Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.

The Outcomes of Hip and Knee Fungal Periprosthetic Joint Infections: A Retrospective Cohort Study.

BACKGROUND: Fungal infections are a rare cause of periprosthetic joint infection (PJI), identified in 1% of all of these cases. Outcomes are not well-established due to small cohort sizes in the published literature. The aims of this study were to establish the patient demographics and infection-free survival of patients presenting to 2 high-volume revision arthroplasty centers who had fungal infection of either a hip or knee arthroplasty. We sought to identify risk factors for poor outcomes. METHODS: A retrospective analysis was performed of patients at 2 high-volume revision arthroplasty centers who had confirmed fungal PJI of the total hip arthroplasty (THA) and total knee arthroplasty (TKA). Consecutive patients treated between 2010 and 2019 were included. Patient outcomes were classified as infection eradication or persistence. A total of 67 patients who had 69 fungal PJI cases were identified. There were 47 cases involving the knee and 22 of the hip. Mean age at presentation was 68 years (THA mean 67, range 46 to 86) (TKA mean 69, range, 45 to 88). A history of sinus or open wound was present in 60 cases (89%) (THA 21 cases, TKA 39 cases). The median number of operations prior to the procedure at which fungal PJI was identified was 4 (range, 0 to 9), THA 5 (range, 3 to 9), and TKA 3 (range, 0 to 9). RESULTS: At a mean follow-up 34 months (range, 2 to 121), remission rates were 11 of 24 (45%) and 22 of 45 (49%) for hip and knee, respectively. There were 7 TKA (16%) and 1 THA cases (4%) that failed treatment resulting in amputations. During the study period, 7 THA and 6 TKA patients had died. Two deaths were directly attributable to PJI. Patient outcome was not associated with the number of prior procedures, patient comorbidities, or organisms. CONCLUSION: Eradication of fungal PJI is achieved in less than half of patients, and outcomes are comparable for TKA and THA. The majority of patients who have fungal PJI present with an open wound or sinus. No factors were identified that increase the risk of persistent infection. Patients who have fungal PJI should be informed of the poor outcomes.

Choline transporter-like proteins 1 and 2 are newly identified plasma membrane and mitochondrial ethanolamine transporters.

The membrane phospholipids phosphatidylcholine and phosphatidylethanolamine (PE) are synthesized de novo by the CDP-choline and CDP-ethanolamine (Kennedy) pathway, in which the extracellular substrates choline and ethanolamine are transported into the cell, phosphorylated, and coupled with diacylglycerol to form the final phospholipid product. Although multiple transport systems have been established for choline, ethanolamine transport is poorly characterized and there is no single protein assigned a transport function for ethanolamine. The solute carriers 44A (SLC44A) known as choline transporter-like proteins-1 and -2 (CTL1 and CTL2) are choline transporter at the plasma membrane and mitochondria. We report a novel function of CTL1 and CTL2 in ethanolamine transport. Using the lack or the gain of gene function in combination with specific antibodies and transport inhibitors we established two distinct ethanolamine transport systems of a high affinity, mediated by CTL1, and of a low affinity, mediated by CTL2. Both transporters are Na+-independent ethanolamine/H+ antiporters. Primary human fibroblasts with separate frameshift mutations in the CTL1 gene (M1= SLC44A1ΔAsp517 and M2= SLC44A1ΔSer126) are devoid of CTL1 ethanolamine transport but maintain unaffected CTL2 transport. The lack of CTL1 in M2 cells reduced the ethanolamine transport, the flux through the CDP-ethanolamine Kennedy pathway, and PE synthesis. In contrast, overexpression of CTL1 in M2 cells improved ethanolamine transport and PE synthesis. These data firmly establish that CTL1 and CTL2 are the first identified ethanolamine transporters in whole cells and mitochondria, with intrinsic roles in de novo PE synthesis by the Kennedy pathway and intracellular redistribution of ethanolamine.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

A process evaluation, with mediation analysis, of a web-based intervention to augment primary care exercise referral schemes: the e-coachER randomised controlled trial.

BACKGROUND: The e-coachER trial aimed to determine whether adding web-based behavioural support to exercise referral schemes (ERS) increased long-term device-measured physical activity (PA) for patients with chronic conditions, compared to ERS alone, within a randomised controlled trial. This study explores the mechanisms of action of the e-coachER intervention using measures of the behaviour change processes integral to the intervention's logic model. METHODS: Four hundred fifty adults with obesity, diabetes, hypertension, osteoarthritis or history of depression referred to an ERS were recruited in Plymouth, Birmingham and Glasgow. The e-coachER intervention comprising 7-Steps to Health was aligned with Self-Determination Theory and mapped against evidence-based behaviour change techniques (BCTs). Participants completed questionnaires at 0, 4, and 12 months to assess PA and self-reported offline engagement with core BCTs in day-to-day life (including action planning and self-monitoring) and beliefs relating to PA (including perceived importance, confidence, competence, autonomy and support). We compared groups at 4 and 12 months, controlling for baseline measures and other covariates. Mediation analysis using the product of coefficients method was used to determine if changes in process variables mediated intervention effects on moderate to vigorous physical activity (MVPA) recorded by accelerometer and self-report at 4- and 12-months. RESULTS: The internal reliability (Cronbach's alpha) for all multi-item scales was > 0.77. At 4-months, those randomised to e-coachER reported higher levels of PA beliefs relating to importance (1.01, 95% confidence interval (CI): 0.42 to 1.61, p = 0.001), confidence (1.28, 95% CI: 0.57 to 1.98, p < 0.001), competence (1.61, 95% CI: .68 to 2.54, p = 0.001), availability of support (0.77, 95% CI: 0.07 to 1.48, p = 0.031), use of action planning (1.54, 95% CI: 0.23 to 2.85, p = 0.021) and use of self-monitoring (0.76, 95% CI: 0.19 to 1.32, p = 0.009) compared to ERS alone. There were no intervention effects on autonomous beliefs or perceived frequency of support, compared to ERS alone. At the 12-month follow-up, participants belief in the importance of PA was the only process measure to remain significantly higher in the e-coachER group when compared to ERS alone (0.75, 95% CI: 0.05 to 1.45). Intervention effects on perceived importance (2.52, 95% CI: 0.45 to 5.39), action planning (1.56, 95% CI: 0.10 to 3.54) and self-monitoring (1.92, 95% CI: 0.21 to 4.33) at 4-months significantly mediated change in accelerometer measured MVPA at 12-months (recorded in ≥ 10-min bouts). CONCLUSIONS: e-coachER led to some short-term changes in most process outcomes. Some of these processes also appeared to mediate e-coachER effects on changes in accelerometer measured MVPA. Further work should be carried out to understand how best to design and implement theoretically underpinned web-based physical activity promotion interventions within ERS. TRIAL REGISTRATION: ISRCTN, ISRCTN15644451 . Registered 12 February 2015.

Utility of pre-operative haemoglobin concentration to guide peri-operative blood tests for hip and knee arthroplasty: A decision curve analysis.

OBJECTIVE: Assess the prognostic value of pre-operative haemoglobin concentration (Hb) for identifying patients who develop severe post-operative anaemia or require blood transfusion following primary total hip or knee, or unicompartmental knee arthroplasty (THA, TKA, UKA). BACKGROUND: Pre-operative group and save (G&S), and post-operative Hb measurement may be unnecessary for many patients undergoing hip and knee arthroplasty provided individuals at greatest risk of severe post-operative anaemia can be identified. METHODS AND MATERIALS: Patients undergoing THA, TKA, or UKA between 2011 and 2018 were included. Outcomes were post-operative Hb below 70 and 80 g/L, and peri-operative blood transfusion. Logistic regression assessed the association between pre-operative Hb and each outcome. Decision curve analysis compared strategies for selecting patients for G&S and post-operative Hb measurement. RESULTS: 10 015 THA, TKA and UKA procedures were performed in 8582 patients. The incidence of blood transfusion (4.5%) decreased during the study. Using procedure specific Hb thresholds to select patients for pre-operative G&S and post-operative Hb testing had a greater net benefit than selecting all patients, no patients, or patients with pre-operative anaemia. CONCLUSIONS: Pre-operative G&S and post-operative Hb measurement may not be indicated for UKA or TKA when adopting restrictive transfusion thresholds, provided clinicians accept a 0.1% risk of patients developing severe undiagnosed post-operative anaemia (Hb < 70 g/L). The decision to perform these blood tests for THA patients should be based on local institutional data and selection of acceptable risk thresholds.

Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration.

Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier-mediated transport. Here, we report on four individuals from three families with neurodegenerative disease and homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in the SLC44A1 gene encoding choline transporter-like protein 1. Clinical features included progressive ataxia, tremor, cognitive decline, dysphagia, optic atrophy, dysarthria, as well as urinary and bowel incontinence. Brain MRI demonstrated cerebellar atrophy and leukoencephalopathy. Moreover, low signal intensity in globus pallidus with hyperintensive streaking and low signal intensity in substantia nigra were seen in two individuals. The Asp517Metfs*19 and Ser126Metfs*8 fibroblasts were structurally and functionally indistinguishable. The most prominent ultrastructural changes of the mutant fibroblasts were reduced presence of free ribosomes, the appearance of elongated endoplasmic reticulum and strikingly increased number of mitochondria and small vesicles. When chronically treated with choline, those characteristics disappeared and mutant ultrastructure resembled healthy control cells. Functional analysis revealed diminished choline transport yet the membrane phosphatidylcholine content remained unchanged. As part of the mechanism to preserve choline and phosphatidylcholine, choline transporter deficiency was implicated in impaired membrane homeostasis of other phospholipids. Choline treatments could restore the membrane lipids, repair cellular organelles and protect mutant cells from acute iron overload. In conclusion, we describe a novel childhood-onset neurometabolic disease caused by choline transporter deficiency with autosomal recessive inheritance.

Randomised controlled trial of an augmented exercise referral scheme using web-based behavioural support for inactive adults with chronic health conditions: the e-coachER trial.

OBJECTIVE: To determine whether adding web-based support (e-coachER) to an exercise referral scheme (ERS) increases objectively assessed physical activity (PA). DESIGN: Multicentre trial with participants randomised to usual ERS alone (control) or usual ERS plus e-coachER (intervention). SETTING: Primary care and ERS in three UK sites from 2015 to 2018. PARTICIPANTS: 450 inactive ERS referees with chronic health conditions. INTERVENTIONS: Participants received a pedometer, PA recording sheets and a user guide for the web-based support. e-coachER interactively encouraged the use of the ERS and other PA options. MAIN OUTCOME MEASURES: Primary and key secondary outcomes were: objective moderate-to-vigorous PA (MVPA) minutes (in ≥10 min bouts and without bouts), respectively, after 12 months. Secondary outcomes were: other accelerometer-derived and self-reported PA measures, ERS attendance, EQ-5D-5L, Hospital Anxiety and Depression Scale and beliefs about PA. All outcomes were collected at baseline, 4 and 12 months. Primary analysis was an intention to treat comparison between intervention and control arms at 12-month follow-up. RESULTS: There was no significant effect of the intervention on weekly MVPA at 12 months between the groups recorded in ≥10 min bouts (mean difference 11.8 min of MVPA, 95% CI: -2.1 to 26.0; p=0.10) or without bouts (mean difference 13.7 min of MVPA, 95% CI: -26.8 to 54.2; p=0.51) for 232 participants with usable data. There was no difference in the primary or secondary PA outcomes at 4 or 12 months. CONCLUSION: Augmenting ERS referrals with web-based behavioural support had only a weak, non-significant effect on MVPA. TRIAL REGISTRATION NUMBER: ISRCTN15644451.

Redesigning walking brochures using behaviour change theory: implications for walking intentions in natural environments.

Natural environments can be used to promote health through facilitating recreational walking. However, efforts to encourage this often neglect messages identified in psychological research that are effective at influencing intentions to walk. This is despite the National Institute for Health and Care Excellence stating that promotional efforts should utilize theoretical frameworks of behaviour change and be targeted towards less active adults. As an illustrative example, this experiment compared a prototypical recreational walking brochure with an "enhanced" version including such persuasive messages on people's intentions to walk for recreation in natural environments. The enhanced brochure heightened intentions for inexperienced recreational walkers through our hypothesized mechanisms, but appeared to dissuade already-experienced walkers. Optimal messaging strategies in recreational walking brochures require tailoring to more and less active readerships. Guidelines are provided for authors of recreational walking brochures, though the principles and techniques could easily be extended to other means of outdoor walking promotion.

Hip replacement.

Total hip replacement is a frequently done and highly successful surgical intervention. The procedure is undertaken to relieve pain and improve function in individuals with advanced arthritis of the hip joint. Symptomatic osteoarthritis is the most common indication for surgery. In paper 1 of this Series, we focus on how patient factors should inform the surgical decision-making process. Substantial demands are placed upon modern implants, because patients expect to remain active for longer. We discuss the advances made in implant performance and the developments in perioperative practice that have reduced complications. Assessment of surgery outcomes should include patient-reported outcome measures and implant survival rates that are based on data from joint replacement registries. The high-profile failure of some widely used metal-on-metal prostheses has shown the shortcomings of the existing regulatory framework. We consider how proposed changes to the regulatory framework could influence safety.

Exercise interventions for smoking cessation.

BACKGROUND: Taking regular exercise, whether cardiovascular-type exercise or resistance exercise, may help people to give up smoking, particularly by reducing cigarette withdrawal symptoms and cravings, and by helping to manage weight gain. OBJECTIVES: To determine the effectiveness of exercise-based interventions alone, or combined with a smoking cessation programme, for achieving long-term smoking cessation, compared with a smoking cessation intervention alone or other non-exercise intervention. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register for studies, using the term 'exercise' or 'physical activity' in the title, abstract or keywords. The date of the most recent search was May 2019. SELECTION CRITERIA: We included randomised controlled trials that compared an exercise programme alone, or an exercise programme as an adjunct to a cessation programme, with a cessation programme alone or another non-exercise control group. Trials were required to recruit smokers wishing to quit or recent quitters, to assess abstinence as an outcome and have follow-up of at least six months. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Smoking cessation was measured after at least six months, using the most rigorous definition available, on an intention-to-treat basis. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study, where possible. We grouped eligible studies according to the type of comparison, as either smoking cessation or relapse prevention. We carried out meta-analyses where appropriate, using Mantel-Haenszel random-effects models. MAIN RESULTS: We identified 24 eligible trials with a total of 7279 adult participants randomised. Two studies focused on relapse prevention among smokers who had recently stopped smoking, and the remaining 22 studies were concerned with smoking cessation for smokers who wished to quit. Eleven studies were with women only and one with men only. Most studies recruited fairly inactive people. Most of the trials employed supervised, group-based cardiovascular-type exercise supplemented by a home-based exercise programme and combined with a multi-session cognitive behavioural smoking cessation programme. The comparator in most cases was a multi-session cognitive behavioural smoking cessation programme alone. Overall, we judged two studies to be at low risk of bias, 11 at high risk of bias, and 11 at unclear risk of bias. Among the 21 studies analysed, we found low-certainty evidence, limited by potential publication bias and by imprecision, comparing the effect of exercise plus smoking cessation support with smoking cessation support alone on smoking cessation outcomes (RR 1.08, 95% CI 0.96 to 1.22; I2 = 0%; 6607 participants). We excluded one study from this analysis as smoking abstinence rates for the study groups were not reported. There was no evidence of subgroup differences according to the type of exercise promoted; the subgroups considered were: cardiovascular-type exercise alone (17 studies), resistance training alone (one study), combined cardiovascular-type and resistance exercise (one study) and type of exercise not specified (two studies). The results were not significantly altered when we excluded trials with high risk of bias, or those with special populations, or those where smoking cessation intervention support was not matched between the intervention and control arms. Among the two relapse prevention studies, we found very low-certainty evidence, limited by risk of bias and imprecision, that adding exercise to relapse prevention did not improve long-term abstinence compared with relapse prevention alone (RR 0.98, 95% CI 0.65 to 1.47; I2 = 0%; 453 participants). AUTHORS' CONCLUSIONS: There is no evidence that adding exercise to smoking cessation support improves abstinence compared with support alone, but the evidence is insufficient to assess whether there is a modest benefit. Estimates of treatment effect were of low or very low certainty, because of concerns about bias in the trials, imprecision and publication bias. Consequently, future trials may change these conclusions.

Real-time analysis of nanopore-based metagenomic sequencing from infected orthopaedic devices.

BACKGROUND: Prosthetic joint infections are clinically difficult to diagnose and treat. Previously, we demonstrated metagenomic sequencing on an Illumina MiSeq replicates the findings of current gold standard microbiological diagnostic techniques. Nanopore sequencing offers advantages in speed of detection over MiSeq. Here, we report a real-time analytical pathway for Nanopore sequence data, designed for detecting bacterial composition of prosthetic joint infections but potentially useful for any microbial sequencing, and compare detection by direct-from-clinical-sample metagenomic nanopore sequencing with Illumina sequencing and standard microbiological diagnostic techniques. RESULTS: DNA was extracted from the sonication fluids of seven explanted orthopaedic devices, and additionally from two culture negative controls, and was sequenced on the Oxford Nanopore Technologies MinION platform. A specific analysis pipeline was assembled to overcome the challenges of identifying the true infecting pathogen, given high levels of host contamination and unavoidable background lab and kit contamination. The majority of DNA classified (> 90%) was host contamination and discarded. Using negative control filtering thresholds, the species identified corresponded with both routine microbiological diagnosis and MiSeq results. By analysing sequences in real time, causes of infection were robustly detected within minutes from initiation of sequencing. CONCLUSIONS: We demonstrate a novel, scalable pipeline for real-time analysis of MinION sequence data and use of this pipeline to show initial proof of concept that metagenomic MinION sequencing can provide rapid, accurate diagnosis for prosthetic joint infections. The high proportion of human DNA in prosthetic joint infection extracts prevents full genome analysis from complete coverage, and methods to reduce this could increase genome depth and allow antimicrobial resistance profiling. The nine samples sequenced in this pilot study have shown a proof of concept for sequencing and analysis that will enable us to investigate further sequencing to improve specificity and sensitivity.

Sonication versus Tissue Sampling for Diagnosis of Prosthetic Joint and Other Orthopedic Device-Related Infections.

Current guidelines recommend collection of multiple tissue samples for diagnosis of prosthetic joint infections (PJI). Sonication of explanted devices has been proposed as a potentially simpler alternative; however, reported microbiological yield varies. We evaluated sonication for diagnosis of PJI and other orthopedic device-related infections (DRI) at the Oxford Bone Infection Unit between October 2012 and August 2016. We compared the performance of paired tissue and sonication cultures against a "gold standard" of published clinical and composite clinical and microbiological definitions of infection. We analyzed explanted devices and a median of five tissue specimens from 505 procedures. Among clinically infected cases the sensitivity of tissue and sonication culture was 69% (95% confidence interval, 63 to 75) and 57% (50 to 63), respectively (P < 0.0001). Tissue culture was more sensitive than sonication for both PJI and other DRI, irrespective of the infection definition used. Tissue culture yield was higher for all subgroups except less virulent infections, among which tissue and sonication culture yield were similar. The combined sensitivity of tissue and sonication culture was 76% (70 to 81) and increased with the number of tissue specimens obtained. Tissue culture specificity was 97% (94 to 99), compared with 94% (90 to 97) for sonication (P = 0.052) and 93% (89 to 96) for the two methods combined. Tissue culture is more sensitive and may be more specific than sonication for diagnosis of orthopedic DRI in our setting. Variable methodology and case mix may explain reported differences between centers in the relative yield of tissue and sonication culture. Culture yield was highest for both methods combined.

Physical activity for antenatal and postnatal depression in women attempting to quit smoking: randomised controlled trial.

BACKGROUND: Antenatal depression is associated with harmful consequences for both the mother and child. One intervention that might be effective is participation in regular physical activity although data on this question in pregnant smokers is currently lacking. METHODS: Women were randomised to six-weekly sessions of smoking cessation behavioural-support, or to the same support plus 14 sessions combining treadmill exercise and physical activity consultations. RESULTS: Among 784 participants (mean gestation 16-weeks), EPDS was significantly higher in the physical activity group versus usual care at end-of-pregnancy (mean group difference (95% confidence intervals (CIs)): 0.95 (0.08 to 1.83). There was no significant difference at six-months postpartum. CONCLUSION: A pragmatic intervention to increase physical activity in pregnant smokers did not prevent depression at end-of-pregnancy or at six-months postpartum. More effective physical activity interventions are needed in this population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48600346 . The trial was prospectively registered on 21/07/2008.

Video-calls to reduce loneliness and social isolation within care environments for older people: an implementation study using collaborative action research.

BACKGROUND: Older people in care may be lonely with insufficient contact if families are unable to visit. Face-to-face contact through video-calls may help reduce loneliness, but little is known about the processes of engaging people in care environments in using video-calls. We aimed to identify the barriers to and facilitators of implementing video-calls for older people in care environments. METHODS: A collaborative action research (CAR) approach was taken to implement a video-call intervention in care environments. We undertook five steps of recruitment, planning, implementation, reflection and re-evaluation, in seven care homes and one hospital in the UK. The video-call intervention 'Skype on Wheels' (SoW) comprised a wheeled device that could hold an iPad and handset, and used Skype to provide a free video-call service. Care staff were collaborators who implemented the intervention within the care-setting by agreeing the intervention, recruiting older people and their family, and setting up video-calls. Field notes and reflective diaries on observations and conversations with staff, older people and family were maintained over 15 months, and analysed using thematic analysis. RESULTS: Four care homes implemented the intervention. Eight older people with their respective social contacts made use of video-calls. Older people were able to use SoW with assistance from staff, and enjoyed the use of video-calls to stay better connected with family. However five barriers towards implementation included staff turnover, risk averseness, the SoW design, lack of family commitment and staff attitudes regarding technology. CONCLUSIONS: The SoW intervention, or something similar, could aid older people to stay better connected with their families in care environments, but if implemented as part of a rigorous evaluation, then co-production of the intervention at each recruitment site may be needed to overcome barriers and maximise engagement.

Web-Based Intervention Using Behavioral Activation and Physical Activity for Adults With Depression (The eMotion Study): Pilot Randomized Controlled Trial.

BACKGROUND: Physical activity is a potentially effective treatment for depression and depressive relapse. However, promoting physical activity in people with depression is challenging. Interventions informed by theory and evidence are therefore needed to support people with depression to become more physically active. eMotion is a Web-based intervention combining behavioral activation and physical activity promotion for people in the community with symptoms of depression. OBJECTIVE: The objectives were to assess the feasibility and acceptability of delivering eMotion to people in the community with symptoms of depression and to explore outcomes. METHODS: Participants with elevated depressive symptoms were recruited from the community through various methods (eg, social media) and randomized to eMotion or a waiting list control group for 8 weeks. eMotion is an administratively supported weekly modular program that helps people use key behavior change techniques (eg, graded tasks, action planning, and self-monitoring) to re-engage in routine, pleasurable, and necessary activities, with a focus on physical activities. Feasibility data were collected that included the following: recruitment and trial retention rates; fidelity of intervention delivery, receipt, and enactment; and acceptability of the intervention and data collection procedures. Data were collected for the primary (depression) and secondary outcomes (eg, anxiety, physical activity, fidelity, and client satisfaction) at baseline and 2 months postrandomization using self-reported Web-based questionnaires and accelerometers. Delivery fidelity (logins, modules accessed, time spent) was tracked using Web usage statistics. Exploratory analyses were conducted on the primary and secondary outcomes. RESULTS: Of the 183 people who contacted the research team, 62 were recruited and randomized. The mean baseline score was 14.6 (SD 3.2) on the 8-item Patient Health Questionnaire depression scale (PHQ-8). Of those randomized, 52 participants provided accelerometer-recorded physical activity data at baseline that showed a median of 35.8 (interquartile range [IQR] 0.0-98.6) minutes of moderate-to-vigorous physical activity (MVPA) recorded in at least 10-minute bouts per week, with only 13% (7/52) people achieving guideline levels (150 minutes of MVPA per week). In total, 81% (50/62) of participants provided follow-up data for the primary outcome (PHQ-8), but only 39% (24/62) provided follow-up accelerometer data. Within the intervention group, the median number of logins, modules accessed, and total minutes spent on eMotion was 3 (IQR 2.0-8.0), 3 (IQR 2.0-5.0), and 41.3 (IQR 18.9-90.4), respectively. Acceptability was mixed. Exploratory data analysis showed that PHQ-8 levels were lower for the intervention group than for the control group at 2 months postrandomization (adjusted mean difference -3.6, 95% CI -6.1 to -1.1). CONCLUSIONS: It was feasible to deliver eMotion in UK communities to inactive populations. eMotion has the potential to be effective and is ready for testing in a full-scale trial. Further work is needed to improve engagement with both the intervention and data collection procedures. TRIAL REGISTRATION: ClinicalTrials.gov NCT03084055; https://clinicaltrials.gov/ct2/show/NCT03084055 (Archived by WebCite at http://www.webcitation.org/6zoyM8UXa).

How do brochures encourage walking in natural environments in the UK? A content analysis.

Although walking for leisure can support health, there has been little systematic attempt to consider how recreational walking is best promoted. In the UK, local authorities create promotional materials for walking networks, but little is known about whether they effectively encourage walking through persuasive messaging. Many of these materials pertain to walks in natural environments which evidence suggests are generally visited less frequently by physically inactive individuals. Consequently the present study explores whether and how recreational walking brochures use persuasive messages in their promotion of walks in natural environments. A coding taxonomy was developed to classify text in recreational walking brochures according to five behavioural content areas and 87 categories of potentially persuasive messages. Reliability of the taxonomy was ascertained and a quantitative content analysis was applied to 26 brochures collected from Devon, UK. Brochures often provided information about an advertised route, highlighted cultural and aesthetic points of interest, and provided directions. Brochures did not use many potentially effective messages. Text seldom prompted behaviour change or built confidence for walking. Social norm related information was rarely provided and there was a general lack of information on physical activity and its benefits for health and well-being. The limited range of message strategies used in recreational walking brochures may not optimally facilitate walking in natural environments for inactive people. Future research should examine the effects of theory-informed brochures on walking intentions and behaviour. The taxonomy could be adapted to suit different media and practices surrounding physical activity in natural environments.

Clinical Outcome of Massive Endoprostheses Used for Managing Periprosthetic Joint Infections of the Hip and Knee.

BACKGROUND: Endoprosthetic replacement (EPR) is an option for management of massive bone loss resulting from infection around failed lower limb implants. The aim of this study is to determine the mid-term outcome of EPRs performed in the treatment of periprosthetic joint infection (PJI) and infected failed osteosyntheses around the hip and knee joint and identify factors that influence it. METHODS: We retrospectively reviewed all hip and knee EPRs performed between 2007 and 2014 for the management of chronic infection following complex arthroplasty or fracture fixation. Data recorded included indication for EPR, number of previous surgeries, comorbidities, and organism identified. Outcome measures included PJI eradication rate, complications, implant survival, mortality, and functional outcome (Oxford Hip or Knee Score). RESULTS: Sixty-nine EPRs (29 knees and 40 hips) were performed with a mean age of 68 years (43-92). Polymicrobial growth was detected in 36% of cases, followed by coagulase-negative staphylococci (28%) and Staphylococcus aureus (10%). Recurrence of infection occurred in 19 patients (28%): 5 were treated with irrigation and debridement, 5 with revision, 1 with above-knee amputation, and 8 remain on long-term antibiotics. PJI eradication was achieved in 50 patients (72%); the chance of PJI eradication was greater in hips (83%) than in knees (59%) (P = .038). The 5-year implant survivorship was 81% (95% confidence interval 74-88). The mean Oxford Hip Score and Oxford Knee Score were 22 (4-39) and 21 (6-43), respectively. CONCLUSION: This study supports the use of EPRs for eradication of PJI in complex, multiply revised cases. We describe PJI eradication rate of 72% with acceptable functional outcome.

Adaptations to excess choline in insulin resistant and Pcyt2 deficient skeletal muscle.

It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2+/-) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2+/- mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2+/- mice, treated Pcyt2+/- mice, and Pcyt2+/+ mice. The major positive effect of choline supplementation on IR muscle was the reduction of glucose utilization for FA and triglyceride (TAG) synthesis and increased muscle glucose storage as glycogen. Choline reduced the expression of genes for FA and TAG formation (Scd1, Fas, Srebp1c, Dgat1/2), upregulated the genes for FA oxidation (Cpt1, Pparα, Pgc1α), and had minor effects on phospholipid and lipolysis genes. Pcyt2+/- muscle had reduced insulin signaling (IRS1), autophagy (LC3), and choline transport (CTL1) proteins that were restored by choline treatment. Additionally, choline activated AMPK and Akt while inhibiting mTORC1 phosphorylation. These data established that choline supplementation could restore muscle glucose metabolism by reducing lipogenesis and improving mitochondrial and intracellular signaling for protein and energy metabolism in insulin resistant Pcyt2 deficient mice.

Molecular Diagnosis of Orthopedic-Device-Related Infection Directly from Sonication Fluid by Metagenomic Sequencing.

Culture of multiple periprosthetic tissue samples is the current gold standard for microbiological diagnosis of prosthetic joint infections (PJI). Additional diagnostic information may be obtained through culture of sonication fluid from explants. However, current techniques can have relatively low sensitivity, with prior antimicrobial therapy and infection by fastidious organisms influencing results. We assessed if metagenomic sequencing of total DNA extracts obtained direct from sonication fluid can provide an alternative rapid and sensitive tool for diagnosis of PJI. We compared metagenomic sequencing with standard aerobic and anaerobic culture in 97 sonication fluid samples from prosthetic joint and other orthopedic device infections. Reads from Illumina MiSeq sequencing were taxonomically classified using Kraken. Using 50 derivation samples, we determined optimal thresholds for the number and proportion of bacterial reads required to identify an infection and confirmed our findings in 47 independent validation samples. Compared to results from sonication fluid culture, the species-level sensitivity of metagenomic sequencing was 61/69 (88%; 95% confidence interval [CI], 77 to 94%; for derivation samples 35/38 [92%; 95% CI, 79 to 98%]; for validation samples, 26/31 [84%; 95% CI, 66 to 95%]), and genus-level sensitivity was 64/69 (93%; 95% CI, 84 to 98%). Species-level specificity, adjusting for plausible fastidious causes of infection, species found in concurrently obtained tissue samples, and prior antibiotics, was 85/97 (88%; 95% CI, 79 to 93%; for derivation samples, 43/50 [86%; 95% CI, 73 to 94%]; for validation samples, 42/47 [89%; 95% CI, 77 to 96%]). High levels of human DNA contamination were seen despite the use of laboratory methods to remove it. Rigorous laboratory good practice was required to minimize bacterial DNA contamination. We demonstrate that metagenomic sequencing can provide accurate diagnostic information in PJI. Our findings, combined with the increasing availability of portable, random-access sequencing technology, offer the potential to translate metagenomic sequencing into a rapid diagnostic tool in PJI.