Identifying and Managing Frailty: A Survey of UK Healthcare Professionals.

Frailty is a common condition that leads to multiple adverse outcomes. Frailty should be identified and managed in a holistic, evidence-based and patient-centered way. We aimed to understand how UK healthcare professionals (HCPs) identify and manage frailty in comparison with UK Fit for Frailty guidelines, their frailty training, their confidence in providing support and organizational pathways for this. An online mixed-methods survey was distributed to UK HCPs supporting older people through professional bodies, special interest groups, key contacts, and social media. From 137 responses, HCPs valued frailty assessment but used a mixture of tools that varied by profession. HCPs felt confident managing frailty and referred older people to a wide range of supportive services, but acknowledged a lack of formalized training opportunities, systems, and pathways for frailty management. Clearer pathways, more training, and stronger interprofessional communication, appropriate to each setting, may further support HCPs in frailty management.

The effects of neuromuscular electrical stimulation on hospitalised adults: systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Neuromuscular electrical stimulation (NMES) is a treatment to prevent or reverse acquired disability in hospitalised adults. We conducted a systematic review and meta-analysis of its effectiveness. METHOD: We searched MEDLINE, EMBASE, Cumulative Index to Nursing & Allied Health (CINAHL) and the Cochrane library. Inclusion criteria: randomised controlled trials of hospitalised adult patients comparing NMES to control or usual care. The primary outcome was muscle strength. Secondary outcomes were muscle size, function, hospital length of stay, molecular and cellular biomarkers, and adverse effects. We assessed risk of bias using the Cochrane risk-of-bias tool. We used Review Manager (RevMan) software for data extraction, critical appraisal and synthesis. We assessed certainty using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: A total of 42 papers were included involving 1,452 participants. Most studies had unclear or high risk of bias. NMES had a small effect on muscle strength (moderate certainty) (standardised mean difference (SMD) = 0.33; P < 0.00001), a moderate effect on muscle size (moderate certainty) (SMD = 0.66; P < 0.005), a small effect on walking performance (moderate certainty) (SMD = 0.48; P < 0.0001) and a small effect on functional mobility (low certainty) (SMD = 0.31; P < 0.05). There was a small and non-significant effect on health-related quality of life (very low certainty) (SMD = 0.35; P > 0.05). In total, 9% of participants reported undesirable experiences. The effects of NMES on length of hospital stay, and molecular and cellular biomarkers were unclear. CONCLUSIONS: NMES is a promising intervention component that might help to reduce or prevent hospital-acquired disability.

Influence of CReatine supplementation on mUScle mass and strength after stroke (ICaRUS Stroke Trial): study protocol for a randomized controlled trial.

BACKGROUND: Stroke is a leading cause of mortality and disability, and its sequelae are associated with inadequate food intake which can lead to sarcopenia. The aim of this study is to verify the effectiveness of creatine supplementation on functional capacity, strength, and changes in muscle mass during hospitalization for stroke compared to usual care. An exploratory subanalysis will be performed to assess the inflammatory profiles of all participants, in addition to a follow-up 90 days after stroke, to verify functional capacity, muscle strength, mortality, and quality of life. METHODS: Randomized, double-blind, unicenter, parallel-group trial including individuals with ischemic stroke in the acute phase. The duration of the trial for the individual subject will be approximately 90 days, and each subject will attend a maximum of three visits. Clinical, biochemical, anthropometric, body composition, muscle strength, functional capacity, degree of dependence, and quality of life assessments will be performed. Thirty participants will be divided into two groups: intervention (patients will intake one sachet containing 10g of creatine twice a day) and control (patients will intake one sachet containing 10g of placebo [maltodextrin] twice a day). Both groups will receive supplementation with powdered milk protein serum isolate to achieve the goal of 1.5g of protein/kg of body weight/day and daily physiotherapy according to the current rehabilitation guidelines for patients with stroke. Supplementation will be offered during the 7-day hospitalization. The primary outcomes will be functional capacity, strength, and changes in muscle mass after the intervention as assessed by the Modified Rankin Scale, Timed Up and Go test, handgrip strength, 30-s chair stand test, muscle ultrasonography, electrical bioimpedance, and identification of muscle degradation markers by D3-methylhistidine. Follow-up will be performed 90 days after stroke to verify functional capacity, muscle strength, mortality, and quality of life. DISCUSSION: The older population has specific nutrient needs, especially for muscle mass and function maintenance. Considering that stroke is a potentially disabling event that can lead the affected individual to present with numerous sequelae, it is crucial to study the mechanisms of muscle mass loss and understand how adequate supplementation can help these patients to better recover. TRIAL REGISTRATION: The Brazilian Clinical Trials Registry (ReBEC) RBR-9q7gg4 . Registered on 21 January 2019.

Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter): a randomised placebo-controlled feasibility trial.

PURPOSE: Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents. METHODS: We performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary nitrate, and ordinal infection/clinical events. RESULTS: Of 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7-12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18-175] v 18 [10-50] mg/L, difference 25 [0-90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was as follows: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common. CONCLUSIONS: Recruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary nitrate. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required. TRIAL REGISTRATION: ISRCTN51124684. Application date 7/12/2020; assignment date 13/1/2021.

A non-randomised feasibility study of the Rehabilitation Potential Assessment Tool (RePAT) in frail older people in the acute healthcare setting.

BACKGROUND: Rehabilitation potential involves predicting who will benefit from rehabilitation. Decisions about rehabilitation potential must take into account personal, clinical and contextual factors, a process which is complicated in the presence of acute ill-health and frailty. This study aimed to evaluate the feasibility and acceptability of the Rehabilitation Potential Assessment Tool (RePAT) - a 15 item holistic, person-centred assessment tool and training package - in the acute hospital setting. METHODS: A non-randomised feasibility study with nested semi-structured interviews explored whether RePAT was feasible and acceptable. Feasibility was tested by recruiting physiotherapy and occupational therapy participants delivering the RePAT intervention to patients alongside usual clinical care. Acceptability was tested by conducting semi-structured interviews with staff, patient and carer participants. Staff and patient characteristics were analysed using descriptive statistics. Interview data were analysed thematically. Fidelity of completed RePAT items was assessed against a priori criteria on how closely they matched tool guidance by two researchers. Mean values of the two scores were calculated. RePAT content was analysed and supported with verbatim quotes. RESULTS: Six staff participants were recruited and trained. They assessed 26 patient participants using RePAT. Mean (SD) patient age was 86.16 (±6.39) years. 32% were vulnerable or mildly frail, 42% moderately frail and 26% severely or very severely frail using the Clinical Frailty Scale. Mean (SD) time to complete RePAT was 32.7 (±9.6) minutes. RePAT fidelity was good where 13 out of 15 items achieved a priori fidelity. RePAT was acceptable and tolerated by staff and patients. Staff participants reported RePAT enabled them to consider rehabilitation decisions in a more structured and consistent way. Patients and carer participants, although unable to comment directly on RePAT, reported being satisfied with their rehabilitation assessments which were found to embrace a person-centred approach. CONCLUSIONS: RePAT was found to be acceptable and feasible by staff, carers and patients. It allowed clinicians to make explicit their reasoning behind rehabilitation assessments and encouraged them to become more cognisant of factors which affected their clinical decision-making. TRIAL REGISTRATION: ID ISRCTN31938453 . Registered 05/10/2021.

Adjunct interventions to standard medical management of buprenorphine in outpatient settings: A systematic review of the evidence.

BACKGROUND: A growing body of research has examined adjunctive interventions supportive of engagement and retention in treatment among patients receiving buprenorphine for opioid use disorder (OUD). We conducted a systematic review of the literature addressing the effect on key outcomes of adjunctive interventions provided alongside standard medical management of buprenorphine in outpatient settings. METHODS: We included prospective studies examining adults receiving buprenorphine paired with an adjunctive intervention for the treatment of OUD in an outpatient setting. Data sources included Medline, Cochrane Central Register of Controlled Trials, CINAHL and PsycINFO from inception through January 2020. Two raters independently reviewed full-text articles, abstracted data and appraised risk of bias. Outcomes examined included abstinence, retention in treatment and non-addiction-related health outcomes. RESULTS: The final review includes 20 manuscripts, 11 randomized control trials (RCTs), three secondary analyses of RCTs and six observational studies. Most studies examined psychosocial interventions (n = 14). Few examined complementary therapies (e.g., yoga; n = 2) or technological interventions (e.g., electronic pill dispensation; n = 3); one study examined an intervention addressing structural barriers to care (patient navigators; n = 1). Low risk of bias RCTs found no evidence that adding psychosocial interventions to buprenorphine treatment improves substance use outcomes. CONCLUSIONS: Research is needed to identify adjunctive interventions with potential to support medication adherence and addiction-related outcomes for patients engaged in buprenorphine treatment. Data from clinical trials suggest that lack of ready access to psychosocial treatments should not discourage clinicians from prescribing buprenorphine.

Overcoming protein-energy malnutrition in older adults in the residential care setting: A narrative review of causes and interventions.

Malnutrition, in particular protein-energy malnutrition, is a highly prevalent condition in older adults, and is associated with low muscle mass and function, and increased prevalence of physical frailty. Malnutrition is often exacerbated in the residential care setting due to factors including lack of dentition and appetite, and increased prevalence of dementia and dysphagia. This review aims to provide an overview of the available literature in older adults in the residential care setting regarding the following: links between sarcopenia, frailty, and malnutrition (in particular, protein-energy malnutrition (PEM)), recognition and diagnosis of malnutrition, factors contributing to PEM, and the effectiveness of different forms of protein supplementation (in particular, oral nutritional supplementation (ONS) and protein-fortified foods (PFF)) to target PEM. This review found a lack of consensus on effective malnutrition diagnostic tools and lack of universal requirement for malnutrition screening in the residential care setting, making identifying and treating malnutrition in this population a challenge. When assessing the use of protein supplementation in the residential care setting, the two primary forms of supplementation were ONS and PFF. There is evidence that ONS and PFF increase protein and energy intakes in residential care setting, yet compliance with supplementation and their impact on functional status is unclear and conflicting. Further research comparing the use of ONS and PFF is needed to fully determine feasibility and efficacy of protein supplementation in the residential care setting.

Polysubstance use and association with opioid use disorder treatment in the US Veterans Health Administration.

AIMS: To understand the role of comorbid substance use disorders (SUDs), or polysubstance use, in the treatment of opioid use disorder (OUD), this study compared patients with OUD only to those with additional SUDs and examined association with OUD treatment receipt. DESIGN, SETTING AND PARTICIPANTS: Retrospective national cohort study of Veterans diagnosed with OUD (n = 65 741) receiving care from the US Veterans Health Administration (VHA) in fiscal year (FY) 2017. MEASUREMENTS: Patient characteristics were compared among those diagnosed with OUD only versus those with one other SUD (OUD + 1 SUD) and with multiple SUDs (OUD + ≥ 2 SUDs). The study examined the relationship between comorbid SUDs and receipt of buprenorphine, methadone and SUD outpatient treatment during 1-year follow-up, adjusting for patient demographic characteristics and clinical conditions. FINDINGS: Among the 65 741 Veterans with OUD in FY 2017, 41.2% had OUD only, 22.9% had OUD + 1 SUD and 35.9% had OUD + ≥ 2 SUDs. Common comorbid SUDs included alcohol use disorder (41.3%), cocaine/stimulant use disorder (30.0%) and cannabis use disorder (22.4%). Adjusting for patient characteristics, patients with OUD + 1 SUD [adjusted odds ratio (aOR) = 0.87, 95% confidence interval (CI) = 0.82-0.93] and patients with OUD +≥ 2 SUDs (aOR = 0.65, 95% CI = 0.61-0.69) had lower odds of receiving buprenorphine compared with OUD only patients. There were also lower odds of receiving methadone for patients with OUD + 1 SUD (aOR = 0.91, 95% CI = 0.86-0.97)and for those with OUD + ≥2 SUDs (aOR = 0.79, 95% CI = 0.74-0.84). Patients with OUD + 1 SUD (aOR = 1.85, 95% CI = 1.77-1.93) and patients with OUD + ≥2 SUDs (aOR = 3.25, 95% CI = 3.103.41) were much more likely to have a SUD clinic visit. CONCLUSIONS: The majority of Veterans in the US Veterans Health Administration diagnosed with opioid use disorder appeared to have at least one comorbid substance use disorder and many have multiple substance use disorders. Despite the higher likelihood of a substance use disorder clinic visit, having a non-opioid substance use disorder is associated with lower likelihood of buprenorphine treatment, suggesting the importance of addressing polysubstance use within efforts to expand treatment for opioid use disorder.

Effect of nonmeat, high-protein supplementation on quality of life and clinical outcomes in older residents of care homes: a systematic review and meta-analysis.

Context: Care home residents are at risk of malnutrition owing to reduced food intake, anabolic resistance in aging muscle, and a high prevalence of medical morbidity and functional dependency. There has been limited consensus regarding the effectiveness of a high-protein diet on quality of life or clinical outcomes in care home residents. Objective: The aim of this review was to evaluate the effectiveness of nonmeat, high-protein supplementation on health-related quality of life (HRQOL) and relevant clinical and nutritional outcomes in older people in a care home setting. Data Sources: The following databases were searched (to February 2018) for randomized controlled trials: Embase, AMED, CINAHL, MEDLINE, the Cochrane Central Registry of Controlled Trials, OpenGrey, clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, the ISRCTN registry, and the NIHR Clinical Research Network Portfolio. Study Selection: Trials were selected if they assessed a nonmeat, high-protein dietary intervention provided to care home residents who were aged 65 years or older. Data Extraction: Data from included trials were extracted if they assessed care home residents aged 65 years or older and compared those residents who received protein supplementation with those who did not. Trial quality was assessed using the Cochrane risk-of-bias tool. Meta-analysis was undertaken when appropriate. Results: Seventeen studies with 1246 participants fulfilled the inclusion criteria. All studies were of low or moderate quality. There was no evidence of improved HRQOL when the Short Form 36 (SF-36) was used to assess outcomes (standardized mean difference [SMD] = -0.10; 95%CI, -0.51 to 0.31; P = 0.62), although significant improvement was seen in the 1 trial that used the EQ-5D instrument (SMD = 2.58; 95%CI, 2.05-3.10; P < 0.00001). Conclusions: Nonmeat, high-protein oral supplements can improve markers of nutritional status in care home residents. However, there is insufficient high-quality evidence to determine the effect of such supplements on HRQOL in older adults in care homes. Systematic Review Registration: PROSPERO registration number: CRD42015029313.

A study paradigm integrating prospective epidemiologic cohorts and electronic health records to identify disease biomarkers.

Defining the full spectrum of human disease associated with a biomarker is necessary to advance the biomarker into clinical practice. We hypothesize that associating biomarker measurements with electronic health record (EHR) populations based on shared genetic architectures would establish the clinical epidemiology of the biomarker. We use Bayesian sparse linear mixed modeling to calculate SNP weightings for 53 biomarkers from the Atherosclerosis Risk in Communities study. We use the SNP weightings to computed predicted biomarker values in an EHR population and test associations with 1139 diagnoses. Here we report 116 associations meeting a Bonferroni level of significance. A false discovery rate (FDR)-based significance threshold reveals more known and undescribed associations across a broad range of biomarkers, including biometric measures, plasma proteins and metabolites, functional assays, and behaviors. We confirm an inverse association between LDL-cholesterol level and septicemia risk in an independent epidemiological cohort. This approach efficiently discovers biomarker-disease associations.

Optimal healthcare delivery to care homes in the UK: a realist evaluation of what supports effective working to improve healthcare outcomes.

INTRODUCTION: care home residents have high healthcare needs not fully met by prevailing healthcare models. This study explored how healthcare configuration influences resource use. METHODS: a realist evaluation using qualitative and quantitative data from case studies of three UK health and social care economies selected for differing patterns of healthcare delivery to care homes. Four homes per area (12 in total) were recruited. A total of 239 residents were followed for 12 months to record resource-use. Overall, 181 participants completed 116 interviews and 13 focus groups including residents, relatives, care home staff, community nurses, allied health professionals and General Practitioners. RESULTS: context-mechanism-outcome configurations were identified explaining what supported effective working between healthcare services and care home staff: (i) investment in care home-specific work that legitimises and values work with care homes; (ii) relational working which over time builds trust between practitioners; (iii) care which 'wraps around' care homes; and (iv) access to specialist care for older people with dementia. Resource use was similar between sites despite differing approaches to healthcare. There was greater utilisation of GP resource where this was specifically commissioned but no difference in costs between sites. CONCLUSION: activities generating opportunities and an interest in healthcare and care home staff working together are integral to optimal healthcare provision in care homes. Outcomes are likely to be better where: focus and activities legitimise ongoing contact between healthcare staff and care homes at an institutional level; link with a wider system of healthcare; and provide access to dementia-specific expertise.

Association of Cannabis, Stimulant, and Alcohol use with Mortality Prognosis Among HIV-Infected Men.

Questionnaires over a 9-year study period (2002-2010) were used to characterize cannabis, stimulant, and alcohol use among 3099 HIV-infected men participating in the Veterans Aging Cohort Study (VACS) to determine whether use of these substances is associated with changes in the VACS Index, a validated prognostic indicator for all-cause mortality. At baseline, 18% of participants reported no substance use in the past year, 24% lower risk alcohol use only, 18% unhealthy alcohol use only, 15% cannabis use (with or without alcohol), and 24% stimulant use (with or without alcohol or cannabis). In adjusted longitudinal analyses, cannabis use [ß = -0.97 (95% CI -1.93, 0.00), p = 0.048] was not associated with mortality risk, while stimulant use [1.08 (0.16, 2.00), p = 0.021] was associated with an increased mortality risk, compared to lower risk alcohol use. Our findings show no evidence of a negative effect of cannabis use on mortality risk, while stimulant use was associated with increased mortality risk among HIV-infected men. Interventions to reduce stimulant use in this patient population may reduce mortality.

Effective health care for older people living and dying in care homes: a realist review.

BACKGROUND: Care home residents in England have variable access to health care services. There is currently no coherent policy or consensus about the best arrangements to meet these needs. The purpose of this review was to explore the evidence for how different service delivery models for care home residents support and/or improve wellbeing and health-related outcomes in older people living and dying in care homes. METHODS: We conceptualised models of health care provision to care homes as complex interventions. We used a realist review approach to develop a preliminary understanding of what supported good health care provision to care homes. We completed a scoping of the literature and interviewed National Health Service and Local Authority commissioners, providers of services to care homes, representatives from the Regulator, care home managers, residents and their families. We used these data to develop theoretical propositions to be tested in the literature to explain why an intervention may be effective in some situations and not others. We searched electronic databases and related grey literature. Finally the findings were reviewed with an external advisory group. RESULTS: Strategies that support and sustain relational working between care home staff and visiting health care professionals explained the observed differences in how health care interventions were accepted and embedded into care home practice. Actions that encouraged visiting health care professionals and care home staff jointly to identify, plan and implement care home appropriate protocols for care, when supported by ongoing facilitation from visiting clinicians, were important. Contextual factors such as financial incentives or sanctions, agreed protocols, clinical expertise and structured approaches to assessment and care planning could support relational working to occur, but of themselves appeared insufficient to achieve change. CONCLUSION: How relational working is structured between health and care home staff is key to whether health service interventions achieve health related outcomes for residents and their respective organisations. The belief that either paying clinicians to do more in care homes and/or investing in training of care home staff is sufficient for better outcomes was not supported.

New horizons in the implementation and research of comprehensive geriatric assessment: knowing, doing and the 'know-do' gap.

In this paper, we outline the relationship between the need to put existing applied health research knowledge into practice (the 'know-do gap') and the need to improve the evidence base (the 'know gap') with respect to the healthcare process used for older people with frailty known as comprehensive geriatric assessment (CGA). We explore the reasons for the know-do gap and the principles of how these barriers to implementation might be overcome. We explore how these principles should affect the conduct of applied health research to close the know gap. We propose that impaired flow of knowledge is an important contributory factor in the failure to implement evidence-based practice in CGA; this could be addressed through specific knowledge mobilisation techniques. We describe that implementation failures are also produced by an inadequate evidence base that requires the co-production of research, addressing not only effectiveness but also the feasibility and acceptability of new services, the educational needs of practitioners, the organisational requirements of services, and the contribution made by policy. Only by tackling these issues in concert and appropriate proportion, will the know and know-do gaps for CGA be closed.

Provision of NHS generalist and specialist services to care homes in England: review of surveys.

BACKGROUND: The number of beds in care homes (with and without nurses) in the United Kingdom is three times greater than the number of beds in National Health Service (NHS) hospitals. Care homes are predominantly owned by a range of commercial, not-for-profit or charitable providers and their residents have high levels of disability, frailty and co-morbidity. NHS support for care home residents is very variable, and it is unclear what models of clinical support work and are cost-effective. OBJECTIVES: To critically evaluate how the NHS works with care homes. METHODS: A review of surveys of NHS services provided to care homes that had been completed since 2008. It included published national surveys, local surveys commissioned by Primary Care organisations, studies from charities and academic centres, grey literature identified across the nine government regions, and information from care home, primary care and other research networks. Data extraction captured forms of NHS service provision for care homes in England in terms of frequency, location, focus and purpose. RESULTS: Five surveys focused primarily on general practitioner services, and 10 on specialist services to care home. Working relationships between the NHS and care homes lack structure and purpose and have generally evolved locally. There are wide variations in provision of both generalist and specialist healthcare services to care homes. Larger care home chains may take a systematic approach to both organising access to NHS generalist and specialist services, and to supplementing gaps with in-house provision. Access to dental care for care home residents appears to be particularly deficient. CONCLUSIONS: Historical differences in innovation and provision of NHS services, the complexities of collaborating across different sectors (private and public, health and social care, general and mental health), and variable levels of organisation of care homes, all lead to persistent and embedded inequity in the distribution of NHS resources to this population. Clinical commissioners seeking to improve the quality of care of care home residents need to consider how best to provide fair access to health care for older people living in a care home, and to establish a specification for service delivery to this vulnerable population.

Relationships, expertise, incentives, and governance: supporting care home residents' access to health care. An interview study from England.

OBJECTIVES: To explore what commissioners of care, regulators, providers, and care home residents in England identify as the key mechanisms or components of different service delivery models that support the provision of National Health Service (NHS) provision to independent care homes. METHODS: Qualitative, semistructured interviews with a purposive sample of people with direct experience of commissioning, providing, and regulating health care provision in care homes and care home residents. Data from interviews were augmented by a secondary analysis of previous interviews with care home residents on their personal experience of and priorities for access to health care. Analysis was framed by the assumptions of realist evaluation and drew on the constant comparative method to identify key themes about what is required to achieve quality health care provision to care homes and resident health. RESULTS: Participants identified 3 overlapping approaches to the provision of NHS that they believed supported access to health care for older people in care homes: (1) Investment in relational working that fostered continuity and shared learning between visiting NHS staff and care home staff, (2) the provision of age-appropriate clinical services, and (3) governance arrangements that used contractual and financial incentives to specify a minimum service that care homes should receive. CONCLUSION: The 3 approaches, and how they were typified as working, provide a rich picture of the stakeholder perspectives and the underlying assumptions about how service delivery models should work with care homes. The findings inform how evidence on effective working in care homes will be interrogated to identify how different approaches, or specifically key elements of those approaches, achieve different health-related outcomes in different situations for residents and associated health and social care organizations.

Exome sequencing reveals novel rare variants in the ryanodine receptor and calcium channel genes in malignant hyperthermia families.

BACKGROUND: About half of malignant hyperthermia (MH) cases are associated with skeletal muscle ryanodine receptor 1 (RYR1) and calcium channel, voltage-dependent, L type, α1S subunit (CACNA1S) gene mutations, leaving many with an unknown cause. The authors chose to apply a sequencing approach to uncover causal variants in unknown cases. Sequencing the exome, the protein-coding region of the genome, has power at low sample sizes and identified the cause of over a dozen Mendelian disorders. METHODS: The authors considered four families with multiple MH cases lacking mutations in RYR1 and CACNA1S by Sanger sequencing of complementary DNA. Exome sequencing in two affecteds per family, chosen for maximum genetic distance, were compared. Variants were ranked by allele frequency, protein change, and measures of conservation among mammals to assess likelihood of causation. Finally, putative pathogenic mutations were genotyped in other family members to verify cosegregation with MH. RESULTS: Exome sequencing revealed one rare RYR1 nonsynonymous variant in each of three families (Asp1056His, Val2627Met, Val4234Leu), and one CACNA1S variant (Thr1009Lys) in the fourth family. These were not seen in variant databases or in our control population sample of 5,379 exomes. Follow-up sequencing in other family members verified cosegregation of alleles with MH. CONCLUSIONS: The authors found that using both exome sequencing and allele frequency data from large sequencing efforts may aid genetic diagnosis of MH. In a sample selected by the authors, this technique was more sensitive for variant detection in known genes than Sanger sequencing of complementary DNA, and allows for the possibility of novel gene discovery.

Treating addiction with tunes: a systematic review of music therapy for the treatment of patients with addictions.

Music therapy is the use of musical interventions in a therapeutic setting to accomplish health-related goals. Descriptions of music therapy exist in the peer-reviewed literature and indicate potential use of music therapy in treatment of patients with addiction disorders. This systematic review describes and compares the types of music therapy demonstrated in the literature and evaluates the evidence that music therapy improves outcomes of patients with addictions. A search and critical review of all the existing published literature on music therapy for the treatment of addictions was conducted using online databases and secondary search strategies. Few studies quantitatively assess the use of music therapy in the treatment of patients with addictions. Music listening provided by music therapists is commonly studied. Music therapy sessions reported were additive, not independent, treatment modalities. In the literature, no consensus exists regarding of the efficacy of music therapy as treatment for patients with addictions.