Conclusion: This review shows that a breadth of factors influence hospitalisation decisions. The views of other stakeholders take great importance but it is not clear how these views are, or should be, should be balanced. Clinician factors, such as experience with palliative care and clinical judgement, are also important. Future research should focus on how different aspects of the decision are balanced and to consider if, and how, this could be improved to optimise patient-centred outcomes and use of health resources., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There is a policy drive in NHS maternity services to improve open disclosure with harmed families and limited information on how better practice can be achieved., Objectives: To identify critical factors for improving open disclosure from the perspectives of families, doctors, midwives and services and to produce actionable evidence for service improvement., Design: A three-phased, qualitative study using realist methodology. Phase 1: two literature reviews: scoping review of post-2013 NHS policy and realist synthesis of initial programme theories for improvement; an interview study with national stakeholders in NHS maternity safety and families. Phase 2: in-depth ethnographic case studies within three NHS maternity services in England. Phase 3: interpretive forums with study participants. A patient and public involvement strategy underpinned all study phases., Setting: National recruitment (study phases 1 and 3); three English maternity services (study phase 2)., Participants: We completed n  = 142 interviews, including 27 with families; 93 hours of ethnographic observations, including 52 service and family meetings over 9 months; and interpretive forums with approximately 69 people, including 11 families., Results: The policy review identified a shift from viewing injured families as passive recipients to active contributors of post-incident learning, but a lack of actionable guidance for improving family involvement. The realist synthesis found weak evidence of the effectiveness of open disclosure interventions in the international maternity literature, but some improvements with organisation-wide interventions. Recent evidence was predominantly from the United Kingdom. The research identified and explored five key mechanisms for open disclosure: meaningful acknowledgement of harm; involvement of those affected in reviews/investigations; support for families' own sense-making; psychological safely of skilled clinicians (doctors and midwives); and knowing that improvements to care have happened. The need for each family to make sense of the incident in their own terms is noted. The selective initiatives of some clinicians to be more open with some families is identified. The challenges of an adversarial medicolegal landscape and limited support for meeting incentivised targets is evidenced., Limitations: Research was conducted after the pandemic, with exceptional pressure on services. Case-study ethnography was of three higher performing services: generalisation from case-study findings is limited. No observations of Health Safety Investigation Branch investigations were possible without researcher access. Family recruitment did not reflect population diversity with limited representation of non-white families, families with disabilities and other socially marginalised groups and disadvantaged groups., Conclusions: We identify the need for service-wide systems to ensure that injured families are positioned at the centre of post-incident events, ensure appropriate training and post-incident care of clinicians, and foster ongoing engagement with families beyond the individual efforts made by some clinicians for some families. The need for legislative revisions to promote openness with families across NHS organisations, and wider changes in organisational family engagement practices, is indicated. Examination of how far the study's findings apply to different English maternity services, and a wider rethinking of how family diversity can be encouraged in maternity services research., Study Registration: This study is registered as PROSPERO CRD42020164061. The study has been assessed following RAMESES realist guidelines., 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: 17/99/85) and is published in full in Health and Social Care Delivery Research ; Vol. 12, No. 22. See the NIHR Funding and Awards website for further award information.

Background: General practice in the UK is under substantial pressure and practices are increasingly including paramedics as part of their workforce. Little is known about how different models of paramedic working may affect successful implementation of the role, as viewed from patient, clinician and system perspectives. This realist synthesis developed theories about 'models of paramedic working in general practice' in different UK contexts to understand their impact., Methods: The rapid realist synthesis comprised data from: (1) empirical and grey literature searches; (2) semi-structured realist interviews with system leaders involved with the implementation of the role; and (3) a stakeholder event with healthcare professionals and the public, to develop initial programme theories that can be tested in future work. Sources were analysed using a realist approach that explored the data for novel or causal insights to generate initial programme theories., Results: Empirical sources (n = 32), grey sources (n = 95), transcripts from system leader interviews (n = 7) and audio summaries from the stakeholder event (n = 22 participants) were synthesised into a single narrative document. The findings confirmed the presence of a wide variety of models of paramedic working in UK general practice. The perceived success of models was influenced by the extent to which the paramedic service was mature and embedded in practice, and according to four theory areas: (1) Primary care staff understanding and acceptance of the paramedic role; (2) Paramedic induction process, including access to training, supervision and development opportunities; (3) Patient understanding and acceptance of the role; (4) Variations in paramedic employment models., Conclusions: Variability in how the paramedic role is operating and embedding into general practice across the UK affects the success of the role. These findings provide a theoretical foundation for future research to investigate various 'models of paramedic working' in different contexts., (© 2024. The Author(s).)

Background: A significant proportion of emergency medical services (EMS) work is for problems that may be amenable to timely primary care management and could benefit from GP input. Utilising GPs in EMS may reduce avoidable emergency department (ED) conveyance, releasing emergency ambulances for higher-acuity care, and meeting patient needs earlier in the evolution of an emergency call., Aim: To collate and summarise evidence on how GPs are utilised in EMS., Design & Setting: Systematic mapping review and narrative synthesis., Method: A systematic literature search was conducted using search terms for general practice and emergency care. Primary research articles investigating the utilisation of GPs in non-critical EMS were included. An inductive framework was used to structure the results alongside a narrative synthesis., Results: Twenty-one articles were included. GPs were embedded in EMS for urgent management of high-acuity patients or used as an intervention to avoid unnecessary ED conveyance in selected lower-acuity patients. The importance of interprofessional relationships and training for GPs involved in EMS was highlighted. No studies explored patient-reported outcomes. Outcomes measured were predominantly ED non-conveyance and admission avoidance, with GP services as an intervention reducing the likelihood of these outcomes., Conclusion: Embedding GPs in EMS might service different purposes depending on context. There is some evidence that GP EMS services may reduce the likelihood of ED conveyance and hospital admission in selected cases; it is unclear whether this is owing to case selection or GP involvement. Future research should incorporate patients' views and experiences., (Copyright © 2023, The Authors.)

The perspective of patients is increasingly recognised as important to care improvement and innovation. Patient questionnaires such as patient-reported outcome measures may often require cross-cultural adaptation (CCA) to gather their intended information most effectively when used in cultures and languages different to those in which they were developed. The use of CCA could be seen as a practical step in addressing the known problems of inclusion, diversity and access in medical research.An example of the recent adaptation of a patient-reported outcome measure for use with ED patients is used to explore some key features of CCA, introduce the importance of CCA to emergency care practitioners and highlight the limitations of CCA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bristol Medical School has adopted a near peer-led teaching approach to deliver Basic Life Support training to first year undergraduate medical students. Challenges arose when trying to identify early in the course which candidates were struggling with their learning, in sessions delivered to large cohorts. We developed and piloted a novel, online performance scoring system to better track and highlight candidate progress., Methods: During this pilot, a 10-point scale was used to evaluate candidate performance at six time-points during their training. The scores were collated and entered on an anonymised secure spreadsheet, which was conditionally formatted to provide a visual representation of the score. A One-Way ANOVA was performed on the scores and trends analysed during each course to review candidate trajectory. Descriptive statistics were assessed. Values are presented as mean scores with standard deviation (x̄±SD)., Results: A significant linear trend was demonstrated (P < 0.001) for the progression of candidates over the course. The average session score increased from 4.61 ± 1.78 at the start to 7.92 ± 1.22 at the end of the final session. A threshold of less than 1SD below the mean was used to identify struggling candidates at any of the six given timepoints. This threshold enabled efficient highlighting of struggling candidates in real time., Conclusions: Although the system will be subject to further validation, our pilot has shown the use of a simple 10-point scoring system in combination with a visual representation of performance helps to identify struggling candidates earlier across large cohorts of students undertaking skills training such as Basic Life Support. This early identification enables effective and efficient remedial support., (© 2023. The Author(s).)

Introduction: We investigated associations between neighborhood racial/ethnic segregation and cognitive change., Methods: We used data (n = 1712) from the Multi-Ethnic Study of Atherosclerosis. Racial/ethnic segregation was assessed using Getis-Ord (Gi*) z-scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z-scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested., Results: Participants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant., Discussion: Segregation was associated with greater processing speed declines among African American/Black participants. Additional follow-ups and comprehensive cognitive batteries may further elucidate these findings., Highlights: A study of neighborhood racial/ethnic segregation and change in cognition. Study was based on a racially and geographically diverse, population-based cohort of older adults. Racial/ethnic segregation (clustering) was measured by the Getis-ord (Gi*) statistic. We saw faster processing speed decline among Black individuals in segregated neighborhoods., (© 2022 the Alzheimer's Association.)