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For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects. This review summarizes research priorities that emerged from the retreat, examples of ongoing collaborations, and opportunities to move science forward. The highest priorities identified include the need to (1) evaluate patient-reported outcome (PRO) measures obtained in clinical practice and assess their use in improving CAC-related outcomes; (2) identify biomarkers (imaging, molecular, and/or behavioral) and novel analytic approaches to accurately predict the early onset of CAC and its progression; and (3) develop and test interventions (pharmacologic, nutritional, exercise-based, and through mathematical modeling) to prevent CAC progression and improve associated symptoms and outcomes.
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BACKGROUND: Unicompartmental knee replacement (UKR) is an effective treatment for end-stage medial compartment osteoarthritis, but there can be problems with fixation. The cementless UKR was introduced to address this issue. It is unknown how its functional outcomes compare with those of the cemented version on a national scale. We performed a matched comparison of the clinical and functional outcomes of cementless and cemented UKRs. METHODS: Using the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR), 14,764 Oxford UKRs with linked data regarding patient-reported outcomes were identified. A total of 6,906 UKRs (3,453 cemented and 3,453 cementless) were propensity score matched on the basis of patient, surgical, and implant factors. RESULTS: The 10-year cumulative implant survival rate was 93.0% (95% confidence interval [CI], 90.0% to 95.1%) for cementless UKRs and 91.3% (95% CI, 89.0% to 93.0%) for cemented UKRs. The cementless UKR group had a significantly lower revision risk (hazard ratio [HR], 0.74; p = 0.02). Subgroup analyses showed a stronger effect size (HR, 0.66) among UKRs performed by high-caseload surgeons (i.e., surgeons performing ≥30 UKRs/year). In the overall cohort, the postoperative Oxford Knee Score (OKS) in the cementless group (mean and standard deviation, 39.1 ± 8.7) was significantly higher (p = 0.001) than that in the cemented group (38.5 ± 8.6). The cementless group gained a mean of 17.6 ± 9.3 points in the OKS postoperatively and the cemented group gained 16.5 ± 9.6 points, with a difference of 1.1 points between the groups (p < 0.001). The difference in OKS points gained postoperatively was highest among UKRs performed by high-caseload surgeons, with the cementless group gaining 1.8 points more (p < 0.001) than the cemented group. CONCLUSIONS: The cementless UKR demonstrated better 10-year implant survival and postoperative functional outcomes than the cemented UKR. The difference was largest among UKRs performed by high-caseload surgeons, with the cementless fixation group having an HR for revision of 0.66 and an approximately 2-point greater improvement in the OKS compared with the cemented fixation group. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Patients who sustain a hip fracture are known to be at imminent refracture risk. Their complex multidisciplinary rehabilitation needs to include falls prevention and anti-osteoporosis medication (AOM) to prevent such fractures. This study aimed to determine which hospital-level organisational factors predict prescription of post-hip fracture AOM, and refracture risk. A cohort of 178 757 patients aged ≥60 years who sustained a hip fracture in England and Wales (2016-19) was examined and followed for 1 year. Patient-level hospital admission datasets from 172 hospitals, the National Hip Fracture Database, and mortality data were linked to 71 metrics extracted from 18 hospital-level organisational reports. Multilevel models determined organisational factors, independent of patient case-mix, associated with (i) AOM prescription, (ii) refracture (by ICD10 coding). Patients were mean (SD) 82.7 (8.6) years old, 71% female, with 18% admitted from care homes. Overall, 101 735 (57%) were prescribed AOM during admission; while 50 354 (28%) died during 1-year follow-up, 12 240 (7%) refractured. Twelve organisational factors were associated with AOM prescription, e.g., orthogeriatrician-led care compared to traditional care models (OR 4.65 [95%CI: 2.25-9.59]); AOM was 9% (95%CI: 6%-13%) more likely to be prescribed in hospitals providing routine bone health assessment to all patients. Refracture occurred at median 126 days (IQR 59-234). Eight organisational factors were associated with refracture risk; hospitals providing orthogeriatrician assessment to all patients within 72-hours of admission had an 18% (95%CI: 2-31%) lower refracture risk, weekend physiotherapy provision an 8% (95%CI: 3-14%) lower risk, and where occupational therapists attended clinical governance meetings, a 7% (95%CI: 2-12%) lower risk. Delays initiating post-discharge community rehabilitation were associated with a 15% (95%CI: 3-29%) greater refracture risk. These novel, national findings highlight the importance of orthogeriatrician, physiotherapist and occupational therapist involvement in secondary fracture prevention post hip fracture; notably fracture risk reductions were seen within 12 months of hip fracture.
Patients who have broken (fractured) a hip are at risk of having another fracture soon after. They have complex needs to avoid more fractures, which include being prescribed bone-strengthening medicines and taking measures to prevent falls. This study looked at which of the measurements, that describe how well a hospital is organised, are associated with whether bone-strengthening medicine is prescribed and the chance of having another fracture. We used data from 178 757 patients aged over 60 years who had a hip fracture at 172 English and Welsh hospitals, linked to their hospital records, and other datasets that describe hospital services. Overall, 57% of patients were prescribed bone-strengthening medicines, and 7% went on to have another fracture. Bone-strengthening medicines were more likely to be prescribed in hospitals where patient care was led by a consultant specialising in the care of older people with fractures (called orthogeriatricians) and in hospitals which routinely checked patients' bone health. Patients attending hospitals that provided orthogeriatrician assessment to all patients within 72 hours of being admitted, physiotherapy services at the weekend, or where occupational therapists attended meetings aimed at improving hospital services had a lower chance of having another fracture.
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Aims: During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the National Institute for Health and Care Excellence (NICE) recommended always resurfacing the patella, rather than never doing so. NICE found insufficient evidence on selective resurfacing (surgeon's decision based on intraoperative findings and symptoms) to make recommendations. If effective, selective resurfacing could result in optimal individualized patient care. This protocol describes a randomized controlled trial to evaluate the clinical and cost-effectiveness of primary TKR with always patellar resurfacing compared to selective patellar resurfacing. Methods: The PAtellar Resurfacing Trial (PART) is a patient- and assessor-blinded multicentre, pragmatic parallel two-arm randomized superiority trial of adults undergoing elective primary TKR for primary osteoarthritis at NHS hospitals in England, with an embedded internal pilot phase (ISRCTN 33276681). Participants will be randomly allocated intraoperatively on a 1:1 basis (stratified by centre and implant type (cruciate-retaining vs cruciate-sacrificing)) to always resurface or selectively resurface the patella, once the surgeon has confirmed sufficient patellar thickness for resurfacing and that constrained implants are not required. The primary analysis will compare the Oxford Knee Score (OKS) one year after surgery. Secondary outcomes include patient-reported outcome measures at three months, six months, and one year (Knee injury and Osteoarthritis Outcome Score, OKS, EuroQol five-dimension five-level questionnaire, patient satisfaction, postoperative complications, need for further surgery, resource use, and costs). Cost-effectiveness will be measured for the lifetime of the patient. Overall, 530 patients will be recruited to obtain 90% power to detect a four-point difference in OKS between the groups one year after surgery, assuming up to 40% resurfacing in the selective group. Conclusion: The trial findings will provide evidence about the clinical and cost-effectiveness of always patellar resurfacing compared to selective patellar resurfacing. This will inform future NICE guidelines on primary TKR and the role of selective patellar resurfacing.
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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.
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Neoplasias del Colon , Proteínas de Drosophila , Insulinas , Ratones , Animales , Humanos , Caquexia/etiología , Caquexia/metabolismo , Drosophila/metabolismo , Dinámicas Mitocondriales , Atrofia Muscular/patología , Músculo Esquelético/metabolismo , Neoplasias del Colon/metabolismo , Insulinas/metabolismo , Lípidos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismoRESUMEN
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.
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Artroplastia de Reemplazo de Rodilla , Cementos para Huesos , Prótesis de la Rodilla , Fracturas Periprotésicas , Sistema de Registros , Humanos , Artroplastia de Reemplazo de Rodilla/instrumentación , Artroplastia de Reemplazo de Rodilla/efectos adversos , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Masculino , Anciano , Femenino , Prótesis de la Rodilla/efectos adversos , Persona de Mediana Edad , Irlanda del Norte/epidemiología , Inglaterra/epidemiología , Gales/epidemiología , Fracturas de la Tibia/cirugía , Diseño de Prótesis , Anciano de 80 o más Años , Cementación , Falla de PrótesisRESUMEN
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.
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Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Disco Intervertebral , Dolor de la Región Lumbar , Estenosis Espinal , Humanos , Persona de Mediana Edad , Preescolar , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/epidemiología , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/complicaciones , Estenosis Espinal/complicaciones , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/patología , Obesidad/complicaciones , Degeneración del Disco Intervertebral/complicaciones , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/epidemiología , Imagen por Resonancia Magnética/métodos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Disco Intervertebral/patologíaRESUMEN
Introduction: Hand osteoarthritis is more common in women, and its risk increases around the time of the menopause. We set out to describe the timing between menopause and the onset of symptomatic hand osteoarthritis (OA), and associations with the use of hormone replacement therapy (HRT) or its discontinuation, describing any identifiable subgroups of women. Methods: Retrospective healthcare-records study of sequential women referred to a specialist hand OA clinic, 2007-2015. Confirmation of hand OA diagnosis was by clinican, by accepted criteria. Demographics and clinical variables were from healthcare-records, recorded by standardised proforma. Outcomes of interest were reported age of onset of hand symptoms, reported age at final menstrual period (FMP), time from FMP to reported onset of hand symptoms and time from cessation of HRT to reported onset of hand symptoms. Exposure categories for systemic HRT use were never users, current users, previous users. Analysis of Variance compared groups; linear regression analysed associations of exposure with outcome. Results: 82/92(89%) of eligible women were post-menopausal, mean age at FMP 49.9 years (SD5.4). In these post-menopausal women, median time from FMP to hand symptom onset was 3 years. 48/82 (59%) developed hand symptoms within the defined peri-menopausal period (FMP ± 4 years), whilst some women developed their symptoms before or after (range -25, 30 years). In women who discontinued HRT prior to symptom onset, the median time from HRT cessation to onset of hand symptoms was 6 months. Past HRT users were older at hand symptom onset than women who had not taken HRT [coeff.4.7 years (0.92, 8.39); P = 0.015]. Conclusions: This study adds to evidence associating the menopause/sex hormone deficiency with hand OA symptom onset in a sizeable subgroup of women (but not all). HRT use/cessation appears to influence the timing of onset of hand OA symptoms. It is not possible to interpret from this type of study whether sex hormone deficiency is causative of disease or modulates its symptoms. It is also not possible to judge whether painful hand osteoarthritis in post-menopausal women is a subtype of disease. Further investigation is indicated of sex-specific subtypes and potential for personalised medicine for post-menopausal women with hand osteoarthritis, as a clearly definable high-risk subgroup.
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Muscle atrophy and weakness are prevalent and debilitating conditions in dogs that cannot be reliably prevented or treated by current approaches. In non-canine species, the natural dietary compound ursolic acid inhibits molecular mechanisms of muscle atrophy, leading to improvements in muscle health. To begin to translate ursolic acid to canine health, we developed a novel ursolic acid dietary supplement for dogs and confirmed its safety and tolerability in dogs. We then conducted a randomized, placebo-controlled, proof-of-concept efficacy study in older beagles with age-related muscle atrophy, also known as sarcopenia. Animals received placebo or ursolic acid dietary supplements once a day for 60 days. To assess the study's primary outcome, we biopsied the quadriceps muscle and quantified atrophy-associated mRNA expression. Additionally, to determine whether the molecular effects of ursolic acid might have functional correlates consistent with improvements in muscle health, we assessed secondary outcomes of exercise participation and T-maze performance. Importantly, in canine skeletal muscle, ursolic acid inhibited numerous mRNA expression changes that are known to promote muscle atrophy and weakness. Furthermore, ursolic acid significantly improved exercise participation and T-maze performance. These findings identify ursolic acid as a natural dietary compound that inhibits molecular mechanisms of muscle atrophy and improves functional performance in dogs.
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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. METHODS: Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. RESULTS: Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. CONCLUSIONS: Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.
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Carcinoma Ductal Pancreático , Neoplasias de Cabeza y Cuello , Neoplasias Pancreáticas , Humanos , Caquexia/genética , Caquexia/complicaciones , Estudios Retrospectivos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/complicacionesRESUMEN
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.
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OBJECTIVES: This study aimed to develop a simulation model to support orthopaedic elective capacity planning. METHODS: An open-source, generalisable discrete-event simulation was developed, including a web-based application. The model used anonymised patient records between 2016 and 2019 of elective orthopaedic procedures from a National Health Service (NHS) Trust in England. In this paper, it is used to investigate scenarios including resourcing (beds and theatres) and productivity (lengths of stay, delayed discharges and theatre activity) to support planning for meeting new NHS targets aimed at reducing elective orthopaedic surgical backlogs in a proposed ring-fenced orthopaedic surgical facility. The simulation is interactive and intended for use by health service planners and clinicians. RESULTS: A higher number of beds (65-70) than the proposed number (40 beds) will be required if lengths of stay and delayed discharge rates remain unchanged. Reducing lengths of stay in line with national benchmarks reduces bed utilisation to an estimated 60%, allowing for additional theatre activity such as weekend working. Further, reducing the proportion of patients with a delayed discharge by 75% reduces bed utilisation to below 40%, even with weekend working. A range of other scenarios can also be investigated directly by NHS planners using the interactive web app. CONCLUSIONS: The simulation model is intended to support capacity planning of orthopaedic elective services by identifying a balance of capacity across theatres and beds and predicting the impact of productivity measures on capacity requirements. It is applicable beyond the study site and can be adapted for other specialties.
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Ortopedia , Humanos , Medicina Estatal , Inglaterra , Simulación por Computador , Procedimientos Quirúrgicos ElectivosRESUMEN
AIMS: Elective hip and knee replacement operations were suspended in April 2020 due to the COVID-19 pandemic. The impact of this suspension and continued disruption to the delivery of joint replacement surgery is still emerging. We describe the impact of the pandemic on the provision of publicly funded elective hip and knee replacement surgery at one teaching hospital in England and on which patients had surgery. METHODS: We included all elective primary and revision hip and knee replacements performed at one hospital between January 2016 and June 2021. Using data for the years 2016-2019, we estimated the expected number of operations and beds occupied per month in January 2020 to June 2021 using time series linear models (adjusting for season and trend). We compared the predictions with the real data for January 2020 to June 2021 to assess the impact of the pandemic on the provision of elective hip and knee replacements. We compared the length of stay and characteristics (age, gender, number of comorbidities, index of multiple deprivation) of patients who had surgery before the pandemic with those who had surgery during the pandemic. RESULTS: We included 6,964 elective primary and revision hip and knee replacements between January 2016 and June 2021. Between January 2020 and June 2021 primary hip replacement volume was 59% of predicted, and 47% for primary knee replacements. Revision hip replacement volume was 77% of predicted, and 42% for revision knee replacement. Median length of stay was one day shorter for primary (4 vs 3 days) and revision (6 vs 5 days) operations during the pandemic compared with before. Patients operated on during the pandemic were younger and had slightly more comorbidities than those operated on before the pandemic. CONCLUSIONS: The restricted provision of elective hip and knee replacements during the COVID-19 pandemic changed the patient casemix, but did not introduce new inequalities in access to these operations. Patients were younger, had more comorbidities, and stayed in hospital for less time than those treated before the pandemic. Approximately half the number of operations were performed during the pandemic than would have been expected and the effect was greatest for revision knee replacements.
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Artroplastia de Reemplazo de Cadera , COVID-19 , Humanos , Pandemias , COVID-19/epidemiología , Inglaterra/epidemiología , Articulación de la RodillaRESUMEN
Aging and many illnesses and injuries impair skeletal muscle mass and function, but the molecular mechanisms are not well understood. To better understand the mechanisms, we generated and studied transgenic mice with skeletal muscle-specific expression of growth arrest and DNA damage inducible α (GADD45A), a signaling protein whose expression in skeletal muscle rises during aging and a wide range of illnesses and injuries. We found that GADD45A induced several cellular changes that are characteristic of skeletal muscle atrophy, including a reduction in skeletal muscle mitochondria and oxidative capacity, selective atrophy of glycolytic muscle fibers, and paradoxical expression of oxidative myosin heavy chains despite mitochondrial loss. These cellular changes were at least partly mediated by MAP kinase kinase kinase 4, a protein kinase that is directly activated by GADD45A. By inducing these changes, GADD45A decreased the mass of muscles that are enriched in glycolytic fibers, and it impaired strength, specific force, and endurance exercise capacity. Furthermore, as predicted by data from mouse models, we found that GADD45A expression in skeletal muscle was associated with muscle weakness in humans. Collectively, these findings identify GADD45A as a mediator of mitochondrial loss, atrophy, and weakness in mouse skeletal muscle and a potential target for muscle weakness in humans.
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Mitocondrias Musculares , Músculo Esquelético , Atrofia Muscular , Animales , Humanos , Ratones , Envejecimiento , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Mitocondrias Musculares/metabolismo , Debilidad Muscular/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/patologíaRESUMEN
Aims: This study describes the variation in the annual volumes of revision hip arthroplasty (RHA) undertaken by consultant surgeons nationally, and the rate of accrual of RHA and corresponding primary hip arthroplasty (PHA) volume for new consultants entering practice. Methods: National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man were received for 84,816 RHAs and 818,979 PHAs recorded between April 2011 and December 2019. RHA data comprised all revision procedures, including first-time revisions of PHA and any subsequent re-revisions recorded in public and private healthcare organizations. Annual procedure volumes undertaken by the responsible consultant surgeon in the 12 months prior to every index procedure were determined. We identified a cohort of 'new' HA consultants who commenced practice from 2012 and describe their rate of accrual of PHA and RHA experience. Results: The median annual consultant RHA volume, averaged across all cases, was 21 (interquartile range (IQR) 11 to 34; range 0 to 181). Of 1,695 consultants submitting RHA cases within the study period, the top 20% of surgeons by annual volume performed 74.2% of total RHA case volume. More than half of all consultants who had ever undertaken a RHA maintained an annual volume of just one or fewer RHA, however, collectively contributed less than 3% of the total RHA case volume. Consultant PHA and RHA volumes were positively correlated. Lower-volume surgeons were more likely to undertake RHA for urgent indications (such as infection) as a proportion of their practice, and to do so on weekends and public holidays. Conclusion: The majority of RHAs were undertaken by higher-volume surgeons. There was considerable variation in RHA volumes by indication, day of the week, and between consultants nationally. The rate of accrual of RHA experience by new consultants is low, and has important implications for establishing an experienced RHA consultant workforce.
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BACKGROUND: Periprosthetic fractures are rare but devastating complications of knee replacement, often requiring complex surgery with substantial morbidity and mortality. It is not known how the fracture rates after total knee replacement (TKR) and unicompartmental knee replacement (UKR) compare. We performed the first matched study comparing TKR and UKR periprosthetic fracture rates. METHODS: This study involved 54,215 UKRs and 54,215 TKRs, identified in the National Joint Registry and Hospital Episodes Statistics database, which were propensity score-matched on patient and surgical factors. The International Classification of Diseases, Tenth Revision, (ICD-10) code M96.6 was used to identify periprosthetic fractures at ≤3 and >3 months postoperatively, as well as estimate rates at up to 10 years. Subgroup analyses were performed in different age groups (<55, 55 to 64, 65 to 74, and ≥75 years), body mass index (BMI) categories (normal, 18.5 to <25 kg/m 2 ; overweight, 25 to <30 kg/m 2 ; obese, 30 to <40 kg/m 2 ; and morbidly obese, ≥40 kg/m 2 ), and sexes. RESULTS: The 3-month fracture rate was 0.09% (n = 50) in the UKR group and 0.05% (n = 25) in the TKR group, with this difference being significant (odds ratio [OR], 2.0; p = 0.004). The rate of fractures occurring at >3 months was 0.32% (n = 171) in the UKR group and 0.61% (n = 329) in the TKR group (OR, 0.51; p < 0.001). At 10 years, the cumulative incidence of fractures was 0.6% after UKR versus 1% after TKR (OR, 0.68; p < 0.001). Fracture rates increased with increasing age, decreasing BMI, and female sex for both UKRs and TKRs. CONCLUSIONS: The fracture risk was small after both UKR and TKR, with small absolute differences between implant types. During the first 3 postoperative months, the fracture rate after UKR was 0.1% and was about twice as high as that after TKR. However, over the first 10 years, the cumulative fracture rate after TKR was 1% and was almost twice as high as that after UKR. Fracture rates after both UKR and TKR were higher in women, patients ≥75 years of age, and patients with normal weight. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Obesidad Mórbida , Osteoartritis de la Rodilla , Fracturas Periprotésicas , Humanos , Femenino , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Gales/epidemiología , Irlanda del Norte/epidemiología , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Reoperación , Falla de Prótesis , Inglaterra/epidemiología , Sistema de Registros , Prótesis de la Rodilla/efectos adversos , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/cirugíaRESUMEN
BACKGROUND: Hip fracture care delivery varies between hospitals, which might explain variations in patient outcomes and health costs. The aim of this study was to identify hospital-level organisational factors associated with long-term patient outcomes and costs after hip fracture. METHODS: REDUCE was a record-linkage cohort study in which national databases for all patients aged 60 years and older who sustained a hip fracture in England and Wales were linked with hospital metrics from 18 organisational data sources. Multilevel models identified organisational factors associated with the case-mix adjusted primary outcomes: cumulative all-cause mortality, days spent in hospital, and inpatient costs over 365 days after hip fracture. FINDINGS: Between April 1, 2016, and March 31, 2019, 178â757 patients with an index hip fracture were identified from 172 hospitals in England and Wales. 126â278 (70·6%) were female, 52â479 (29·4%) were male, and median age was 84 years (IQR 77-89) in England and 83 years (77-89) in Wales. 365 days after hip fracture, 50â354 (28·2%) patients had died. Patients spent a median 21 days (IQR 11-41) in hospital, incurring costs of £14â642 (95% CI 14â600-14â683) per patient, ranging from £10â867 (SD 5880) to £23â188 (17â223) between hospitals. 11 organisational factors were independently associated with mortality, 24 with number of days in hospital, and 25 with inpatient costs. Having all patients assessed by an orthogeriatrician within 72 h of admission was associated with a mean cost saving of £529 (95% CI 148-910) per patient and a lower 365-day mortality (odds ratio 0·85 [95% CI 0·76-0·94]). Consultant orthogeriatrician attendance at clinical governance meetings was associated with cost savings of £356 (95% CI 188-525) and 1·47 fewer days (95% CI 0·89-2·05) in the hospital in the 365 days after hip fracture per patient. The provision of physiotherapy to patients on weekends was associated with a cost saving of £676 (95% CI 67-1285) per patient and with 2·32 fewer days (0·35-4·29) in hospital in the 365 days after hip fracture. INTERPRETATION: Multiple, potentially modifiable hospital-level organisational factors associated with important clinical outcomes and inpatient costs were identified that should inform initiatives to improve the effectiveness and efficiency of hip fracture services. FUNDING: Versus Arthritis.
Asunto(s)
Fracturas de Cadera , Costos de Hospital , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Gales/epidemiología , Estudios de Cohortes , Fracturas de Cadera/terapia , Inglaterra/epidemiologíaRESUMEN
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.
Asunto(s)
Fracturas de Cadera , Humanos , Estudios de Cohortes , Fracturas de Cadera/epidemiología , Fracturas de Cadera/terapia , Hospitales , Alta del Paciente , Gales/epidemiología , Persona de Mediana Edad , AncianoRESUMEN
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.
Asunto(s)
Obesidad , Políticas , Humanos , Índice de Masa Corporal , Análisis de Series de Tiempo Interrumpido , Inglaterra , Sistema de RegistrosRESUMEN
OBJECTIVES: To explore the impact of a temporary cancellation of elective surgery in winter 2017 on trends in primary hip and knee replacement at a major National Health Service (NHS) Trust, and whether lessons can be learnt about efficient surgery provision. DESIGN AND SETTING: Observational descriptive study using interrupted time series analysis of hospital records to explore trends in primary hip and knee replacement surgery at a major NHS Trust, as well as patient characteristics, 2016-2019. INTERVENTION: A temporary cancellation of elective services for 2 months in winter 2017. OUTCOMES: NHS-funded hospital admissions for primary hip or knee replacement, length of stay and bed occupancy. Additionally, we explored the ratio of elective to emergency admissions at the Trust as a measure of elective capacity, and the ratio of public to private provision of NHS-funded hip and knee surgery. RESULTS: After winter 2017, there was a sustained reduction in the number of knee replacements, a decrease in the proportion of most deprived people having knee replacements and an increase in average age for knee replacement and comorbidity for both types of surgery. The ratio of public to private provision dropped after winter 2017, and elective capacity generally has reduced over time. There was clear seasonality in provision of elective surgery, with less complex patients admitted during winter. CONCLUSIONS: Declining elective capacity and seasonality has a marked effect on the provision of joint replacement, despite efficiency improvements in hospital treatment. The Trust has outsourced less complex patients to independent providers, and/or treated them during winter when capacity is most limited. There is a need to explore whether these are strategies that could be used explicitly to maximise the use of limited elective capacity, provide benefit to patients and value for money for taxpayers.