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Objectives: To evaluate the feasibility and acceptability of a primary care-based intervention for improving post-diagnostic dementia care and support (PriDem), and implementation study procedures., Design: A non-randomised, mixed methods, feasibility study., Setting: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England., Participants: We aimed to recruit 80 people with dementia (PWD) and 66 carers INTERVENTION: Clinical Dementia Leads delivered a 12-month intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to PWD and carers., Outcomes: Recruitment and retention rates were measured. A mixed methods process evaluation evaluated feasibility and acceptability of the intervention and study procedures. Using electronic care records, researchers extracted service use data and undertook a dementia care plan audit, preintervention and postintervention, assessing feasibility of measuring the primary implementation outcome: adoption of personalised care planning by participating general practices. Participants completed quality of life, and service use measures at baseline, 4 and 9 months., Results: 60 PWD (75% of recruitment target) and 51 carers (77% of recruitment target) were recruited from seven general practices across four PCNs. Retention rate at 9 months was 70.0% of PWD and 76.5% of carers. The recruitment approach showed potential for including under-represented groups within dementia. Despite implementation challenges, the intervention was feasible and acceptable, and showed early signs of sustainability. Study procedures were feasible and accessible, although researcher capacity was crucial. Participants needed time and support to engage with the study. Care plan audit procedures were feasible and acceptable., Conclusions: The PriDem model is an acceptable and feasible intervention. A definitive study is warranted to fully inform dementia care policy and personalised dementia care planning guidance. Successful strategies to support inclusion of PWD and their carers in future research were developed., Trial Registration Number: ISRCTN11677384., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Provision of personalised care planning is a national priority for people with dementia. Research suggests a lack of quality and consistency of care plans and reviews. The PriDem model of care was developed to deliver feasible and acceptable primary care-based postdiagnostic dementia care. We aimed to increase the adoption of personalised care planning for people with dementia, exploring implementation facilitators and barriers., Design: Mixed-method feasibility and implementation study., Setting: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England., Participants: A medical records audit collected data on 179 community-dwelling people with dementia preintervention, and 215 during the intervention year. The qualitative study recruited 26 health and social care professionals, 14 people with dementia and 16 carers linked to participating practices., Intervention: Clinical dementia leads (CDL) delivered a 12-month, systems-level intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to people with dementia and their carers., Primary and Secondary Outcome Measures: Adoption of personalised care planning was assessed through a preintervention and postintervention audit of medical records. Implementation barriers and facilitators were explored through semistructured qualitative interviews and non-participant observation, analysed using codebook thematic analysis informed by Normalisation Process Theory., Results: The proportion of personalised care plans increased from 37.4% (95% CI 30.3% to 44.5%) preintervention to 64.7% (95% CI 58.3% to 71.0%) in the intervention year. Qualitative findings suggest that the flexible nature of the PriDem intervention enabled staff to overcome contextual barriers through harnessing the skills of the wider multidisciplinary team, delivering increasingly holistic care to patients., Conclusions: Meaningful personalised care planning can be achieved through a team-based approach. Although improved guidelines for care planning are required, commissioners should consider the benefits of a CDL-led approach., Trial Registration Number: ISRCTN11677384., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Care is often inadequate and poorly integrated after a dementia diagnosis. Research and policy highlight the unaffordability and unsustainability of specialist-led support, and instead suggest a task-shared model, led by primary care. This study is part of the PriDem primary care led postdiagnostic dementia care research programme and will assess delivery of an evidence-informed, primary care based, person-centred intervention. The intervention involves Clinical Dementia Leads (CDLs) working in primary care to develop effective dementia care systems that build workforce capacity and support teams to deliver tailored support to people living with dementia and their carers., Methods and Analysis: This is a 15-month mixed-methods feasibility and implementation study, situated in four National Health Service (NHS) primary care networks in England. The primary outcome is adoption of personalised care planning by participating general practices, assessed through a patient records audit. Feasibility outcomes include recruitment and retention; appropriateness and acceptability of outcome measures; acceptability, feasibility and fidelity of intervention components. People living with dementia (n=80) and carers (n=66) will be recruited through participating general practices and will complete standardised measures of health and well-being. Participant service use data will be extracted from electronic medical records. A process evaluation will explore implementation barriers and facilitators through methods including semistructured interviews with people living with dementia, carers and professionals; observation of CDL engagement with practice staff; and a practice fidelity log. Process evaluation data will be analysed qualitatively using codebook thematic analysis, and quantitatively using descriptive statistics. Economic analysis will determine intervention cost-effectiveness., Ethics and Dissemination: The study has received favourable ethical opinion from Wales REC4. NHS Confidentiality Advisory Group support allows researchers preconsent access to patient data. Results will inform intervention adaptations and a future large-scale evaluation. Dissemination through peer-review journals, engagement with policy-makers and conferences will inform recommendations for dementia services commissioning., Trial Registration Number: ISRCTN11677384., Competing Interests: Competing interests: LA acknowledges support of the National Institute for Health Research Applied Research Collaboration Southwest Peninsula., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate delivery of smoking cessation interventions, recorded quit attempts and successful quitting rates within primary care in smokers with depression or severe mental illness (SMI) compared with those without., Design: Longitudinal cohort study using primary healthcare records., Setting: English primary care., Participants: 882 849 patients registered with participating practices recorded as current smokers during 2007-2014, including three groups: (1) 13 078 with SMI, (2) 55 630 with no SMI but recent depression and (3) 814 141 with no SMI nor recent depression., Outcomes: Recorded advice to quit smoking, referrals to smoking cessation services, prescriptions for smoking cessation medication, recorded quit attempts and changes of smoking status., Results: The majority (>70%) of smokers had recorded smoking cessation advice. This was consistently higher in those with SMI than the other cohorts of patients, although the gap greatly reduced in more recent years. Increases in smoking cessation advice over time were not accompanied by increases in recorded attempts to quit or changes of smoking status. Overall nicotine replacement therapy prescribing by general practitioners (GPs) was higher in those with SMI (10.1%) and depression (8.7%) than those without (5.9%), but a downward time trend was observed in all groups. Bupropion and varenicline prescribing was very low and lower for those with SMI. Few smokers (<5%) had referrals to stop smoking services, though this increased over time, but no significant differences were observed between those with and without mental health problems., Conclusions: There was no evidence of consistent inequalities in access to GP-delivered smoking cessation interventions for people with mental health conditions. Smoking cessation advice was widely reported as taking place in all groups. In order to address the widening gap in smoking prevalence in those with poor mental health compared with those without, the emphasis should be on addressing the quality of advice and support given., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The COVID-19 pandemic has created a period of global economic uncertainty. Financial strain, personal debt, recent job loss and housing insecurity are important risk factors for the mental health of working-age adults. Community interventions have the potential to attenuate the mental health impact of these stressors. We examined the effectiveness of community interventions for protecting and promoting the mental health of working-age adults in high-income countries during periods of financial insecurity., Methods: Eight electronic databases were systematically screened for experimental and observational studies published since 2000 measuring the effectiveness of community interventions on mental health outcomes. We included any non-clinical intervention that aimed to address the financial, employment, food or housing insecurity of participants. A review protocol was registered on the PROSPERO database (CRD42019156364) and results are reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: From 2326 studies screened, 15 met our inclusion criteria. Five categories of community intervention were identified: advice services colocated in healthcare settings; link worker social prescribing; telephone debt advice; food insecurity interventions; and active labour market programmes. In general, the evidence for effective and cost-effective community interventions delivered to individuals experiencing financial insecurity was lacking. From the small number of studies without a high risk of bias, there was some evidence that financial insecurity and associated mental health problems were amenable to change and differences by subpopulations were observed., Conclusion: There is a need for well-controlled studies and trials to better understand effective ingredients and to identify those interventions warranting wider implementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Despite community efforts to support and enable older and vulnerable people during the COVID-19 pandemic, many people with dementia and their family carers are still finding it difficult to adjust their daily living in light of the disruption that the pandemic has caused. There may be needs specific to black, Asian and minority ethnic (BAME) populations in these circumstances that remain thus far unexplored., Objective: The aim of the study was to explore the effects of the COVID-19 pandemic on people living with dementia and their family carers of BAME backgrounds, in relation to their experiences of community dementia care and the impact on their daily lives., Design: 15 participants (persons with dementia and carers) were recruited for semistructured qualitative interviews. Respondents were of South Asian and Afro-Caribbean backgrounds. We used thematic analysis to analyse our data from a constructivist perspective, which emphasises the importance of multiple perspectives, contexts and values., Results: There were a number of ways that the COVID-19 pandemic has impacted BAME persons with dementia and carers with regard to their experiences of dementia community care and the impact on their everyday lives. In particular we identified eight key themes, with subthemes: fear and anxiety, food and eating (encompassing food shopping and eating patterns), isolation and identity, community and social relationships, adapting to COVID-19, social isolation and support structures, and medical interactions. Fear and anxiety formed an overarching theme that encompassed all others., Discussion: This paper covers unique and underexplored topics in a COVID-19-vulnerable group. There is limited work with these groups in the UK and this is especially true in COVID-19. The results showed that such impacts were far-reaching and affected not only day-to-day concerns, but also care decisions with long-ranging consequences, and existential interests around fear, faith, death and identity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To explore how the self-management of comorbid long-term conditions is experienced and negotiated by people with dementia and their carers., Design: Secondary thematic analysis of 82 semi-structured interviews., Setting: Community settings across the United Kingdom., Participants: 11 people with dementia, 22 family carers, 19 health professionals and 30 homecare staff., Results: We identified three overarching themes: (1) The process of substituting self-management : stakeholders balanced the wishes of people with dementia to retain autonomy with the risks of lower adherence to medical treatments. The task of helping a person with dementia to take medication was perceived as intermediate between a personal care and a medical activity; rules about which professionals could perform this activity sometimes caused conflict. (2) Communication in the care network: family carers often communicated with services and made decisions about how to implement medical advice. In situations where family carers or homecare workers were not substituting self-management, it could be challenging for general practitioners to identify changes in self-management and decide when to intervene. (3) Impact of physical health on and from dementia : healthcare professionals acknowledged the inter-relatedness of physical health and cognition to adapt care accordingly. Some treatments prescribed for long-term conditions were perceived as unhelpful when not adapted to the context of dementia. Healthcare professionals and homecare workers sometimes felt that family carers were unable to accept that available treatments may not be helpful to people with dementia and that this sometimes led to the continuation of treatments of questionable benefit., Conclusion: The process of substituting self-management evolves with advancement of dementia symptoms and relies on communication in the care network, while considering the impact on and from dementia to achieve holistic physical health management. Care decisions must consider people with dementia as a whole, and be based on realistic outcomes and best interests., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Public mental health (PMH) is a global challenge and a UK priority area for action. However, to progress, practitioners require a stronger evidence base regarding the effectiveness of approaches, particularly regarding promotion and prevention through community-centred interventions. In addition, policy-makers need to understand what is being delivered, particularly in areas of high need, to identify promising practices or gaps in PMH provision. Finally, and importantly, the public need better information regarding what approaches and services are available to them. We report a protocol designed to (1) identify the types of community-centred interventions used in purposively selected diverse geographical areas of England to improve PMH outcomes and (2) describe the type, target population, content and outcome measures of each intervention., Methods and Analysis: Five local authority areas of England were selected based on either high social deprivation or differing ethnic population statistics and geographical locations. Community-centred interventions in each area will be identified through: (1) desk-based data capture from standardised searches of publicly-available information (eg, policy, strategy and intervention advertising), (2) established professional networks and service contacts, (3) chain-referral sampling of individuals involved in local mental health promotion and prevention and (4) peer researchers, who will use their personal experience and local knowledge to help identify potentially relevant organisations. Data on the key features of the interventions will be extracted from individuals either by structured interviews or by electronic questionnaires with information regarding the intervention(s) of which they have knowledge. Initial data analysis will involve tabulating descriptive information and grouping interventions according to intervention type, target population, risk/protective factor and intended primary outcome. A descriptive comparison will be made between selected geographical areas., Ethics and Dissemination: Ethical approval was obtained from Durham University's Department of Sport and Exercise Sciences Research Ethics Committee. We plan to disseminate our findings at relevant conferences, meetings and through peer-reviewed journals. We also plan to disseminate to the public and intervention providers through social media and/or newsletters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: We examined the association between frailty and disability in rural community-dwelling older adults in Kegalle district of Sri Lanka., Design: A population-based cross-sectional study., Participants: A total of 746 community-dwelling adults aged ≥60 years., Primary and Secondary Outcome Measures: Frailty was assessed using the Fried phenotype. Disability was operationalised in terms of having one or more activity limitation/s in instrumental activities of daily living (IADL) and basic activities of daily living (BADL)., Results: The median age of the sample was (median 68; IQR 64-75) years and 56.7% were female. 15.2% were frail and 48.5% were prefrail. The prevalence of ≥1 IADL limitations was high, 84.4% among frail adults. 38.7% of frail adults reported ≥1 BADL limitations. Over half of frail older adults (58.3%) reported both ≥1 physical and cognitive IADL limitations. Being frail decreased the odds of having no IADL limitations, and was associated with a higher count of IADL limitations. No significant association was found between prefrailty and number of IADL limitations., Conclusions: The prevalence of ≥1 IADL limitations was high among rural community-dwelling frail older adults. Findings imply the greater support and care required for rural Sri Lankan frail older adults to live independently in the community., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Late-life depression is a major societal concern, but older adults' attitudes toward its treatment remain complex. We aimed to explore older adults' views regarding depression and its treatment., Research Design and Methods: We undertook a systematic review and thematic synthesis of qualitative studies that explored the views of older community-dwelling adults with depression (not actively engaged in treatment), about depression and its treatment. We searched 7 databases (inception-November 2018) and 2 reviewers independently quality-appraised studies using the CASP checklist., Results: Out of 8,351 records, we included 11 studies for thematic synthesis. Depression was viewed as a normal reaction to life stressors and ageing. Consequently, older adults preferred self-management strategies (e.g., socializing, prayer) that aligned with their lived experiences and self-image. Professional interventions (e.g., antidepressants, psychological therapies) were sometimes considered necessary for more severe depression, but participants had mixed views. Willingness to try treatments was based on a balance of different judgments, including perceptions about potential harm and attitudes based on trust, familiarity, and past experiences. Societal and structural factors, including stigma, ethnicity, and ageism, also influenced treatment attitudes., Discussion and Implications: Supporting older adults to self-manage milder depressive symptoms may be more acceptable than professional interventions. Assisting older adults with accessing professional help for more severe symptoms might be better achieved by integrating access to help within familiar, convenient locations to reduce stigma and increase accessibility. Discussing treatment choices using narratives that engage with older adults' lived experiences of depression may lead to greater acceptability and engagement., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The objective of this study was to estimate the cross-sectional association of frailty status with overall and domain-specific quality of life (QoL) in rural community-dwelling older adults in Kegalle district of Sri Lanka., Methods: A population-based cross-sectional study was conducted with 746 community-dwelling older adults aged ≥ 60 years living in the rural areas of Kegalle district of Sri Lanka in 2016. A three-stage probability sampling design was used to recruit participants. Frailty and QoL were assessed using the Fried phenotype and Older People's Quality of Life Questionnaire, respectively. Multivariable linear regression was used to estimate the association of frailty with QoL after accounting for the complex sampling design., Results: The median (IQR) age of the sample was 68 (64:75) years and comprised of 56.7% women. 15.2% (95% CI 12.4%, 18.7%) were frail and 48.5% (95% CI 43.9%, 53.2%) were pre-frail. The unadjusted means (SE) of the total QoL score for the robust, pre-frail and frail groups were 139.2 (0.64), 131.8 (1.04) and 119.2 (1.35), respectively. After adjusting for covariates in the final multivariable model, the estimated differences in mean QoL were lower for both frail and pre-frail groups versus robust. The estimated reduction in the total QoL score was 7.3% for those frail and 2.1% for those pre-frail. All QoL domains apart from 'social relationships and participation', 'home and neighbourhood' and 'financial circumstances' were associated with frailty., Conclusions: Frailty was associated with a small but significant lower quality of life in this rural Sri Lankan population, which appears largely explained by 'health' and 'independence, control over life and freedom' QoL domains. Interventions aiming to improve quality of life in frail older adults should consider targeting these aspects.

Objective: Our main objective was to describe the prevalence and associated sociodemographic factors of frailty and pre-frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka., Design: Community-based cross-sectional study., Setting: The study was conducted in rural areas of Kegalle district in Sri Lanka., Participants: A total of 746 community-dwelling older adults aged ≥60 years were included in the study., Results: The prevalence of frailty and pre-frailty in rural Kegalle district was 15.2% (95% CI 12.3% to 18.6%) and 48.5% (95% CI 43.8% to 53.2%), respectively. We found a strong association between age and both frailty and pre-frailty. There were strong associations between longest-held occupation and frailty and education level and pre-frailty., Conclusions: The prevalence of frailty in this rural Sri Lankan older population was high compared with high-income and upper middle-income countries. The profile of health and social care services in Sri Lanka needs to address frailty and its consequences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate how depression is recognised in the year after child birth and treatment given in clinical practice., Design: Cohort study based on UK primary care electronic health records., Setting: Primary care., Participants: Women who have given live birth between 2000 and 2013., Outcomes: Prevalence of postnatal depression, depression diagnoses, depressive symptoms, antidepressant and non-pharmacological treatment within a year after birth., Results: Of 206 517 women, 23 623 (11%) had a record of depressive diagnosis or symptoms in the year after delivery and more than one in eight women received antidepressant treatment. Recording and treatment peaked 6-8 weeks after delivery. Initiation of selective serotonin reuptake inhibitors (SSRI) treatment has become earlier in the more recent years. Thus, the initiation rate of SSRI treatment per 100 pregnancies (95% CI) at 8 weeks were 2.6 (2.5 to 2.8) in 2000-2004, increasing to 3.0 (2.9 to 3.1) in 2005-2009 and 3.8 (3.6 to 3.9) in 2010-2013. The overall rate of initiation of SSRI within the year after delivery, however, has not changed noticeably. A third of the women had at least one record suggestive of depression at any time prior to delivery and of these one in four received SSRI treatment in the year after delivery.Younger women were most likely to have records of depression and depressive symptoms. (Relative risk for postnatal depression: age 15-19: 1.92 (1.76 to 2.10), age 20-24: 1.49 (1.39 to 1.59) versus age 30-34). The risk of depression, postnatal depression and depressive symptoms increased with increasing social deprivation., Conclusions: More than 1 in 10 women had electronic health records indicating depression diagnoses or depressive symptoms within a year after delivery and more than one in eight women received antidepressant treatment in this period. Women aged below 30 and from the most deprived areas were at highest risk of depression and most likely to receive antidepressant treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Objective: To systematically review the research conducted on prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries (LMICs) and to estimate the pooled prevalence of frailty and prefrailty in community-dwelling older adults in LMICs., Design: Systematic review and meta-analysis. PROSPERO registration number is CRD42016036083., Data Sources: MEDLINE, EMBASE, AMED, Web of Science, CINAHL and WHO Global Health Library were searched from their inception to 12 September 2017., Setting: Low-income and middle-income countries., Participants: Community-dwelling older adults aged ≥60 years., Results: We screened 7057 citations and 56 studies were included. Forty-seven and 42 studies were included in the frailty and prefrailty meta-analysis, respectively. The majority of studies were from upper middle-income countries. One study was available from low-income countries. The prevalence of frailty varied from 3.9% (China) to 51.4% (Cuba) and prevalence of prefrailty ranged from 13.4% (Tanzania) to 71.6% (Brazil). The pooled prevalence of frailty was 17.4% (95% CI 14.4% to 20.7%, I 2 =99.2%) and prefrailty was 49.3% (95% CI 46.4% to 52.2%, I 2 =97.5%). The wide variation in prevalence rates across studies was largely explained by differences in frailty assessment method and the geographic region. These findings are for the studies with a minimum recruitment age 60, 65 and 70 years., Conclusion: The prevalence of frailty and prefrailty appears higher in community-dwelling older adults in upper middle-income countries compared with high-income countries, which has important implications for healthcare planning. There is limited evidence on frailty prevalence in lower middle-income and low-income countries., Prospero Registration Number: CRD42016036083., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Little is known about vision impairment and frailty in older age. We investigated the relationship of poor vision and incident prefrailty and frailty., Methods: Cross-sectional and longitudinal analyses with 4-year follow-up of 2836 English community-dwellers aged ≥60 years. Vision impairment was defined as poor self-reported vision. A score of 0 out of the 5 Fried phenotype components was defined as non-frail, 1-2 prefrail and ≥3 as frail. Participants non-frail at baseline were followed-up for incident prefrailty and frailty. Participants prefrail at baseline were followed-up for incident frailty., Results: 49% of participants (n=1396) were non-frail, 42% (n=1178) prefrail and 9% (n=262) frail. At follow-up, there were 367 new cases of prefrailty and frailty among those non-frail at baseline, and 133 new cases of frailty among those prefrail at baseline. In cross-sectional analysis, vision impairment was associated with frailty (age-adjustedandsex-adjusted OR 2.53, 95% CI 1.95 to 3.30). The association remained after further adjustment for wealth, education, cardiovascular disease, diabetes, falls, cognition and depression. In longitudinal analysis, compared with non-frail participants with no vision impairment, non-frail participants with vision impairment had twofold increased risks of prefrailty or frailty at follow-up (OR 2.07, 95% CI 1.32 to 3.24). The association remained after further adjustment. Prefrail participants with vision impairment did not have greater risks of becoming frail at follow-up., Conclusion: Non-frail older adults who experience poor vision have increased risks of becoming prefrail and frail over 4 years. This is of public health importance as both vision impairment and frailty affect a large number of older adults., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Medically unexplained symptoms (MUS) present frequently in healthcare, can be complex and frustrating for clinicians and patients and are often associated with overinvestigation and significant costs. Doctors need to be aware of appropriate management strategies for such patients early in their training. A previous qualitative study with foundation year doctors (junior doctors in their first 2 years postqualification) indicated significant lack of knowledge about this topic and appropriate management strategies. This study reviewed whether, and in what format, UK foundation training programmes for newly qualified doctors include any teaching about MUS and sought recommendations for further development of such training., Design: Mixed-methods design comprising a web-based questionnaire survey and an expert consultation workshop., Setting: Nineteen foundation schools in England, Wales and Northern Ireland PARTICIPANTS: Questionnaire administered via email to 155 foundation training programme directors (FTPDs) attached to the 19 foundation schools, followed by an expert consultation workshop attended by 13 medical educationalists, FTPDs and junior doctors., Results: The 53/155 (34.2%) FTPDs responding to the questionnaire represented 15 of the 19 foundation schools, but only 6/53 (11%) reported any current formal teaching about MUS within their programmes. However, most recognised the importance of providing such teaching, suggesting 2-3 hours per year. All those attending the expert consultation workshop recommended case-based discussions, role-play and the use of videos to illustrate positive and negative examples of doctor-patient interactions as educational methods of choice. Educational sessions should cover the skills needed to provide appropriate explanations for patients' symptoms as well as avoid unnecessary investigations, and providing information about suitable treatment options., Conclusions: There is an urgent need to improve foundation level training about MUS, as current provision is very limited. An interactive approach covering a range of topics is recommended, but must be delivered within a realistic time frame for the curriculum., Competing Interests: Competing interests: MB, KW, JR and AW provide lectures on the topic of MUS for fourth-year and fifth-year medical students and foundation year doctors in the Department of Primary Care and Population Health, UCL., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate how smoking status is recorded in UK primary care; to evaluate whether appropriate multiple imputation (MI) of smoking status yields results consistent with health surveys., Setting: UK primary care and a population survey conducted in the community., Participants: We identified 354 204 patients aged 16 or over in The Health Improvement Network (THIN) primary care database registered with their general practice 2008-2009 and 15 102 individuals aged 16 or over in the Health Survey for England (HSE)., Outcome Measures: Age-standardised and age-specific proportions of smokers, ex-smokers and non-smokers in THIN and the HSE before and after MI. Using information on time since quitting in the HSE, we estimated when ex-smokers are typically recorded as non-smokers in primary care records., Results: In THIN, smoking status was recorded for 84% of patients within 1 year of registration. Of these, 28% were smokers (21% in the HSE). After MI of missing smoking data, the proportion of smokers was 25% (missing at random) and 20% (missing not at random). With increasing age, more were identified as ex-smokers in the HSE than THIN. It appears that those who quit before age 30 were less likely to be recorded as an ex-smoker in primary care than people who quit later., Conclusions: Smoking status was relatively well recorded in primary care. Misclassification of ex-smokers as non-smokers is likely to occur in those quitting smoking at an early age and/or a long time ago. Those with no smoking status information are more likely to be ex-smokers or non-smokers than smokers.

Methamphetamine (MA) appears to produce neurotoxic effects, in part, through disruptions of energy metabolism. A recent study of the whole-body proteome of Drosophila melanogaster showed many changes in energy metabolism-related proteins, leading us to hypothesize that MA toxicity may cause whole-body disruptions of energy metabolism. To test this, we monitored the response of energy reserves and other metabolites to MA-exposure with and without the addition of dietary glucose. We also monitored changes in feeding behavior, locomotor activity and respiration rates associated with MA-exposure to investigate how MA affects energy balance. We observed that glycogen and triglyceride levels decreased dramatically within 48 hr of MA-exposure, indicating a strongly negative caloric balance. Behavioral assays revealed that MA-treated flies decreased food consumption by 60-80% and exhibited a 2-fold increase in locomotion. Caloric expenditure decreased with MA-exposure, apparently due to a compensatory decrease in resting metabolism, showing that anorexia was the primary driver of the negative caloric balance. Additionally, we observed that glucose supplementation of MA-containing diet increased glycogen reserves by 44% at 48 hr, leading to a commensurate increase in survivorship. We conclude that dietary sugar supplementation enhances survivorship by partially compensating for decreased caloric intake resulting from MA-induced anorexia. The observation that MA produces similar behavioral changes in Drosophila and humans, i.e. increased locomotor activity and anorexia, further supports the use of Drosophila as a model organism for the study of the effects of MA.

Freeze-avoiding insects must resist freezing or die. A suite of adaptations to low temperatures, including the production of antifreeze proteins, colligative antifreezes (polyols), and dehydration allows most individuals to prevent freezing below the lowest ambient temperatures experienced in situ; however, there can be a wide variance in the minimum temperatures that individuals of freeze-avoiding species reach before freezing. We used logistic regression to explore factors that affect this variance and to estimate the probability of freezing in larvae of the freeze-avoiding beetle Cucujus clavipes puniceus. We hypothesized that water content ≤0.5 mg mg(-1) dry mass would lead to deep supercooling (avoidance of freezing below -58°C). We found a significant interaction between water content and ambient below-snow temperature and a significant difference between individuals collected from two locations in Alaska: Wiseman and Fairbanks. Individuals collected in Wiseman deep supercooled with greater water content and to a greater range of ambient temperatures than individuals collected in Fairbanks, leading to significantly different lethal water contents associated with 50% probability of freezing., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The presence of large-molecular-mass, thermal hysteresis (TH)-producing antifreezes (e.g., antifreeze proteins) has been reported in numerous and diverse taxa, including representative species of fish, arthropods, plants, fungi, and bacteria. However, relatively few of these antifreeze molecules have been chemically characterized. We screened diverse species by subjecting their homogenates to ice-affinity purification and discovered the presence of a newly identified class of antifreeze, a xylomannan-based TH-producing glycolipid that was previously reported in one species of freeze-tolerant Alaskan beetle. We isolated xylomannan-based antifreeze glycolipids from one plant species, six insect species, and the first frog species to be shown to produce a large-molecular-mass antifreeze. (1)H NMR spectra of the ice-purified molecules isolated from these diverse freeze-tolerant and freeze-avoiding organisms were nearly identical, indicating that the chemical structures of the glycolipids were highly similar. Although the exact functions remain uncertain, it appears that antifreeze glycolipids play a role in cold tolerance.

Background: Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced., Methodology/results: We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis/contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level., Conclusion: Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions.

Purpose: Missing data are a substantial problem in clinical databases. This paper aims to examine patterns of missing data in a primary care database, compare this to nationally representative datasets and explore the use of multiple imputation (MI) for these data., Methods: The patterns and extent of missing health indicators in a UK primary care database (THIN) were quantified using 488 384 patients aged 16 or over in their first year after registration with a GP from 354 General Practices. MI models were developed and the resulting data compared to that from nationally representative datasets (14 142 participants aged 16 or over from the Health Survey for England 2006 (HSE) and 4 252 men from the British Regional Heart Study (BRHS))., Results: Between 22% (smoking) and 38% (height) of health indicator data were missing in newly registered patients, 2004-2006. Distributions of height, weight and blood pressure were comparable to HSE and BRHS, but alcohol and smoking were not. After MI the percentage of smokers and non-drinkers was higher in THIN than the comparison datasets, while the percentage of ex-smokers and heavy drinkers was lower. Height, weight and blood pressure remained similar to the comparison datasets., Conclusions: Given available data, the results are consistent with smoking and alcohol data missing not at random whereas height, weight and blood pressure missing at random. Further research is required on suitable imputation methods for smoking and alcohol in such databases.

Thermal hysteresis (TH), a difference between the melting and freezing points of a solution that is indicative of the presence of large-molecular-mass antifreezes (e.g., antifreeze proteins), has been described in animals, plants, bacteria, and fungi. Although all previously described TH-producing biomolecules are proteins, most thermal hysteresis factors (THFs) have not yet been structurally characterized, and none have been characterized from a freeze-tolerant animal. We isolated a highly active THF from the freeze-tolerant beetle, Upis ceramboides, by means of ice affinity. Amino acid chromatographic analysis, polyacrylamide gel electrophoresis, UV-Vis spectrophotometry, and NMR spectroscopy indicated that the THF contained little or no protein, yet it produced 3.7 +/- 0.3 degrees C of TH at 5 mg/ml, comparable to that of the most active insect antifreeze proteins. Compositional and structural analyses indicated that this antifreeze contains a beta-mannopyranosyl-(1-->4) beta-xylopyranose backbone and a fatty acid component, although the lipid may not be covalently linked to the saccharide. Consistent with the proposed structure, treatment with endo-beta-(1-->4)xylanase ablated TH activity. This xylomannan is the first TH-producing antifreeze isolated from a freeze-tolerant animal and the first in a new class of highly active THFs that contain little or no protein.

Adult Upis ceramboides do not survive freezing in the summer but tolerate freezing to -60 degrees C in midwinter. The accumulation of two cryoprotective polyols, sorbitol and threitol, is integral to the extraordinary cold-hardiness of this beetle. U. ceramboides are the only animals known to accumulate high concentrations of threitol; however, the biosynthetic pathway has not been studied. A series of (13)C-labeled compounds was employed to investigate this biosynthetic pathway using (13)C{(1)H} NMR spectroscopy. In vivo metabolism of (13)C-labeled glucose isotopomers demonstrates that C-3-C-6 of glucose become C-1-C-4 of threitol. This labeling pattern is expected for 4-carbon saccharides arising from the pentose phosphate pathway. In vitro experiments show that threitol is synthesized from erythrose 4-phosphate, a C(4) intermediate in the PPP. Erythrose 4-phosphate is epimerized and/or isomerized to threose 4-phosphate, which is subsequently reduced by a NADPH-dependent polyol dehydrogenase and dephosphorylated by a sugar phosphatase to form threitol. Threitol 4-phosphate appears to be the preferred substrate of the sugar phosphatase(s), promoting threitol synthesis over that of erythritol. In contrast, the NADPH-dependent polyol dehydrogenase exhibits broad substrate specificity. Efficient erythritol catabolism under conditions that promote threitol synthesis, coupled with preferential threitol biosynthesis, appear to be responsible for the accumulation of high concentrations of threitol (250 mm) without concomitant accumulation of erythritol.

Most aquatic insects do not survive subzero temperatures and, for those that do, the physiology has not been well characterized. Nemoura arctica is a species of stonefly widely distributed throughout arctic and subarctic Alaska. We collected nymphs from the headwaters of the Chandalar River, where we recorded streambed temperatures as low as -12.7 degrees C in midwinter. When in contact with ice, autumn-collected N. arctica cool to -1.5+/-0.4 degrees C before freezing, but individuals survived temperatures as low as -15 degrees C, making this the first described species of freeze-tolerant stonefly. N. arctica clearly survive freezing in nature, as winter-collected nymphs encased in ice demonstrated high survivorship when thawed. In the laboratory, 87% of N. arctica nymphs frozen to -15 degrees C for 2.5 weeks survived and, within one month of thawing, 95% of the last-instar nymphs emerged. N. arctica produce both glycerol and ice-binding factors (e.g. antifreeze protein) in response to low temperature. Hemolymph glycerol concentrations increased from 3 mmol l(-1) to 930+/-114 mmol l(-1) when temperatures were decreased from 4 degrees C to -8 degrees C, and N. arctica continued to produce glycerol even while frozen. Although the hemolymph of individual cold-acclimated nymphs occasionally exhibited more than a degree of thermal hysteresis, typically the hemolymph exhibited only hexagonal crystal growth, indicating a low concentration of ice-binding factor. Hemolymph of nymphs acclimated to subzero temperatures had recrystallization inhibition. These results demonstrate that, in the face of freezing conditions, N. arctica exhibit overwintering adaptations similar to those of terrestrial insects.