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Abstract Background Human activities, such as agriculture, hunting, and habitat modification, exert a significant effect on native species. Although many species have suffered population declines, increased population fragmentation, or even extinction in connection with these human impacts, others seem to have benefitted from human modification of their habitat. Here we examine whether population growth in an insectivorous bat (Tadarida brasiliensis mexicana) can be attributed to the widespread expansion of agriculture in North America following European settlement. Colonies of T. b. mexicana are extremely large (~106 individuals) and, in the modern era, major agricultural insect pests form an important component of their food resource. It is thus hypothesized that the growth of these insectivorous bat populations was coupled to the expansion of agricultural land use in North America over the last few centuries. Results We sequenced one haploid and one autosomal locus to determine the rate and time of onset of population growth in T. b. mexicana. Using an approximate Maximum Likelihood method, we have determined that T. b. mexicana populations began to grow ~220 kya from a relatively small ancestral effective population size before reaching the large effective population size observed today. Conclusions Our analyses reject the hypothesis that T. b. mexicana populations grew in connection with the expansion of human agriculture in North America, and instead suggest that this growth commenced long before the arrival of humans. As T. brasiliensis is a subtropical species, we hypothesize that the observed signals of population growth may instead reflect range expansions of ancestral bat populations from southern glacial refugia during the tail end of the Pleistocene.

Background and Aims: Alcohol use disorder (AUD) is characterized by low levels of engagement with effective treatments. Enhancing awareness of AUD treatments and how to navigate the treatment system is crucial. Many individuals use online sources (e.g. search engines) for answers to health-related questions; web-based results include a mix of high- and low-quality information. Artificial intelligence may improve access to quality health information by providing concise, high-quality responses to complex health-related questions. This study evaluated the quality of ChatGPT-4 responses to AUD-related queries., Method: A comprehensive list of 64 AUD-related questions was developed through a combination of Google Trends analysis and expert consultation. ChatGPT-4 was prompted with each question, followed by a request to provide 3-5 peer-reviewed scientific citations supporting each response. Responses were evaluated for whether they were evidence-based, provided a referral and provided supporting documentation., Results: ChatGPT-4 responded to all AUD-related queries, with 92.2% (59/64) of responses being fully evidence-based. Although only 12.5% (8/64) of responses included referrals to external resources, all responses (100%; 5/5) to location-specific ('near me') queries directed individuals to appropriate resources like the NIAAA Treatment Navigator. Most (85.9%; 55/64) responses to the follow-up question provided supporting documentation., Conclusions: ChatGPT-4 responds to alcohol use disorder-related questions with evidence-based information and supporting documentation. ChatGPT-4 could be promoted as a reasonable resource for those looking online for alcohol use disorder-related information., (© 2024 Society for the Study of Addiction.)

Objectives: We investigated how individuals with chronic obstructive pulmonary disease (COPD) and multi-morbidity (MM) navigate barriers and facilitators to their health management., Methods: We conducted a mixed-methods study using semi-structured interviews and survey assessments of adults with COPD, hypertension, and/or diabetes. We recruited 18 participants with an average age of 65, with 39% being male, 50% Black, and 22% Hispanic/Latino/a. Five investigators used an iterative, hybrid-coding process combining a priori and emergent codes to analyze transcripts and compare quantitative and qualitative data for themes., Results: Participants reported a generalized approach to their health rather than managing MMs separately. Individuals with good or mixed adherence found daily routines facilitated regular medication use, while those with poor adherence experienced complex prescriptions and life stressors as barriers. Walking was viewed as beneficial but challenging due to limited mobility. Most participants viewed diet as important to their MMs, but only two reported high diet quality and many held inaccurate beliefs about healthy diet choices., Discussion: Participants with MM were highly motivated to engage in self-management activities, but some individuals experienced barriers to maintaining them. Emphasizing an individualized clinical approach to assessing and solving patient barriers may improve self-management outcomes in this complex population., Competing Interests: Declaration of Conflicting InterestsNo conflicts of interest exist for the following authors: KAM, ROC, AMR, GW, JWG, and ADF. Author JPW has received consulting honoraria from Sanofi, Atea, PPD, Prospero, and Banook and a research grant from Sanofi, Regeneron, and Arnold Consultant. Author MSW has received research grants from the Gordon and Betty Moore Foundation and Eli Lilly and personal fees from Pfizer, Sanofi, Luto UK, University of Westminster, and Lundbeck.

Background: The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) is designed to facilitate meaningful discussions between healthcare professionals, patients, and their family about preferences for treatment in future medical emergencies. People with a learning disability may face particular barriers in completing health care plans and receiving emergency treatment, however little is known about their preferences towards emergency care treatment planning. This study explores the views of people with a learning disability, and family carers about ReSPECT., Methods: A reference group of 5 people with a learning disability contributed to the design of the workshops and evaluation of outputs. Online, arts-based interactive workshops were held with 2 groups of 6 people with a learning disability to explore how they felt about emergency care treatment planning, and to co-produce materials to support ReSPECT conversations. Carers of people with a learning disability participated in focus groups or interviews. Data from workshops, focus groups and interviews were analysed thematically., Results: Themes were; Getting the Process Right, Lack of trust a barrier to ReSPECT planning, and Person-Centred Care. All groups supported the ReSPECT process feeling that ReSPECT plans could support person-centred care, enhancing the autonomy of a person with a learning disability and supporting the advocacy of carers. However, drawing on their previous experiences of the health care system some expressed doubt that their wishes would be carried out. Suggestions were made for improving the ReSPECT process and used to develop resources to support ReSPECT planning., Conclusions: Emergency care planning and ReSPECT are viewed positively by people with a learning disability and family carers. To ensure this works well for people with a learning disability attention should be given to reasonable, personalised adjustments to support their participation in planning conversations. There is a wider challenge of fostering trust in the health care system., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Russell AM et al.)

Background: People living with serious respiratory illness experience a high burden of distressing symptoms. Although opioids are prescribed for symptom management, they generate adverse events, and their benefits are unclear., Methods: We examined the efficacy and safety of opioids for symptom management in people with serious respiratory illness. Embase, MEDLINE and the Cochrane Central Register of Controlled Trials were searched up to 11 July 2022. Reports of randomised controlled trials administering opioids to treat symptoms in people with serious respiratory illness were included. Key exclusion criteria included <80% of participants having a nonmalignant lung disease. Data were extracted regarding study characteristics, outcomes of breathlessness, cough, health-related quality of life (HRQoL) and adverse events. Treatment effects were pooled using a generic inverse variance model with random effects. Risk of bias was assessed using the Cochrane Risk of Bias tool version 1., Results: Out of 17 included trials, six were laboratory-based exercise trials (n=70), 10 were home studies measuring breathlessness in daily life (n=788) and one (n=18) was conducted in both settings. Overall certainty of evidence was "very low" to "low". Opioids reduced breathlessness intensity during laboratory exercise testing (standardised mean difference (SMD) -0.37, 95% CI -0.67- -0.07), but not breathlessness measured in daily life (SMD -0.10, 95% CI -0.64-0.44). No effects on HRQoL (SMD -0.42, 95% CI -0.98-0.13) or cough (SMD -1.42, 95% CI -3.99-1.16) were detected. In at-home studies, opioids led to increased frequency of nausea/vomiting (OR 3.32, 95% CI 1.70-6.51), constipation (OR 3.08, 95% CI 1.69-5.61) and drowsiness (OR 1.37, 95% CI 1.01-1.86), with serious adverse events including hospitalisation and death identified., Conclusions: Opioids improved exertional breathlessness in laboratory exercise studies, but did not improve breathlessness, cough or HRQoL measured in daily life at home. There were significant adverse events, which may outweigh any benefits., Competing Interests: Conflict of interest: N.E. Smallwood reports grants from NHMRC, MRFF, Cancer Council Australia, Fisher & Paykel Healthcare (FPH), Windermere Foundation, Lung Foundation Australia, Lord Mayor's Foundation Melbourne and Bethlehem Griffiths Foundation, consulting fees from The Limbic and Orchard Consulting, lecture honoraria from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, FPH and Health Ed, travel support from Chiesi and Boehringer Ingelheim, leadership roles as Board Director and past state president of the Thoracic Society of Australia and New Zealand, Board Director of Victorian Doctors’ Program and co-chair of the guidelines committee for European Respiratory Society; and receipt of equipment from FPH, outside the submitted work. M. Wijsenbeek reports grants from The Netherlands Organisation for Health Research and Development, The Dutch Lung Foundation, The Dutch Pulmonary Fibrosis organization, Sarcoidosis.nl, Boehringer Ingelheim, Hoffman la Roche and AstraZeneca-Daiichi, consulting fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Galapagos, Galecto, GSK, Hoffman la Roche, Horizon therapeutics, Kinevant Sciences, Molecure, Nerre Therapeutics, Novartis, PureTech Health, Thyron, Trevi and Vicore, lecture honoraria from Boehringer Ingelheim, CSL Behring, Hoffman la Roche and Novartis, travel support from Boehringer Ingelheim, GSK, Hoffman la Roche and Galapagos, advisory board participation with Galapagos, and leadership roles as Chair of the Idiopathic Interstitial Pneumonia group of the European Respiratory Society, Member of the board of the Netherlands Respiratory Society, Member of the scientific advisory board of the European Idiopathic Pulmonary Fibrosis and related disorders federation, Chair of the educational committee of the European Reference Network for rare Lung Diseases, and membership of the advisory board of the Dutch Lungfibrosis and Sarcoidosis patient associations, outside the submitted work. A-M. Russell reports consulting fees from Boehringer Ingelheim, and lecture honoraria from Boehringer Ingelheim, Hoffman La Roche and the Irish Lung Fibrosis Association, outside the submitted work. A.E. Holland is President of Thoracic Society of Australia and New Zealand, an unpaid position unrelated to the present work. All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: Emergency care treatment plans provide recommendations about treatment, including cardiopulmonary resuscitation, to be considered in emergency medical situations. In 2016, the Resuscitation Council United Kingdom developed a standardised emergency care treatment plan, the recommended summary plan for emergency care and treatment, known as ReSPECT. There are advantages and potential difficulties in initiating the ReSPECT process in primary care. Hospital doctors and general practitioners may use the process differently and recommendations do not always translate between settings. There are no large studies of the use of ReSPECT in the community., Study Aim: To evaluate how, when and why ReSPECT is used in primary care and what effect it has on patient treatment and care., Design: A mixed-methods approach using interviews, focus groups, surveys and evaluation of ReSPECT forms within an analytical framework of normalisation process theory., Setting: A total of 13 general practices and 13 care homes across 3 areas of England., Participants: General practitioners, senior primary care nurses, senior care home staff, patients and their relatives, community and emergency department clinicians and home care workers, people with learning disability and their carers. National surveys of (1) the public and (2) general practitioners., Results: Members of the public are supportive of emergency care treatment plans. Respondents recognised benefits of plans but also potential risks if the recommendations become out of date. The ReSPECT plans were used by 345/842 (41%) of general practitioner survey respondents. Those who used ReSPECT were more likely to be comfortable having emergency care treatment conversations than respondents who used standalone 'do not attempt cardiopulmonary resuscitation' forms. The recommended summary plan for emergency care and treatment was conceptualised by all participants as person centred, enabling patients to have some say over future treatment decisions. Including families in the discussion is seen as important so they know the patient's wishes, which facilitates decision-making in an emergency. Writing recommendations is challenging because of uncertainty around future clinical events and treatment options. Care home staff described conflict over treatment decisions with clinicians attending in an emergency, with treatment decisions not always reflecting recommendations. People with a ReSPECT plan and their relatives trusted that recommendations would be followed in an emergency, but carers of people with a learning disability had less confidence that this would be the case. The ReSPECT form evaluation showed 87% (122/141) recorded free-text treatment recommendations other than cardiopulmonary resuscitation. Patient preferences were recorded in 57% (81/141). Where a patient lacked capacity the presence of a relative or lasting power of attorney was recorded in two-thirds of forms., Limitations: Recruitment for patient/relative interviews was less than anticipated so caution is required in interpreting these data. Minority ethnic groups were under-represented across our studies., Conclusions: The aims of ReSPECT are supported by health and social care professionals, patients, and the public. Uncertainty around illness trajectory and treatment options for a patient in a community setting cannot be easily translated into specific recommendations. This can lead to conflict and variation in how recommendations are interpreted., Future Work: Future research should explore how best to integrate patient values into treatment decision-making in an emergency., Study Registration: This study is registered as NCT05046197., 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: NIHR131316) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 42. See the NIHR Funding and Awards website for further award information.

Background: With changing cognitive abilities, individuals with mild cognitive impairment (MCI) and dementia face challenges in successfully managing multidrug regimens. We sought to understand how individuals with MCI or dementia and their family caregivers manage multidrug regimens and better understand patient-to-caregiver transitions in medication management responsibilities., Methods: We conducted qualitative interviews among patient-caregiver dyads. Eligibility included: patients with a diagnosis of MCI, mild or moderate dementia, managing ≥3 chronic conditions, ≥5 prescription medications, who also had a family caregiver ≥18 years old. Semi-structured interview guides, informed by the Medication Self-Management model, ascertained roles and responsibilities for medication management and patient-to-caregiver transitions in medication responsibilities., Results: We interviewed 32 patient-caregiver dyads. Older adults and caregivers favored older adult autonomy in medication management, and individuals with MCI and mild dementia largely managed their medications independently using multiple strategies (e.g., establishing daily routines, using pillboxes). Among individuals with moderate dementia, caregivers assumed all medication-related responsibilities except when living separately. In those scenarios, caregivers set up organizers and made reminder calls, but did not observe family members taking medications. Patient-to-caregiver transitions in medication responsibilities frequently occurred after caregivers observed older adults making errors with medications. As caregivers sought to assume greater responsibilities with family members' medicines, they faced multiple barriers. Most barriers were dyadic; they affected both the older adult and the caregiver and/or the relationship. Some barriers were specific to caregivers; these included caregivers' competing responsibilities or inaccurate perceptions of dementia, while other barriers were related to the healthcare system., Conclusions: To ease medication management transitions, balance must be sought between preservation of older adult autonomy and early family caregiver involvement. Clinicians should work to initiate conversations with family caregivers and individuals living with MCI or dementia about transitioning medication responsibilities as memory loss progresses, simplify regimens, and deprescribe, as appropriate., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Objectives: Measures of right heart size and function are prognostic in systemic sclerosis-associated pulmonary hypertension (SSc-PH), but the importance of myocardial tissue characterisation remains unclear. We aimed to investigate the predictive potential and interaction of cardiovascular magnetic resonance (CMR) myocardial tissue characterisation and right heart size and function in SSc-PH., Methods: A retrospective, single-centre, observational study of 148 SSc-PH patients confirmed by right heart catheterization who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2023 was performed., Results: Sixty-six (45%) patients died during follow-up (median 3.5 years, range 0.1-7.3). Patients who died were older (65 vs 60 years, P = 0.035) with more dilated (P < 0.001), hypertrophied (P = 0.013) and impaired (P < 0.001) right ventricles, more dilated right atria (P = 0.043) and higher native myocardial T1 (P < 0.001).After adjustment for age, indexed right ventricular end-systolic volume (RVESVi, P = 0.0023) and native T1 (P = 0.0024) were independent predictors of all-cause mortality. Both RVESVi and native T1 remained independently predictive after adjusting for age and PH subtype (RVESVi P < 0.001, T1 P = 0.0056). Optimal prognostic thresholds for RVESVi and native T1 were ≤38 mL/m2 and ≤1119 ms, respectively (P < 0.001). Patients with RVESVi ≤ 38 mL/m2 and native T1 ≤ 1119 ms had significantly better outcomes than all other combinations (P < 0.001). Furthermore, patients with RVESVi > 38mL/m2 and native T1 ≤ 1119 ms had significantly better survival than patients with RVESVi > 38mL/m2 and native T1 > 1119ms (P = 0.017)., Conclusion: We identified prognostically relevant CMR metrics and thresholds for patients with SSc-PH. Assessing myocardial tissue characterisation alongside right ventricular function confers added value in SSc-PH and may represent an additional treatment target., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: Health research bodies recommend patient involvement and engagement in research and healthcare planning, although their implementation is not yet widespread. This deficiency extends to progressive pulmonary fibrosis (PPF), where crucial aspects remain unknown, including causal mechanisms, curative treatments and optimal symptom management. This study addresses these gaps by seeking stakeholders' perspectives to guide research and treatment directions., Method: A priority-setting partnership was established to explore stakeholders' priorities in the diagnosis, treatment, management and care of PPF, including idiopathic pulmonary fibrosis which is the archetypal PPF. Stakeholders included people living with PPF, their carers, relatives and healthcare professionals involved in their management., Results: Through an online open-ended survey, 2542 responses were collected from 638 stakeholders. Thematic analysis identified 48 specific research questions, which were then cross-referenced with academic literature to pinpoint research gaps. Following the evidence check, 44 unanswered questions were shortlisted by 834 stakeholders in a second online survey. Ultimately, a top 10 priority list was established through consensus.The prioritised research questions include (1) improved diagnosis accuracy and timing, (2) development of new treatments, (3) enhanced accuracy in primary care, (4) optimal timing for drug and non-drug interventions, (5) effective cough treatment, (6) early intervention for PPF, (7) improved survival rates, (8) symptom reduction, (9) impact of interventions on life expectancy and (10) new treatments with reduced side effects., Conclusion: Stakeholders' priorities can be summarised into five areas: early diagnosis, drug and non-drug treatments, survival and symptom management. Ideally, these topics should guide funding bodies and health policies., Competing Interests: Competing interests: AMR discloses payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, Hoffman La Roche, Irish Lung Fibrosis Association, Aerogen. Support for attending meetings and travel from Boehringer Ingelheim, Hoffman La Roche, Interstitial Lung Disease Interdisciplinary Network. GJ discloses grants or contracts from any entity from AstraZeneca, Biogen, Galecto, GlaxoSmithKline, Nordic Biosciences, RedX, Pliant; consulting fees from Apollo Therapeutics, AstraZeneca, Brainomix. Bristol Myers Squibb, Chiesi, Cohbar, Daewoong, GlaxoSmithKline, Veracyte, Resolution Therapeutics, Pliant; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, Chiesi, Roche, PatientMPower, AstraZeneca; payment for expert testimony from Pinsent Masons; participation on a Data Safety Monitoring Board or Advisory Board with Boehringer Ingelheim, Galapagos, Vicore; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with NuMedii and Action for Pulmonary Fibrosis., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Respiratory symptoms are ubiquitous and impair health-related quality of life in people with respiratory disease. This European Respiratory Society (ERS) task force aimed to provide recommendations for symptomatic treatment in people with serious respiratory illness. The ERS task force comprised 16 members, including representatives of people with serious respiratory illness and informal caregivers. Seven questions were formulated, six in the PICO (Population, Intervention, Comparison, Outcome) format, which were addressed with full systematic reviews and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One question was addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations. To treat symptoms in people with serious respiratory illness, the task force suggests the use of graded exercise therapy (conditional recommendation, low certainty of evidence); and suggests the use of a multicomponent services, handheld fan and breathing techniques (conditional recommendations, very low certainty of evidence). The task force suggests not to use opioids (conditional recommendation, very low certainty of evidence); and suggests either administering or not administering supplemental oxygen therapy (conditional recommendation, low certainty of evidence). The task force suggests that needs assessment tools may be used as part of a comprehensive needs assessment, but do not replace patient-centred care and shared decision making (conditional recommendation, low certainty of evidence). The low certainty of evidence, modest impact of interventions on patient-centred outcomes, and absence of effective strategies to ameliorate cough highlight the need for new approaches to reduce symptoms and enhance wellbeing for individuals who live with serious respiratory illness., Competing Interests: Conflict of interest: A.E. Holland reports non-financial support from BOC Australia and Air Liquide Australia for oxygen therapy clinical trials, outside the submitted work. K. Marsaa reports lectures fees from GlaxoSmithKline, AstraZeneca, Novartis and Boehringer Ingelheim, outside the submitted work. A-M. Russell declares speaker fees and support for the development of a podcast series from Boehringer Ingelheim, and speaker fees from Hoffman La Roche, outside the submitted work. R. Saggu reports, within the past 2 years, speaker fees from GSK and TEVA, support for conference attendance and advisory board participation from GSK, Sanofi, AZ and TEVA, and has carried out clinical educator commissioned work for RCGP and RPS. J. Solheim declares membership of the Pulmonary Fibrosis Early Research Steering Committee, Boehringer Ingelheim. M. Wijsenbeek reports grants (paid to institution) from The Dutch Pulmonary Fibrosis Patients Association, The Dutch Lung Foundation, The Netherlands Organisation for Health Research and Development, The Thorax Foundation, Sarcoidosis.nl, AstraZeneca/Daiichi-Sankyo, Boehringer Ingelheim (BI) and Hoffmann-La Roche, and consulting or speaker fees (paid to institution) from AstraZeneca, BI, Bristol Myers Squibb, CSL Behring, Galapagos, Galecto, Hoffmann-La Roche, Horizon, Kinevant Sciences, Molecure, NeRRe, Novartis, PureTech, Thyron, Trevi and Vicore. T. Tonia declares acting as ERS methodologist. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Pulmonary Fibrosis (PF) describes a group of lung diseases characterised by progressive scarring (fibrosis). Symptoms worsen over time and include breathlessness, tiredness, and cough, giving rise to psychological distress. Significant morbidity accompanies PF, so ensuring patients' care needs are well defined and provided for, represents an important treatment strategy. The purpose of this systematic review was to synthesise what is currently known about the psychosocial morbidity, illness experience and needs of people with pulmonary fibrosis and their informal caregivers. Eight databases (MEDLINE, EMBASE, PUBMED, Cochrane database of Systematic reviews (CDSR), Web of Science Social Sciences Citation Index, PsycINFO, PsycARTICLES and CINAHL) were used to identify studies exploring the supportive needs of adults with PF and/or their caregivers. Methodological quality was assessed using the Mixed Methods Appraisal Tool. 53 studies were included, the majority using qualitative methodology (79 %, 42/53), 6 as part of mixed methodological studies. Supportive care needs were mapped to eight domains using an a priori framework analysis. Findings highlight a lack of psychological support throughout the course of the illness, misconceptions about and barriers to, the provision of palliative care despite its potential positive impacts. Patients and caregivers express a desire for greater disease specific education and information provision throughout the illness. Trials of complex interventions are needed to address the unique set of challenges for patients and carers living with PF., Competing Interests: Declaration of competing interest S. L. Barratt reports personal fees for an advisory board and financial support to attend an educational conference from Boehringer Ingelheim, outside the submitted work. The authors have no further declarations., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness., Design: Parallel two-arm, cluster-level randomized controlled trial., Methods: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses., Results: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup., Conclusion: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care., Implications for the Profession And/or Patient Care: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required., Impact: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care., Reporting Method: CONSORT and CONSERVE., Patient or Public Contribution: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: Extensive research has explored the impact of traumatic births on mothers, capturing enduring adverse outcomes as well as post-traumatic growth. The literature on fathers' experiences of birth trauma is more limited and little is known of the ongoing impact. The present study aimed to investigate the long-term effects of attending a traumatic birth., Method: Semi-structured interviews were completed with fathers who identified as having a traumatic birth experience two or more years ago. Thematic analysis was conducted on eight interview transcripts., Results: Despite the time since the birth trauma, fathers described ongoing impact, which is captured in five themes. Four of these focus on the negative impacts: their attempts to cope by boxing away emotions, which they thought they should not feel; anxieties over having further children; negative effects on parenting; and ongoing distress or negative impact on their wellbeing. The final theme highlighted some positives from the experience, primarily a strengthened relationship with their partner., Conclusions: Traumatic birth can result in fathers experiencing difficulties beyond the perinatal period, whilst thinking that they should not feel or discuss their distress. As a result of a traumatic birth fathers can experience ongoing guilt and poor mental health, which may lead them to delay subsequent pregnancies. Most participants had not accessed support regarding the traumatic birth, instead coping by trying to avoid their memories and emotional reaction. These findings highlight the need for increased acknowledgement of the impact of birth trauma and intervention for fathers, during and after the perinatal period.

Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5Δ35"). We found that wild-type (WT) human APOA5, but not APOA5Δ35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5Δ40"). Mouse WT-APOA5, but not APOA5Δ40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5Δ40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5 -/- mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5Δ40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo., Competing Interests: Competing interests statement:S.G.Y. is on the scientific advisory board of Kyttaro; he has received consulting fees from Kyttaro and holds stock in that company. All authors from Eli Lilly & Co. own stock in the company.