Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging.

Clonal hematopoiesis (CH) arises when hematopoietic stem cells (HSCs) acquire mutations, most frequently in the DNMT3A and TET2 genes, conferring a competitive advantage through mechanisms that remain unclear. To gain insight into how CH mutations enable gradual clonal expansion, we used single-cell multi-omics with high-fidelity genotyping on human CH bone marrow (BM) samples. Most of the selective advantage of mutant cells occurs within HSCs. DNMT3A- and TET2-mutant clones expand further in early progenitors, while TET2 mutations accelerate myeloid maturation in a dose-dependent manner. Unexpectedly, both mutant and non-mutant HSCs from CH samples are enriched for inflammatory and aging transcriptomic signatures, compared with HSCs from non-CH samples, revealing a non-cell-autonomous effect. However, DNMT3A- and TET2-mutant HSCs have an attenuated inflammatory response relative to wild-type HSCs within the same sample. Our data support a model whereby CH clones are gradually selected because they are resistant to the deleterious impact of inflammation and aging.

Early radiological outcomes of a fully porous bridging collar in lower-limb endoprosthetic reconstructions: a case-matched retrospective series to assess osseointegration.

BACKGROUND: Limb-salvage surgery involving the utilization of endoprosthetic replacements is commonly employed following segmental bone resection for primary and secondary bone tumors. This study aimed to evaluate whether a fully porous bridging collar promotes early osseous integration in endoprosthetic replacements. METHODS: We undertook a retrospective review of all lower-limb endoprostheses utilizing a fully porous endosteal bridging collar design. We matched this cohort with a conventional extra-osteal non-porous fully hydroxyapatite-coated grooved collar cohort according to surgical indication, implant type, resection length, age, and follow-up time. At 6, 12, and 24 months post-implantation, radiographs were assessed for the number of cortices with or without osseointegration on orthogonal radiographs. Each radiograph was scored on a scale of -4 to + 4 for the number of cortices bridging the ongrowth between the bone and the collar of the prosthesis. Implant survival was estimated using the Kaplan-Meier method, and the mean number of osseointegrated cortices at each time point between the collar designs was compared using a paired t-test. RESULTS: Ninety patients were retrospectively identified and analyzed. After exclusion, 40 patients with porous bridging collars matched with 40 patients with conventional extra-osteal non-porous collars were included in the study (n = 80). The mean age was 63.4 years (range 16-91 years); there were 37 males and 43 females. The groups showed no difference in implant survival (P = 0.54). The mean number of cortices with radiographic ongrowth for the porous bridging collar and non-porous collar groups was 2.1 and 0.3, respectively, at 6-month (P < 0.0001), 2.4 and 0.5, respectively, at 12-month (P = 0.044), and 3.2 and -0.2, respectively, at 24-month (P = 0.18) radiological follow-up. CONCLUSION: These findings indicate that fully porous bridging collars increased the number of cortices, with evidence of bone ongrowth between 6 and 24 months post-implantation. By contrast, extra-osteal collars exhibited reduced evidence of ongrowth between 6 and 24 months post-implantation. In the medium term, the use of a fully porous bridging collar may translate to a reduced incidence of aseptic loosening.

Epidemiology of revision hip replacement surgery in the UK over the past 15 years-an analysis from the National Joint Registry.

OBJECTIVES: To investigate trends in the incidence rate and main indication for revision hip replacement (rHR) over the past 15 years in the UK. DESIGN: Repeated national cross-sectional study from 2006 to 2020. SETTING/PARTICIPANTS: rHR procedures were identified from the National Joint Registry for England, Wales, Northern Ireland, the Isle of Man and the States of Guernsey. Population statistics were obtained from the Office for National Statistics. MAIN OUTCOME MEASURES: Crude incidence rates of rHR. RESULTS: The incidence rate of rHR doubled from 11 per 100 000 adults in 2006 (95% CI 10.7 to 11.3) to a peak of 22 per 100 000 adults (95% CI 22 to 23) in 2012, before falling to 17 per 100 000 adults in 2019 (95% CI 16 to 17) (24.5% decrease from peak). The incidence rate of rHR reduced by 39% in 2020 compared with 2019 (during the COVID-19 pandemic). The most frequent indications for rHR between 2006 and 2019 were loosening/lysis (27.8%), unexplained pain (15.1%) and dislocation/instability (14.7%). There were incremental increases in the annual number and incidence rates of rHR for fracture, infection, dislocation/instability and a decrease in rHR for aseptic loosening/lysis. CONCLUSIONS: The incidence rate of rHR doubled from 2006 to 2012, likely due to high early failure rates of metal-on-metal hip replacements. The incidence of rHR then decreased by approximately 25% from 2012 to 2019, followed by a large decrease during the COVID-19 pandemic. The decrease in the number of rHR performed for aseptic loosening/lysis may reflect improved wear and implant longevity. Increased healthcare resource will be required to care for the increasing numbers of patients undergoing rHR for fracture and infection.

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.

Motivational support intervention to reduce smoking and increase physical activity in smokers not ready to quit: the TARS RCT.

Background: Physical activity can support smoking cessation for smokers wanting to quit, but there have been no studies on supporting smokers wanting only to reduce. More broadly, the effect of motivational support for such smokers is unclear. Objectives: The objectives were to determine if motivational support to increase physical activity and reduce smoking for smokers not wanting to immediately quit helps reduce smoking and increase abstinence and physical activity, and to determine if this intervention is cost-effective. Design: This was a multicentred, two-arm, parallel-group, randomised (1 : 1) controlled superiority trial with accompanying trial-based and model-based economic evaluations, and a process evaluation. Setting and participants: Participants from health and other community settings in four English cities received either the intervention (n = 457) or usual support (n = 458). Intervention: The intervention consisted of up to eight face-to-face or telephone behavioural support sessions to reduce smoking and increase physical activity. Main outcome measures: The main outcome measures were carbon monoxide-verified 6- and 12-month floating prolonged abstinence (primary outcome), self-reported number of cigarettes smoked per day, number of quit attempts and carbon monoxide-verified abstinence at 3 and 9 months. Furthermore, self-reported (3 and 9 months) and accelerometer-recorded (3 months) physical activity data were gathered. Process items, intervention costs and cost-effectiveness were also assessed. Results: The average age of the sample was 49.8 years, and participants were predominantly from areas with socioeconomic deprivation and were moderately heavy smokers. The intervention was delivered with good fidelity. Few participants achieved carbon monoxide-verified 6-month prolonged abstinence [nine (2.0%) in the intervention group and four (0.9%) in the control group; adjusted odds ratio 2.30 (95% confidence interval 0.70 to 7.56)] or 12-month prolonged abstinence [six (1.3%) in the intervention group and one (0.2%) in the control group; adjusted odds ratio 6.33 (95% confidence interval 0.76 to 53.10)]. At 3 months, the intervention participants smoked fewer cigarettes than the control participants (21.1 vs. 26.8 per day). Intervention participants were more likely to reduce cigarettes by ≥ 50% by 3 months [18.9% vs. 10.5%; adjusted odds ratio 1.98 (95% confidence interval 1.35 to 2.90] and 9 months [14.4% vs. 10.0%; adjusted odds ratio 1.52 (95% confidence interval 1.01 to 2.29)], and reported more moderate-to-vigorous physical activity at 3 months [adjusted weekly mean difference of 81.61 minutes (95% confidence interval 28.75 to 134.47 minutes)], but not at 9 months. Increased physical activity did not mediate intervention effects on smoking. The intervention positively influenced most smoking and physical activity beliefs, with some intervention effects mediating changes in smoking and physical activity outcomes. The average intervention cost was estimated to be £239.18 per person, with an overall additional cost of £173.50 (95% confidence interval -£353.82 to £513.77) when considering intervention and health-care costs. The 1.1% absolute between-group difference in carbon monoxide-verified 6-month prolonged abstinence provided a small gain in lifetime quality-adjusted life-years (0.006), and a minimal saving in lifetime health-care costs (net saving £236). Conclusions: There was no evidence that behavioural support for smoking reduction and increased physical activity led to meaningful increases in prolonged abstinence among smokers with no immediate plans to quit smoking. The intervention is not cost-effective. Limitations: Prolonged abstinence rates were much lower than expected, meaning that the trial was underpowered to provide confidence that the intervention doubled prolonged abstinence. Future work: Further research should explore the effects of the present intervention to support smokers who want to reduce prior to quitting, and/or extend the support available for prolonged reduction and abstinence. Trial registration: This trial is registered as ISRCTN47776579. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 4. See the NIHR Journals Library website for further project information.

NHS pharmacological and behavioural support helps smokers wanting to quit, and physical activity may also help. It is unclear if behavioural support for those not ready to quit may lead to more quit attempts and abstinence from smoking. A total of 915 smokers who wanted to reduce their smoking, but who had not yet quit, were recruited and randomised to receive an intervention or brief support as usual (brief advice to quit), in Plymouth, London, Oxford and Nottingham. The intervention involved up to eight sessions (by telephone or in person) of motivational support to reduce smoking and increase physical activity (and more sessions to support a quit attempt). Participants self-reported smoking and physical activity information at the start of the trial and after 3 and 9 months. Self-reported quitters confirmed their abstinence with a biochemical test of expired air or saliva. Our main interest was in whether or not the groups differed in the proportion who remained abstinent for at least 6 months. Overall, only 1­2% remained abstinent for 6 months. Although it appeared that a greater proportion did so after receiving the intervention, because few participants were abstinent, the results are not conclusive. However, the intervention had beneficial effects on less rigorous outcomes, including a reduction in the self-reported number of cigarettes smoked, and a greater proportion of intervention than control participants with self-reported and biochemically verified abstinence at 3 months. The intervention also helped participants to reduce, by at least half, the number of cigarettes they smoked at 3 and 9 months, and to report more physical activity, but only at 3 months. Despite reasonable intervention engagement and some short-term changes in smoking and physical activity, the trial does not provide evidence that this intervention would help smokers to quit for at least 6 months nor would it be cost-effective, with an average cost of £239 per smoker.

Effectiveness and cost-effectiveness of behavioural support for prolonged abstinence for smokers wishing to reduce but not quit: Randomised controlled trial of physical activity assisted reduction of smoking (TARS).

AIMS: For smokers unmotivated to quit, we assessed the effectiveness and cost-effectiveness of behavioural support to reduce smoking and increase physical activity on prolonged abstinence and related outcomes. DESIGN: A multi-centred pragmatic two-arm parallel randomised controlled trial. SETTING: Primary care and the community across four United Kingdom sites. PARTICIPANTS: Nine hundred and fifteen adult smokers (55% female, 85% White), recruited via primary and secondary care and the community, who wished to reduce their smoking but not quit. INTERVENTIONS: Participants were randomised to support as usual (SAU) (n = 458) versus multi-component community-based behavioural support (n = 457), involving up to eight weekly person-centred face-to-face or phone sessions with additional 6-week support for those wishing to quit. MEASUREMENTS: Ideally, cessation follows smoking reduction so the primary pre-defined outcome was biochemically verified 6-month prolonged abstinence (from 3-9 months, with a secondary endpoint also considering abstinence between 9 and 15 months). Secondary outcomes included biochemically verified 12-month prolonged abstinence and point prevalent biochemically verified and self-reported abstinence, quit attempts, number of cigarettes smoked, pharmacological aids used, SF12, EQ-5D and moderate-to-vigorous physical activity (MVPA) at 3 and 9 months. Intervention costs were assessed for a cost-effectiveness analysis. FINDINGS: Assuming missing data at follow-up implied continued smoking, nine (2.0%) intervention participants and four (0.9%) SAU participants achieved the primary outcome (adjusted odds ratio, 2.30; 95% confidence interval [CI] = 0.70-7.56, P = 0.169). At 3 and 9 months, the proportions self-reporting reducing cigarettes smoked from baseline by ≥50%, for intervention versus SAU, were 18.9% versus 10.5% (P = 0.009) and 14.4% versus 10% (P = 0.044), respectively. Mean difference in weekly MVPA at 3 months was 81.6 minutes in favour of the intervention group (95% CI = 28.75, 134.47: P = 0.003), but there was no significant difference at 9 months (23.70, 95% CI = -33.07, 80.47: P = 0.143). Changes in MVPA did not mediate changes in smoking outcomes. The intervention cost was £239.18 per person, with no evidence of cost-effectiveness. CONCLUSIONS: For United Kingdom smokers wanting to reduce but not quit smoking, behavioural support to reduce smoking and increase physical activity improved some short-term smoking cessation and reduction outcomes and moderate-to-vigorous physical activity, but had no long-term effects on smoking cessation or physical activity.

PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing.

Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health. Human deficiency in PCYT2 causes a severe disease with failure to thrive and progressive weakness. pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice recapitulate the participant phenotypes, with failure to thrive, progressive muscle weakness and accelerated ageing. Mechanistically, muscle Pcyt2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure and stability. PCYT2 activity declines in ageing muscles of mice and humans, and adeno-associated virus-based delivery of PCYT2 ameliorates muscle weakness in Pcyt2-knockout and old mice, offering a therapy for individuals with a rare disease and muscle ageing. Thus, PCYT2 plays a fundamental and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2-synthesized lipids to severe muscle dystrophy and ageing.

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.

A group-based behavioural intervention for weight management (PROGROUP) versus usual care in adults with severe obesity: a feasibility randomised controlled trial protocol.

BACKGROUND: Approximately 15 million people in the UK live with obesity, around 5 million of whom have severe obesity (body mass index (BMI) ≥35kg/m2). Having severe obesity markedly compromises health, well-being and quality of life, and substantially reduces life expectancy. These adverse outcomes are prevented or ameliorated by weight loss, for which sustained behavioural change is the cornerstone of treatment. Although NHS specialist 'Tier 3' Weight Management Services (T3WMS) support people with severe obesity, using individual and group-based treatment, the current evidence on optimal intervention design and outcomes is limited. Due to heterogeneity of severe obesity, there is a need to tailor treatment to address individual needs. Despite this heterogeneity, there are good reasons to suspect that a structured group-based behavioural intervention may be more effective and cost-effective for the treatment of severe obesity compared to usual care. The aims of this study are to test the feasibility of establishing and delivering a multi-centre randomised controlled clinical trial to compare a group-based behavioural intervention versus usual care in people with severe obesity. METHODS: This feasibility randomised controlled study is a partially clustered multi-centre trial of PROGROUP (a novel group-based behavioural intervention) versus usual care. Adults ≥18 years of age who have been newly referred to and accepted by NHS T3WMS will be eligible if they have a BMI ≥40, or ≥35 kg/m2 with comorbidity, are suitable for group-based care and are willing to be randomised. Exclusion criteria are participation in another weight management study, planned bariatric surgery during the trial, and unwillingness or inability to attend group sessions. Outcome assessors will be blinded to treatment allocation and success of blinding will be evaluated. Clinical measures will be collected at baseline, 6 and 12 months post-randomisation. Secondary outcome measures will be self-reported and collected remotely. Process and economic evaluations will be conducted. DISCUSSION: This randomised feasibility study has been designed to test all the required research procedures and additionally explore three key issues; the feasibility of implementing a complex trial at participating NHS T3WMS, training the multidisciplinary healthcare teams in a standard intervention, and the acceptability of a group intervention for these particularly complex patients. TRIAL REGISTRATION: ISRCTN number 22088800.

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.

A guide to debridement, antibiotics, and implant retention.

Debridement, antibiotics, and implant retention (DAIR) is an alternative management strategy for the treatment of periprosthetic joint infection (PJI). While infection eradication rates are lower with DAIR, the benefits including decreased morbidity, improved functional outcomes, and decreased cost may justify the risks when considering this form of treatment compared to traditional one or two stage exchange arthroplasty. Implant longevity in the setting of a successful DAIR is similar to matched patients who have not experienced a PJI. An experienced arthroplasty surgeon well versed in extensile exposure should perform the DAIR. This procedure should not be viewed as a simple "washout." While PJI may be considered a surgical urgency, DAIR can be performed on a planned list if it allows for appropriate staffing and implants for the procedure. Arthroscopic irrigation may be performed for a patient in extremis but it should not be viewed as a definitive procedure to address PJI. Keys to a successful DAIR include accurate tissue sampling to determine the infective organism, meticulous, radical debridement, and exchange of modular components if possible. A multidisciplinary team (MDT) including an infectious disease specialist should be involved prior to surgery in order to guide appropriate antimicrobial therapy throughout the patient's course of treatment. In the article below we present our indications, considerations, and technique for performing a DAIR for PJI for hip and knee arthroplasty.

The Joint-Specific BACH classification: A predictor of outcome in prosthetic joint infection.

BACKGROUND: There is currently no commonly accepted method of stratifying complexity of prosthetic joint infection (PJI). This study assesses a new classification, the Joint-Specific, Bone involvement, Anti-microbial options, Coverage of the soft tissues, Host status (JS-BACH) classification, for predicting clinical and patient reported outcomes in PJI. METHODS: Patients who received surgery for PJI at two centres in the UK between 2010 and 2015 were classified using JS-BACH as 'uncomplicated', 'complex' or 'limited treatment options'. Patient reported outcomes were recorded at 365-days following the index operation and included the EuroQol EQ-5D-3L index score and the EQ-visual analogue score (VAS). Clinical outcome data were obtained from the most recent follow-up appointment. FINDINGS: 220 patients met the inclusion criteria. At 365-days following the index operation, patients with 'uncomplicated' PJI reported similar EQ-index scores (0.730, SD:0.326) and EQ-VAS (79.4, SD:20.9) compared to the age-matched population. Scores for 'uncomplicated' PJI were significantly higher than patients classified as having 'complex' (EQ-index:0.515 SD:0.323, p = 0.012; EQ-VAS:68.4 SD:19.4, p = 0.042) and 'limited treatment options' PJI (EQ-index:0.333 SD:0.383, p < 0.001; EQ-VAS:60.2, SD:23.1, p = 0.005). The median time to final follow-up was 4.7 years (inter-quartile range 2.7-6.7 years) where there were 74 cases (33.6%) of confirmed recurrence. Using death as a competing risk, the Cox proportional-hazards ratio of recurrence for 'complex' versus 'uncomplicated' PJI was 23.7 (95% CI:3.23-174.0, p = 0.002) and having 'limited options' verses 'uncomplicated' PJI was 57.7 (95% CI:7.66-433.9, p < 0.001). INTERPRETATION: The JS-BACH classification can help predict likelihood of recurrence and quality of life following surgery for PJI. This will aid clinicians in sharing prognostic information with patients and help guide referral for specialist management of PJI.

Feasibility of school students Skyping care home residents to reduce loneliness.

BACKGROUND: Intergenerational friendship has proved useful for older people in increasing socialisation. We explored the feasibility of school students Skyping older people in care homes with the long-term aim of reducing loneliness. METHODS: Six school students from one secondary school and twenty older people, including seven with mild to moderate dementia, from three care homes, engaged in Skype video-calls over six weeks. A conversational aid aimed to help school students maintain conversations was employed. Students and care staff completed feedback forms after each session on video-call usage, usefulness of the conversational aid, and barriers and benefits of video-calls. Six care staff provided further feedback on residents' experiences through unstructured interviews. Interviews and field notes were thematically analysed. RESULTS: Residents enjoyed Skype-calls with school students. Over six weeks, video-calls became longer, and more residents participated. Analysis revealed four themes. First, the intervention led to increased mobility for three older people and improved self-care in regard to personal appearance for five residents. Second, school students and older people formed friendships which inspired the need to meet in person. Third, the use of video-calls enabled participants to view each other's environments in real time. Last, directly experiencing the intervention was important for the continued participation of the care staff in the study. Skype-calls between schools and care homes are feasible and may help reduce loneliness. CONCLUSIONS: Institutional collaboration between educational settings and care homes through cost effective video-calls can be useful to increase socialisation for older people, and promote later on-going use with other external organisations to help reduce loneliness and social isolation.

Primary stability of a proximally coated and tapered stem.

AIMS: The aim of this prospective cohort study was to evaluate the early migration of the TriFit cementless proximally coated tapered femoral stem using radiostereometric analysis (RSA). METHODS: A total of 21 patients (eight men and 13 women) undergoing primary total hip arthroplasty (THA) for osteoarthritis of the hip were recruited in this study and followed up for two years. Two patients were lost to follow-up. All patients received a TriFit stem and Trinity Cup with a vitamin E-infused highly cross-linked ultra-high molecular weight polyethylene liner. Radiographs for RSA were taken postoperatively and then at three, 12, and 24 months. Oxford Hip Score (OHS), EuroQol five-dimension questionnaire (EQ-5D), and adverse events were reported. RESULTS: At two years, the mean subsidence of the head and tip for the TriFit stem was 0.38 mm (SD 0.32) and 0.52 mm (SD 0.36), respectively. The total migration of the head and tip was 0.55 mm (SD 0.32) and 0.71 mm (SD 0.38), respectively. There were no statistically significant differences between the three to 12 months' migration (p = 0.105) and 12 to 24 months' migration (p = 0.694). The OHS and EQ-5D showed significant improvements at two years. CONCLUSION: The results of this study suggest that the TriFit femoral stem achieves initial stability and is likely to be stable in the mid and long term. A long-term outcome study is required to assess late mechanisms of failure and the effects of bone mineral density (BMD) related changes. Cite this article: Bone Joint J 2021;103-B(4):644-649.

Efficacy of vision-based treatments for children and teens with amblyopia: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To identify differences in efficacy between vision-based treatments for improving visual acuity (VA) of the amblyopic eye in persons aged 4-17 years old. DATA SOURCES: Ovid Embase, PubMed (Medline), the Cochrane Library, Vision Cite and Scopus were systematically searched from 1975 to 17 June 2020. METHODS: Two independent reviewers screened search results for randomised controlled trials of vision-based amblyopia treatments that specified change in amblyopic eye VA (logMAR) as the primary outcome measure. Quality was assessed via risk of bias and GRADE (Grading of Recommendations, Assessment, Development, and Evaluations). RESULTS: Of the 3346 studies identified, 36 were included in a narrative synthesis. A random effects meta-analysis (five studies) compared the efficacy of binocular treatments versus patching: mean difference -0.03 logMAR; 95% CI 0.01 to 0.04 (p<0.001), favouring patching. An exploratory study-level regression (18 studies) showed no statistically significant differences between vision-based treatments and a reference group of 2-5 hours of patching. Age, sample size and pre-randomisation optical treatment were not statistically significantly associated with changes in amblyopic eye acuity. A network meta-analysis (26 studies) comparing vision-based treatments to patching 2-5 hours found one statistically significant comparison, namely, the favouring of a combination of two treatment arms comparing combination and binocular treatments, against patching 2-5 hours: standard mean difference: 2.63; 95% CI 1.18 to 4.09. However, this result was an indirect comparison calculated from a single study. A linear regression analysis (17 studies) found a significant relationship between adherence and effect size, but the model did not completely fit the data: regression coefficient 0.022; 95% CI 0.004 to 0.040 (p=0.02). CONCLUSION: We found no clinically relevant differences in treatment efficacy between the treatments included in this review. Adherence to the prescribed hours of treatment varied considerably and may have had an effect on treatment success.

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.

Aesthetically Designing Video-Call Technology With Care Home Residents: A Focus Group Study.

BACKGROUND: Video-calls have proven to be useful for older care home residents in improving socialization and reducing loneliness. Nonetheless, to facilitate the acceptability and usability of a new technological intervention, especially among people with dementia, there is a need for user-led design improvements. The current study conducted focus groups with an embedded activity with older people to allow for a person-centered design of a video-call intervention. METHODS: Twenty-eight residents across four care homes in the South West of England participated in focus groups to aesthetically personalize and 'dress-up' the equipment used in a video-call intervention. Each care home was provided with a 'Skype on Wheels' (SoW) device, a wheelable 'chassis' comprising an iPad or tablet for access to Skype, and a telephone handset. During the focus group, residents were encouraged to participate in an activity using colorful materials to 'dress-up' SoW. Comments before, during and after the 'dress up' activity were audio recorded. Framework analysis was used to analyze the focus group data. RESULTS: Older people, including seven with dementia were able to interact with and implement design changes to SoW through aesthetic personalization. Themes arising from the data included estrangement, anthropomorphism, reminiscence, personalization, need for socialization versus fear of socialization and attitudes toward technology. After this brief exposure to SoW, residents expressed the likelihood of using video-calls for socialization in the future. CONCLUSION: Care home residents enjoy engaging with new technologies when given the opportunity to interact with it, to personalize it and to understand its purpose. Low cost aesthetic personalization of technologies can improve their acceptability, usability, and implementation within complex care environments.