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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.
Correlations between objective and self-reported step count adherence following total knee replacement: A longitudinal repeated-measures cohort study.
OBJECTIVE: To determine how physically active individuals are following total knee replacement (TKR) and how accurately they self-report their step count adherence compared to objective measure following TKR. METHODS: Observational cohort study, nested within the PATHway randomised-clinical trial. Participants (n = 102) who had recently undergone TKR were recruited for the main trial. Only participant data from the intervention group were used for this study (n = 51). Participants in the intervention group received an activity tracker to monitor their physical activity and fortnightly health-coaching sessions for 3 months. Adherence was objectively measured as percentage of steps completed divided by the amount prescribed by the health coach. Participants were asked to self-report their adherence on a 1-10 numerical rating scale during health coaching sessions. RESULTS: Data from 44 participants were available, resulting in a total of 224 paired measurements. Participant step count increased over the first 8 weeks of follow-up, and plateaued from 8 weeks onwards at approximately 7500 steps/day. About two-thirds (65.8%) of participants accurately self-reported their step count adherence up until 12 weeks, the remaining one-third (34.2%) underestimated their adherence. Paired t-tests demonstrated statistically significant differences between the paired measurements from weeks 2 to 10. DISCUSSION: Participants were generally active and completed the step goal most occasions. Two-thirds accurately self-reported their step goal adherence. Self-reported measures should be combined with an objective measure of adherence for greater accuracy. A further understanding of how people engage with activity trackers can be used to promote behaviour change in physiotherapy-led interventions.
The Clinical Effectiveness of a Physiotherapy Delivered Physical and Psychological Group Intervention for Older Adults With Neurogenic Claudication: The BOOST Randomized Controlled Trial.
BACKGROUND: Neurogenic claudication (NC) is a debilitating spinal condition affecting older adults' mobility and quality of life. METHODS: A randomized controlled trial of 438 participants evaluated the effectiveness of a physical and psychological group intervention (BOOST program) compared to physiotherapy assessment and tailored advice (best practice advice [BPA]) for older adults with NC. Participants were identified from spinal clinics (community and secondary care) and general practice records and randomized 2:1 to the BOOST program or BPA. The primary outcome was the Oswestry Disability Index (ODI) at 12 months. Data were also collected at 6 months. Other outcomes included ODI walking item, 6-minute walk test (6MWT), and falls. The primary analysis was intention-to-treat. RESULTS: The average age of participants was 74.9 years (standard deviation [SD] 6.0) and 57% (246/435) were female. There was no significant difference in ODI scores between treatment groups at 12 months (adjusted mean difference [MD]: -1.4 [95% confidence intervals (CI) -4.03, 1.17]), but, at 6 months, ODI scores favored the BOOST program (adjusted MD: -3.7 [95% CI -6.27, -1.06]). At 12 months, the BOOST program resulted in greater improvements in walking capacity (6MWT MD: 21.7m [95% CI 5.96, 37.38]) and ODI walking item (MD: -0.2 [95% CI -0.45, -0.01]) and reduced falls risk (odds ratio: 0.6 [95% CI 0.40, 0.98]) compared to BPA. No serious adverse events were related to either treatment. CONCLUSIONS: The BOOST program substantially improved mobility for older adults with NC. Future iterations of the program will consider ways to improve long-term pain-related disability. Clinical Trials Registration Number: ISRCTN12698674.
Complementary and alternative medicine: Do physicians believe they can meet the requirements of the Collège des médecins du Québec?
OBJECTIVE: To determine whether medical training prepares FPs to meet the requirements of the Collège des médecins du Québec for their role in advising patients on the use of complementary and alternative medicine (CAM). DESIGN: Secondary analysis of survey results. SETTING: Quebec. PARTICIPANTS: Family physicians and GPs in active practice. MAIN OUTCOME MEASURES: Perceptions of the role of the physician as an advisor on CAM; level of comfort responding to questions and advising patients on CAM; frequency with which patients ask their physicians about CAM; personal position on CAM; and desire for training on CAM. RESULTS: The response rate was 19.5% (195 respondents of 1000) and the sample appears to be representative of the target population. Most respondents (85.8%) reported being asked about CAM several times a month. A similar proportion (86.7%) believed it was their role to advise patients on CAM. However, of this group, only 33.1% reported being able to do so. There is an association between an urban practice and knowledge of the advisory role of physicians. More than three-quarters of respondents expressed interest in receiving additional training on CAM. CONCLUSION: There is a gap between the training that Quebec physicians receive on CAM and their need to meet legal and ethical obligations designed to protect the public where CAM products and therapies are concerned. One solution might be more thorough training on CAM to help physicians meet the Collège des médecins du Québec requirements.
Hospital-Treated Infections and 15-year Incidence of Musculoskeletal Disorders: A Large Population-Based Cohort Study.
BACKGROUND: Basic science evidence reveals interactions between the immune and bone systems. However, population studies linking infectious diseases and musculoskeletal (MSK) disorders are limited and inconsistent. We aimed to examine the risk of six main MSK disorders (osteoarthritis, rheumatoid arthritis, osteoporosis, gout, low back pain, and neck pain) following hospital-treated infections in a large cohort with long follow-up periods. METHODS: We analysed data from 502,409 UK Biobank participants. Participants free of specific MSK disorders at baseline were included in each analysis. Hospital-treated infections before baseline were identified using national inpatient data, while incident MSK outcomes were ascertained from inpatient records, primary care, and death registers. Participants with prior infections were propensity score matched (1:5) with those without. Hazard ratios (HRs) and absolute rate differences (ARDs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. To assess potential reverse causality due to delayed diagnosis of preexisting illness, analyses were repeated excluding MSK disorder cases that occurred within the first 5 and 10 years post-baseline. RESULTS: A hospital-treated infection was associated with increased risks of all six MSK disorders, with particularly strong associations for osteoporosis (HR, 1.55 [1.48-1.63]; ARD, 1.48 [95% CI 1.29-1.68] per 1000 person-years) and rheumatoid arthritis (HR, 1.53 [1.41-1.65]; ARD, 0.58 [0.46-0.71] per 1000 person-years), while other disorders showed HRs of 1.28-1.32. Bacterial and viral infections showed similar associations, with MSK infections (generally stronger risk) and other locations both linked to increased risks. Associations remained significant even for incident cases that occurred more than 10 years post-baseline. CONCLUSION: Hospital-treated infections are associated with long-term MSK disorder risks, regardless of pathogen type or disorder nature (inflammatory or degenerative). Long-term monitoring and care for MSK health in patients with prior hospital-treated infections are recommended.
Next-generation sequencing for guiding matched targeted therapies in people with relapsed or metastatic cancer.
BACKGROUND: Matched targeted therapies (MTT) given alone or in combination with systemic anti-cancer therapies have delivered proven survival benefit for many people with newly diagnosed cancer. However, there is little evidence of their effectiveness in the recurrent or late-stage setting. With this uncertainty, alongside the perception that late-stage cancers are too genetically heterogenous or too mutationally diverse to benefit from matched targeted therapies, next-generation sequencing (NGS) of tumours in people with refractory cancer remains a low priority. As a result, next-generation sequencing testing of recurrent or late-stage disease is discouraged. We lack evidence to support the utility of next generation sequencing in guiding matched targeted therapies in this setting. OBJECTIVES: To evaluate the benefits and harms of matched targeted therapies in people with advanced cancers in randomised controlled trials. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organisation International Clinical Trials Registry Platform (WHO-ICTRP) search portal up to 30th October 2024. We also screened reference lists of included studies and also the publications that cited these studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that had enroled participants with advanced/refractory solid or haematological cancers who had progressed through at least one line of standard anti-cancer systemic therapy. To be eligible, all participants should have received matched targeted therapy based on next-generation sequencing carried out on their tumour (tumour tissue, blood or bone marrow). DATA COLLECTION AND ANALYSIS: We systematically searched medical databases (e.g. MEDLINE, Embase) and trial registers for randomised controlled trials (RCTs). Outcomes of interest were progression-free survival (PFS), overall survival (OS), overall response rates (ORR), serious (grade 3 or 4) adverse events (AEs) and quality of life (QOL). We used a random-effects model to pool outcomes across studies and compared predefined subgroups using interaction tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment of certainty was used to evaluate the quality of evidence. MAIN RESULTS: We identified a total of 37 studies, out of which 35 studies (including 9819 participants) were included in the meta-analysis. All included studies compared a matched targeted therapy intervention to standard-of-care treatment, non-matched targeted therapies or no treatment (best supportive care): Matched targeted therapy versus standard-of-care treatment Matched targeted therapy (MTT) compared with standard systematic therapy probably reduces the risk of disease progression by 34% (hazard ratio (HR) = 0.66, 95% confidence interval (CI) 0.59 to 0.74; 14 studies, 3848 participants; moderate-certainty evidence). However, MTT might have little to no difference in risk of death (HR = 0.85, 95% CI 0.75 to 0.97; 14 studies, 3848 participants; low-certainty evidence) and may increase overall response rates (low-certainty evidence). There was no clear evidence of a difference in severe (grade 3/4) adverse events between matched targeted therapy and standard-of-care treatment (low-certainty evidence). There was limited evidence of a difference in quality of life between groups (very low-certainty of evidence). Matched targeted therapy in combination with standard-of-care treatment versus standard-of-care treatment alone Matched targeted therapy in combination with standard-of-care treatment compared with standard-of-care treatment alone probably reduces the risk of disease progression by 39% (HR = 0.61, 95% CI 0.53-0.70, 14 studies, 2,637 participants; moderate-certainty evidence) and risk of death by 21% (HR = 0.79, 95% CI 0.70 to 0.89; 11 studies, 2575 participants, moderate-certainty evidence). The combination of MTT and standard-of-care treatment may also increase overall response rates (low-certainty evidence). There was limited evidence of a difference in the incidence of severe adverse events (very low-certainty evidence) and quality of life between the groups (very low-certainty of evidence). Matched targeted therapy versus non-matched targeted therapy Matched targeted therapy compared with non-matched targeted therapy probably reduces the risk of disease progression by 24% (HR = 0.76, 95% CI 0.64 to 0.89; 3 studies, 1568 participants; moderate-certainty evidence) and may reduce the risk of death by 25% (HR = 0.75, 95% CI 0.65 to 0.86, 1307 participants; low-certainty evidence). There was little to no effect on overall response rates between MTT and non-MTT. There was no clear evidence of a difference in overall response rates (low-certainty evidence) and severe adverse events between MTT and non-MTT (low-certainty evidence). None of the studies comparing MTT and non-MTT reported quality of life. Matched targeted therapy versus best supportive care Matched targeted therapy compared with the best supportive care (BSC) i.e. no active treatment probably reduces the risk of disease progression by 63% (HR 0.37, 95% CI 0.28 to 0.50; 4 studies, 858 participants; moderate-certainty evidence). There was no clear evidence of a difference in overall survival between groups (HR = 0.88, 95% CI 0.73 to 1.06, 3 studies, 783 participants; low-certainty evidence). There was no clear evidence of a difference in overall response rates (very low-certainty of evidence) and incidence of severe adverse events (very low-certainty of evidence) between the groups. Quality of life was reported in a single study but did not provide composite scores. Risk of bias The overall risk of bias was judged low for eight studies, unclear for two studies, and the remaining 27 studies were high risk. AUTHORS' CONCLUSIONS: Matched targeted therapies guided by next-generation sequencing in people with advanced cancer prolongs the time before cancer progresses compared to standard therapies. However, there is limited evidence to suggest that it prolongs overall survival, improves the quality of life or increases adverse events. Importantly, this review supports equitable access to next-generation sequencing technology for all people with advanced cancer and offers them the opportunity to access genotype-matched targeted therapies.
Lower limb muscle strength and balance in older adults with a distal radius fracture: a systematic review.
BACKGROUND: Distal radius fractures are common fractures in older adults and associated with increased risk of future functional decline and hip fracture. Whether lower limb muscle strength and balance are impaired in this patient population is uncertain. To help inform rehabilitation requirements, this systematic review aimed to compare lower limb muscle strength and balance between older adults with a distal radius fracture with matched controls, and to synthesise lower limb muscle strength and balance outcomes in older adults with a distal radius fracture. METHODS: We searched Embase, MEDLINE, and CINAHL (1990 to 25 May 2022) for randomised and non-randomised controlled clinical trials and observational studies that measured lower limb muscle strength and/or balance using instrumented measurements or validated tests, in adults aged ≥ 50 years enrolled within one year after distal radius fracture. We appraised included observational studies using a modified Newcastle-Ottawa Scale and included randomised controlled trials using the Cochrane risk-of-bias tool. Due to the clinical and methodological heterogeneity in included studies, we synthesised results narratively in tables and text. RESULTS: Nineteen studies (10 case-control studies, five case series, and four randomised controlled trials) of variable methodological quality and including 1835 participants (96% women, mean age 55-73 years, median sample size 82) were included. Twelve included studies (63%) assessed strength using 10 different methods with knee extension strength most commonly assessed (6/12 (50%) studies). Five included case-control studies (50%) assessed lower limb strength. Cases demonstrated impaired strength during functional tests (two studies), but knee extension strength assessment findings were conflicting (three studies). Eighteen included studies (95%) assessed balance using 14 different methods. Single leg balance was most commonly assessed (6/18 (33%) studies). All case-control studies assessed balance with inconsistent findings. CONCLUSION: Compared to controls, there is some evidence that older adults with a distal radius fracture have impaired lower limb muscle strength and balance. A cautious interpretation is required due to inconsistent findings across studies and/or outcome measures. Heterogeneity in control participants' characteristics, study design, study quality, and assessment methods limited synthesis of results. Robust case-control and/or prospective observational studies are needed. REGISTRATION: International prospective register of systematic reviews (date of registration: 02 July 2020, registration identifier: CRD42020196274).
Predictors of Adherence to a Step Count Intervention Following Total Knee Replacement: An Exploratory Cohort Study.
OBJECTIVE: To explore the person-level predictors of adherence to a step count intervention following total knee replacement (TKR). DESIGN: Prospective cohort study, nested within the PATHway trial. METHODS: Participants who had recently undergone TKR were recruited from 3 rehabilitation hospitals in Sydney, Australia, for the main trial. Only data from participants who were randomized to the TKR intervention group were analyzed. Participants in the intervention group (n = 51) received a wearable tracker to monitor the number of steps taken per day. Step count adherence was objectively measured at 3 months as the number of steps completed divided by the number prescribed and multiplied by 100 to express adherence as a percentage. Participants were classified into 4 groups: withdrawal, low adherence (0%-79%), adherent (80%-100%), and >100% adherent. Ordinal logistic regression was used to identify which factors predicted adherence to the prescribed step count. RESULTS: Of the 51 participants enrolled, nine (18% of 51) withdrew from the study before 3 months. Half of participants were classified as >100% adherent (n = 24%, 47%). Ten were classified as low adherence (20%), and 8 participants were classified as adherent (16%). In the univariable model, lower age (OR 0.90; 95% CI 0.83-0.97), higher patient activation (OR 1.03; 95% CI 1.00-1.06), and higher technology self-efficacy (OR 1.03; 95% CI 1.00-1.06) were associated with higher adherence. After adjusting for age in the multivariable model, patient activation and technology self-efficacy were not significant. CONCLUSION: Younger age, higher patient activation, and higher technology self-efficacy were associated with higher adherence to a step count intervention following TKR in the univariable model. Patient activation and technology self-efficacy were not associated with higher adherence following adjustment for age. J Orthop Sports Phys Ther 2022;52(9):620-629. Epub: 9 July 2022. doi:10.2519/jospt.2022.11133.
Microglial depletion increases aggrecan and hyaluronan levels in the diffuse and aggregated extracellular matrix of the mouse brain.
The extracellular matrix (ECM) in the brain can be divided into aggregated ECM, such as perineuronal nets (PNNs) around neurons, and diffuse ECM, which is present throughout the brain parenchyma. Both aggregated and diffuse ECM restrict synaptic plasticity and stabilize neural circuits in the adult brain. Hyaluronan (HA) acts as a scaffold for the brain ECM, and multiple proteoglycans, such as aggrecan, bind to HA to form a macromolecular complex. Recent evidence suggests that microglia, the resident immune cells of the brain, play a crucial role in ECM homeostasis. However, it remains unclear how microglia influence the molecular composition of the ECM. Using a tissue-clearing technique and histochemical analysis, we found that microglial depletion increased the staining intensity of aggrecan and HA in both PNNs and diffuse ECM. Biochemical analyses further confirmed the accumulation of the aggrecan core protein and HA following microglial depletion. Our findings highlight the essential role of microglia in regulating the ECM composition and provide new insights into the mechanisms by which microglia influence neuronal function.