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The role of biomarkers in risk-based early detection of lung cancer may enable screening to become cost effective and widely accessible. EarlyCDT-Lung is an example of such a blood-based autoantibody biomarker which may improve accessibility to Low dose Computed Tomography (LDCT) screening for those at highest risk. We randomized 12 208 individuals aged 50-75 at high risk of developing lung cancer to either the test or to standard clinical care. Outcomes were ascertained from Register of Deaths and Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio of the rate of deaths from all causes and lung cancer. Additional analyses were performed for cases of lung cancer diagnosed within two years of the initial test. After 5 years 326 lung cancers were detected (2.7% of those enrolled). The total number of deaths reported from all causes in the intervention group was 344 compared to 388 in the control group. There were 73 lung cancer deaths in the intervention arm and 90 in the controls (Adjusted HR 0.789 (0.636, 0.978). An analysis of cases of lung cancer detected within 2 years of randomization in the intervention group showed that there were 34 deaths from all causes and 29 from lung cancer. In the control group there were 56 deaths with 49 from lung cancer. In those diagnosed with lung cancer within 2 years of randomization the hazard ratio for all cause mortality was 0.615 (0.401,0.942) and for lung cancer 0.598 (0.378, 0.946). Further large-scale studies of the role of biomarkers to target lung cancer screening, in addition to LDCT, are likely to provide additional value., Competing Interests: F.M. Sullivan reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. F.S. Mair reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. W. Anderson has nothing to disclose. C. Chew has nothing to disclose. A. Dorward has nothing to disclose. J. Haughney has nothing to disclose. F. Hogarth reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and from Oncimmune, during the conduct of the study. D. Kendrick has nothing to disclose. R. Littleford reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and Oncimmune, during the conduct of the study. A. McConnachie reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. C. McCowan has nothing to disclose. N. McMeekin reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. M. Patel has nothing to disclose. P. Rauchhaus reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. L. Ritchie has nothing to disclose. J. Robertson reports other funding from Oncimmune, during the conduct of the study; and other funding from Oncimmune, outside the study. J. Robertson was a founder of Oncimmune, a company spun out from the University of Nottingham based on his academic research. Between 2003 and 2013 he was Chief Scientific Officer of Oncimmune and a Director of the company. During this time, he was responsible for the original drafting of the ECLS protocol. Since 2013 he has had no involvement in the science or management of the company. He has been and remains a shareholder in the company. J. Sarvesvaran has nothing to disclose. H. Sewell reports other funding from Oncimmune, outside the submitted work; and was an external member of the Oncimmune Scientific Advisory Board from 2006 to 2013. T. Taylor reports grants, nonfinancial support and other funding from Oncimmune, grants and personal fees from the Chief Scientist Office for Scotland, and grants and nonfinancial support from the Scottish Government, outside the submitted work. S. Treweek reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. K. Vedhara has nothing to disclose. S. Schembri reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study., (Copyright: © 2025 Sullivan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A large number of individuals suffer from post-COVID-19 condition (PCC), characterised by persistent symptoms following a SARS-CoV-2 infection with an impact on daily personal and professional activities. This study aims at examining which (health) care services are used by PCC patients in the German federal state of Lower Saxony, and how these patients manage their condition. The perspectives of patients, informal caregivers and general practitioners (GPs) will be considered., Methods: The study will employ a mixed methods design. Patients' perspective will be evaluated through an online survey of: (1) 21,000 adult individuals with a PCC diagnosis (ICD10 U09.9!) in their statutory health insurance claims data in 2022 ("AOK survey") and (2) a self-selected sample of adult individuals with a proven SARS-CoV-2 infection in 2023 and persistent symptoms ("public survey"). Additional data sources will be claims data (n = 27,275) and 25-30 semi-structured interviews. Informal caregivers' perspective will be collected through an online survey and semi-structured interviews. GPs' perspective will be evaluated through four focus groups involving six to eight participants each and an online survey of all registered and practicing GPs in Lower Saxony (approximately 5,000). All survey data will be descriptively analysed. In addition, correlation analyses and multivariable regression analyses will be conducted, for example on factors influencing affected individuals' use of medical services. Interview and focus group data will be subjected to qualitative content analysis. A health economic analysis will be used to determine the costs of PCC to health care payers, patients and society. The project will conclude with an expert workshop to discuss the results and derive recommendations., Discussion: The results of the study will provide a multidimensional description of the (health) care situation and needs of patients with PCC, and derive recommendations for improving health care., Trial Registration: The VePoKaP study is registered at the German Clinical Trials Register (DRKS00032846)., Competing Interests: CH-L has received a lecture honorarium from Novartis and royalties from Hogrefe Publish-ers for the German version of the Hospital Anxiety and Depression Scale. His research is supported by grants from the German Ministry of Education and Research, the German Re-search Foundation and the European Commission. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare that they have no competing interests., (Copyright: © 2024 Brinkmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic had a global impact on daily lives, and this study aimed to assess the effects on broader aspects of health in the general population of Norway. This population-based cohort study assessed changes in health of the Norwegian general population from 3 months before to 9 months during the COVID-19 pandemic. Sampling was based on the results of Norwegian surveys designed for collecting general population norms for health measurement instruments. In December 2019, 12,790 randomly selected adults aged ≥18 years received a postal questionnaire. The 3,200 respondents received a similar follow-up postal questionnaire including the EQ-5D-5L, PROMIS-29 instruments, and questions about respondents having or having had COVID-19. Score changes were compared to estimates for the minimal important change (MIC) and age-related change. Association of instrument change scores with baseline characteristics, health problems, and having had COVID-19 was determined using multivariable linear regression. Of 3101 respondents with unchanged addresses, 2423 (78.1%) responded to the second survey. For all respondents, EQ VAS and PROMIS-29 scores for 6 of 8 domains were slightly poorer (p<0.01) than before COVID-19, and the mean change was below the MIC. In multivariable analyses, the greatest number of poorer outcomes were associated with being female, 18-29 years, or ≥80 years of age (p<0.01); > MIC for ≥ 80 years of age and EQ-5D index, PROMIS-29 physical function and social participation. Respondents who had COVID-19 had poorer outcomes for PROMIS-29 social participation (> MIC). Those reporting COVID-19 in their partner/family and not themselves, had poorer outcomes for PROMIS-29 anxiety and social participation. About 9 months into the COVID-19 pandemic, EQ-5D-5L and PROMIS-29 domain scores showed slightly poorer health in the Norwegian adult general population compared to 1 year earlier in the same respondents. The overall changes were less than expected for age-related change. Relatively poor outcomes defined as important, included general health and social participation for the elderly, and the latter for those having had COVID-19. In conclusion, this study found no evidence for a decline in important aspects of adult general population health in Norway that might be attributed to the pandemic at approximately 9 months., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Garratt, Stavem. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic was associated with an increase in child and adolescent mental health disorders, with subsequent worsening of patient access to specialist mental health care. Clinicians working in the community were faced with increased demands to diagnose and manage pediatric mental health disorders, without always having the confidence and knowledge to do so. We therefore developed COnnecting Mental-health PAediatric Specialists and community Services (COMPASS)-a collaborative model designed to upskill community clinicians in child and adolescent mental health care and provide them with better access to child and adolescent psychiatry expertise. COMPASS comprises (1) an online Community of Practice (CoP) with fortnightly one-hour sessions covering: anxiety; aggression and challenging behaviours; depression; self-harm and suicidality; eating disorders; and autism spectrum disorder/complex cases and (2) primary and secondary consultations for general practitioners and paediatricians with an experienced child psychiatrist. We aimed to assess the impact of COMPASS on community clinician self-reported confidence in: managing common child and adolescent mental health disorders (Objective 1, primary outcome); navigating the mental health care system (i.e. knowing how services are organised, accessed, and how to refer patients, Objective 2); diagnosing conditions (Objective 3); prescribing psychotropic medications (Objective 4) as well as the impact on, clinician practice and wellbeing (Objective 5) and outcomes of patients referred by COMPASS clinicians to the child psychiatrist (Objective 6)., Methods: We evaluated COMPASS in its first year, with COMPASS running from March to July 2021. Participating clinicians completed pre-post surveys evaluating change in Objectives 1 to 4 above, using study-designed measures. A purposive sample of clinicians was then invited to a semi-structured interview to understand their experience of COMPASS and its impacts on practice and wellbeing (Objective 5). We adopted an inductive approach to the qualitative analysis using the Framework Method. This involved selecting five random transcripts which were double coded and categorized, to generate an initial framework against which all subsequent transcripts were analysed. Themes and subthemes were generated from the data set, by reviewing the matrix and making connections within and between clinicians, codes and categories One child psychiatrist completed a 2-week logbook of the nature and outcomes of primary and secondary consultations (Objective 6)., Findings: 51 (86%) clinicians attended CoP sessions and completed pre-post surveys, with 92% recommending COMPASS to peers. Clinicians reported increased confidence in the pharmacological and non-pharmacological management of all conditions, most notably for management of self-harm. They also reported increased knowledge of how to navigate the mental health system and prescribe medications. Qualitative analysis (n = 27 interviews) found that COMPASS increased clinician wellbeing and reduced feelings of professional isolation and burnout. Over the 2-week snapshot, the child psychiatrist consulted on 22 patients and referred all back to the community clinician., Conclusions: COMPASS is associated with improved clinician confidence to manage child and adolescent mental health concerns, navigate the mental health system, improved clinician wellbeing, and reduced need for ongoing mental health care by specialists., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 D’Abaco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia., Methods: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures., Results: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019)., Conclusion: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shrestha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Maintaining continuity of care between doctors and patients is considered a fundamental aspect of quality in primary healthcare. In this study, we aim to examine continuity in Norway over time by computing two commonly used indicators of continuity: the St Leonard's Index of Continuity of Care (SLICC) and the Usual Provider of Care Index (UPC)., Method: We employ individual-level data, which covers all primary care consultations. This data includes the identities of each patient and physician, and we can identify each patient's regular general practitioner (GP). The SLICC is calculated as the share of consultations conducted by the patient's regular GP annually from 2006 to 2021. Additionally, we identify each patient's most visited physician and compute the UPC as the share of total consultations conducted by the most visited physician during the same period. Our analysis is conducted at the national level and stratified according to the level of centrality, differentiating between areas of high, moderate, and low centrality., Results: Our findings reveal that, at the national level, SLICC and UPC exhibit remarkable stability, reaching 64 and 71 percent, respectively, in 2021. However, there is significant geographical variation, with the least central areas experiencing less continuous healthcare (SLICC at 49 percent in 2021) than patients residing in more central areas (SLICC at 68 in 2021)., Conclusion: Our results demonstrate a high degree of continuity that has been stable over time. However, large geographical variations suggest that policymakers should strive to reduce geographical disparities in healthcare quality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Delalic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The Mexican government has pursued multiple initiatives to improve healthcare coverage and financial protection. Yet, out-of-pocket health spending and use of private sector providers in Mexico remains high. In this paper, we sought to describe the characteristics of public and private healthcare users, describe recent visit quality across provider types, and to assess whether perceiving the public healthcare sector as poor quality is associated with private health sector use., Methods and Findings: We analyzed the cross-sectional People's Voice Survey conducted from December 2022 to January 2023. We used Chi-square tests to compare contextual, individual, and need-for-care factors and ratings of most recent visits between users of public (social security and other public providers) and private sector providers (stand-alone private providers and providers adjacent to pharmacies). We used a multivariable Poisson regression model to assess associations between low ratings of public healthcare sources and the use of private care. Among the 811 respondents with a healthcare visit in the past year, 31.2% used private sources. Private healthcare users were more educated and had higher incomes than public healthcare users. Quality of most recent visit was rated more highly in private providers (70.2% rating the visit as excellent or very good for stand-alone private providers and 54.3% for pharmacy-adjacent doctors) compared to social security (41.6%) and other public providers (46.6%). Those who perceived public health institutions as low quality had a higher probability of seeking private healthcare., Conclusion: Users rated public care visits poorly relative to private care; at the population level, perceptions of poor quality care may drive private care use and hence out-of-pocket costs. Improving public healthcare quality is necessary to ensure universal health coverage., Competing Interests: HHL is an academic Editor for PLOS Global Public Health. Other authors have declared no competing interests., (Copyright: © 2024 Doubova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Changes in alcohol consumption may affect older adults' health. We examined prevalence and changes in the alcohol consumption of older women and men (≥65 years) in Norway over a 24-year period., Methods: Data from three population-based health surveys (The Trøndelag Health Study-HUNT2 1995-97, HUNT3 2006-08, HUNT4 2017-19) were used. Alcohol consumption was measured using self-reported measures and an objective measure of alcohol consumption (Phosphatidylethanol 16:0/18:1, PEth). Self-reported lifetime abstinence, former drinking, current drinking, frequent drinking (≥4 times/week), and risk drinking (≥8 units/week) were measured. The PEth concentrations were stratified: <0.03 μmol/l (abstinence/very low level of alcohol consumption); >0.06 μmol/l (indicating >1 unit/day); >0.10 μmol/l (indicating >3 units/day), and >0.30 μmol/l (heavy alcohol consumption)., Results: In HUNT4, the prevalence of self-reported lifetime abstinence, frequent drinking, and risk drinking was 5.2%, 4.4%, and 5.6%, respectively, while prevalence of PEth <0.03 μmol/l was 68.1% and PEth >0.06 μmol/l was 21.2%. Over the course of the three surveys, the prevalence of self-reported lifetime abstinence decreased, while the prevalence of frequent drinking and risk drinking increased. Men were less often abstainers and more often frequent and risky drinkers than women in all three surveys. Gender differences for abstinence and current drinking reduced with time. From HUNT3 to HUNT4, the prevalence of PEth <0.03 μmol/l decreased, while the prevalence of PEth >0.06 μmol/l increased. Men compared to women, had less often PEth <0.03 μmol/l and more often PEth >0.06 and >0.10 μmol/l in HUNT3 and HUNT4. Women and men ≥75 years were just as likely to have PEth >0.30 μmol/l in HUNT4. The gender differences in PEth concentrations were reduced in HUNT4 among those aged 70-74 years or ≥75 years., Conclusion: Alcohol consumption has increased among Norwegian older adults over a 24-year period, but at a slower pace during the last decade., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2024 Tevik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To investigate changes in chest CT between 3 and 12 months and associations with disease severity in patients hospitalized for COVID-19 during the first wave in 2020., Materials and Methods: Longitudinal cohort study of patients hospitalized for COVID-19 in 2020. Chest CT was performed 3 and 12 months after admission. CT images were evaluated using a CT severity score (CSS) (0-12 scale) and recoded to an abbreviated version (0-3 scale). We analyzed determinants of the abbreviated CSS with multivariable mixed effects ordinal regression., Results: 242 patients completed CT at 3 months, and 124 (mean age 62.3±13.3, 78 men) also at 12 months. Between 3 and 12 months (n = 124) CSS (0-12 scale) for ground-glass opacities (GGO) decreased from median 3 (25th-75th percentile: 0-12) at 3 months to 0.5 (0-12) at 12 months (p<0.001), but increased for parenchymal bands (p<0.001). In multivariable analysis of GGO, the odds ratio for more severe abbreviated CSS (0-3 scale) at 12 months was 0.11 (95%CI 0.11 0.05 to 0.21, p<0.001) compared to 3 months, for WHO severity category 5-7 (high-flow oxygen/non-invasive ventilation/ventilator) versus 3 (non-oxygen use) 37.16 (1.18 to 43.47, p = 0.032), and for age ≥60 compared to <60 years 4.8 (1.33 to 17.6, p = 0.016). Mosaicism was reduced at 12 compared to 3 months, OR 0.33 (95%CI 0.16 to 0.66, p = 0.002)., Conclusions: GGO and mosaicism decreased, while parenchymal bands increased from 3 to 12 months. Persistent GGO were associated with initial COVID-19 severity and age ≥60 years., Competing Interests: Haseem Ashraf reports grant from Boehringer-Ingelheim, Norway. Knut Stavem reports personal fees from UCB Pharma and MSD Norway, unrelated to this study., (Copyright: © 2024 Aaløkken et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To inform interventions focused on safely reducing urgent paediatric short stay admissions (SSAs) for convulsions., Methods: Routinely acquired administrative data from hospital admissions in Scotland between 2015-2017 investigated characteristics of unscheduled SSAs (an urgent admission where admission and discharge occur on the same day) for a diagnosis of febrile and/or afebrile convulsions. Semi-structured interviews to explore perspectives of health professionals (n = 19) making referral or admission decisions about convulsions were undertaken. Interpretation of mixed methods findings was complemented by interviews with four parents with experience of unscheduled SSAs of children with convulsion., Results: Most SSAs for convulsions present initially at hospital emergency departments (ED). In a subset of 10,588 (11%) of all cause SSAs with linked general practice data available, 72 (37%) children with a convulsion contacted both the GP and ED pre-admission. Within 30 days of discharge, 10% (n = 141) of children admitted with afebrile convulsions had been readmitted to hospital with a further convulsion. Interview data suggest that panic and anxiety, through fear that the situation is life threatening, was a primary factor driving hospital attendance and admission. Lengthy waits to speak to appropriate professionals exacerbate parental anxiety and can trigger direct attendance at ED, whereas some children with complex needs had direct access to convulsion professionals., Conclusions: SSAs for convulsions are different to SSAs for other conditions and our findings could inform new efficient convulsion-specific pre and post hospital pathways designed to improve family experiences and reduce admissions and readmissions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Malcolm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Long COVID is a devastating, long-term, debilitating illness which disproportionately affects healthcare workers, due to the nature of their work. There is currently limited evidence specific to healthcare workers about the experience of living with Long COVID, or its prevalence, pattern of recovery or impact on healthcare., Objective: Our objective was to assess the effects of Long COVID among healthcare workers and its impact on health status, working lives, personal circumstances, and use of health service resources., Methods: We conducted a systematic rapid review according to current methodological standards and reported it in adherence to the PRISMA 2020 and ENTREQ statements., Results: We searched relevant electronic databases and identified 3770 articles of which two studies providing qualitative evidence and 28 survey studies providing quantitative evidence were eligible. Thematic analysis of the two qualitative studies identified five themes: uncertainty about symptoms, difficulty accessing services, importance of being listened to and supported, patient versus professional identity and suggestions to improve communication and services for people with Long COVID. Common long-term symptoms in the survey studies included fatigue, headache, loss of taste and/or smell, breathlessness, dyspnoea, difficulty concentrating, depression and anxiety., Conclusion: Healthcare workers struggled with their dual identity (patient/doctor) and felt dismissed or not taken seriously by their doctors. Our findings are in line with those in the literature showing that there are barriers to healthcare professionals accessing healthcare and highlighting the challenges of receiving care due to their professional role. A more representative approach in Long COVID research is needed to reflect the diverse nature of healthcare staff and their occupations. This rapid review was conducted using robust methods with the codicil that the pace of research into Long COVID may mean relevant evidence was not identified., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cruickshank et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vision loss has been associated with mental health problems such as depression, anxiety, and post-traumatic stress disorder, which significantly impact lives of working age adults with adventitious total bilateral blindness and low vision. It is imperative, therefore, to prioritize the mental health in this population by exploring and understanding the factors that impact on their mental health. Hence, the objective of this scoping review is to identify and chart existing literature on the protective and risk factors of mental health of working age adults with adventitious total bilateral blindness and low vision. We developed this scoping review protocol in line with the Joanna Briggs Institute guidance. This scoping review will include publications in English language with no date restrictions exploring the protective and risk factors of mental health of our study population. A three-step search strategy will be employed. Searches will be carried out in the following databases: Medline, Embase, PsycInfo, PsycArticles, CINAHL and Web of Science. Search for grey literature will be conducted in Google, Google Scholar and Websites dedicated to information on visual impairment. Collated results will be imported into Endnote Basic (Clarivate) for deduplication. Two reviewers will independently conduct double screening of all the titles and abstracts in Rayyan- a web application, and full texts in Endnote while three other reviewers will conduct screening of a subset of for example 10% of titles and abstracts and full texts. Furthermore, two reviewers will independently conduct double data extraction while three other reviewers will revise, cross check, and correct any extraction errors. Extracted data will be presented in tabular formats and summarized descriptively in line with the research objectives. This scoping review will generate evidence on factors impacting the mental health of the working age adults with adventitious total bilateral blindness and low vision as well as critically highlight gaps in the literature. The findings will inform and critically underpin future empirical research which will explore the lived experiences of working age people with adventitious total bilateral blindness. Additionally, evidence from this review will inform the development of interventions in the promotion of mental health as well as assisting rehabilitation specialists and workers, public health practitioners and other relevant stakeholders in addressing the mental health needs of working age adults with adventitious total bilateral blindness and low vision., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dike et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patient and public involvement (PPI) in trials aims to enhance research by improving its relevance and transparency. Planning for statistical analysis begins at the design stage of a trial within the protocol and is refined and detailed in a Statistical Analysis Plan (SAP). While PPI is common in design and protocol development it is less common within SAPs. This study aimed to reach consensus on the most important and relevant statistical analysis items within an SAP to involve patients and the public., Methods: We developed a UK-based, two-round Delphi survey through an iterative consultation with public partners, statisticians, and trialists. The consultation process started with 55 items from international guidance for statistical analysis plans. We aimed to recruit at least 20 participants per key stakeholder group for inclusion in the final analysis of the Delphi survey. Participants were asked to vote on each item using a Likert scale from 1 to 9, where a rating of 1 to 3 was labelled as having 'limited importance'; 4 to 6 as 'important but not critical' and 7 to 9 as 'critical' to involve patients and the public. Results from the second round determined consensus on critical items for PPI., Results: The consultation exercise led to the inclusion of 15 statistical items in the Delphi survey. We recruited 179 participants, of whom 72% (129: 36 statisticians, 29 patients or public partners, 25 clinical researchers or methodologists, 27 trial managers, and 12 PPI coordinators) completed both rounds. Participants were on average 48 years old, 60% were female, 84% were White, 64% were based in England and 84% had at least five years' experience in trials. Four items reached consensus regarding critical importance for patient and public involvement: presentation of results to trial participants; summary and presentation of harms; interpretation and presentation of findings in an academic setting; factors impacting how well a treatment works. No consensus was reached for the remaining 11 items. In general, the results were consistent across stakeholder groups., Discussion: We identified four critical items to involve patients and the public in statistical analysis plans. The remaining 11 items did not reach consensus and need to be considered in a case-by-case basis with most responders considering patient and public involvement important (but not critical). Our research provides a platform to enable focused future efforts to improve patient and public involvement in trials and enhance the relevance of statistical analyses to patients and the public., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Goulão et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Social differences in body mass index and health behaviors are a major public health challenge. The uneven distribution of unhealthy body mass index and of unhealthy behaviors such as smoking, physical inactivity, and harmful alcohol consumption has been shown to mediate social inequalities in chronic diseases. While differential exposures to these health variables have been investigated, the extent to which they vary over the lifetime in the same population and their relationship with level of education is not well understood. This study examines patterns of body mass index and multiple health behaviors (smoking, physical activity and alcohol consumption), and investigates their association with education level among adults living in Northern Norway. It presents findings from a longitudinal multiple correspondence analysis of the Tromsø Study. Longitudinal data from 8,906 adults aged 32-87 in 2007-2008, with repeated measurements in 2015-2016 were retrieved from the survey's sixth and seventh waves. The findings suggest that most in the study population remained in the same categories of body mass index and the three health behaviors at the follow-up, with a clear educational gradient in healthy patterns. That is, both healthy changes and maintained healthy categories were associated with the highest education levels. Estimating differential exposures to mediators of health inequalities could benefit policy priority setting for tackling inequalities in health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ibarra-Sanchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia., Methods: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial., Results: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone., Conclusion: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bashir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study., Methods: Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables., Results: Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo., Conclusion: Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rossios et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Functional social support is one of the most established predictors of health, and the Duke-UNC Functional Social Support Questionnaire (DUFSS) is one of the most commonly used instruments to measure this parameter. The objective of this study is to systematically review the available evidence on the psychometric and administration characteristics of the different versions of the DUFSS and perform a standardized assessment though to a specifically designed tool., Methods: A systematic review was performed in the PubMed/MEDLINE, SCOPUS, WOS and SCIELO databases. All articles that contained information on the development process of the instrument, the psychometric properties and aspects related to its administration were included, without restrictions based on publication date, language, or the version of the questionnaire that was studied. The selection and extraction procedure were carried out by two researchers. The articles finally included were peer-reviewed through a standardised assessment using the Evaluating the Measurement of Patient-Reported Outcomes (EMPRO) tool. PROSPERO registration number: CRD42022342977., Results: A total of 54 articles were identified. After eliminating duplicates and screening articles based on the selection criteria, 15 studies that examined the DUFSS questionnaire resulting in 4 different versions: 3 articles obtained the 8-item version; 11 the 11-item version; and a single article obtained two versions, the 14-item version and the 5-item version. At least 60% of them did so in a young adult population, predominantly female and with a medium-low socio-economic level or with characteristics of social vulnerability. The EMPRO evaluation showed that the 11-item version (54.01 total score) was the only one that had been studied on all recommended attributes and had higher total scores than the other versions: 8 items (36.31 total score), 14 items (27.48 total score) and 5 items (23.81 total score). This difference appears in all attributes studied, with the highest scores in "reliability (internal consistency)" and "validity"., Conclusions: Of the 4 versions identified in the DUFSS questionnaire, the 11-item version was found to be optimal based on the EMPRO standardized tool. Although, a priori, we could prioritise its use in epidemiological studies over the other versions, it should be noted that this version should also be used with caution because there are attributes that have not been studied., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lozano-Hernández et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Information graphics or infographics combine visual representations of information or data with text. They have been used in health research to disseminate research findings, translate knowledge and address challenges in health communication to lay audiences. There is emerging evidence of the design of infographics with the involvement of patients and the public in health research. Approaches to involvement include public and patient involvement, patient engagement and participatory research approaches. To date, there has been no comprehensive review of the literature on the design of infographics with patients and the public in health research. This paper presents a protocol and methodological framework for a scoping review to identify and map the available evidence for the involvement of patients and the public in infographics design in health research. It has been informed by preliminary searches and discussions and will guide the conduct and reporting of this review., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Beecher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Non-alcoholic steato-hepatitis (NASH) is the inflammatory, progressive form of non-alcoholic fatty liver disease (NAFLD). A delayed diagnose interval is typical for the majority of the patients because of the asymptomatic natural course. However, serious sequelae may develop such as cirrhosis or hepatocellular carcinoma. NASH is also associated with an increased risk of metabolic diseases. Obesity developed due to a lack of exercise or a disadvantageous diet often leads to NAFLD or NASH, thereby interventions including enhanced physical activity and calorie reduction form the actual gold standard of treatment. To date, patients rarely use these. The project aims to model lifestyle interventions based on the preferences of the NASH patients., Methods: Based on a systematic review and focus group discussions, two discrete choice experiments (DCE) will be designed, one on aspects influencing successful uptake of lifestyle interventions and one to analyses parameters contributing to long-term participation. An online survey will be used to elicit patient's preferences on program design and on motivational aspects in a cross-sectional design. The recruitment will take place in nine certified specialist practices and hospital outpatient clinics aiming to reach a sample size of n = 500 which is also required for the DCE design., Discussion: The results will provide an overview of the NASH patient's preferences regarding the successful uptake and long-term implementation of lifestyle interventions. Recommendations for optimized lifestyle change programs will be derived and an intervention manual will be developed to facilitate target group-specific inclusion in programs in practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Krüger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Antimicrobial resistance (AMR) is an economic, food security, and global health threat accelerated by a multitude of factors including the overuse and misuse of antimicrobials in the human health, animal health, and agriculture sectors. Given the rapid emergence and spread of AMR and the relative lack of development of new antimicrobials or alternative therapies, there is a need to develop and implement non-pharmaceutical AMR mitigation policies and interventions that improve antimicrobial stewardship (AMS) practices across all sectors where antimicrobials are used. We conducted a systematic literature review per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify peer-reviewed studies that described behavior-change interventions that aimed to improve AMS and/or reduce inappropriate antimicrobial use (AMU) among human health, animal health, and livestock agriculture stakeholders. We identified 301 total publications- 11 in the animal health sector and 290 in the human health sector-and assessed described interventions using metrics across five thematic areas- (1) AMU, (2) adherence to clinical guidelines, (3) AMS, (4) AMR, and (5) clinical outcomes. The lack of studies describing the animal health sector precluded a meta-analysis. Variation across intervention type, study type, and outcome precluded a meta-analysis for studies describing the human health sector; however, a summary descriptive analysis was conducted. Among studies in the human health sector, 35.7% reported significant (p<0.05) pre- to post-intervention decreases in AMU, 73.7% reported significant improvements in adherence of antimicrobial therapies to clinical guidelines, 45% demonstrated significant improvements in AMS practices, 45.5% reported significant decreases in the proportion of isolates that were resistant to antibiotics or the proportion of patients with drug-resistant infections across 17 antimicrobial-organism combinations. Few studies reported significant changes in clinical outcomes. We did not identify any overarching intervention type nor characteristics associated with successful improvement in AMS, AMR, AMU, adherence, nor clinical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Craig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The introduction of robot-assisted surgery is costly and requires whole system transformation, which makes the assessment of benefits (or drawbacks) complex. To date, there has been little agreement on which outcomes should be used in this regard. The aim of the RoboCOS study was to develop a core outcome set for the evaluation of robot-assisted surgery that would account for its impact on the whole system., Methods: Identification of a long-list of potentially relevant outcomes through systematic review of trials and health technology assessments; interviews with individuals from a range of stakeholder groups (surgeons, service managers, policy makers and evaluators) and a focus group with patients and public; prioritisation of outcomes via a 2-round online international Delphi survey; consensus meeting., Results: 721 outcomes were extracted from the systematic reviews, interviews and focus group which were conceptualised into 83 different outcome domains across four distinct levels (patient, surgeon, organisation and population) for inclusion in the international Delphi prioritisation survey (128 completed both rounds). The consensus meeting led to the agreement of a 10-item core outcome set including outcomes at: patient level (treatment effectiveness; overall quality of life; disease-specific quality of life; complications (including mortality); surgeon level (precision/accuracy; visualisation); organisation (equipment failure; standardisation of operative quality; cost-effectiveness); and population (equity of access)., Conclusion: The RoboCOS core outcome set, which includes the outcomes of importance to all stakeholders, is recommended for use in all future evaluations of robot-assisted surgery to ensure relevant and comparable reporting of outcomes., Competing Interests: MC, KG, DB have been in receipt of unrestricted educational grant funding from Intuitive Surgical’s European Research Board. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Robertson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is limited evidence regarding predictors of functional trajectories after hip fracture. We aimed to identify groups with different trajectories of functional recovery the first year after hip fracture, and to determine predictors for belonging to such groups., Methods: This longitudinal study combined data from two large randomized controlled trials including patients with hip fracture. Participants were assessed at baseline, four and 12 months. We used the Nottingham Extended Activities of Daily Living (NEADL) as a measure of instrumental ADL (iADL) and Barthel Index for personal ADL (pADL). A growth mixture model was estimated to identify groups of patients following distinct trajectories of functioning. Baseline characteristics potentially predicting group-belonging were assessed by multiple nominal regression., Results: Among 726 participants (mean age 83.0; 74.7% women), we identified four groups of patients following distinct ADL trajectories. None of the groups regained their pre-fracture ADL. For one of the groups identified in both ADL outcomes, a steep decline in function was shown the first four months after surgery, and none of the groups showed functional recovery between four and 12 months after surgery., Conclusions: No groups regained their pre-fracture ADL. Some of the patients with relatively high pre-fracture function, had a steep ADL decline. For this group there is a potential for recovery, but more knowledge and research is needed in this group. These findings could be useful in uncovering groups of patients with different functioning after a hip fracture, and aid in discharge planning., Competing Interests: I. Saltvedt has performed Alzheimer a drug trial for Boehringer-Ingelheim 1346.0023. This trial was concluded in 2019. The remaining authors declare that they have no competing interests., (Copyright: © 2023 Dakhil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Several screening tools are developed to identify frailty in the increasing number of older patients with cancer. Edmonton Frail Scale (EFS) performs well in geriatric settings but is less studied in oncology. We aimed to investigate if EFS score (continuous and categorical) predicts survival in patients referred for radiotherapy, and to assess the concurrent validity of EFS compared with a modified geriatric assessment (mGA)., Methods: Prospective observational, single-center study including patients ≥65 years, referred for curative or palliative radiotherapy for confirmed cancer. Patients underwent mGA (assessment of cognition, mobility, falls, comorbidity, polypharmacy, depression, nutrition, and activities of daily living) and screening with EFS prior to radiotherapy. The predictive value of EFS score of two-year overall survival (OS) was assessed by Kaplan-Meier plots and compared by log-rank test. Cox proportional hazards regression model was estimated to adjust the associations for major cancer-related factors. Concurrent validity of EFS in relation to mGA was estimated by Spearman`s correlation coefficient and ordinal regression. Sensitivity and specificity for different cut-offs was assessed., Results: Patients' (n = 301) mean age was 73.6 (SD 6.3) years, 159 (52.8%) were men, 54% received curative-intent treatment, breast cancer (32%) was the most prevalent diagnosis. According to EFS≥6, 101 (33.7%) were classified as frail. EFS score was predictive of OS [hazard ratio (HR) 1.20 (95% confidence interval (CI) 1.10-1.30)], as was increasing severity assessed by categorical EFS (p<0.001). There was a strong correlation between EFS score and number of geriatric impairments (Spearman`s correlation coefficient 0.77). EFS cut-off ≥6 had a sensitivity of 0.97 and specificity of 0.57 for identifying patients with minimum two geriatric impairments., Conclusion: EFS predicts mortality in older patients with cancer receiving radiotherapy, and it is a quick (<5 minutes) and sensitive screening tool to identify patients who may benefit from a geriatric assessment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Røyset et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Mental health problems, such as behavioural and emotional problems, are prevalent in children. These problems can have long lasting, detrimental effects on the child, their parents and society. Most children with a mental health problem do not receive professional help. Those that do get help can face long wait times. While waiting, parents want to learn how they can help their child. To address this need, we co-designed a new website to help parents find ways of helping their child's mental health problem while waiting to get specialist help., Objectives: To assess the acceptability and feasibility of a new co-designed website, FindWays, through a pilot randomised controlled trial. The protocol is registered with ISRCTN (ISRCTN64605513)., Methods: This study will recruit up to 60 parents of children aged two-twelve years old referred to a paediatrician for behavioural and/or emotional problems. Participants will be randomly allocated by computer generated number sequence to either the intervention or control group. Intervention group participants will receive access to the FindWays website to help them manage their child's mental health problem while they wait to see the paediatrician. Acceptability and feasibility will be assessed over the 4-month intervention through mixed methods including: recruitment, adherence, retention, net promoter score (quantitative measures) and semi-structured interviews to gain an in-depth understanding of parents' experience and potential adverse effects (qualitative measure). Secondary outcomes measured by parent survey at 4-months post randomisation include child mental health, parent mental health, impact of the child's mental health problem on their functioning and family, and health service use and associated costs., Results: Recruitment commenced June 2022 with publication expected in October 2023., Conclusion: This study will provide novel data on the acceptability and feasibility of a new website co-designed with parents to help them find ways of managing their child's behaviour and emotions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Peyton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aims to explore the perspectives of medical trainees on the impartation of digital competencies in Singapore's medical school curricula. It also considers how the medical school experience can be strengthened in order to bridge potential gaps in the integration of these competencies in the local curricula. Findings were drawn from individual interviews with 44 junior doctors from Singapore's public healthcare institutions including hospitals and national specialty centers. House officers and residents from different medical and surgical specialties were recruited using purposive sampling. Data was interpreted using qualitative thematic analysis. The doctors were in their first to tenth year of post-graduate training. Thirty of them graduated from the three local medical schools whereas 14 others were trained overseas. Overall, they felt insufficiently prepared to utilize digital technologies in view of their limited exposure to such technologies in medical school. Six key reasons were identified: lack of flexibility and dynamism within the curriculum, dated learning style, limited access to electronic health records, gradual uptake of digital technologies in the healthcare sector, lack of an ecosystem that promotes innovation, and lack of guidance from qualified and available mentors. Equipping medical students with skills relevant to the digital age would benefit from a concerted effort from multiple stakeholders: medical schools, medical educators and innovators, as well as the government. This study bears important implications for countries that seek to bridge the 'transformation gap' brought about by the digital age, which is defined as the sharp divergence between innovations that healthcare providers recognize as important but for which they feel insufficiently prepared., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zainal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Healthcare technologies are becoming more commonplace, however clinical and patient perspectives regarding the use of technology in the management of childhood asthma have yet to be investigated. Within a clinical trial of asthma management in children, we conducted a qualitative process evaluation that provided insights into the experiences and perspectives of healthcare staff and families on (i) the use of smart inhalers to monitor medication adherence and (ii) the use of algorithm generated treatment recommendations., Methods: We interviewed trial staff (n = 15) and families (n = 6) who were involved in the trial to gauge perspectives around the use of smart inhalers to monitor adherence and the algorithm to guide clinical decision making., Findings: Staff and families indicated that there were technical issues associated with the smart inhalers. While staff suggested that the smart inhalers were good for monitoring adherence and enabling communication regarding medication use, parents and children indicated that smart inhaler use increased motivation to adhere to medication and provided the patient (child) with a sense of responsibility for the management of their asthma. Staff were open-minded about the use of the algorithm to guide treatment recommendations, but some were not familiar with its' use in clinical care. There were some concerns expressed regarding treatment step-down decisions generated by the algorithm, and some staff highlighted the importance of using clinical judgement. Families perceived the algorithm to be a useful technology, but indicated that they felt comforted by the clinicians' own judgements., Conclusion: The use of technology and individual data within appointments was considered useful to both staff and families: closer monitoring and the educational impacts were especially highlighted. Utilising an algorithm was broadly acceptable, with caveats around clinicians using the recommendations as a guide only and wariness around extreme step-ups/downs considering contextual factors not taken into account., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lawrie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The overall aim was to explore the prevalence and persistent regular prescription of opioids and paracetamol among nursing home (NH) residents with dementia at admission and over time. A total of 996 residents with dementia, mean (SD) age 84.5 (7.6) years and (36.1% men), were included at admission (A1). Yearly assessments were performed for two years (A2 and A3) or until death. Pain was assessed using the Mobilization-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) Pain Scale. Information regarding prescription of analgesics, general physical health, personal activities of daily living, severity of dementia, neuropsychiatric symptoms, and prescription of psychotropic drugs was collected. A generalized linear mixed model was used to explore whether pain severity was associated with persistent and persistent prescription of opioids and/or paracetamol across timepoints. At A1, 495 of 996 (49.7%) NH residents were prescribed analgesics and prevalence increased at the follow-ups (A2: n = 630, 65.1%; A3: n = 382, 71.2%). Paracetamol was the most frequently prescribed analgesic at all assessments (A1: 45.5%; A2: 59.5%; A3: 67.1%). Opioid prescriptions were quite prevalent (A1: 18.1%; A2: 25.1%; A3: 28.3%), with odds approximately 13 times (OR = 13.3, 95% CI 6.8-26.0) and 9 times (OR = 8.6, 95% CI 3.7-20.3) higher for prescription at follow-up A2 and A3, respectively, relative to prescription at A1. In adjusted analyses, higher pain intensity and poor physical health were associated with prescription and persistent prescription of opioids and paracetamol. In conclusion, prevalence and persistent prescription of analgesics were high in NH residents with dementia. The odds for the prescription of opioids at follow-up were high if prescribed at baseline. Interdisciplinary collaboration, routine assessment of pain at admission and regularly thereafter, and systematic drug reviews are essential to adequately assess and treat pain in NH residents with dementia., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2022 Helvik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study determined the association between respiratory symptoms and death from cardiovascular (CV) diseases during 45 years in a pooled sample of four cohorts of random samples of the Norwegian population with 95,704 participants. Respiratory symptoms were assessed using a modification of the MRC questionnaire on chronic bronchitis. We analyzed the association between respiratory symptoms and specific cardiovascular deaths by using Cox regression analysis with age as the time variable, accounting for cluster-specific random effects using shared frailty for study cohort. Hazard ratios (HR) for death were adjusted for sex, highest attained education, smoking habits, occupational air pollution, and birth cohort. Overall, 12,491 (13%) of participants died from CV diseases: 4,123 (33%) acute myocardial infarction, 2,326 (18%) other ischemic heart disease, 2,246 (18%) other heart diseases, 2,553 (20%) cerebrovascular diseases, and 1,120 (9%) other vascular diseases. The adjusted HR (95% confidence interval) for CV deaths was 1.9 (1.7-2.1) in men and 1.5 (1.2-1.9) in women for "yes" to the question "Are you breathless when you walk on level ground at an ordinary pace?". The same item response showed an adjusted HR for death from acute myocardial infarction of 1.8 (1.5-2.1), other ischemic heart disease 2.2 (1.8-2.7), other heart diseases 1.5 (1.1-1.9), cerebrovascular disease 1.8 (1.5-2.3), and other circulatory diseases 1.7 (1.2-2.4). The adjusted HR for CV death was 1.3 (1.2-1.4) when answering positive to the question" Are you more breathless than people of your own age when walking uphill?". However, positive answers to questions on cough, phlegm, wheezing and attacks of breathlessness were after adjustments not associated with early CV deaths. The associations between CV deaths and breathlessness were also present in never smokers. Self-reported breathlessness was associated with CV deaths and could be an early marker of CV deaths., Competing Interests: The authors have declared that no competing interests exist.

Background: Diabetes mellitus (DM) is a growing global health problem. In Singapore, the prevalence of Type 2 DM is rising, but comprehensive information about trends in DM-related complications is lacking., Objectives: We utilized the Singapore Health Services (SingHealth) diabetes registry (SDR) to assess trends in DM micro and macro-vascular complications at the population level, explore factors influencing these trends., Methods: We studied trends for ten DM-related complications: ischemic heart disease (IHD), acute myocardial infarction (AMI), peripheral arterial disease (PAD) and strokes, diabetic eye complications, nephropathy, neuropathy, diabetic foot, major and minor lower extremity amputation (LEA). The complications were determined through clinical coding in hospital (inpatient and outpatient) and primary care settings within the SingHealth cluster. We described event rates for the complications in 4 age-bands. Joinpoint regression was used to identify significant changes in trends., Results: Among 222,705 patients studied between 2013 and 2020. 48.6% were female, 70.7% Chinese, 14.7% Malay and 10.6% Indian with a mean (SD) age varying between 64.6 (12.5) years in 2013 and 65.7 (13.2) years in 2020. We observed an increase in event rates in IHD, PAD, stroke, diabetic eye complications nephropathy, and neuropathy. Joinpoints was observed for IHD and PAD between 2016 to 2018, with subsequent plateauing of event rates. Major and minor LEA event rates decreased through the study period., Conclusion: We found that DM and its complications represent an important challenge for healthcare in Singapore. Improvements in the trends of DM macrovascular complications were observed. However, trends in DM microvascular complications remain a cause for concern., Competing Interests: The authors have declared that no competing interests exist.

Background: Implementation of Robotic Assisted Surgery (RAS) is complex as it requires adjustments to associated physical infrastructure, but also changes to processes and behaviours. With the global objective of optimising and improving RAS implementation, this study aimed to: 1) Explore the barriers and enablers to RAS service adoption, incorporating an assessment of behavioural influences; 2) Provide an optimised plan for effective RAS implementation, with the incorporation of theory-informed implementation strategies that have been adapted to address the barriers/enablers that affect RAS service adoption., Methods: Semi-structured interviews were conducted with RAS personnel and stakeholders, including: surgeons, theatre staff, managers, industry representatives, and policy-makers/commissioners. The Theoretical Domains Framework (TDF) and the Consolidated Framework for Implementation Research (CFIR) was used to identify barriers and enablers that represent individual behaviours, capabilities, attitudes, beliefs, and external organisational factors that influence the implementation of RAS., Results: Findings suggest that implementation planning has three separate phases-pre-, early, and late implementation. For pre-implementation, barriers and enablers identified included the cost of RAS equipment and issues of economic viability, weak outcome evidence for RAS, a preponderance of an eminence driven model, the clinician/manager relationship, and views around the uptake and expansion of RAS in the future. Early implementation findings revealed role changes for theatre personnel and an enhanced team approach, reliance on industry for training provision, and changes in skill sets and attentional processes. Late implementation factors included equipment maintenance costs, technological limitations, changes to cognition during RAS routine use, and benefits to institutions/healthcare professionals (such as ergonomic improvement)., Conclusion: Together, findings suggest the factors that affect RAS implementation are multi-faceted and change across the life-cycle of intervention adoption. Theory-informed strategies are suggested which can optimise implementation of RAS. Optimisation strategies need planning from the outset., Competing Interests: The authors have declared that no competing interests exist.

Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score <-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8-13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4-14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6-9 symptoms vs. 0-5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study aimed to explore current data collection and feedback practice, in the form of monitoring and evaluation, among youth mental health (YMH) services and healthcare commissioners; and to identify barriers and enablers to this practice., Design: Qualitative semi-structured interviews were conducted via Zoom videoconferencing software. Data collection and analysis were informed by the Theoretical Domains Framework (TDF). Data were deductively coded to the 14 domains of the TDF and inductively coded to generate belief statements., Setting: Healthcare commissioning organisations and YMH services in Australia., Participants: Twenty staff from healthcare commissioning organisations and twenty staff from YMH services., Results: The umbrella behaviour 'monitoring and evaluation' (ME) can be sub-divided into 10 specific sub-behaviours (e.g. planning and preparing, providing technical assistance, reviewing and interpreting data) performed by healthcare commissioners and YMH services. One hundred belief statements relating to individual, social, or environmental barriers and enablers were generated. Both participant groups articulated a desire to improve the use of ME for quality improvement and had particular interest in understanding the experiences of young people and families. Identified enablers included services and commissioners working in partnership, data literacy (including the ability to set appropriate performance indicators), relational skills, and provision of meaningful feedback. Barriers included data that did not adequately depict service performance, problems with data processes and tools, and the significant burden that data collection places on YMH services with the limited resources they have to do it., Conclusions: Importantly, this study illustrated that the use of ME could be improved. YMH services, healthcare commissioners should collaborate on ME plans and meaningfully involve young people and families where possible. Targets, performance indicators, and outcome measures should explicitly link to YMH service quality improvement; and ME plans should include qualitative data. Streamlined data collection processes will reduce unnecessary burden, and YMH services should have the capability to interrogate their own data and generate reports. Healthcare commissioners should also ensure that they provide meaningful feedback to their commissioned services, and local and national organisations collecting youth mental health data should facilitate the sharing of this data. The results of the study should be used to design theory-informed strategies to improve ME use., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Complete and understandable information is vital for informed consent and this includes how and when potential participants can expect to receive trial results. Informing participants during informed consent about the sharing of trial results is important for addressing participants' needs, ensuring adherence to regulatory guidance, and in fulfilling a moral obligation., Methods: Patient Information Leaflets (PILs) were collated from across the UK and Ireland. Trial characteristics and data on disseminating trial results was extracted. Analysis included descriptive statistics and a directed content analysis approach. The content analysis framework was informed by regulatory guidance on PIL content and existing research on dissemination of trial results. Results were analysed using descriptive statistics and presented as a narrative summary as appropriate., Results: 238 PILs from 178 trials were analysed. Of the 238 PILs, 74% (n = 176) provided information on sharing results with participants, 70% (n = 123) of which described passive methods of disseminating results that require active engagement from the trial participants, i.e., effort required by the participant to seek the results. The majority (90%) of PILs included more than one proposed mode of dissemination that largely targeted healthcare professionals rather than participants. Only 8% of PILs specified a time period for when results could be expected, 47% did not specify a time period (e.g. at end of trial), and 45% included no information on when trial results would be available., Conclusion: This study found that majority of the PILs included did include some information about dissemination of trial results. However, modes of dissemination tended to target researchers and clinicians rather than participants and information on when results would be available was often lacking. The findings highlight the need for further research that includes stakeholder input to identify what information on results summaries participants need at the point of making a decision about trial participation., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Information on laboratory test availability and current testing scope among general hospitals in Kenya is not readily available. We sought to explore the reporting trends and test availability within clinical laboratories in Kenya over a 24-months period through analysis of the laboratory data reported in the District Health Information System (DHIS2)., Methods: Monthly hospital laboratory testing data were extracted from the Kenyan DHIS2 between January 2018 and December 2019. We used the national laboratory testing summary tool (MoH 706) to identify the tests of interest among 204 general hospitals in Kenya. A local practitioner panel consisting of individuals with laboratory expertise was used to classify the tests as common and uncommon. We compared the tests on the MoH 706 template with the Essential Diagnostic List (EDL) of the World Health Organisation and further reclassified them into test categories based on the EDL for generalisability of our findings. Evaluation of the number of monthly test types reported in each facility and the largest number of tests ever reported in any of the 24 months were used to assess test availability and testing scope, respectively., Results: Out of the 204 general hospitals assessed, 179 (179/204) reported at least one of the 80 tests of interest in any of the 24 months. Only 41% (74/179) of the reporting hospitals submitted all their monthly DHIS2 laboratory reports for the entire 24 months. The median testing capacity across the hospitals was 40% with a wide variation in testing scope from one hospital laboratory to another (% IQR: 33.8-51.9). Testing scope was inconsistent within facilities as indicated by often large monthly fluctuations in the total number of recommended and EDL tests reported. Tests of anatomical pathology and cancer were the least reported with 4 counties' hospitals not reporting any cancer or anatomical pathology tests for the entire 24 months., Conclusion: The current reporting of laboratory testing information in DHIS2 is poor. Monitoring access and utilisation of laboratory testing across the country would require significant improvements in consistency and coverage of routine laboratory test reporting in DHIS2. Nonetheless, the available data suggest unequal and intermittent population access to laboratory testing provided by general hospitals in Kenya., Competing Interests: The authors have declared that no competing interests exist.

Background: Older patients are often users of prolonged Central Nervous System Depressants (CNSD) (Z-hypnotics, benzodiazepines and opioids), which may be associated with reduced cognition. The long-term effects of CNSD use and reduced cognitive function in older patients are unclear. The aim of this study was to examine whether cognitive function and CNSD use at baseline hospitalisation were associated with all-cause mortality two years after discharge., Methods: We conducted a prospective observational study, including baseline data (2017-2018) from previously hospitalised older patients (65-90 years), assessing all-cause mortality two years after discharge. We used logistic regression to assess the primary outcome, all-cause mortality two years after baseline hospitalisation. The primary predictors were cognitive function measured by The Mini Mental State Examination (MMSE) and prolonged CNSD use (continuous use ≥ 4 weeks). Adjustment variables: age, gender, education, the Hospital Anxiety and Depression Scale (HADS) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), using receiver operating characteristics (ROC) to compare the predictive power of the models. In a sub-analysis we used, the Neurobehavioural Cognitive State Examination (Cognistat) and the Clock Drawing Test., Results: Two years after discharge, out of 246 baseline patients, 43 were deceased at follow-up, among these 27 (63%) were CNSD users, and 16 (36%) were non-users at baseline, (p = 0.002). In the multivariable models cognitive function (MMSE score) was a predictor of mortality (OR 0.81 (95% CI 0.69; 0.96), p = 0.014). CNSD use was associated with mortality (OR 2.71 (95% CI 1.06; 6.95), p = 0.038), with ROC AUC: 0.74-0.77 for these models. Results using Cognistat supported the findings. The Clock Drawing Test was not significant predictor of mortality., Conclusion: Two years after discharge from the hospital, older patients with reduced cognitive function and CNSD use during hospital stay had higher mortality. This underlines that inappropriate (prolonged and concurrent) use of CNSDs should be avoided by older patients, particularly in patients with reduced cognitive function., Trial Registration: NCT03162081, 22 May 2017., Competing Interests: CL has participated on an advisory board and received payment for lectures arranged by Abbvie Pharma AS, Novartis AS and Roche AS, Norway. He has also received research sponsorship from Abbvie pharma, but not for the current project. All other authors declare that they have no conflicts of interest.

Background: Health complexity includes biological, psychological, social, and health systems. Having complex health needs is associated with poorer clinical outcomes and higher healthcare costs. Care management for people with health complexity is increasingly recommended in primary health care (PHC). The INTERMED complexity assessment grid showed adequate psychometric properties in specialized settings. This study aimed to evaluate INTERMED's validity and feasibility to assess health complexity in an adult PHC population., Method: The biopsychosocial health care needs of 230 consecutive adult patients from three Brazilian PHC services were assessed using the INTERMED interview. Participants with a total score >20 were classified as "complex". Quality of life was measured using the World Health Organization Quality of Life BREF (WHOQOL-BREF); symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS); social support using the Medical Outcomes Study-Social Support Survey (MOS-SSS); comorbidity levels using the Charlson Comorbidity Index (CCI). We developed two questionnaires to evaluate health services use, and patient perceived feasibility of INTERMED., Results: 42 participants (18.3%) were classified as "complex". A moderate correlation was found between the total INTERMED score and the total scores of WHOQOL-BREF (rho = - 0.59) and HADS (rho = 0.56), and between the social domains of INTERMED and MOS-SSS (rho = -0.44). After adjustment, the use of PHC (β = 2.12, t = 2.10, p < 0.05), any other health care services (β = 3.05, t = 3.97, p < 0.01), and any medication (β = 3.64, t = 4.16, p < 0.01) were associated with higher INTERMED scores. The INTERMED internal consistency was good (ω = 0.83), and the median application time was 7 min. Patients reported satisfaction with the questions, answers, and application time., Conclusion: INTERMED displayed good psychometric values in a PHC population and proved promising for practical use in PHC., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Policy makers in developed countries have long considered the education system an avenue for supporting mental health care for children. Whilst educators have identified many challenges to providing this support (e.g. non-core role, stigma, overcrowded curriculum), understanding clinicians' views on the role of educators and schools and how clinicians and schools could work together to achieve good mental health outcomes are important questions. However, clinician voices in how schools and health should work together for children's mental health care are frequently missing from the debate. We aimed to report clinicians' views about how the education system could support student's mental health and improve access to mental health care for children and adolescents., Methods: 143 clinicians (approximately 35 each of child and adolescent psychiatrists, pediatricians, child psychologists and general practitioners (GPs)) from the states of Victoria and South Australia participated in semi-structured phone interviews between March 2018 and February 2019. Inductive content analysis was applied to address the broad study aims., Findings: Key themes emerged: (1) The role of schools in supporting individual children; (2) School based programs to support children and families; and (3) Challenges of implementing these suggestions. Clinicians across all professional groups suggested the education system could play an important role in improving access to mental health services through harnessing existing staff or co-locating mental health clinicians. They also suggested schools could identify at risk children and implement coping and social skills programs., Conclusions: Schools and educators could play a key role in prevention and early intervention of children's mental health problems. However, before recommending exactly how to do this, key evidence gaps need to be addressed., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Professor Coghill reports grants and personal fees from Shire, personal fees from Eli Lilly, personal fees from Medice, personal fees from Novartis, personal fees from Oxford University Press, grants from Vifor, personal fees from Servier, all outside the submitted work. All other authors have no financial relationships relevant to this article to disclose.

Background: Readmission to hospital is frequent among older patients and reported as a post-discharge adverse outcome. The effect of treatment in a geriatric ward for acutely admitted older patients on mortality and function is well established, but less is known about the possible influence of such treatment on the risk of readmission, particularly in the oldest and most vulnerable patients. Our aim was to assess the risk for early readmission for multimorbid patients > 75 years treated in a geriatric ward compared to medical wards and to identify risk factors for 30-day readmissions., Methods: Prospective cohort study of patients acutely admitted to a medical department at a Norwegian regional hospital. Eligible patients were community-dwelling, multimorbid, receiving home care services, and aged 75+. Patients were consecutively included in the period from 1 April to 31 October 2012. Clinical data were retrieved from the referral letter and medical records., Results: We included 227 patients with a mean (SD) age of 86.0 (5.7) years, 134 (59%) were female and 59 (26%) were readmitted within 30 days after discharge. We found no statistically significant difference in readmission rate between patients treated in a geriatric ward versus other medical wards. In adjusted Cox proportional hazards regression analyses, lower age (hazard ratio (95% confidence interval) 0.95 (0.91-0.99) per year), female gender (2.17 (1.15-4.00)) and higher MMSE score (1.03 (1.00-1.06) per point) were significant risk factors for readmission., Conclusions: Lower age, female gender and higher cognitive function were the main risk factors for 30-day readmission to hospital among old patients with multimorbidity. We found no impact of geriatric care on the readmission rate., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Desmoid tumor is a locally-invasive neoplasm that causes significant morbidity. There is recent interest in cryotherapy for treatment of extra-abdominal desmoid tumors. This systematic review assesses evidence on safety and efficacy of cryotherapy in the treatment of extra-abdominal desmoid tumors., Materials and Methods: The systematic review was conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials. 9 full text papers were reviewed and meta-analysis was performed for measures of safety, efficacy and symptom relief., Results: The estimated pooled proportion of major and minor complications was 4.2% (95% CI, 1.8-9.6; I 2 = 0%) and 10.2% (95% CI, 5.7-17.8; I 2 = 0%) respectively. The estimated pooled proportion of non-progressive disease rate of all studies was 85.8% (95% CI, 73.4-93.0; I 2 = 32.9%). The estimated progression free survival rate at 1 year was 84.5% (95% CI:74.6-95.8) and 78.0% at 3 years (95% CI: 63.8-95.3). As for pain control, the estimated pooled proportion of patients with decrease in visual analogue scale (VAS) > = 3 for those with VAS > = 3 before treatment for 2 studies was 87.5% (95% CI, 0.06-100; I 2 = 71.5%) while 37.5% to 96.9% of patients were reported to have experienced partial or complete symptom relief in the other studies., Conclusion: Cryotherapy is a safe and effective treatment modality for extra-abdominal desmoid tumors with efficacy similar to those treated with traditional strategies in the short to medium term., Competing Interests: The authors have declared that no competing interests exist.

This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1-3.2) for breathlessness score 3 and 2.1 (95% CI 1.7-2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4-7.7) for breathlessness score 3 and 3.0 (2.4-3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4-1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2-1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RN reports grants and personal fees from AstraZeneca, grants from GlaxoSmithKline, grants from Boehringer Ingelheim, outside the submitted work. All other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Multiple sclerosis (MS) is the most common autoimmune inflammatory disease of the central nervous system in Europe, often causing severe physical, cognitive and emotional impairments. Currently, it is unclear whether the healthcare provisions of people with MS (PwMS) are in line with the recommendations for treatment based on guidelines or patients' needs. The main objectives of the study are as follows: (a) to investigate how well PwMS are treated; and (b) to develop a needs-oriented, patient-centred care model., Methods: This mixed-methods study focuses on adult PwMS living in Lower Saxony, a federal state in Germany. The qualitative study comprises focus groups with PwMS, physicians and people involved in the healthcare process as well as a future workshop. The quantitative study comprises a cross-sectional online survey and addresses the patient-relevant outcomes and needs, as previously determined by literature searches and focus groups. It will be administered to all PwMS who are insured by the statutory health insurance company involved in the project (n~7,000). The survey data will be linked to the longitudinal secondary data from the statutory health insurance company and data from the German MS registry where available. The linked and single data sources will be statistically analysed., Discussion: By comprehensively comparing the current healthcare provisions with the needs and requirements of PwMS, the strengths and weaknesses of the overall healthcare process and provision of assistive devices can be identified. The barriers and facilitators of the health service providers and their impact on daily life will be explored (qualitative analyses). Reliable recommendations for improvements will be given based on a study population drawn from the largest statutory health insurance company in Lower Saxony (quantitative analyses). However, the inherent advantages and limitations of the qualitative and quantitative research approaches need to be considered., Trial Registration: The study is registered at German Clinical Trials Register DRKS00021741., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following interests to disclose: AS has no personal pecuniary interests to disclose, other than being the lead of the German MS Registry, which receives (project) funding from a range of public and corporate sponsors, recently including The German Innovation Fund (G-BA), The German Retirement Insurance, The German MS Trust, German MS Society, Biogen, Celgene (BristolMyersSquibb), Merck, Novartis, Roche, and Sanofi. None resulted in a conflict of interest. All remaining authors have declared that no competing interests exist.

Background: Sharing trial results with participants is an ethical imperative but often does not happen. We tested an Enhanced Webpage versus a Basic Webpage, Mailed Printed Summary versus no Mailed Printed Summary, and Email List Invitation versus no Email List Invitation to see which approach resulted in the highest patient satisfaction with how the results were communicated., Methods and Findings: We carried out a cluster randomised, 2 by 2 by 2 factorial, nonblinded study within a trial, with semistructured qualitative interviews with some patients (ISRCTN96189403). Each cluster was a UK hospital participating in the ICON8 ovarian cancer trial. Interventions were shared with 384 ICON8 participants who were alive and considered well enough to be contacted, at 43 hospitals. Hospitals were allocated to share results with participants through one of the 8 intervention combinations based on random permutation within blocks of 8, stratified by number of participants. All interventions contained a written plain English summary of the results. The Enhanced Webpage also contained a short video. Both the Enhanced Webpage and Email contained links to further information and support. The Mailed Printed Summary was opt-out. Follow-up questionnaires were sent 1 month after patients had been offered the interventions. Patients' reported satisfaction was measured using a 5-point scale, analysed by ordinal logistic regression estimating main effects for all 3 interventions, with random effects for site, restricted to those who reported receiving the results and assuming no interaction. Data collection took place in 2018 to 2019. Questionnaires were sent to 275/384 randomly selected participants and returned by 180: 90/142 allocated Basic Webpage, 90/133 Enhanced Webpage; 91/141 no Mailed Printed Summary, 89/134 Mailed Printed Summary; 82/129 no Email List Invitation, 98/146 Email List Invitation. Only 3 patients opted out of receiving the Mailed Printed Summary; no patients signed up to the email list. Patients' satisfaction was greater at sites allocated the Mailed Printed Summary, where 65/81 (80%) were quite or very satisfied compared to sites with no Mailed Printed Summary 39/64 (61%), ordinal odds ratio (OR) = 3.15 (1.66 to 5.98, p < 0.001). We found no effect on patient satisfaction from the Enhanced Webpage, OR = 1.47 (0.78 to 2.76, p = 0.235) or Email List Invitation, OR = 1.38 (0.72 to 2.63, p = 0.327). Interviewees described the results as interesting, important, and disappointing (the ICON8 trial found no benefit). Finding out the results made some feel their trial participation had been more worthwhile. Regardless of allocated group, patients who received results generally reported that the information was easy to understand and find, were glad and did not regret finding out the results. The main limitation of our study is the 65% response rate., Conclusions: Nearly all respondents wanted to know the results and were glad to receive them. Adding an opt-out Mailed Printed Summary alongside a webpage yielded the highest reported satisfaction. This study provides evidence on how to share results with other similar trial populations. Further research is needed to look at different results scenarios and patient populations., Trial Registration: ISRCTN: ISRCTN96189403., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AS, ECJ, CP, CT, CS, AM, AJC, NJH, CDM, KG, TI, BEB and WJC have nothing to declare. MRS reports grants and non-financial support from Astellas, grants from Clovis, grants and non-financial support from Janssen, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, grants and non-financial support from Sanofi, personal fees from Lilly Oncology, personal fees from Janssen, outside the submitted work.

Background: To date, there has been no systematic research on the intermediate level service (level 2) in outpatient palliative care that was introduced in Germany in 2017. Accordingly, the Polite research project aims at: (1) investigating the current state of level 2 palliative care and (2) developing recommendations for its optimisation., Methods: The multi-perspective, observational study will follow a mixed-methods approach across two study phases. In phase 1a, quantitative routinely collected data from a statutory general local health insurance provider will be used to identify patients who received level 2 or other outpatient palliative care in the years 2017-2019. In phase 1b, a questionnaire will be sent to all registered general practitioners (GPs) in Lower Saxony to collect information on the number and characteristics of physicians offering level 2 palliative care. In phase 1c, a quantitative, standardised online questionnaire for teams providing specialised outpatient palliative care will be administered to assess the interfaces of level 2 palliative care. In phase 2a, the results from phases 1a-c will be discussed in an expert workshop with the aim of developing ideas to adapt and optimise level 2 outpatient palliative care. Finally, in phase 2b, the empirically derived recommendations from phases 1 and 2a will be agreed upon via a multi-round Delphi survey involving experts with sufficient influence to promote the project results and recommendations nationally., Discussion: The results of the project will facilitate the optimisation of outpatient palliative care, as well as its administration, nationwide., Trial Registration: The study was registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00024785); date of registration: 06th May 2021) and is searchable under the International Clinical Trials Registry Platform Search Portal of the World Health Organization, under the German Clinical Trials Register number., Competing Interests: The authors declare that they have no competing interests.

Objective: To evaluate factors associated with COVID-19 preventive health behaviors among adults in Mexico City and the State of Mexico., Methods and Findings: We conducted a cross-sectional survey from June to October 2020 through a structured, internet-based questionnaire in a non-probabilistic sample of adults >18 years living in Mexico City and the State of Mexico. The independent variables included sociodemographic and clinical factors; health literacy; access to COVID-19 information; and perception of COVID-19 risk and of preventive measures' effectiveness. The dependent variable was COVID-19 preventive health behaviors, defined as the number of preventive actions adopted by participants. The data were analyzed through multivariate negative binomial regression analysis. The survey was completed by 1,030 participants. Most participants were women (70.7%), had a high school or above level of education (98.8%), and had adequate health literacy and access to COVID-19 information. Only 18% perceived having a high susceptibility to COVID-19, though 83.8% recognized the disease's severity and 87.1% the effectiveness of preventive measures. The median number of COVID-19 preventive actions was 13.5 (range 0-19). The factors associated with preventive health behavior were being female, of older age, a professional worker, a homemaker, or a retiree; engaging in regular physical exercise; having high health literacy and access to COVID-19 information sources; and perceiving COVID-19 as severe and preventive measures as effective., Conclusion: People with high education and internet access in Mexico City and the State of Mexico reported significant engagement in COVID-19 preventive actions during the first wave of the COVID-19 pandemic., Competing Interests: The authors have declared that no competing interests exist.

Background: There is no agreement which outcomes should be measured when investigating interventions for periodontal diseases. It is difficult to compare or combine studies with different outcomes; resulting in research wastage and uncertainty for patients and healthcare professionals., Objective: Develop a core outcome set (COS) relevant to key stakeholders for use in effectiveness trials investigating prevention and management of periodontal diseases., Methods: Mixed method study involving literature review; online Delphi Study; and face-to-face consensus meeting., Participants: Key stakeholders: patients, dentists, hygienist/therapists, periodontists, researchers., Results: The literature review identified 37 unique outcomes. Delphi round 1: 20 patients and 51 dental professional and researchers prioritised 25 and suggested an additional 11 outcomes. Delphi round 2: from the resulting 36 outcomes, 13 patients and 39 dental professionals and researchers prioritised 22 outcomes. A face-to-face consensus meeting was hosted in Dundee, Scotland by an independent chair. Eight patients and six dental professional and researchers participated. The final COS contains: Probing depths, Quality of life, Quantified levels of gingivitis, Quantified levels of plaque, Tooth loss., Conclusions: Implementation of this COS will ensure the results of future effectiveness trials for periodontal diseases are more relevant to patients and dental professionals, reducing research wastage. This could reduce uncertainty for patients and dental professionals by ensuring the evidence used to inform their choices is meaningful to them. It could also strengthen the quality and certainty of the evidence about the relative effectiveness of interventions., Registration: COMET Database: http://www.comet-initiative.org/studies/details/265?result=true., Competing Interests: The authors have declared that no competing interests exist.

Improved understanding of multimorbidity (MM) treatment adherence in primary health care (PHC) in Brazil is needed to achieve better healthcare and service outcomes. This study explored experiences of healthcare providers (HCP) and primary care patients (PCP) with mental-physical MM treatment adherence. Adults PCP with mental-physical MM and their primary care and community mental health care providers were recruited through maximum variation sampling from nine cities in São Paulo State, Southeast of Brazil. Experiences across quality domains of the Primary Care Assessment Tool-Brazil were explored through semi-structured in-depth interviews with 19 PCP and 62 HCP, conducted between April 2016 and April 2017. Through thematic conent analysis ten meta-themes concerning treatment adherence were developed: 1) variability and accessibility of treatment options available through PHC; 2) importance of coming to terms with a disease for treatment initation; 3) importance of person-centred communication for treatment initiation and maintenance; 4) information sources about received medication; 5) monitoring medication adherence; 6) taking medication unsafely; 7) perceived reasons for medication non-adherence; 8) most challenging health behavior change goals; 9) main motives for initiation or maintenance of treatment; 10) methods deployed to improve treatment adherence. Our analysis has advanced the understanding of complexity inherent to treatment adherence in mental-physical MM and revealed opportunities for improvement and specific solutions to effect adherence in Brazil. Our findings can inform research efforts to transform MM care through optimization., Competing Interests: The authors have declared that no competing interests exist.

Lung cancer (LC) generally lacks unique core symptoms or signs. However, there are a multitude of bodily sensations that are often non-specific, not easily understood, and many times initially not recognized as indicative of LC by the affected person, which often leads to late diagnosis. In this international qualitative study, we inductively analyzed retrospective accounts of 61 people diagnosed with LC in Denmark, England and Sweden. Using the bodily sensations they most commonly spoke about (tiredness, breathlessness, pain, and cough), we constructed four sensation-based cases to understand the pre-diagnostic processes of reasoning and practice triggered by these key indicators of LC. We thereafter critically applied Hay's model of sensations to symptoms transformation, examining its central concepts of duration, disability and vulnerability, to support understanding of these processes. We found that while duration and disability are clearly relevant, vulnerability is more implicitly expressed in relation to perceived threat. Tiredness, even when of long duration and causing disability, was often related to normal aging, rather than a health threat. Regardless of duration, breathlessness was disturbing and threatening enough to lead to care-seeking. Pain varied by location, duration and degree of disability, and thus also varied in degree of threat perceived. Preconceived, but unmet expectations of what LC-related cough and pain would entail could cause delays by misleading participants; if cough lasted long enough, it could trigger health care contact. Duration, disability, and sense of threat, rather than vulnerability, were found to be relevant concepts for understanding the trajectory to diagnosis for LC among these participants. The process by which an individual, their family and health care providers legitimize sensations, allowing them to be seen as potential symptoms of disease, is also an essential, but varying part of the diagnostic processes described here., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Family carers are cornerstones in the care of older people living with dementia. Family carers report extensive carer burden, reduced health-related quality of life (HRQoL), and extensive time spent on informal care (Time). Health literacy (HL) is a concept associated with people's ability to access health services, and navigate the healthcare system. This study's aim was to investigate HL among family carers, and investigate the associations between HL and carer burden, HRQoL, and Time spent on informal care., Method: We designed a self-administered survey comprising validated instruments, including the Health Literacy Scale (HLS-N-Q12) to measure HL, Relative Stress Scale (RSS) to measure carer burden, the EQ-5D-5L instrument to measure HRQoL, and some modified questions from the Resource Utilization in Dementia (RUD) questionnaire to measure time spent on informal care (Time). Descriptive analysis in addition to bivariate and multiple linear regressions were undertaken. In multiple linear regression analysis, we used HL as the independent variable to predict the outcomes (carer burden, HRQoL, Time). Analyses were adjusted for the effects of explanatory independent variables: age, gender, education levels, urban residency, having worked as health personnel, caring for someone with severe/mild dementia, and being born abroad., Findings: In a non-probability sample of 188 family carers from across Norway, most of them female and over the age of 60, we found high levels of HL. In the bivariate analysis, carer burden and HRQoL (EQvalue) showed significant associations with HL. In the multiple regression analyses, HL was statistically significantly associated with carer burden (B = -0.18 CI:-0.33,-0.02 p = 0.02), HRQoL (EQvalue: B = 0.003 with 95% CI: 0.001, 0.006 p = 0.04), and Time (B = -0.03 with 95% CI: -0.06, 0.000, p = 0.046), after adjusting for the effect of independent variables., Conclusion: This is one of the first studies to investigate the associations between HL and different outcomes for family carers of older people living with dementia. Additional research into the associations identified here is needed to further develop our understanding of how to support family carers in their roles. Targeted support that increases family carers' HL may have potential to enhance their ability to provide sustainable care over time., Competing Interests: The authors have declared that no competing interests exist.

Background: Effective risk communication is challenging. Ensuring potential trial participants' understand 'risk' information presented to them is a key aspect of the informed consent process within clinical trials, yet minimal research has looked specifically at how to communicate probabilities to support decisions about trial participation. This study reports a systematic review of the literature focusing on presentation of probabilistic information or understanding of risk by potential trial participants., Methods: A search strategy for risk communication in clinical trials was designed and informed by systematic reviews of risk communication in treatment and screening contexts and supplemented with trial participation terms. Extracted data included study characteristics and the main interventions/findings of each study. Explanatory studies that investigated the methods for presenting probabilistic information within participant information leaflets for a clinical trial were included, as were interventions that focused on optimising understanding of probabilistic information within the context of a clinical trial., Results: The search strategy identified a total of 4931 studies. Nineteen papers were selected for full text screening, and seven studies included. All reported results from risk communication studies that aimed to support potential trial participants' decision making set within hypothetical trials. Five of these were randomised comparisons of risk communication interventions, and two were prospectively designed, non-randomised studies. Study interventions focused on probability presentation, risk framing and risk interpretation with a wide variety of interventions being evaluated and considerable heterogeneity in terms of outcomes assessed. Studies show conflicting findings when it comes to how best to present information, although numerical, particularly frequency formats and some visual aids appear to have promise., Conclusions: The evidence base surrounding risk communication in clinical trials indicates that there is as yet no clear optimal method for improving participant understanding, or clear consensus on how it affects their willingness to participate. Further research into risk communication within trials is needed to help illuminate the mechanisms underlying risk perception and understanding and provide appropriate ways to present and communicate risk in a trial context so as to further promote informed choices about participation. A key focus for future research should be to investigate the potential for learning in the evidence on risk communication from treatment and screening decisions when applied to decisions about trial participation., Competing Interests: The authors have declared that no competing interests exist.

The aim of the study was to assess the reliability and construct validity of the Croatian translation of the Safety Attitudes Questionnaire-Ambulatory version (SAQ-AV) in the out-of-hours (OOH) primary care setting. A cross-sectional observational study using anonymous web-survey was carried out targeting a convenience sample of 358 health professionals working in the Croatian OOH primary care service. The final sample consisted of 185 questionnaires (response rate 51.7%). Psychometric properties were assessed using exploratory hierarchical factor analysis with Schmid-Leiman rotation to bifactor solution, McDonald's ω, and Cronbach's α. Five group factors were identified: Organization climate, Teamwork climate, Stress recognition, Ambulatory process of care, and Perceptions of workload. Items loading on the Stress recognition and Perceptions of workload factor had low loadings on the general factor. Cronbach's α ranged between 0.79 and 0.93. All items had corrected item-total correlation above 0.5. McDonalds' ω total for group factors ranged between 0.76 and 0.91. Values of ω general for factors Organization climate, Teamwork climate, and Ambulatory process of care ranged between 0.41 and 0.56. McDonalds' ω general for Stress recognition and Perceptions of workload were 0.13 and 0.16, respectively. Even though SAQ-AV may not be a reliable tool for international comparisons, subsets of items may be reliable tools in several national settings, including Croatia. Results confirmed that Stress recognition is not a dimension of patient safety culture, while Ambulatory process of care might be. Future studies should investigate the relationship of patient safety culture to treatment outcome., Competing Interests: The authors have declared that no competing interests exist.