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Measuring adherence to unsupervised, conservative treatment for knee osteoarthritis: A systematic review.
OBJECTIVE: To describe the measurement of adherence to unsupervised, conservative treatments for knee osteoarthritis (OA), including the methods of adherence measurement, parameters for assessing adherence and any values used to quantify adherence. METHODS: A systematic review with search terms related to knee OA, conservative treatments and adherence was conducted. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number CRD42020158188). Seven electronic databases (MEDLINE, AMED, EMBASE, CINAHL, SportDiscus, PsychINFO, PEDro) were searched from inception to February 02, 2021. Studies that included unsupervised, conservative treatment(s) for knee OA measuring adherence were eligible. Studies were independently screened for inclusion by two researchers. Data was extracted by one researcher and verified by a second researcher. Extracted data included: study type, population, type of treatment, adherence measurement methods, time-points, recall, parameters and values used to quantify adherence. RESULTS: Of 5033 references identified, 242 studies comprising of 261 treatments were included in the review. The majority of studies were randomised controlled trials investigating therapeutic exercise (n = 107, 41.0%). The most common adherence measurement across all treatments was through self-reported diary (n = 137, 52.5%) and the most common parameter was assessing the frequency of the treatment (n = 79, 30.3%). Only a small number of studies provided values for quantifying satisfactory adherence (n = 26, 9.3%). CONCLUSION: There is a wide variety in the reporting of adherence to conservative treatments for knee OA and standardised methods for measuring and reporting adherence are needed. Developing a tool to measure adherence to conservative treatments for knee OA is a priority.
History taking & physical assessment
History taking and physical assessment are essential first steps in any clinical encounter. Comprehensive and accurate history taking and physical assessment allow the “complete picture” of an individual presenting with possible osteoarthritis to be established. A person-centered approach is key, with active, open communication. Using techniques such as active listening, empathy, building rapport, open-ended questions, closed-ended probing questions, avoiding leading and “why” questions, allowing silence, and using nonverbal communication enable rich information to be elicited. A holistic approach to history taking ensures that all aspects of the individual are considered. Key components include systematically reviewing symptoms, participation, previous history, comorbidities, psychological factors, sleep and fatigue, support, attitudes and beliefs, red flag screening, using person-reported outcome measures, and setting goals. The physical assessment should be viewed as an extension of history taking. Adopting a systematic approach to physical assessment focusing on the four components: look (general and local observation), feel (palpation), move (range of movement), and measure (range of movement assessment, muscle strength and length, function, neurological features, and special tests) ensures comprehensive information is gained. Together, history taking and physical assessment form the foundation on which a personalized management plan can be built and to optimize engagement and adherence with management in long term.
Dysfunctional mitochondria in ageing T cells: a perspective on mitochondrial quality control mechanisms.
Dysfunctional mitochondria are a hallmark of T cell ageing and contribute to organismal ageing. This arises from the accumulation of reactive oxygen species (ROS), impaired mitochondrial dynamics, and inefficient removal of dysfunctional mitochondria. Both cell-intrinsic and cell-extrinsic mechanisms for removing mitochondria and their byproducts have been identified in T cells. In this review, we explore how T cells manage mitochondrial damage through changes in mitochondrial metabolism, mitophagy, asymmetric mitochondrial inheritance, and mitochondrial transfer, highlighting the impact of these mechanisms on T cell ageing and overall organismal ageing. We also discuss current therapeutic strategies aimed at removing dysfunctional mitochondria and their byproducts and propose potential new therapeutic targets that may reverse immune ageing or organismal ageing.
High-Dose vs. Standard-Dose Influenza Vaccine in Heart Failure: A Prespecified Analysis of the DANFLU-2 Trial
<jats:p> <jats:bold>Background:</jats:bold> Influenza contributes substantially to disease burden in individuals with heart failure (HF) and is an established trigger of cardiovascular (CV) and HF events. Standard-dose inactivated influenza vaccine (SD-IIV) is recommended for HF, though immune responses may be attenuated. High-dose IIV (HD-IIV) was developed to enhance immunogenicity, but its effectiveness compared with SD-IIV against hospitalization for influenza and CV disease by HF status remains uncertain. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> This was a prespecified analysis of a pragmatic, prospective, individually randomized, open-label trial with registry-based endpoint-evaluation conducted in Denmark across the 2022/2023 to 2024/2025 influenza seasons. Citizens ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Outcomes included hospitalization for influenza-related illness, laboratory-confirmed influenza (LCI), any CV disease, cardio-respiratory disease, and HF, assessed by HF status. Effect of HD-IIV vs. SD-IIV in reducing risk of outcomes assessed was expressed as risk ratios (RR). </jats:p> <jats:p> <jats:bold>Results:</jats:bold> The trial randomized 332,438 participants (48.6% female, mean age 73.7±5.8 years), including 10,410 with HF at baseline (27.4% female, mean age 76.0±6.3 years). Overall, HD-IIV was associated with a statistically significant lower incidence of hospitalization for influenza-related illness, LCI, cardio-respiratory disease, CV disease, and HF compared with SD-IIV. In participants with HF, effect estimates were similar: RR for influenza-related hospitalization was 0.48 (95%CI, 0.20-1.06; p <jats:sub>interaction</jats:sub> =0.64), for LCI hospitalization 0.55 (95%CI, 0.29-1.02; p <jats:sub>interaction</jats:sub> =0.59), for cardio-respiratory hospitalization 0.89 (95%CI, 0.77-1.02; p <jats:sub>interaction</jats:sub> =0.34), for CV hospitalization 0.86 (95%CI, 0.72-1.02; p <jats:sub>interaction</jats:sub> =0.34), and for HF hospitalization 0.82 (95%CI, 0.61-1.11; p <jats:sub>interaction</jats:sub> =0.83). Findings were consistent across HF subgroups by disease duration, recency of hospitalization, most recent N-terminal pro-B-type natriuretic peptide, and presence of device therapy. </jats:p> <jats:p> <jats:bold>Conclusions:</jats:bold> In this prespecified exploratory analysis of the largest individually randomized influenza vaccine trial ever conducted, HD-IIV was associated with lower rates of influenza and CV hospitalizations compared with SD-IIV, with effect estimates similar across HF status at baseline and HF subgroups. </jats:p>
Paediatric case of invasive group A streptococcal necrotising myositis: diagnostic challenges and lessons learned.
Necrotising myositis is a rare but devastating consequence of invasive group A streptococcal infection. Early presentation could be non-specific, and clinicians might have a low index of clinical suspicion due to the rarity of cases. Prompt recognition and early aggressive surgical management are the cornerstones of treatment to reduce morbidity and mortality. We report the case of a child aged 5 years with necrotising myositis and highlight the successes and potential pitfalls in the treatment of this life-threatening condition.
Use of a shared decision-making intervention to support treatment decision-making for patients following an anterior cruciate ligament rupture: a mixed methods feasibility study
Objectives To understand feasibility, acceptability and indicators of effectiveness of a shared decision-making (SDM) intervention with patients following an anterior cruciate ligament (ACL) rupture. Design Non-randomised feasibility study with embedded qualitative interviews. Setting Orthopaedic and physiotherapy service at an acute National Health Service (NHS) Teaching Hospital in the Midlands, UK, between 29 January and 5 June 2024. Participants Patients diagnosed with an ACL rupture following MRI. Intervention Delivery of a SDM intervention which comprised of two components: (1) patient information leaflet and (2) option grid. Outcome measures The primary outcome was to determine feasibility for a definitive trial using four outcomes: (1) recruitment rate, (2) fidelity of intervention delivery, (3) acceptability and (4) follow-up questionnaire completion. The secondary outcome was to explore indicators of the intervention’s effectiveness using quantitative data from patient reported outcome measures (acceptability questionnaire and satisfaction with decision scale) and qualitative data from patient and clinician interviews. Results 21 patients were approached to take part in the study, 20 were recruited with a mean age of 32.2 (SD 9.7), 40% were female. The recruitment rate was 95.2%, fidelity of intervention 100%, acceptability 94% and follow-up questionnaire completion 100%. The mean overall satisfaction with decision scale score was 24.85/30 (SD 3.82). There were no adverse events. Data from qualitative interviews with patients (n=5) and physiotherapists (n=5) suggested the SDM was acceptable and appeared effective in: (1) supporting decision-making about treatment, (2) conversations between patients and clinicians, (3) improving patient knowledge, (4) providing patients with access to health language and (5) supporting patients to ask questions deemed important to them. Conclusion The novel SDM intervention is acceptable to both patients and physiotherapists. Indicators of effectiveness explored through quantitative and qualitative data suggest the intervention to be beneficial to decision-making processes for patients and clinicians deciding on treatment following an ACL rupture. All four feasibility outcomes were achieved, indicating a full trial is feasible to run in the NHS. Trial registration number ISRCTN17801081.
The clinical effectiveness of clarithromycin versus endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps (MACRO): a pragmatic, multicentre, three-arm, randomised, placebo-controlled phase 4 trial
Background: A paucity of evidence regarding use of endoscopic sinus surgery and antibiotics in managing chronic rhinosinusitis has contributed to a five-times variation in endoscopic sinus surgery rates, as well as variation in the use of antibiotics. The main aim of the present trial was to compare the clinical effectiveness of endoscopic sinus surgery or 3 months of clarithromycin treatment alongside intranasal medication in adults with chronic rhinosinusitis with or without nasal polyps. Methods: In this pragmatic, three-arm, randomised, placebo-controlled phase 4 trial, participants were recruited from 20 secondary and tertiary care sites in the UK. Adults (aged ≥18 years) with chronic rhinosinusitis remaining symptomatic following appropriate medical therapy (intranasal corticosteroids, saline nasal irrigations, and a short course of antibiotics) were randomly assigned (1:1:1) to receive endoscopic sinus surgery (within 6 weeks of randomisation if waiting lists allowed) plus intranasal medication, clarithromycin (250 mg twice a day for 2 weeks then 250 mg once a day for 10 weeks) plus intranasal medication, or placebo plus intranasal medication. Intranasal medication comprised intranasal corticosteroids and saline irrigations. Participants were allocated with an automated, web-based secure randomisation system in permuted blocks of varying size (block sizes of three and six), stratified by the presence of polyps and trial site. Participants and site teams were masked to the clarithromycin and placebo allocations, including for outcome assessment. The primary outcome measure was the total score on the 22-item Sino-Nasal Outcome Test (SNOT-22) quality-of-life questionnaire at 6 months after randomisation, with analysis by intention to treat (ITT; available-case basis). Adverse reactions were assessed in the safety population (clarithromycin and placebo), and serious adverse events in the ITT population (all groups). The trial was registered on the ISRCTN registry, ISRCTN36962030, and EudraCT, 2018-001100-11, and is complete, with optional long-term follow-up ongoing. Findings: Between Nov 1, 2018, and Oct 13, 2023, 514 participants (181 [35%] female and 333 [65%] male), with chronic rhinosinusitis with nasal polyps (n=410) or chronic rhinosinusitis without nasal polyps (n=104), were recruited and randomly assigned to receive endoscopic sinus surgery (n=171), clarithromycin (n=172), or placebo (n=171), all with intranasal medication. SNOT-22 scores at 6 months after randomisation were significantly lower (at the 98·33% confidence level after Bonferroni adjustment) in the endoscopic sinus surgery group than in the clarithromycin group (adjusted mean difference –18·13 [98·33% CI –24·26 to –11·99], p<0·0001) and placebo group (–20·44 [–26·42 to –14·46], p<0·0001). 6-month SNOT-22 scores did not differ significantly between participants randomly assigned to clarithromycin versus placebo (–3·11 [–8·56 to 2·33], p=0·17). Ten serious adverse events occurred in nine participants (two events in two [1%] of 172 participants allocated to clarithromycin, three events in three [2%] of 171 allocated to placebo, and five events in four [2%] of 171 allocated to endoscopic sinus surgery), none of which were fatal. Interpretation: The MACRO trial shows that endoscopic sinus surgery has clinical effectiveness in patients with chronic rhinosinusitis, providing significantly improved disease-specific quality of life at 6 months. Conversely, the trial findings do not support routine long-term use of low-dose clarithromycin. Endoscopic sinus surgery should be recommended if intranasal medication alone is unable to achieve symptom control. Funding: National Institute for Health and Care Research Programme Grants for Applied Research.
MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines.
Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses and reactogenicity, but underpinning mechanisms remain unclear. We longitudinally compared homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination, focusing on cytokine-responsive innate-like lymphocytes-mucosal-associated invariant T (MAIT) cells and Vδ2+ γδ T cells-which sense and tune innate-adaptive cross-talk. Ad priming elicited robust type I interferon (IFN)-mediated innate-like T cell activation, augmenting T cell responses (innate-to-adaptive signaling), which was dampened at boost by antivector immunity. Conversely, mRNA boosting enhanced innate-like responses, driven by prime-induced spike-specific memory T cell-derived IFN-γ (adaptive-to-innate signaling). Extending the dosing interval dampened inflammation at boost because of waning T cell memory. In a separate vaccine trial, preboost spike-specific T cells predicted severe mRNA reactogenicity regardless of the priming platform or interval. Overall, bidirectional innate-like and adaptive cross-talk, and IFN-γ-licensed innate-like T cells, orchestrate interval-dependent early vaccine responses, suggesting modifiable targets for safer, more effective regimens.
The effect of minimum volume recommendations on surgeon activity for first revision total knee replacement: an analysis of 2009-2019 United Kingdom National Joint Registry data.
AIMS: The aim of this study was to investigate changes in first time revision knee replacement (RevKR) volumes following the publication of a report identifying low surgeon volumes in England. As a secondary aim we sought to investigate the rate of accrual of volumes for early career surgeons. METHODS: This population-based cohort study used data from the United Kingdom National Joint Registry. Patients undergoing first time RevKR between 1st January 2009 and 31 December 2019. Annual revision volumes for each surgeon were calculated and trends in surgeon volumes plotted as medians and bootstrapped 95% confidence intervals. Data before and after the report was compared. The rate of accrual of experience for new surgeons inclusive of both first-time revisions and re-revisions was calculated and adjusted for unit volume. RESULTS: A total of 21,067 patients were included. Over the whole study period, 123/1433 (8.58%) of surgeons achieved a mean annual volume of 15 or more revisions. Temporal trends in surgeon revision volumes observed an increase for non-acute indications. New surgeons in lower volume units have 42% lower chance of reaching 15 operations per year compared to those in the highest volume units (HR 0.52; 95% CI 0.33 to 0.83). CONCLUSIONS: We observed an increase in surgeon volumes following the report in first time non acute RevKRs. New RevKR surgeons were more likely to achieve and maintain revision volume targets in higher volume centres, this supports the drive for dual consultant operating and prospective revision knee consultants being appointed to highest volume units.
European Paediatric Orthopaedic Society consensus study to identify research priorities in paediatric orthopaedic surgery.
BACKGROUND: Paediatric orthopaedic surgery is rarely supported by high-quality evidence, with treatment decisions generally informed by experience or case series. The European Paediatric Orthopaedic Society recognises the need to establish research priorities in the field. This study builds on previous UK research priorities to discover the most important unanswered clinical effectiveness research questions in elective and trauma care and basic science, amongst Paediatric Orthopaedic surgeons across Europe. METHODS: A modified Delphi technique, including an initial scoping survey and a two-round Delphi process conducted amongst paediatric orthopaedic surgeons in Europe. RESULTS: An average of 113 surgeon responses were received in each round, scoring questions from 1 (low priority) to 5 (high priority). The mean score for importance was 3.59 in elective questions, 3.13 in trauma and 3.54 in basic science. The top questions in each group were identified. The top five research priorities for elective care related to the care of - Perthes Disease, Slipped Upper Femoral Epiphysis and Developmental Dysplasia of the Hip. Those in trauma related to the treatment of fractures around the elbow, forearm and femur Basic science priorities related to pharmaceuticals in the management of paediatric orthopaedic conditions and the pathology of Perthes' Disease and Developmental Dysplasia of the Hip. CONCLUSIONS: The results will help guide clinicians, researchers and funding bodies to focus research towards important topics and improve the evidence for practice in paediatric orthopaedic surgery. We hope that this study will encourage the development of collaborative international studies to improve care in paediatric orthopaedics. LEVEL OF EVIDENCE: Level V - decision analysis.