Mitochondrial fusion and altered beta-oxidation drive muscle wasting in a Drosophila cachexia model.

Cancer cachexia is a tumour-induced wasting syndrome, characterised by extreme loss of skeletal muscle. Defective mitochondria can contribute to muscle wasting; however, the underlying mechanisms remain unclear. Using a Drosophila larval model of cancer cachexia, we observed enlarged and dysfunctional muscle mitochondria. Morphological changes were accompanied by upregulation of beta-oxidation proteins and depletion of muscle glycogen and lipid stores. Muscle lipid stores were also decreased in Colon-26 adenocarcinoma mouse muscle samples, and expression of the beta-oxidation gene CPT1A was negatively associated with muscle quality in cachectic patients. Mechanistically, mitochondrial defects result from reduced muscle insulin signalling, downstream of tumour-secreted insulin growth factor binding protein (IGFBP) homologue ImpL2. Strikingly, muscle-specific inhibition of Forkhead box O (FOXO), mitochondrial fusion, or beta-oxidation in tumour-bearing animals preserved muscle integrity. Finally, dietary supplementation with nicotinamide or lipids, improved muscle health in tumour-bearing animals. Overall, our work demonstrates that muscle FOXO, mitochondria dynamics/beta-oxidation and lipid utilisation are key regulators of muscle wasting in cancer cachexia.

Obesity increases the odds of intervertebral disc herniation and spinal stenosis; an MRI study of 1634 low back pain patients.

PURPOSE: The objective of this study was to examine the relationships between BMI and intervertebral disc degeneration (DD), disc herniation (DH) and spinal stenosis (SS) using a large, prospectively recruited and heterogeneous patient population. METHODS: Patients were recruited through the European Genodisc Study. An experienced radiologist scored MRI images for DD, DH and SS. Multivariate linear and logistic regression analyses were used to model the relationship between these variables and BMI with adjustment for patient and MRI confounders. RESULTS: We analysed 1684 patients with a mean age of 51 years and BMI of 27.2 kg/m2.The mean DD score was 2.6 (out of 5) with greater DD severity with increasing age (R2 = 0.44). In the fully adjusted model, a 10-year increase in age and a 5 kg/m2 increase in BMI were associated, respectively, with a 0.31-unit [95% CI 0.29,0.34] and 0.04-unit [CI 0.01,0.07] increase in degeneration. Age (OR 1.23 [CI 1.06,1.43]) and BMI (OR 2.60 [CI 2.28,2.96]) were positively associated with SS. For DH, age was a negative predictor (OR 0.70 [CI 0.64,0.76]) but for BMI (OR 1.19 [CI 1.07,1.33]), the association was positive. BMI was the strongest predictor of all three features in the upper lumbar spine. CONCLUSIONS: While an increase in BMI was associated with only a slight increase in DD, it was a stronger predictor for DH and SS, particularly in the upper lumbar discs, suggesting weight loss could be a useful strategy for helping prevent disorders associated with these pathologies.

A Comparison of the Periprosthetic Fracture Rate of Cemented and Cementless Mobile Bearing Unicompartmental Knee Arthroplasties: An Analysis of Data From the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man.

BACKGROUND: Periprosthetic fractures are rare but serious complications of unicompartmental knee arthroplasty (UKA). Although cementless UKA has a lower risk of loosening than cemented, there are concerns that tibial fracture risk may be higher given the reliance on interference fit for primary stability. The risk of fracture and the effect of surgical fixation are currently unknown. We compared the periprosthetic fracture rate following cemented and cementless UKA surgery. METHODS: A total of 14,122 medial mobile-bearing UKAs (7,061 cemented and 7,061 cementless) from the National Joint Registry and Hospital Episodes Statistics database were propensity score-matched. Cumulative fracture rates were calculated and Cox regressions were used to compare fixation groups. RESULTS: The three-month periprosthetic fracture rates were similar (P = .80), being 0.10% in the cemented group and 0.11% in the cementless group. The fracture rates were highest during the first three months postoperatively, but then decreased and remained constant between one and 10 years after surgery. The one-year cumulative fracture rates were 0.2% (confidence interval [CI]: 0.1 to 0.3) for cemented and 0.2% (CI: 0.1 to 0.3) for cementless cases. The 10-year cumulative fracture rates were 0.8% (CI: 0.2 to 1.3) and 0.8% (CI: 0.3 to 1.3), respectively. The hazard ratio during the whole study period was 1.06 (CI: 0.64 to 1.77; P = .79). CONCLUSIONS: The periprosthetic fracture rate following mobile bearing UKA surgery is low, being about 1% at 10 years. There were no significant differences in fracture rates between cemented and cementless implants after matching. We surmise that surgeons are aware of the higher theoretical risk of early fracture with cementless components and take care with tibial preparation. LEVELS OF EVIDENCE: III.

Inequalities in provision of hip and knee replacement surgery for osteoarthritis by age, sex, and social deprivation in England between 2007-2017: A population-based cohort study of the National Joint Registry.

BACKGROUND: While the United Kingdom National Health Service aimed to reduce social inequalities in the provision of joint replacement, it is unclear whether these gaps have reduced. We describe secular trends in the provision of primary hip and knee replacement surgery between social deprivation groups. METHODS AND FINDINGS: We used the National Joint Registry to identify all hip and knee replacements performed for osteoarthritis from 2007 to 2017 in England. The Index of Multiple Deprivation (IMD) 2015 was used to identify the relative level of deprivation of the patient living area. Multilevel negative binomial regression models were used to model the differences in rates of joint replacement. Choropleth maps of hip and knee replacement provision were produced to identify the geographical variation in provision by Clinical Commissioning Groups (CCGs). A total of 675,342 primary hip and 834,146 primary knee replacements were studied. The mean age was 70 years old (standard deviation: 9) with 60% and 56% of women undergoing hip and knee replacements, respectively. The overall rate of hip replacement increased from 27 to 36 per 10,000 person-years and knee replacement from 33 to 46. Inequalities of provision between the most (reference) and least affluent areas have remained constant for both joints (hip: rate ratio (RR) = 0.58, 95% confidence interval [0.56, 0.60] in 2007, RR = 0.59 [0.58, 0.61] in 2017; knee: RR = 0.82 [0.80, 0.85] in 2007, RR = 0.81 [0.80, 0.83] in 2017). For hip replacement, CCGs with the highest concentration of deprived areas had lower overall provision rates, and CCGs with very few deprived areas had higher provision rates. There was no clear pattern of provision inequalities between CCGs and deprivation concentration for knee replacement. Study limitations include the lack of publicly available information to explore these inequalities beyond age, sex, and geographical area. Information on clinical need for surgery or patient willingness to access care were unavailable. CONCLUSIONS: In this study, we found that there were inequalities, which remained constant over time, especially in the provision of hip replacement, by degree of social deprivation. Providers of healthcare need to take action to reduce this unwarranted variation in provision of surgery.

What effect have commissioners' policies for body mass index had on hip replacement surgery?: an interrupted time series analysis from the National Joint Registry for England.

BACKGROUND: Despite their widespread use, the impact of commissioners' policies for body mass index (BMI) for access to elective surgery is not clear. Policy use varies by locality, and there are concerns that these policies may worsen health inequalities. The aim of this study was to assess the impact of policies for BMI on access to hip replacement surgery in England. METHODS: A natural experimental study using interrupted time series and difference-in-differences analysis. We used National Joint Registry data for 480,364 patients who had primary hip replacement surgery in England between January 2009 and December 2019. Clinical commissioning group policies introduced before June 2018 to alter access to hip replacement for patients with overweight or obesity were considered the intervention. The main outcome measures were rate of surgery and patient demographics (BMI, index of multiple deprivation, independently funded surgery) over time. RESULTS: Commissioning localities which introduced a policy had higher surgery rates at baseline than those which did not. Rates of surgery fell after policy introduction, whereas rates rose in localities with no policy. 'Strict' policies mandating a BMI threshold for access to surgery were associated with the sharpest fall in rates (trend change of - 1.39 operations per 100,000 population aged 40 + per quarter-year, 95% confidence interval - 1.81 to - 0.97, P < 0.001). Localities with BMI policies have higher proportions of independently funded surgery and more affluent patients receiving surgery, indicating increasing health inequalities. Policies enforcing extra waiting time before surgery were associated with worsening mean pre-operative symptom scores and rising obesity. CONCLUSIONS: Commissioners and policymakers should be aware of the counterproductive effects of BMI policies on patient outcomes and inequalities. We recommend that BMI policies involving extra waiting time or mandatory BMI thresholds are no longer used to reduce access to hip replacement surgery.

Patients' recovery of mobility and return to original residence after hip fracture are associated with multiple modifiable components of hospital service organisation: the REDUCE record-linkage cohort study in England and Wales.

BACKGROUND: Hip fractures are devastating injuries causing disability, dependence, and institutionalisation, yet hospital care is highly variable. This study aimed to determine hospital organisational factors associated with recovery of mobility and change in patient residence after hip fracture. METHODS: A cohort of patients aged 60 + years in England and Wales, who sustained a hip fracture from 2016 to 2019 was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality records were linked to 101 factors derived from 18 hospital-level organisational metrics. After adjustment for patient case-mix, multilevel models were used to identify organisational factors associated with patient residence at discharge, and mobility and residence at 120 days after hip fracture. RESULTS: Across 172 hospitals, 165,350 patients survived to discharge, of whom 163,230 (99%) had post-hospital discharge destination recorded. 18,323 (11%) died within 120 days. Among 147,027 survivors, 58,344 (40%) across 143 hospitals had their residence recorded, and 56,959 (39%) across 140 hospitals had their mobility recorded, at 120 days. Nineteen organisational factors independently predicted residence on hospital discharge e.g., return to original residence was 31% (95% confidence interval, CI:17-43%) more likely if the anaesthetic lead for hip fracture had time allocated in their job plan, and 8-13% more likely if hip fracture service clinical governance meetings were attended by an orthopaedic surgeon, physiotherapist or anaesthetist. Seven organisational factors independently predicted residence at 120 days. Patients returning to their pre-fracture residence was 26% (95%CI:4-42%) more likely if hospitals had a dedicated hip fracture ward, and 20% (95%CI:8-30%) more likely if treatment plans were proactively discussed with patients and families on admission. Seventeen organisational factors predicted mobility at 120 days. More patients re-attained their pre-fracture mobility in hospitals where (i) care involved an orthogeriatrician (15% [95%CI:1-28%] improvement), (ii) general anaesthesia was usually accompanied by a nerve block (7% [95%CI:1-12%], and (iii) bedside haemoglobin testing was routine in theatre recovery (13% [95%CI:6-20%]). CONCLUSIONS: Multiple, potentially modifiable, organisational factors are associated with patient outcomes up to 120 days after a hip fracture, these factors if causal should be targeted by service improvement initiatives to reduce variability, improve hospital hip fracture care, and maximise patient independence.

Access to hip and knee arthroplasty in England: commissioners' policies for body mass index and smoking status and implications for integrated care systems.

BACKGROUND: Commissioning policies are in place in England that alter access to hip and knee arthroplasty based on patients' body mass index and smoking status. Our objectives were to ascertain the prevalence, trend and nature of these policies, and consider the implications for new integrated care systems (ICSs). METHODS: Policy data were obtained from an internet search for all current and historic clinical commissioning group (CCG) hip and knee arthroplasty policies and use of Freedom of Information (FOI) requests to each CCG. Descriptive analyses of policy type, explicit threshold criteria and geography are reported. Estimates were made of the uptake of policies by ICSs based on the modal policy type of their constituent CCGs. RESULTS: There were 106 current and 143 historic CCGs in England at the time of the search in June 2021. Policy information was available online for 56.2% (140/249) CCGs. With the addition of information from FOIs, complete policy information was available for 94.4% (235/249) of CCGs. Prevalence and severity of policies have increased over time. For current CCGs, 67.9% (72/106) had a policy for body mass index (BMI) and 75.5% (80/106) had a policy for smoking status for hip or knee arthroplasty. Where BMI policies were in place, 61.1% (44/72) introduced extra waiting time before surgery or restricted access to surgery based on BMI thresholds (modal threshold: BMI of 40 kg/m2, range 30-45). In contrast, where smoking status policies were in place, most offered patients advice or optional smoking cessation support and only 15% (12/80) introduced extra waiting time or mandatory cessation before surgery. It is estimated that 40% of ICSs may adopt a BMI policy restrictive to access to arthroplasty. CONCLUSIONS: Access policies to arthroplasty based on BMI and smoking status are widespread in England, have increased in prevalence since 2013, and persist within new ICSs. The high variation in policy stringency on BMI between regions is likely to cause inequality in access to arthroplasty and to specialist support for affected patients. Further work should determine the impact of different types of policy on access to surgery and health inequalities.

Association between outpatient follow-up and incidence of revision after knee and hip replacements: a population-based cohort study.

BACKGROUND: Follow-up visits 5 or 7 years after surgery were recommended for people having primary hip or knee replacement. The benefits of this practice to patients and the healthcare system, however, have not yet been specifically examined. The aim of this study was to investigate the association between long-term follow-up outpatient hospital visits and revision rates for patients who undergo primary knee or hip replacement surgery. METHODS: Cohorts were identified for patients undergoing knee or hip replacement surgery using medical records from primary care practices within the UK Clinical Practice Research Datalink (CPRD) GOLD dataset linked to hospital records from the English Hospital Episodes Statistics (HES) data. Two groups of patients were compared in terms of revision and mortality rates: those with at least one long-term (between five and 10 years since primary surgery) follow-up visit at the orthopaedic department ('Follow-up' group), and those without ('No follow-up' group). RESULTS: A total of 9856 (4349 in the Follow-up group) patients with knee replacement and 10,837 (4870 in the Follow-up group) with hip replacement were included in the analysis. For knee replacement, the incidence of revision was 3.6% for those followed-up and 0.6% for those not followed-up. An adjusted regression model confirmed the difference in the hazard ratio (HR) for revision was statistically significant (HR: 5.65 [95% CI 3.62 to 8.81]). Mortality at 4 years was lower for the Follow-up (17%) compared to the No follow-up group (21%), but this difference was not statistically significant (HR: 0.95 [0.84 to 1.07]). For hip replacement, the incidence of revision rates were 3.2 and 1.4% for the follow-up and not follow-up groups, respectively, the difference being statistically significant (HR: 2.34 [1.71 to 3.20]). Mortality was lower for the Follow-up (15%) compared to the No follow-up group (21%), but the difference was not statistically significant (HR: 0.91 [0.81 to 1.02]). CONCLUSION: Patients attending follow-up orthopaedic consultations show a higher risk of revision surgery compared to those who are not followed-up. A cause for this difference could not be identified in this study but a likely explanation is that surgeons play an effective role as ultimate arbitrators when identifying patients to be included in long-term follow-up lists.

The effect of body mass index on the outcomes of cementless medial mobile-bearing unicompartmental knee replacements.

PURPOSE: Given an increasingly overweight population, unicompartmental knee replacements (UKRs) are being performed in patients with higher body mass indices (BMIs). There are concerns that cemented fixation will not last. Cementless fixation may offer a solution, but the long term results in different BMI groups has not been assessed. We studied the effect of BMI on the outcomes of cementless UKRs. METHODS: A prospective cohort of 1000 medial cementless mobile-bearing UKR with a mean follow up of 6.6 years (SD 2.7) were analysed. UKRs were categorised into four BMI groups: (1) ≥ 18.5 to < 25 kg/m2 (normal), (2) 25 to < 30 kg/m2 (overweight), (3) 30 to < 35 kg/m2 (obese class 1) and (4) ≥ 35 kg/m2 (obese class 2). Implant survival was assessed using endpoints reoperation and revision. Functional outcomes were assessed. RESULTS: Ten-year cumulative revision rate for the normal (n = 186), overweight (n = 434), obese class 1 (n = 213) and obese class 2 (n = 127) groups were 1.8% (CI 0.4-7.4), 2.6% (CI 1.3-5.1), 3.8% (CI 1.5-9.2) and 1.7% (CI 0.4-6.8) with no significant differences between groups (p = 0.79). The 10-year cumulative reoperation rates were 2.7% (CI 0.8-8.2), 3.8% (CI 2.2-6.6), 5.2% (CI 2.5-10.7) and 1.7% (CI 0.4-6.8) with no significant differences between groups (p = 0.44). The 10-year median Oxford Knee Score were 43.0, 46.0, 44.0 and 38.0 respectively. CONCLUSION: Cementless mobile-bearing UKR has low 10-year reoperation and revision rates across in all BMI groups, and there are no significant differences between the groups. Although higher BMI groups had slightly worse functional outcomes, the improvement in function compared to preoperatively  tended to be better. This study suggests that BMI should not be considered a contraindication for the cementless mobile-bearing UKR.

The Effect of Age on the Relative Outcomes of Cemented and Cementless Mobile-Bearing Unicompartmental Knee Arthroplasty, Based on Data From National Databases.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an effective treatment for medial compartment arthritis. A challenge is that patients requiring knee arthroplasty are becoming younger. It is currently unknown what the relative performances of cemented and cementless UKAs are, in different age groups. METHODS: A total of 12,882 cemented and cementless UKAs from the National Joint Registry and Hospital Episodes Statistics databases were matched on patient and surgical factors. Patients were stratified into 3 groups: (1) <60 years; (2) 60-69 years; and (3) ≥70 years. Revision and reoperation rates were compared using Cox regression analyses. RESULTS: The 10-year implant survival for the matched cemented and cementless UKAs for (1) <60 years were 81.4% (CI 73.6-87.0) and 86.7% (CI 80.7-90.9) (hazard ratio [HR] 0.73, CI 0.56-0.94, P = .02); (2) for 60-69 years were 91.8% (CI 88.9-94.0) and 94.5% (CI 92.9-95.7) (HR 0.90, CI 0.67-1.22, P = .51); and (3) ≥70 years were 93.5% (CI 91.1-95.3) and 94.2% (CI 92.0-95.8) (HR 1.0, CI 0.71-1.40, P = .99). The same trend was observed for reoperations. In the <60 years and 60-69 years groups there were significantly fewer revisions for aseptic loosening in the cementless group (0.5% versus 1.6% [P < .001] and 0.4% versus 1.3% [P = .002], respectively). CONCLUSION: Younger ages were associated with higher revision rates in both cemented and cementless UKA groups. Cementless fixation has reduced long-term revision rates compared to cemented fixation in the <60 years group with aseptic loosening rates 3 times lower. LEVEL OF EVIDENCE: III.

The Influence of Surgeon Caseload and Usage on the Long-Term Outcomes of Mobile-Bearing Unicompartmental Knee Arthroplasty: An Analysis of Data From the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) revision rates are variable and known to be influenced by a surgeon's caseload (number of UKAs performed annually) and usage (UKA as a proportion of overall knee arthroplasty practice). It is not known which is more important. We explored the influence of caseload and usage on cemented and cementless UKA. METHODS: A total of 34,277 medial Oxford UKAs (23,707 cemented and 10,570 cementless) from the National Joint Registry were analyzed. UKAs were subdivided by the following: (1) surgeon caseload, into low (<10 UKAs/y) and high (≥10 UKAs/y) categories; and (2) usage, into low (<20%) and high (≥20%) categories. The 10-year revision rates were compared. RESULTS: The 10-year survival of the low-caseload/low-usage cemented and cementless UKA was 82.8% (CI 81.6-83.9) and 86.2% (CI 72.1-93.4), respectively. The 10-year survival of the high-caseload/high-usage cemented and cementless UKA was 90.0% (CI 89.2-90.6) and 93.3% (CI 91.3-94.8), respectively. For cemented UKA, the high-caseload/high-usage group had lower revision rates (hazard ratio [HR] 0.57, CI 0.52-0.63, P < .001) compared to the low-caseload/low-usage group. The high-caseload/low-usage (HR 0.74, CI 0.66-0.83, P < .001) and the low-caseload/high-usage (HR 0.86, CI 0.74-0.99, P = .04) groups also had lower revision rates than the low-caseload/low-usage group. CONCLUSION: Mobile-bearing UKA revision rates improve with both increasing surgeon UKA caseload and usage. Surgeons using cemented UKA who have usage ≥20% and caseload ≥10/year had a 10-year survival of 90%. Higher survivorship was associated with higher caseload, higher usage, and cementless fixation. LEVELS OF EVIDENCE: III.

A Comparison of the Periprosthetic Fracture Rate of Cemented and Cementless Total Knee Arthroplasties: An Analysis of Data From the National Joint Registry.

BACKGROUND: Periprosthetic fractures are serious complications of knee arthroplasty often requiring complex surgery. There is concern of increased periprosthetic fracture risk with cementless components given the reliance on interference fit for primary stability. It is unknown how the periprosthetic fracture risk compares between cemented and cementless total knee arthroplasties (TKAs). METHODS: A total of 22,477 cemented and 22,477 cementless TKAs from the National Joint Registry and Hospital Episodes Statistics database were propensity score matched on patient and surgical factors. Cumulative periprosthetic fracture rates were calculated using Kaplan-Meier analyses and compared with Cox regressions. Subgroup analyses were performed in different age, body mass index, and sex groups. RESULTS: The 3-month fracture rate in the cemented and cementless TKA groups were 0.02% and 0.04%, respectively. At 10 years, the cumulative fracture rate after cemented TKA was 1.2%, and after cementless was 1.4%. During the study period, there were no significant differences in fracture rates between cemented and cementless TKAs with a hazards ratio 1.14 (confidence interval 0.94 to 1.37, P = .20) at 10 years postoperatively. There were no significant differences in fracture rates between fixation types on subgroup analyses of sex, body mass index, and age groups. Female sex was a risk factor for fracture in both cemented (odds ratio 2.35, P < .001) and cementless TKAs (odds ratio 2.97, P < .001). CONCLUSIONS: The periprosthetic fracture rates following cemented and cementless TKA surgery are low being approximately 1.2% and 1.4%, respectively at 10 years. There were no significant differences in periprosthetic fracture rates requiring readmission between cemented and cementless TKAs. LEVEL OF EVIDENCE: III.

Re-operation rates of arthroscopic management versus arthrotomy in treatment of septic arthritis of native shoulder joint in adults. A systematic review and meta-analysis.

AIMS: Previous studies have reported concern regarding high reoperation rates when septic arthritis of the native shoulder is treated arthroscopically, compared to open arthrotomy. We aimed to compare re-operation rate between the two strategies. PATIENTS AND METHODS: The review was registered prospectively at PROSPERO, (CRD42021226518). We searched common databases and references lists (8 February 2021). The inclusion criteria included interventional or observational studies of adult patients with a confirmed diagnosis of native shoulder joint septic arthritis and had either arthroscopy or arthrotomy. The exclusion criteria included patients with periprosthetic or post-surgical infections, patients who had atypical infections, and studies that did not report re-operation rate. Cochrane Collaboration's tool for assessing risk of bias (ROBINS-I) was used. RESULTS: Nine studies (retrospective cohort studies) were included that involved 5,643 patients (5,645 shoulders). Mean age ranged from 55.6 to 75.5 years, and follow-up time ranged from 1-41 months. Mean duration of symptoms prior to presentation ranged from 8.3-23.3 days. Metanalysis observed a higher re-operation rate for reinfection at any time point following initial arthroscopy in comparison to arthrotomy, odds ratio 2.61 (95% confidence interval 1.04, 6.56). There was marked heterogeneity (I2 = 78.8%) among studies including surgical techniques and missing data. CONCLUSION: This metanalysis observed a higher reoperation rate in arthroscopy in comparison to arthrotomy for the treatment of native shoulder septic arthritis in adults. The quality of the included evidence is low and the heterogeneity among included studies is marked. Higher quality evidence is still needed that address limitations of previous studies.

Learning From England's Best Practice Tariff: Process Measure Pay-for-Performance Can Improve Hip Fracture Outcomes.

OBJECTIVE: The objective of this study was to evaluate England's Best Practice Tariff (BPT) and consider potential implications for Medicare patients should the US adopt a similar plan. SUMMARY BACKGROUND DATA: Since the beginning of the Affordable Care Act, Medicare has renewed efforts to improve the outcomes of older adults through introduction of an expanding set of alternative-payment models. Among trauma patients, recommended arrangements met with mixed success given concerns about the heterogeneous nature of trauma patients and resulting outcome variation. A novel approach taken for hip fractures in England could offer a viable alternative. METHODS: Linear regression, interrupted time-series, difference-in-difference, and counterfactual models of 2000 to 2016 Medicare (US), HES-APC (England) death certificate-linked claims (≥65 years) were used to: track US hip fracture trends, look at changes in English hip fracture trends before-and-after BPT implementation, compare changes in US-versus-English mortality, and estimate total/theoretical lives saved. RESULTS: A total of 806,036 English and 3,221,109 US hospitalizations were included. After BPT implementation, England's 30-day mortality decreased by 2.6 percentage-points (95%CI: 1.7-3.5) from a baseline of 9.9% (relative reduction 26.3%). 90- and 365-day mortality decreased by 5.6 and 5.4 percentage-points. 30/90/365-day readmissions also declined with a concurrent shortening of hospital length-of-stay. From 2000 to 2016, US outcomes were stagnant (P > 0.05), resulting in an inversion of the countries' mortality and >38,000 potential annual US lives saved. CONCLUSIONS: Process measure pay-for-performance led to significant improvements in English hip fracture outcomes. As efforts to improve US older adult health continue to increase, there are important lessons to be learned from a successful initiative like the BPT.

The influence of mode of anaesthesia on perioperative outcomes in people with hip fracture: a prospective cohort study from the National Hip Fracture Database for England, Wales and Northern Ireland.

BACKGROUND: Delirium is common after hip fracture surgery, affecting up to 50% of patients. The incidence of delirium may be influenced by mode and conduct of anaesthesia. We examined the effect of spinal anaesthesia (with and without sedation) compared with general anaesthesia on early outcomes following hip fracture surgery, including delirium. METHODS: We used prospective data on 107,028 patients (2018 to 2019) from the National Hip Fracture Database, which records all hip fractures in patients aged 60 years and over in England, Wales and Northern Ireland. Patients were grouped by anaesthesia: general (58,727; 55%), spinal without sedation (31,484; 29%), and spinal with sedation (16,817; 16%). Outcomes (4AT score on post-operative delirium screening; mobilisation day one post-operatively; length of hospital stay; discharge destination; 30-day mortality) were compared between anaesthetic groups using multivariable logistic and linear regression models. RESULTS: Compared with general anaesthesia, spinal anaesthesia without sedation (but not spinal with sedation) was associated with a significantly reduced risk of delirium (odds ratio (OR)=0.95, 95% confidence interval (CI)=0.92-0.98), increased likelihood of day one mobilisation (OR=1.06, CI=1.02-1.10) and return to original residence (OR=1.04, CI=1.00-1.07). Spinal without sedation (p<0.001) and spinal with sedation (p=0.001) were both associated with shorter hospital stays compared with general anaesthesia. No differences in mortality were observed between anaesthetic groups. CONCLUSIONS: Spinal and general anaesthesia achieve similar outcomes for patients with hip fracture. However, this equivalence appears to reflect improved perioperative outcomes (including a reduced risk of delirium, increased likelihood of mobilisation day one post-operatively, shorter length of hospital stay and improved likelihood of returning to previous residence on discharge) among the sub-set of patients who received spinal anaesthesia without sedation. The role and effect of sedation should be studied in future trials of hip fracture patients undergoing spinal anaesthesia.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis.

OBJECTIVE: To develop and validate classification criteria for microscopic polyangiitis (MPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (-3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (-1) and eosinophil count ≥1×109/L (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% CI 85% to 95%) and the specificity was 94% (95% CI 92% to 96%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis.

OBJECTIVE: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting or sino-nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3 ANCA positivity (+5); pulmonary nodules, mass or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci-immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (-1); and eosinophil count ≥1×109 /L (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% CI 87% to 96%) and the specificity was 94% (95% CI 89% to 97%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis.

OBJECTIVE: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1×109/L (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3-ANCA positivity (-3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1) and haematuria (-1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% CI 77% to 91%) and the specificity was 99% (95% CI 98% to 100%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis demonstrate strong performance characteristics and are validated for use in research.

2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis.

OBJECTIVE: To develop and validate new classification criteria for Takayasu arteritis (TAK). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate criteria items, (2) collection of candidate items present at diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based classification score in a development data set and (6) validation in an independent data set. RESULTS: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large-vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1) and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% CI 0.94 to 0.99) with a sensitivity of 93.8% (95% CI 88.6% to 97.1%) and specificity of 99.2% (95% CI 96.7% to 100.0%). CONCLUSION: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.

2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis.

OBJECTIVE: To develop and validate updated classification criteria for giant cell arteritis (GCA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate items, (2) prospective collection of candidate items present at the time of diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based risk classification score in a development data set and (6) validation in an independent data set. RESULTS: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C reactive protein ≥10 mg/L (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging and fluorodeoxyglucose-positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% CI 0.88 to 0.94) with a sensitivity of 87.0% (95% CI 82.0% to 91.0%) and specificity of 94.8% (95% CI 91.0% to 97.4%). CONCLUSION: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.