Diet modification reduces pain and improves function in adults with osteoarthritis: a systematic review.

BACKGROUND: The effect of dietary modifications on pain and joint function in adults with osteoarthritis (OA) is an emerging area of study. This systematic review aimed to evaluate if adults with OA who consume diets with a higher proportion of plant phenols and omega-3 fatty acids would have less pain and improved joint function than those with a higher proportion of saturated fatty acids, omega-6 fatty acids and refined carbohydrates. METHODS: Database searches of CINAHL (EBSCO), Clinical Trials (NIH-NLM), Cochrane Library (Wiley), Dissertation & Thesis Global (ProQuest), Embase (Elsevier), Medline (OVID), PubMed (NLM), Scopus (Elsevier), Web of Sciences (Clarivate) for clinical trials identified 7763 articles published between January 2015 and May 2023. After an independent review of the articles, seven randomised clinical trials and one nonrandomised clinical trial were included in the analysis. Because of the heterogeneity of the outcome measures, a meta-analysis was not possible. RESULTS: Participants who were instructed to consume high-phenol/high-omega-3 fatty acid diets reported significant improvements in pain and physical function scores. The greatest improvement was reported by those who consumed a diet that had the most omega-3 fatty acids. CONCLUSION: Because of the high risk of bias, the strength of the evidence is limited. However, there is evidence that counselling adults with OA to replace refined grains and processed foods with whole plant foods, fish and plant oils may have a favourable effect on pain and physical function. Routine follow-up care regarding these diet modifications may be necessary to ensure adherence to this therapy.

Development of a bronchopulmonary dysplasia nutrition focused physical examination tool: A modified Delphi study.

OBJECTIVE: The objectives of this study were to identify factors impacting nutrition needs in infants and children with bronchopulmonary dysplasia (BPD). A modified Delphi approach to obtain consensus among pediatric registered dietitian nutritionists (RDNs) was used to create a BPD-specific nutrition focused physical examination (NFPE) tool. STUDY DESIGN: RDNs, recruited through pediatric nutrition professional associations, completed a survey rating proposed NFPE components on a Likert scale of 1-5 allowing open-ended responses in a two-round Delphi. Responses were analyzed, deidentified, and results were returned to panelists for in-round feedback. Consensus was defined a priori as 75% agreement for usefulness or relevance ± 1 standard deviation. RESULTS: Six domains (anthropometrics, body composition, development, gastrointestinal, respiratory, and physical signs) and 38 components achieved consensus. CONCLUSION: Components for an evidence-based tool to enhance nutrition assessment in infants and children with BPD were identified with consensus agreement by an expert panel of 19 pediatric RDNs.

Impact of the COVID-19 pandemic on hospital episodes for falls and fractures associated with new-onset disability and frailty in England: a national cohort study.

BACKGROUND: Older people with frailty are at risk of harm from immobility or isolation, yet data about how COVID-19 lockdowns affected them are limited. Falls and fractures are easily measurable adverse outcomes correlated with frailty. We investigated whether English hospital admission rates for falls and fractures varied from the expected trajectory during the COVID-19 pandemic, and how these varied by frailty status. METHODS: NHS England Hospital Episode Statistics Admitted Patient Care data were analysed for observed versus predicted outcome rates for 24 January 2020 to 31 December 2021. An auto-regressive integrated moving average time-series model was trained using falls and fracture incidence data from 2013 to 2018 and validated using data from 2019. Models included national and age-, sex- and region-stratified forecasts. Outcome measures were hospital admissions for falls, fractures, and falls and fractures combined. Frailty was defined using the Hospital Frailty Risk Score. RESULTS: 144,148,915 pre-pandemic hospital admissions were compared with 42,267,318 admissions after pandemic onset. For the whole population, falls and fracture rates were below predicted for the first period of national lockdown, followed by a rapid return to rates close to predicted. Thereafter, rates followed expected trends. For people living with frailty, however, falls and fractures increased above expected rates during periods of national lockdown and remained elevated throughout the study period. Effects of frailty were independent of age. CONCLUSIONS: People living with frailty experienced increased fall and fracture rates above expected during and following periods of national lockdown. These remained persistently elevated throughout the study period.

Potential Determinants of Subjective Global Assessment Among Patients on Maintenance Hemodialysis.

OBJECTIVE: The Subjective Global Assessment (SGA) is a validated tool for identifying nutritional status in patients receiving maintenance dialysis (MHD), but it is not without limitations. Current research identifies additional clinical characteristics such as phase angle (PhA) associated with SGA. This study aimed to assess the overall correlation between PhA and SGA; associations between PhA and SGA by body mass index (BMI), and to identify clinical characteristics associated with SGA. DESIGN AND METHODS: This is a secondary analysis of the Rutgers Nutrition & Kidney Database, which enrolled participants from four primary studies that included adults diagnosed with chronic kidney disease who were receiving MHD. Multivariable binary logistic regression analyses were conducted to estimate odds ratio (OR) and corresponding 95% confidence intervals. RESULTS: The study sample included 60.0% males with 81.1% of the sample identifying as African American. Additionally, 38.9% were obese according to the BMI classification, and 57.0% were moderately malnourished. Patients with obesity had 44% lower odds of being moderately malnourished (OR=0.56, 95% CI= 0.37, 0.85). In the model adjusted for age and ethnicity and other clinical characteristics, increasing PhA values by one unit was associated with 28% lower odds (OR= 0.72, 95% CI= 0.53, 0.97) of being moderately malnourished while increasing waist circumference (WC) values by one unit was associated with 12% higher odds (OR= 1.12; 95% CI= 1.06, 1.19) of being moderately malnourished than well-nourished. In this fully adjusted model, increasing FFM (OR= 0.95, 95% CI=0.91, 0.99) and FM (OR = 0.92, 95% CI= 0.87, 0.97) by 1 kg was also associated with a 5% and 8% lower odds of being moderately malnourished, respectively. CONCLUSION: PhA and SGA were significantly associated only among patients classified as obese. PhA, WC, FM, and FFM were identified as potential clinical determinants of SGA. Patients receiving MHD and who have obesity may benefit from utilizing SGA along with WC, PhA, FM, and FFM to assess nutritional status.

Uptake of self-management education programmes for people with type 2 diabetes in primary care through the embedding package: a cluster randomised control trial and ethnographic study.

BACKGROUND: Self-management education programmes are cost-effective in helping people with type 2 diabetes manage their diabetes, but referral and attendance rates are low. This study reports on the effectiveness of the Embedding Package, a programme designed to increase type 2 diabetes self-management programme attendance in primary care. METHODS: Using a cluster randomised design, 66 practices were randomised to: (1) a wait-list group that provided usual care for nine months before receiving the Embedding Package for nine months, or (2) an immediate group that received the Embedding Package for 18 months. 'Embedders' supported practices and self-management programme providers to embed programme referral into routine practice, and an online 'toolkit' contained embedding support resources. Patient-level HbA1c (primary outcome), programme referral and attendance data, and clinical data from 92,977 patients with type 2 diabetes were collected at baseline (months - 3-0), step one (months 1-9), step 2 (months 10-18), and 12 months post-intervention. An integrated ethnographic study including observations, interviews, and document analysis was conducted using interpretive thematic analysis and Normalisation Process Theory. RESULTS: No significant difference was found in HbA1c between intervention and control conditions (adjusted mean difference [95% confidence interval]: -0.10 [-0.38, 0.18] mmol/mol; -0.01 [-0.03, 0.02] %). Statistically but not clinically significantly lower levels of HbA1c were found in people of ethnic minority groups compared with non-ethnic minority groups during the intervention condition (-0.64 [-1.08, -0.20] mmol/mol; -0.06% [-0.10, -0.02], p = 0.004), but not greater self-management programme attendance. Twelve months post-intervention data showed statistically but not clinically significantly lower HbA1c (-0.56 [95% confidence interval: -0.71, -0.42] mmol/mol; -0.05 [-0.06, -0.04] %; p < 0.001), and higher self-management programme attendance (adjusted odds ratio: 1.13; 95% confidence interval: 1.02, 1.25; p = 0.017) during intervention conditions. Themes identified through the ethnographic study included challenges for Embedders in making and sustaining contact with practices and providers, and around practices' interactions with the toolkit. CONCLUSIONS: Barriers to implementing the Embedding Package may have compromised its effectiveness. Statistically but not clinically significantly improved HbA1c among ethnic minority groups and in longer-term follow-up suggest that future research exploring methods of embedding diabetes self-management programmes into routine care is warranted. TRIAL REGISTRATION: ISRCTN23474120, registered 05/04/2018.

Incorporating polygenic risk into the Leicester Risk Assessment score for 10-year risk prediction of type 2 diabetes.

AIMS: We evaluated whether incorporating information on ethnic background and polygenic risk enhanced the Leicester Risk Assessment (LRA) score for predicting 10-year risk of type 2 diabetes. METHODS: The sample included 202,529 UK Biobank participants aged 40-69 years. We computed the LRA score, and developed two new risk scores using training data (80% sample): LRArev, which incorporated additional information on ethnic background, and LRAprs, which incorporated polygenic risk for type 2 diabetes. We assessed discriminative and reclassification performance in a test set (20% sample). Type 2 diabetes was ascertained using primary care, hospital inpatient and death registry records. RESULTS: Over 10 years, 7,476 participants developed type 2 diabetes. The Harrell's C indexes were 0.796 (95% Confidence Interval [CI] 0.785, 0.806), 0.802 (95% CI 0.792, 0.813), and 0.829 (95% CI 0.820, 0.839) for the LRA, LRArev and LRAprs scores, respectively. The LRAprs score significantly improved the overall reclassification compared to the LRA (net reclassification index [NRI] = 0.033, 95% CI 0.015, 0.049) and LRArev (NRI = 0.040, 95% CI 0.024, 0.055) scores. CONCLUSIONS: Polygenic risk moderately improved the performance of the existing LRA score for 10-year risk prediction of type 2 diabetes.

The Effectiveness of Lifestyle Interventions in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To perform a network meta-analysis to determine the effectiveness of lifestyle interventions in exercise tolerance and quality of life (QoL) in people with HFpEF. METHODS: Ten databases were searched for randomized controlled trials that evaluated a diet and/or exercise intervention in people with heart failure with preserved ejection fraction until May 2022. The co-primary outcomes were peak oxygen uptake (V̇O2peak) and Quality of Life as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). We synthesized data using network meta-analysis. RESULTS: We identified 13 trials, including a total of 869 participants, and we incorporated 6 different interventions. Improvements in V̇O2peak compared to controls were seen for all exercise interventions (2.88 [95% CI: 1.36; 4.39] mL/kg/min) for high-intensity interval training (HIIT); 2.37 [95% CI: 1.02; 3.71] mL/kg/min for low-intensity exercise (LIT) combined with a hypocaloric diet; 2.05 [95% CI: 0.81; 3.29] mL/kg/min for moderate-intensity continuous training (MICT); 1.94 [95% CI: 0.59; 3.29] mL/kg/min for LIT; 1.85 [95% CI: 0.27; 3.44] mL/kg/min for MICT combined with resistance training) but not a hypocaloric diet alone (1.26 [95%CI: -0.08; 2.61] mL/kg/min). Only HIIT (-14.45 [95%CI: -24.81; -4.10] points) and LIT (95% CI: -11.05 [-20.55; -1.54] mL/kg/min) significantly improved MLHFQ scores. Network meta-analysis indicated that HIIT was the most effective intervention for improving both V̇O2peak (mean improvement 2.88 [95% CI: 1.36; 4.39] mL/kg/min, follow-up range, 4 weeks-3 years) and QoL (-14.45 [95% CI: -24.81; -4.10] points, follow-up range, 12-26 weeks) compared to usual care. CONCLUSIONS: This network meta-analysis indicates that HIIT is the most effective lifestyle intervention studied to improve exercise capacity and QoL, with mean improvements exceeding the minimum clinically meaningful thresholds. HIIT is likely to be an underused management strategy in HFpEF, but further studies are needed to confirm long-term improvements in symptoms and clinical outcomes.

The Role of Dietary Acid Load on Progression of Estimated Glomerular Filtration Rate Among Individuals Diagnosed With Chronic Kidney Disease.

OBJECTIVE: Individuals with chronic kidney disease (CKD) are at an increased risk for developing metabolic acidosis. Metabolic acidosis has been shown to worsen kidney function and exacerbate systemic inflammation. Diets high in protein foods can exacerbate metabolic acidosis as protein foods tend to be more acidic, while fruits and vegetables are more alkalotic. The main objective of this systematic review was to determine if higher consumption of fruits and vegetables in adults with CKD stages 1-5 reduces the rate of decline of estimated glomerular filtration rate. METHODS: Searches of Cumulated Index to Nursing and Allied Health Literature (CINAHL -Elton B. Stephens Company [EBSCO]), Cochrane Library (Wiley), Dissertation & Thesis Global (ProQuest), Embase (Elsevier), Medline (OVID), PubMed (National Library of Medicine), Scopus (Elsevier), and Web of Sciences (Clarivate) identified 1,451 articles published between January 2015 and June 2023. RESULTS: After independent review, 7 total studies were included. Six of the studies found an association between dietary acid load and progression of CKD. CONCLUSIONS: Dietary counseling focusing on decreasing dietary acid load may be beneficial for individuals with CKD.

Knowledge and clinical practice of ASPEN registered dietitian nutritionist members regarding blenderized tube feedings.

BACKGROUND: Blenderized tube feedings (BTFs) are used by patients/caregivers who report improvements in gastrointestinal tolerance compared with standard commercial feedings. Despite positive outcomes, registered dietitian nutritionists or international equivalents (RDN/Is) hesitate to recommend BTFs. We aimed to determine if an association exists between dietitian characteristics and willingness to recommend BTFs. METHODS: A BTF-specific survey (N = 157) assessed for validity and reliability was administered to the American Society for Parenteral and Enteral Nutrition (ASPEN) RDN/I members. Binary logistic regression analyses examined the association between age, years of clinical practice, BTF training/education, patient population served, and willingness to recommend BTFs. RESULTS: The response rate was 4.3% of ASPEN RDN/I members. Most respondents were White females with a median age of 39.0 years and 12 years of clinical experience. Although 98.7% of respondents expressed a willingness to support and 73% to recommend BTFs, 60% were not using BTFs in clinical practice. For 94.8% of RDN/Is, the primary reason for BTF use was patient/caregiver requests. After adjustment for age and years of clinical practice, RDN/Is who served pediatric populations (odds ratio [OR] = 4.28; 95% CI, 1.52-12.09) or used three or more professional resources (OR = 2.49; 95% CI, 1.12-5.57), industry-sponsored resources (OR = 3.15; 95% CI, 1.39-7.15), or one or more experiential learning resources (OR = 3.14; 95% CI, 1.38-7.17) were more likely to recommend BTFs whereas those serving adults were less likely to recommend BTFs (OR = 0.33; 95% CI, 0.12-0.95). CONCLUSION: Pediatric RDN/Is and individuals with BTF-specific education/training were more inclined to recommend BTFs.

Cost-effectiveness analysis of two interventions to promote physical activity in a multiethnic population at high risk of diabetes: an economic evaluation of the 48-month PROPELS randomized controlled trial.

INTRODUCTION: Physical activity (PA) is protective against type 2 diabetes (T2D). However, data on pragmatic long-term interventions to reduce the risk of developing T2D via increased PA are lacking. This study investigated the cost-effectiveness of a pragmatic PA intervention in a multiethnic population at high risk of T2D. MATERIALS AND METHODS: We adapted the School for Public Health Research diabetes prevention model, using the PROPELS trial data and analyses of the NAVIGATOR trial. Lifetime costs, lifetime quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each intervention (Walking Away (WA) and Walking Away Plus (WA+)) versus usual care and compared with National Institute for Health and Care Excellence's willingness-to-pay of £20 000-£30 000 per QALY gained. We conducted scenario analyses on the outcomes of the PROPELS trial data and a threshold analysis to determine the change in step count that would be needed for the interventions to be cost-effective. RESULTS: Estimated lifetime costs for usual care, WA, and WA+ were £22 598, £23 018, and £22 945, respectively. Estimated QALYs were 9.323, 9.312, and 9.330, respectively. WA+ was estimated to be more effective and cheaper than WA. WA+ had an ICER of £49 273 per QALY gained versus usual care. In none of our scenario analyses did either WA or WA+ have an ICER below £20 000 per QALY gained. Our threshold analysis suggested that a PA intervention costing the same as WA+ would have an ICER below £20 000/QALY if it were to achieve an increase in step count of 500 steps per day which was 100% maintained at 4 years. CONCLUSIONS: We found that neither WA nor WA+ was cost-effective at a limit of £20 000 per QALY gained. Our threshold analysis showed that interventions to increase step count can be cost-effective at this limit if they achieve greater long-term maintenance of effect. TRIAL REGISTRATION NUMBER: ISRCTN registration: ISRCTN83465245: The PRomotion Of Physical activity through structuredEducation with differing Levels of ongoing Support for those with pre-diabetes (PROPELS)https://doi.org/10.1186/ISRCTN83465245.

Predictors of skeletal muscle index for patients treated with hemodialysis.

OBJECTIVE: There is an increased risk of skeletal muscle mass (SMM) loss among patients with stage 5 chronic kidney disease (CKD) treated with maintenance hemodialysis (MHD). The reduced SMM considerably influences the development of protein-energy wasting (PEW). Patients who develop PEW have higher hospitalization and mortality rates than those without PEW. This study determined if key variables could predict SMM Index (SMM adjusted for height) in patients receiving MHD. METHODS: We conducted a secondary analysis of cross-sectional data obtained from the Rutgers Nutrition and Kidney Database (n=178). Data were utilized to calculate both SMM and SMM Index. Univariate and multiple linear regression models explored the relationship between SMM Index and the following variables: serum albumin (ALB), Kt/V, normalized protein catabolic rate (nPCR), serum creatinine (SCr), and urea reduction ratio (URR). RESULTS: Most participants were Black/African American (82.9%), male (59.1%), and obese (39%), with a mean age of 55.9 ± 11.9 years. The median SGA score was 5, indicating a lower risk of malnutrition. Participants had a mean SMM of 26.4kg and a median SMM Index of 8.9kg/m2. Univariate regression modeling found URR to be a significant predictor of SMM Index, with increases in the percentage of URR predicting lower SMM Index values. The adjusted regression modeling found similar results, with increases in URR percentage predicting declines in SMM Index. CONCLUSION: This study found that URR was a predictor of SMM Index in patients receiving MHD. Further research is required to explore these relationships and provide clinicians with a more extensive array of tools to recognize early signs of SMM loss to prevent the progression of PEW.

The potential of baicalin to enhance neuroprotection and mitochondrial function in a human neuronal cell model.

Baicalin is a flavone glycoside derived from flowering plants belonging to the Scutellaria genus. Previous studies have reported baicalin's anti-inflammatory and neuroprotective properties in rodent models, indicating the potential of baicalin in neuropsychiatric disorders where alterations in numerous processes are observed. However, the extent of baicalin's therapeutic effects remains undetermined in a human cell model, more specifically, neuronal cells to mimic the brain environment in vitro. As a proof of concept, we treated C8-B4 cells (murine cell model) with three different doses of baicalin (0.1, 1 and 5 µM) and vehicle control (DMSO) for 24 h after liposaccharide-induced inflammation and measured the levels of TNF-α in the medium by ELISA. NT2-N cells (human neuronal-like cell model) underwent identical baicalin treatment, followed by RNA extraction, genome-wide mRNA expression profiles and gene set enrichment analysis (GSEA). We also performed neurite outgrowth assays and mitochondrial flux bioanalysis (Seahorse) in NT2-N cells. We found that in C8-B4 cells, baicalin at ≥ 1 µM exhibited anti-inflammatory effects, lowering TNF-α levels in the cell culture media. In NT2-N cells, baicalin positively affected neurite outgrowth and transcriptionally up-regulated genes in the tricarboxylic acid cycle and the glycolysis pathway. Similarly, Seahorse analysis showed increased oxygen consumption rate in baicalin-treated NT2-N cells, an indicator of enhanced mitochondrial function. Together, our findings have confirmed the neuroprotective and mitochondria enhancing effects of baicalin in human-neuronal like cells. Given the increased prominence of mitochondrial mechanisms in diverse neuropsychiatric disorders and the paucity of mitochondrial therapeutics, this suggests the potential therapeutic application of baicalin in human neuropsychiatric disorders where these processes are altered.

Non-pharmacological interventions to improve cardiovascular risk factors in people with diabetic foot disease: A systematic review and meta-analysis.

Cardiovascular disease (CVD) risk in those with diabetic foot disease is very high. Non-pharmacological interventions may improve this risk, though no previous evidence synthesis has been completed. This systematic review aimed to investigate the impact of non-pharmacological interventions on CVD risk factors in diabetic ulcer disease. Multiple databases and trials registers were searched from inception to December 6th 2023. We included reports of randomised controlled trials investigating the impact of non-pharmacological interventions on cardiovascular risk in those with type 1 or type 2 diabetes and current or previous diabetic foot disease. Twenty studies were included. Extracted data included: study design and setting; participant sociodemographic factors; and change in cardiovascular risk factors. Data were synthesised using random effects meta-analyses and narrative syntheses. Interventions included nutritional supplementation, collaborative care, hyperbaric oxygen therapy, patient education, nurse-led intervention, self-management, family support, relaxation and exercise, over a median duration of 12 weeks. Significant post-intervention changes were observed in fasting plasma glucose, serum insulin levels, insulin sensitivity and resistance, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol and C-reactive protein. No effects were detected in very low- or high-density lipoprotein-cholesterol or body mass index. Non-pharmacological interventions show promise in improving CVD risk in diabetic foot disease.

Mapping Short Warwick and Edinburgh Mental Wellbeing Scale (SWEMWBS) to Recovering Quality of Life (ReQoL) to estimate health utilities.

BACKGROUND: The Short Warwick and Edinburgh Mental Wellbeing Scale (SWEMWBS) is a widely used non-preference-based measure of mental health in the UK. The primary aim of this paper is to construct an algorithm to translate the SWEMWBS scores to utilities using the Recovering Quality of Life Utility Index (ReQoL-UI) measure. METHODS: Service users experiencing mental health difficulties were recruited in two separate cross-sectional studies in the UK. The following direct mapping functions were used: Ordinary Least Square, Tobit, Generalised Linear Models. Indirect (response) mapping was performed using seemingly unrelated ordered probit to predict responses to each of the ReQoL-UI items and subsequently to predict using UK tariffs of the ReQoL-UI from SWEMWBS. The performance of all models was assessed by the mean absolute errors, root mean square errors between the predicted and observed utilities and graphical representations across the SWEMWBS score range. RESULTS: Analyses were based on 2573 respondents who had complete data on the ReQoL-UI items, SWEMWBS items, age and sex. The direct mapping methods predicted ReQoL-UI scores across the range of SWEMWBS scores reasonably well. Very little differences were found among the three regression specifications in terms of model fit and visual inspection when comparing modelled and actual utility values across the score range of the SWEMWBS. However, when running simulations to consider uncertainty, it is clear that response mapping is superior. CONCLUSIONS: This study presents mapping algorithms from SWEMWBS to ReQoL as an alternative way to generate utilities from SWEMWBS. The algorithm from the indirect mapping is recommended to predict utilities from the SWEMWBS.

A critical review and analysis of the context, current burden, and application of policy to improve cancer equity in Ghana.

BACKGROUND: Cancer causes a major disease burden worldwide. This is increasingly being realised in low and middle-income countries, which account disproportionately for preventable cancer deaths. Despite the World Health Organization calling for governments to develop policies to address this and alleviate cancer inequality, numerous challenges in executing effective cancer policies remain, which require consideration of the country-specific context. As this has not yet been considered in Ghana, the aim of this review was to bring together and critique the social-environmental, health policy and system factors to identifying opportunities for future health policies to reduce cancer burden in the Ghanian context. A critical policy-focused review was conducted to bring together and critique the current health systems context relating to cancer in Ghana, considering the unmet policy need, health system and social factors contributing to the burden and policy advances related to cancer. CONCLUSION: The findings highlight the changing burden of cancer in Ghana and the contextual factors within the socio-ecosystem that contribute to this. Policies around expanding access to and coverage of services, as well as the harmonization with medical pluralism have potential to improve outcomes and increase equity but their implementation and robust data to monitor their impact pose significant barriers.

Effects of antipsychotic drugs on energy metabolism.

Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with altered bioenergetic pathways and mitochondrial dysfunction. Antipsychotic medications, both first and second-generation, are commonly prescribed to manage SCZ symptoms, but their direct impact on mitochondrial function remains poorly understood. In this study, we investigated the effects of commonly prescribed antipsychotics on bioenergetic pathways in cultured neurons. We examined the impact of risperidone, aripiprazole, amisulpride, and clozapine on gene expression, mitochondrial bioenergetic profile, and targeted metabolomics after 24-h treatment, using RNA-seq, Seahorse XF24 Flux Analyser, and gas chromatography-mass spectrometry (GC-MS), respectively. Risperidone treatment reduced the expression of genes involved in oxidative phosphorylation, the tricarboxylic acid cycle, and glycolysis pathways, and it showed a tendency to decrease basal mitochondrial respiration. Aripiprazole led to dose-dependent reductions in various mitochondrial function parameters without significantly affecting gene expression. Aripiprazole, amisulpride and clozapine treatment showed an effect on the tricarboxylic acid cycle metabolism, leading to more abundant metabolite levels. Antipsychotic drug effects on mitochondrial function in SCZ are multifaceted. While some drugs have greater effects on gene expression, others appear to exert their effects through enzymatic post-translational or allosteric modification of enzymatic activity. Understanding these effects is crucial for optimising treatment strategies for SCZ. Novel therapeutic interventions targeting energy metabolism by post-transcriptional pathways might be more effective as these can more directly and efficiently regulate energy production.

Participant and workplace champion experiences of an intervention designed to reduce sitting time in desk-based workers: SMART work & life.

BACKGROUND: A cluster randomised controlled trial demonstrated the effectiveness of the SMART Work & Life (SWAL) behaviour change intervention, with and without a height-adjustable desk, for reducing sitting time in desk-based workers. Staff within organisations volunteered to be trained to facilitate delivery of the SWAL intervention and act as workplace champions. This paper presents the experiences of these champions on the training and intervention delivery, and from participants on their intervention participation. METHODS: Quantitative and qualitative feedback from workplace champions on their training session was collected. Participants provided quantitative feedback via questionnaires at 3 and 12 month follow-up on the intervention strategies (education, group catch ups, sitting less challenges, self-monitoring and prompts, and the height-adjustable desk [SWAL plus desk group only]). Interviews and focus groups were also conducted at 12 month follow-up with workplace champions and participants respectively to gather more detailed feedback. Transcripts were uploaded to NVivo and the constant comparative approach informed the analysis of the interviews and focus groups. RESULTS: Workplace champions rated the training highly with mean scores ranging from 5.3/6 to 5.7/6 for the eight parts. Most participants felt the education increased their awareness of the health consequences of high levels of sitting (SWAL: 90.7%; SWAL plus desk: 88.2%) and motivated them to change their sitting time (SWAL: 77.5%; SWAL plus desk: 85.77%). A high percentage of participants (70%) reported finding the group catch up session helpful and worthwhile. However, focus groups highlighted mixed responses to the group catch-up sessions, sitting less challenges and self-monitoring intervention components. Participants in the SWAL plus desk group felt that having a height-adjustable desk was key in changing their behaviour, with intrinsic as well as time based factors reported as key influences on the height-adjustable desk usage. In both intervention groups, participants reported a range of benefits from the intervention including more energy, less fatigue, an increase in focus, alertness, productivity and concentration as well as less musculoskeletal problems (SWAL plus desk group only). Work-related, interpersonal, personal attributes, physical office environment and physical barriers were identified as barriers when trying to sit less and move more. CONCLUSIONS: Workplace champion and participant feedback on the intervention was largely positive but it is clear that different behaviour change strategies worked for different people indicating that a 'one size fits all' approach may not be appropriate for this type of intervention. The SWAL intervention could be tested in a broader range of organisations following a few minor adaptations based on the champion and participant feedback. TRIAL REGISTRATION: ISCRCTN registry (ISRCTN11618007).

Implementation and engagement of the SMART Work & Life sitting reduction intervention: an exploratory analysis on intervention effectiveness.

BACKGROUND: To enhance the impact of interventions, it is important to understand how intervention engagement relates to study outcomes. We report on the level of implementation and engagement with the SMART Work & Life (SWAL) programme (delivered with (SWAL plus desk) and without a height-adjustable desk (SWAL)) and explore the effects of different levels of this on change in daily sitting time in comparison to the control group. METHODS: The extent of intervention delivery by workplace champions and the extent of engagement by champions and participants (staff) with each intervention activity was assessed by training attendance logs, workplace champion withdrawal dates, intervention activities logs and questionnaires. These data were used to assess whether a cluster met defined criteria for low, medium, or high implementation and engagement or none of these. Mixed effects linear regression analyses tested whether change in sitting time varied by: (i) the number of intervention activities implemented and engaged with, and (ii) the percentage of implementation and engagement with all intervention strategies. RESULTS: Workplace champions were recruited for all clusters, with 51/52 (98%) attending training. Overall, 12/27 (44.4%) SWAL and 9/25 (36.0%) SWAL plus desk clusters implemented all main intervention strategies. Across remaining clusters, the level of intervention implementation varied. Those in the SWAL (n = 8 (29.6%) clusters, 80 (32.1%) participants) and SWAL plus desk (n = 5 (20.0%) clusters, 41 (17.1%) participants) intervention groups who implemented and engaged with the most intervention strategies and had the highest percentage of cluster implementation and engagement with all intervention strategies sat for 30.9 (95% CI -53.9 to -7.9, p = 0.01) and 75.6 (95% CI -103.6 to -47.7, p < 0.001) fewer minutes/day respectively compared to the control group at 12 month follow up. These differences were larger than the complete case analysis. The differences in sitting time observed for the medium and low levels were similar to the complete case analysis. CONCLUSIONS: Most intervention strategies were delivered to some extent across the clusters although there was large variation. Superior effects for sitting reduction were seen for those intervention groups who implemented and engaged with the most intervention components and had the highest level of cluster implementation and engagement. TRIAL REGISTRATION: ISRCTN11618007. Registered on 24 January 2018. https://www.isrctn.com/ISRCTNISRCTN11618007 .

A systematic review of simulation studies which compare existing statistical methods to account for non-compliance in randomised controlled trials.

INTRODUCTION: Non-compliance is a common challenge for researchers and may reduce the power of an intention-to-treat analysis. Whilst a per protocol approach attempts to deal with this issue, it can result in biased estimates. Several methods to resolve this issue have been identified in previous reviews, but there is limited evidence supporting their use. This review aimed to identify simulation studies which compare such methods, assess the extent to which certain methods have been investigated and determine their performance under various scenarios. METHODS: A systematic search of several electronic databases including MEDLINE and Scopus was carried out from conception to 30th November 2022. Included papers were published in a peer-reviewed journal, readily available in the English language and focused on comparing relevant methods in a superiority randomised controlled trial under a simulation study. Articles were screened using these criteria and a predetermined extraction form used to identify relevant information. A quality assessment appraised the risk of bias in individual studies. Extracted data was synthesised using tables, figures and a narrative summary. Both screening and data extraction were performed by two independent reviewers with disagreements resolved by consensus. RESULTS: Of 2325 papers identified, 267 full texts were screened and 17 studies finally included. Twelve methods were identified across papers. Instrumental variable methods were commonly considered, but many authors found them to be biased in some settings. Non-compliance was generally assumed to be all-or-nothing and only occurring in the intervention group, although some methods considered it as time-varying. Simulation studies commonly varied the level and type of non-compliance and factors such as effect size and strength of confounding. The quality of papers was generally good, although some lacked detail and justification. Therefore, their conclusions were deemed to be less reliable. CONCLUSIONS: It is common for papers to consider instrumental variable methods but more studies are needed that consider G-methods and compare a wide range of methods in realistic scenarios. It is difficult to make conclusions about the best method to deal with non-compliance due to a limited body of evidence and the difficulty in combining results from independent simulation studies. PROSPERO REGISTRATION NUMBER: CRD42022370910.

Incorporation of patient and public involvement in statistical methodology research: development of an animation.

BACKGROUND: Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects. METHODS: This project was conducted between August 2022 and August 2023. The aim is to report the process of the development of an accessible animation to describe what statistical methodology is and the importance of PPIE in statistical methodology research projects. For this, we combined storyboarding and scriptwriting with feedback from PPIE members and researchers. RESULTS: After three stages that incorporated feedback from the relevant stakeholders, we produced a final animation about PPIE in statistical methodology. The resulting animation used minimal text, simple animation techniques and was of short duration (< 3 min) to optimise the communication of the key messages clearly and effectively. CONCLUSIONS: The resulting animation provides a starting point for members of the public to learn about PPIE in statistical methodology research and for methodologists who wish to conduct PPIE. We recommend further work to explore ways in which members of the public can be more meaningfully involved in methodology research.

Patient and public involvement and engagement (PPIE) is when members of the public are directly involved in carrying out research projects. This is important because we as researchers want to make sure we are focusing on what matters most to patients, so that the research has as large an impact as possible. PPIE has typically been used in more applied research projects, such as clinical trials, but is equally as important in statistical methodology research, where we focus on making sure the statistical tools that we use in the applied projects are as good as possible. The aim of this project was to create a short animation that helps to explain the importance of PPIE in statistical methodology research projects. Researchers sometimes incorrectly assume that PPIE is less important in these projects as this type of research has a less obvious benefit to patients. The animation helps to further explain these concepts. It describes what statistical methodology research is and why involving members of the public is still important. This paper explains the process of developing the animation, including receiving feedback from members of the public to make sure the animation is accessible to as many people as possible. The result is a short, 3-min animation that is free to view on the NIHR website. This can be used by other researchers to help them when recruiting members of the public to their research projects.