Assessing deprescribing tools for implementation in care homes: A qualitative study of the views of care home staff.

BACKGROUND: Care home residents often experience polypharmacy (defined as taking five or more regular medicines). Therefore, we need to ensure that residents only take the medications that are appropriate or provide value (also known as medicines optimisation). To achieve this, deprescribing, or the reduction or stopping of prescription medicines that may no longer be providing benefit, can help manage polypharmacy and improve outcomes. Various tools, guides, and approaches have been developed to help support health professionals to deprescribe in regular practice. Little evaluation of these tools has been conducted and no work has been done in the care home setting. OBJECTIVE: This qualitative study aimed to assess distinct types of deprescribing tools for acceptability, feasibility, and suitability for the care home setting. METHODS: Cognitive (think-aloud) interviews with care home staff in England were conducted (from December 2021 to June 2022) to assess five different deprescribing tools. The tools included a general deprescribing guidance, a generic (non-drug specific) deprescribing framework, a drug-specific deprescribing guideline/guide, a tool for identifying potentially inappropriate medications, and an electronic clinical decision support tool. Participants were recruited via their participation in another deprescribing study. The Consolidated Framework for Implementation Research informed the data collection and analysis. RESULTS: Eight care home staff from 7 different care homes were interviewed. The five deprescribing tools were reviewed and assessed as not acceptable, feasible, or suitable for the care home setting. All would require significant modifications for use in the care home setting (e.g., language, design, and its function or use with different stakeholders). CONCLUSIONS: As none of the tools were deemed acceptable, feasible, and suitable, future work is warranted to develop and tailor deprescribing tools for the care home setting, considering its specific context and users. Deprescribing implemented safely and successfully in care homes can benefit residents and the wider health economy.

Determinants of implementing deprescribing for older adults in English care homes: a qualitative interview study.

OBJECTIVES: To explore the factors that may help or hinder deprescribing practice for older people within care homes. DESIGN: Qualitative semistructured interviews using framework analysis informed by the Consolidated Framework for Implementation Research (CFIR). SETTING: Participants were recruited from two care home provider organisations (a smaller independently owned organisation and a large organisation) in England. PARTICIPANTS: A sample of 23 care home staff, 8 residents, 4 family members and 1 general practitioner were associated with 15 care homes. RESULTS: Participants discussed their experiences and perceptions of implementing deprescribing within care homes. Major themes of (1) deprescribing as a complex process and (2) internal and external contextual factors influencing deprescribing practice (such as beliefs, abilities and relationships) were interrelated and spanned several CFIR constructs and domains. The quality of local relationships with and support from healthcare professionals were considered more crucial factors than the type of care home management structure. CONCLUSIONS: Several influencing social and contextual factors need to be considered for implementing deprescribing for older adults in care homes. Additional training, tools, support and opportunities need to be made available to care home staff, so they can feel confident and able to question or raise concerns about medicines with prescribers. Further work is warranted to design and adopt a deprescribing approach which addresses these determinants to ensure successful implementation.

Understanding the psychological experiences of loneliness in later life: qualitative protocol to inform technology development.

OBJECTIVES: Loneliness is a public health issue impacting the health and well-being of older adults. This protocol focuses on understanding the psychological experiences of loneliness in later life to inform technology development as part of the 'Design for health ageing: a smart system to detect loneliness in older people' (DELONELINESS) study. METHODS AND ANALYSIS: Data will be collected from semi-structured interviews with up to 60 people over the age of 65 on their experiences of loneliness and preferences for sensor-based technologies. The interviews will be audio-recorded, transcribed and analysed using a thematic codebook approach on NVivo software. ETHICS AND DISSEMINATION: This study has received ethical approval by Research Ethics Committee's at King's College London (reference number: LRS/DP-21/22-33376) and the University of Sussex (reference number: ER/JH878/1). All participants will be required to provide informed consent. Results will be used to inform technology development within the DELONELINESS study and will be disseminated in peer-reviewed publications and conferences.

Regional differences in susceptibility to spinosyn insecticides registered for Colorado potato beetle management in Canada.

The Colorado potato beetle (CPB) is the most economically important pest of Canadian potato, and if left uncontrolled, it can completely consume the crop. In the past decade, the control of CPB has relied heavily on systemic insecticides, principally the neonicotinoids thiamethoxam and clothianidin. Resistance to neonicotinoids in CPB has been well documented in the past 2 decades and mechanisms underlying the resistance better understood. In contrast, resistance to other insecticide classes, including spinosyns (spinosad and spinetoram) and anthranillic diamides (chlorantraniliprole and cyantraniliprole), have not been studied to the same degree in CPB. Spinosyns are the only insecticide certified for organic potato growers in Canada and are frequently applied as a mid-season foliar spray by conventional growers when seed treatments with neoniconitoid or diamide experience control breaks. Improved knowledge on resistance to spinosyns in CPB would allow for the development of regional management strategies. A survey of insecticide susceptibility in CPB populations from 6 potato growing regions between 2018 and 2022 observed: 1) spatial and temporal resistance trends; 2) cross-resistance; and 3) evidence of regional differences in susceptibility to spinosyns. The proportion of populations within each province considered resistant to spinosyns was, in descending order: Québec (16%) > Ontario (14%) > Manitoba (13%) > New Brunswick (9%) > Prince Edward Island (2%) > Alberta (0%). There was a significant change in CPB mortality at the diagnostic concentration (DC = LC90) for spinosad and spinetoram in the 6 provinces but only for year 5 relative to the previous 4 years. Moderate cross-resistance was determined between spinosad and spinetoram with the DC mortality for all populations based on a positive and significant correlation (adjusted R2 = 0.3758; P = 1.263e-13). There was also a positive relationship observed between the number of spinosyn applications (years applied at the sampling location) and declining susceptibility to spinosad (R2 = 0.0927; P < 0.002). Cross-resistance was observed between spinosyns and insecticides in the other two classes, the more significant correlation was between spinosad and tetraniliprole (R2 = 0.3025; P < 0.0002). In Québec, the greater spinosad use in organic potato farms led to resistance in those CPB populations, but spinosyn resistance at conventional farms was not related to greater application of neonicotinoids and diamides. Spinosyns remain relatively effective, nevertheless growers should be concerned over the increasing cases of reduced susceptibility in conventional potato farms and resistance where organic production occurs. Resistance management should continue to encourage rotation with products from the other classes in season and between years in order to extend spinosyn use for CPB control.

Exploring the provision and support of care for long-term conditions in dementia: A qualitative study combining interviews and document analysis.

BACKGROUND: The challenge of managing multiple long-term conditions is a prevalent issue for people with dementia and those who support their care. The presence of dementia complicates healthcare delivery and the development of personalised care plans, as health systems and clinical guidelines are often designed around single condition services. OBJECTIVE: This study aimed to explore how care for long-term conditions is provided and supported for people with dementia in the community. METHODS: In a qualitative, case study design, consecutive telephone or video-call interviews were conducted with people with dementia, their family carers and healthcare providers over a four-month period. Participant accounts were triangulated with documentary analysis of primary care medical records and event-based diaries kept by participants with dementia. Thematic analysis was used to develop across-group themes. FINDINGS: Six main themes were identified from eight case studies: 1) Balancing support and independence, 2) Implementing and adapting advice for dementia contexts, 3) Prioritising physical, cognitive and mental health needs, 4) Competing and entwined needs and priorities, 5) Curating supportive professional networks, 6) Family carer support and coping. DISCUSSION: These findings reflect the dynamic nature of dementia care which requires the adaptation of support in response to changing need. We witnessed the daily realities for families of implementing care recommendations in the community, which were often adapted for the contexts of family carers' priorities for care of the person living with dementia and what they were able to provide. Realistic self-management plans which are deliverable in practice must consider the intersection of physical, cognitive and mental health needs and priorities, and family carers needs and resources.

Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast-Induced Nephropathy: A Failure of Academic Clinical Science.

Contrast-induced nephropathy (CIN) is a major complication of imaging in patients with chronic kidney disease (CKD). The publication of an academic randomized controlled trial (RCT; n = 83) reporting oral (N)-acetylcysteine (NAC) to reduce CIN led to > 70 clinical trials, 23 systematic reviews, and 2 large RCTs showing no benefit. However, no mechanistic studies were conducted to determine how NAC might work; proposed mechanisms included renal artery vasodilatation and antioxidant boosting. We evaluated the proposed mechanisms of NAC action in participants with healthy and diseased kidneys. Four substudies were performed. Two randomized, double-blind, placebo-controlled, three-period crossover studies (n = 8) assessed the effect of oral and intravenous (i.v.) NAC in healthy kidneys in the presence/absence of iso-osmolar contrast (iodixanol). A third crossover study in patients with CKD stage III (CKD3) (n = 8) assessed the effect of oral and i.v. NAC without contrast. A three-arm randomized, double-blind, placebo-controlled parallel-group study, recruiting patients with CKD3 (n = 66) undergoing coronary angiography, assessed the effect of oral and i.v. NAC in the presence of contrast. We recorded systemic (blood pressure and heart rate) and renal (renal blood flow (RBF) and glomerular filtration rate (GFR)) hemodynamics, and antioxidant status, plus biomarkers of renal injury in patients with CKD3 undergoing angiography. Primary outcome for all studies was RBF over 8 hours after the start of i.v. NAC/placebo. NAC at doses used in previous trials of renal prophylaxis was essentially undetectable in plasma after oral administration. In healthy volunteers, i.v. NAC, but not oral NAC, increased blood pressure (mean area under the curve (AUC) mean arterial pressure (MAP): mean difference 29 h⋅mmHg, P = 0.019 vs. placebo), heart rate (28 h⋅bpm, P < 0.001), and RBF (714 h⋅mL/min, 8.0% increase, P = 0.006). Renal vasodilatation also occurred in the presence of contrast (RBF 917 h⋅mL/min, 12% increase, P = 0.005). In patients with CKD3 without contrast, only a rise in heart rate (34 h⋅bpm, P = 0.010) and RBF (288 h⋅mL/min, 6.0% increase, P = 0.001) occurred with i.v. NAC, with no significant effect on blood pressure (MAP rise 26 h⋅mmHg, P = 0.156). Oral NAC showed no effect. In patients with CKD3 receiving contrast, i.v. NAC increased blood pressure (MAP rise 52 h⋅mmHg, P = 0.008) but had no effect on RBF (151 h⋅mL/min, 3.0% increase, P = 0.470), GFR (29 h⋅mL/min/1.73m², P = 0.122), or markers of renal injury. Neither i.v. nor oral NAC affected plasma antioxidant status. We found oral NAC to be poorly absorbed and have no reno-protective effects. Intravenous, not oral, NAC caused renal artery vasodilatation in healthy volunteers but offered no protection to patients with CKD3 at risk of CIN. These findings emphasize the importance of mechanistic clinical studies before progressing to RCTs for novel interventions. Thousands were recruited to academic clinical trials without the necessary mechanistic studies being performed to confirm the approach had any chance of working.

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS).

BACKGROUND: Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. METHODS: In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic-pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. FINDINGS: Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin-gentamicin, ceftazidime-amikacin, piperacillin-tazobactam-amikacin, and amoxicillin clavulanate-amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime-amikacin than for neonates treated with ampicillin-gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14-0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin-gentamicin; 286 (73·3%) to amoxicillin clavulanate-amikacin; 301 (77·2%) to ceftazidime-amikacin; and 312 (80·0%) to piperacillin-tazobactam-amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin-gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate-amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime-amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin-tazobactam-amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. INTERPRETATION: Our data raise questions about the empirical use of combined ampicillin-gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. FUNDING: The Bill & Melinda Gates Foundation.

The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses.

BACKGROUND: The causal nature of the observed associations between serum lipids and apolipoproteins and kidney function are unclear. METHODS: Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by the glomerular-filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys) and the urinary albumin-to-creatinine ratio (UACR). We obtained lipid- and apolipoprotein-associated genetic variants from the Global Lipids Genetics Consortium (n = 331 368) and UK Biobank (n = 441 016), respectively, and kidney-function markers from the Trøndelag Health Study (HUNT; n = 69 736) and UK Biobank (n = 464 207). The reverse causal direction was examined using variants associated with kidney-function markers selected from recent genome-wide association studies. RESULTS: There were no strong associations between genetically predicted lipid and apolipoprotein levels with kidney-function markers. Some, but inconsistent, evidence suggested a weak association of higher genetically predicted atherogenic lipid levels [indicated by low-density lipoprotein cholesterol (LDL-C), triglycerides and apolipoprotein B] with increased eGFR and UACR. For high-density lipoprotein cholesterol (HDL-C), results differed between eGFRcrea and eGFRcys, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but higher UACR was associated with higher LDL-C, triglyceride and apolipoprotein B levels. CONCLUSION: Our MR estimates suggest that serum lipid and apolipoprotein levels do not cause substantial changes in kidney function. A possible weak effect of higher atherogenic lipids on increased eGFR and UACR warrants further investigation. Processes leading to higher UACR may lead to more atherogenic lipid levels.

How are people with mild cognitive impairment or subjective memory complaints managed in primary care? A systematic review.

BACKGROUND: Primary care is typically the first point of contact in the health care system for people raising concerns about their memory. However, there is still a lack of high-quality evidence and understanding about how primary care professionals (PCPs) currently manage people at higher risk of developing dementia. OBJECTIVES: To systematically review management strategies provided by PCPs to reduce cognitive decline in people with mild cognitive impairment and subjective memory complaints. METHOD: A systematic search for studies was conducted in December 2019 across five databases (EMBASE, Medline, PsycInfo, CINAHL and Web of Science). Methodological quality of included studies was independently assessed by two authors using the Mixed Methods Appraisal Tool. RESULTS: An initial 11 719 were found, 7250 were screened and 9 studies were included in the review. Most studies were self-reported behaviour surveys. For non-pharmacological strategies, the most frequent advice PCPs provided was to increase physical activity, cognitive stimulation, diet and social stimulation. For pharmacological strategies, PCPs would most frequently not prescribe any treatment. If PCPs did prescribe, the most frequent prescriptions targeted vascular risk factors to reduce the risk of further cognitive decline. CONCLUSION: PCPs reported that they are much more likely to provide non-pharmacological strategies than pharmacological strategies in line with guidelines on preventing the onset of dementia. However, the quality of evidence within the included studies is low and relies on subjective self-reported behaviours. Observational research is needed to provide an accurate reflection of how people with memory problems are managed in primary care.

People will typically go to their general practitioners, also known as primary care professionals (PCPs), to raise concerns about their memory. However, there is no clear understanding of what advice or treatment PCPs provide to people with memory concerns who are at high risk of dementia. This review aims to summarize the findings from research that studied what advice or treatments PCPs would give to a person with memory concerns. Nine studies were included in the review after screening through 11 719 studies. The current review found that PCPs were more likely to provide advice rather than prescribe any drug treatment. The most common advice that PCPs provided was to increase physical activity, cognitive stimulation and social stimulation. If PCPs decided to prescribe drugs, the most common prescriptions were to improve blood flow. Improving blood flow has been linked with reducing the risk of developing dementia. However, the quality of the studies included in this review is low because many relied on PCPs answering questionnaires on their intentions to manage people with memory concerns. Therefore, future research needs to observe PCPs' real-life practice to provide an accurate reflection of how people with memory problems are managed in primary care.

Service user experiences of community services for complex emotional needs: A qualitative thematic synthesis.

BACKGROUND: There is a recognised need to develop clear service models and pathways to provide high quality care in the community for people with complex emotional needs, who may have been given a "personality disorder" diagnosis. Services should be informed by the views of people with these experiences. AIMS: To identify and synthesise qualitative studies on service user experiences of community mental health care for Complex Emotional Needs. METHODS: We searched six bibliographic databases for papers published since 2003. We included peer reviewed studies reporting data on service user experiences and views about good care from community-based mental health services for adults with CEN, including generic mental health services and specialist "personality disorder" services. Studies using any qualitative method were included and thematic synthesis used to identify over-arching themes. RESULTS: Forty-seven papers were included. Main themes were: 1) The need for a long-term perspective on treatment journeys; 2) The need for individualised and holistic care; 3) Large variations in accessibility and quality of mental health services; 4) The centrality of therapeutic relationships; 5) Impacts of 'personality disorder' diagnosis. Themes tended to recur across studies from different countries and years. DISCUSSION: Recurrent major themes included wanting support that is individualised and holistic, provides continuity over long journeys towards recovery, and that is delivered by empathetic and well-informed clinicians who are hopeful but realistic about the prospects of treatment. Care that met these simple and clearly stated priorities tended to be restricted to often limited periods of treatment by specialist "personality disorder" services: generic and primary care services were often reported as far from adequate. There is an urgent need to co-design and test strategies for improving long-term support and treatment care for people with "personality disorders" throughout the mental health care system.

A two-arm parallel-group individually randomised prison pilot study of a male remand alcohol intervention for self-efficacy enhancement: the APPRAISE study protocol.

INTRODUCTION: The prevalence of at-risk drinking is far higher among those in contact with the criminal justice system (73%) than the general population (35%). However, there is little evidence on the effectiveness of alcohol brief interventions (ABIs) in reducing risky drinking among those in the criminal justice system, including the prison system and, in particular, those on remand. Building on earlier work, A two-arm parallel group individually randomised Prison Pilot study of a male Remand Alcohol Intervention for Self-efficacy Enhancement (APPRAISE) is a pilot study designed to assess the feasibility and acceptability of an ABI, delivered to male prisoners on remand. The findings of APPRAISE should provide the information required to design a future definitive randomised controlled trial (RCT). METHODS AND ANALYSIS: APPRAISE will use mixed methods, with two linked phases, across two prisons in the UK, recruiting 180 adult men on remand: 90 from Scotland and 90 from England. Phase I will involve a two-arm, parallel-group, individually randomised pilot study. The pilot evaluation will provide data on the likely impact of A two-arm parallel group individually randomised Prison Pilot study of a male Remand Alcohol Intervention for Self-efficacy Enhancement (APPRAISE), which will be used to inform a future definitive multicentre RCT. Phase II will be a process evaluation assessing how the ABI has been implemented to explore the change mechanisms underpinning the ABI (figure 1) and to assess the context within which the ABI is delivered. ETHICS AND DISSEMINATION: The APPRAISE protocol has been approved by the East of Scotland Research Ethics Committee (19/ES/0068), National Offender Management System (2019-240), Health Board Research and Development (2019/0268), Scottish Prison Service research and ethics committee, and by the University of Edinburgh's internal ethics department. The findings will be disseminated via peer-reviewed journal publications, presentations at local, national and international conferences, infographics and shared with relevant stakeholders through meetings and events. TRIAL REGISTRATION NUMBER: ISRCTN27417180.

Improving lives not just saying no to substances: Evaluating outcomes for a young people's substance use team trained in the AMBIT approach.

Adaptive Mentalization Based Integrative Therapy (AMBIT) is a systemic, mentalization based intervention designed for young people with multiple problems including mental health problems. The purpose of this paper is to examine the impact of this approach both on clinical and functional outcomes for young people seen by a specialist young people's substance use service between 2015 and 2018. About 499 cases were seen by the service during this period. Substance use outcomes were obtained for 383 cases using the Treatment Outcome Profile (TOP). Cannabis and alcohol use were the key substance use problems for 81% and 63% respectively. Functional outcomes using the AMBIT Integrative Measure (AIM) were obtained for 100 cases covering domains of daily living, socio-economic context, peer relationships and mental health. At treatment end, cannabis use reduced significantly (t = 10.78; df = 311; p = .00; Cohen's d ES.61 as did alcohol use (t = 6.938; df = 242; p = .000; ES 0.44). Functional improvements were shown in five out of seven domains with highly significant total functional improvements on key problems selected by the client (t = 14.01; df = 99; p = .000; ES1.34). Measuring functional as well as clinical outcomes appears to reflect more accurately the overall benefit of the service to clients.

Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study.

BACKGROUND: We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat. METHODS: Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs. RESULTS: We found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively. CONCLUSION: These findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.

Exploring how triads of people living with dementia, carers and health care professionals function in dementia health care: A systematic qualitative review and thematic synthesis.

BACKGROUND: Many qualitative studies report the post-diagnostic care experiences of carers and people living with dementia; however, this is not often accompanied by opportunities to hear the corresponding views of their health care professionals and how this triadic relationship functions. The aim of this review was to identify and thematically synthesize the experiences of health care services reported by people living with dementia, their carers and health care professionals. METHODS: Medline, PsycINFO, Embase and CINAHL were searched from inception to 31 July 2019 for qualitative research including people living with dementia, carers and health care professionals. Data were coded and thematically synthesised using NVivo. RESULTS: Of 10,045 search results, 29 papers relating to 27 studies were included in the final synthesis, including 261 people living with dementia, 444 carers and 530 health care professionals. Six themes emerged related to the functioning of a dementia care triad: (1) involving the person living with dementia, (2) establishing expectations of care and the roles of the members of the triad, (3) building trust, (4) effective communication, (5) continuity of care and (6) understanding the unique relationship dynamics within each triad. DISCUSSION: The interactions and complexity of triadic dementia care relationships further our understanding of how to improve dementia care. Awareness of possible diverging attitudes highlights areas of necessary improvement and further research into facilitating engagement, such as when multiple professionals are involved or where there are mismatched expectations of the roles of triad members. In order to operate efficiently as a triad member, professionals should be aware of how pre-existing relations can influence the composition of a triad, encourage the involvement of the person living with dementia, clarify the expectations of all parties, establish trusting relationships and enable communication within the direct triad and beyond.

Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses.

PURPOSE: The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. METHODS: We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. RESULTS: We found 872 eligible sources from 28 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. CONCLUSION: Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research.

Supporting self-care of long-term conditions in people with dementia: A systematic review.

BACKGROUND: Long-term conditions are common in people living with dementia; their self-management is an important determinant of wellbeing. Family carers often support or substitute self-care activities, and act as proxies for self-management, as dementia progresses. OBJECTIVES: To conduct the first systematic review of how management of long-term conditions in people with dementia is best enabled and supported, including factors that facilitate or inhibit self-management and management by a proxy. DESIGN: Systematic review. DATA SOURCES: We systematically searched MEDLINE, PsychINFO, Embase and Allied and Complementary Medicine databases up to November 2018. REVIEW METHODS: We identified the long-term conditions most prevalent in people with dementia that require an element of self-management. We then developed our inclusion criteria to identify qualitative and quantitative studies describing the self-management (or self-management assisted by family carers) of long-term conditions in people with dementia. Two authors independently rated study validity using a standardised checklist. We synthesised qualitative and quantitative findings using a data driven convergent synthesis approach. RESULTS: We included 12 articles meeting predetermined inclusion criteria: seven qualitative, two case studies, two quantitative and one mixed methods study. We identified four main themes across these studies: (1) dementia symptoms impeding treatment regimens (forgetfulness, decreased understanding, ability to communicate symptoms and behavioural and psychological symptoms); (2) adapting routines to be simpler, (using memory aids and accommodating physical limitations); (3) negotiating self-management support (carer availability and knowledge; balancing needs for safety and empowerment); and (4) interface with professionals, (Routine simplification, condition specific education, and acknowledging carer role). CONCLUSIONS: People living with dementia can be supported to manage their own health for as long as possible, through simplifying routines and reminding, but where this can no longer be negotiated, carers take over responsibility for self-management, often due to safety concerns. Empowerment of people with dementia to remain involved in their care reduces the loss experienced by this transition. Communication and partnership between clinicians and carers is critical when supporting people living with a long-term condition and dementia. Care planning for people living with dementia and a long-term condition should include explicit discussion of how these partnerships will work and guidance on strategies carers can use to support people to self-manage long-term conditions.

Exploring how people with dementia can be best supported to manage long-term conditions: a qualitative study of stakeholder perspectives.

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.

Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian randomization study.

AIMS: The causal role of adiposity for several cardiovascular diseases (CVDs) is unclear. Our primary aim was to apply the Mendelian randomization design to investigate the associations of body mass index (BMI) with 13 CVDs and arterial hypertension. We also assessed the roles of fat mass and fat-free mass on the same outcomes. METHODS AND RESULTS: Single-nucleotide polymorphisms associated with BMI and fat mass and fat-free mass indices were used as instrumental variables to estimate the associations with the cardiovascular conditions among 367 703 UK Biobank participants. After correcting for multiple testing, genetically predicted BMI was significantly positively associated with eight outcomes, including and with decreasing magnitude of association: aortic valve stenosis, heart failure, deep vein thrombosis, arterial hypertension, peripheral artery disease, coronary artery disease, atrial fibrillation, and pulmonary embolism. The odds ratio (OR) per 1 kg/m2 increase in BMI ranged from 1.06 [95% confidence interval (CI) 1.02-1.11; P = 2.6 × 10-3] for pulmonary embolism to 1.13 (95% CI 1.05-1.21; P = 1.2 × 10-3) for aortic valve stenosis. There was suggestive evidence of positive associations of genetically predicted fat mass index with nine outcomes (P < 0.05). The strongest magnitude of association was with aortic valve stenosis (OR per 1 kg/m2 increase in fat mass index 1.46, 95% CI 1.13-1.88; P = 3.9 × 10-3). There was suggestive evidence of inverse associations of fat-free mass index with atrial fibrillation, ischaemic stroke, and abdominal aortic aneurysm. CONCLUSION: This study provides evidence that higher BMI and particularly fat mass index are associated with increased risk of aortic valve stenosis and most other cardiovascular conditions.

Factorial Mendelian randomization: using genetic variants to assess interactions.

BACKGROUND: Factorial Mendelian randomization is the use of genetic variants to answer questions about interactions. Although the approach has been used in applied investigations, little methodological advice is available on how to design or perform a factorial Mendelian randomization analysis. Previous analyses have employed a 2 × 2 approach, using dichotomized genetic scores to divide the population into four subgroups as in a factorial randomized trial. METHODS: We describe two distinct contexts for factorial Mendelian randomization: investigating interactions between risk factors, and investigating interactions between pharmacological interventions on risk factors. We propose two-stage least squares methods using all available genetic variants and their interactions as instrumental variables, and using continuous genetic scores as instrumental variables rather than dichotomized scores. We illustrate our methods using data from UK Biobank to investigate the interaction between body mass index and alcohol consumption on systolic blood pressure. RESULTS: Simulated and real data show that efficiency is maximized using the full set of interactions between genetic variants as instruments. In the applied example, between 4- and 10-fold improvement in efficiency is demonstrated over the 2 × 2 approach. Analyses using continuous genetic scores are more efficient than those using dichotomized scores. Efficiency is improved by finding genetic variants that divide the population at a natural break in the distribution of the risk factor, or else divide the population into more equal-sized groups. CONCLUSIONS: Previous factorial Mendelian randomization analyses may have been underpowered. Efficiency can be improved by using all genetic variants and their interactions as instrumental variables, rather than the 2 × 2 approach.