Search results
Found 30036 matches for
Higher hospital volume reduces early failure rates in single-stage revision TKR for infection: An analysis of the United Kingdom National Joint Registry and National Administrative Databases.
PURPOSE: Revision knee replacement (RevKR) for infection is rare but increasing. It is hypothesised that higher hospital volume reduces adverse outcomes. The aim was to estimate the association of surgical unit volume with outcomes following first, single-stage RevKR for infection. METHODS: This population-based cohort study merged data from the United Kingdom National Joint Registry, Hospital Episode Statistics, National Patient Reported Outcome Measures and the Civil Registrations of Death. Patients undergoing procedures between 1 January 2009 and 30 June 2019 were included. Early outcomes were chosen to reflect the quality of the surgical provision and included re-revision at 2 years, mortality, serious medical complications, length of stay and patient-reported outcome measures (PROMs). Adjusted fixed effect multivariable regression models were used to examine the association between surgical unit mean annual caseload and the risk of adverse outcomes. RESULTS: A total of 1477 patients underwent first-time single-stage RevKRs for infection across 267 surgical units and 716 surgeons. Following adjustment for age, gender, American Society of Anaesthesiologists grade, surgeon volume, year of surgery and operation funder and modelling surgical unit volume with restricted cubic spline, a greater mean annual volume was associated with a lower risk of re-revision at 2 years. The odds of re-revision in hospitals performing fewer than or equal to 12 cases per year was 2.53 (95% confidence interval = 1.50-4.31) times more likely than hospitals performing three to four cases per month. Annual variation in surgical unit volume was not associated with mortality and serious medical complications within 90 days. Only 99 out of 1477 (7%) of patients had linked PROMs which precluded subsequent analysis. CONCLUSION: Overall, higher volume surgical units had lower rates of early re-revision following the first RevKR for infection. We were unable to provide recommended specific volume thresholds for units; however, the probability of re-revision appears to be lowest in the highest volume units. LEVEL OF EVIDENCE: Level III, retrospective cohort study of prospectively collected data.
Preventing pressure sores after hip fracture
Hip fractures commonly occur in older patients, with high levels of frailty and comorbidity. Many of these patients have limited mobility before their fracture, and even after surgery, their mobility may remain limited. It is therefore not surprising that they are at a high risk of developing pressure sores, particularly on their heels, and a variety of devices and interventions have been proposed to reduce this risk. Foam or air mattresses, designed to reduce contact pressure on the patient’s whole body, are now routinely used in many healthcare systems. However, there is wide variation in their design. We developed the WHiTE 14;PRESSURE 3 trial to address the lack of evidence in this area. This is a three-arm multicentre randomized trial including health economic evaluation and recruiting patients from NHS hospitals in the UK. The trial compares standard strategies for the prevention of pressure sores with standard care plus a constant low-pressure device and with standard care plus a heel off-loading device. This annotation describes the development of this trial.Cite this article: Bone Joint J 2025;107-B(2):135–138.
Haemodynamic measurements during hip hemiarthroplasty surgery for hip fracture.
AIMS: There is compelling evidence for the use of cemented hip hemiarthroplasty for displaced intracapsular hip fractures; however, the risks of cement are well reported and in rare cases may be associated with haemodynamic collapse. It is therefore important to improve our understanding of haemodynamic instability, intraoperative monitoring, and strategies to reduce the risk to patients. METHODS: We measured arterial blood pressure using the LiDCOrapid Continuous Non-invasive Arterial Pressure (CNAP) finger cuff during surgery in patients enrolled in the WHiTE 5 trial randomized to cemented or modern uncemented hip hemiarthroplasty at a single recruiting site. We observed the incidence, timing, and magnitude of haemodynamic instability at key stages of the surgical procedure. RESULTS: We obtained measurements from 56 patients, of whom 46 had complete recordings and were used in the analysis. Modest falls in systolic blood pressure (20% to 30%) occurred in four patients (15%) who received a cemented hemiarthroplasty and one patient (5%) in the uncemented group. The fall in blood pressure occurred either within five minutes of cementing or at final hip reduction. We observed concurrent drops in cardiac output (CO) and stroke volume (SV). CONCLUSION: We observed the presence of two potential periods for haemodynamic instability during hip hemiarthroplasty surgery: the first was within five minutes of cementing the femoral canal and the second after final reduction of the prosthesis (observed in both cemented and uncemented hemiarthroplasty). The falls in blood pressure appeared to be driven by reduced CO and SV.
Do patients with minimally displaced distal radial fractures need a plaster cast?
Traditionally, patients with a fracture of the distal radius are treated in a cast if they do not require surgery. If the fracture requires manipulation, the cast is moulded to hold the reduction and maintain normal anatomical alignment during healing. However, is a cast necessary for patients whose fracture does not require manipulation? Removable splints are an alternative treatment option. Such splints have the advantage that they can be adjusted to improve fit around the wrist as swelling reduces, and can be removed and reapplied for the purpose of washing or, in some cases, exercise. However, evidence for their safety and effectiveness in the management of distal radius fractures is lacking. DRAFT3 is a multicentre randomized non-inferiority trial and economic analysis designed to determine the safety and effectiveness of removable splints as an alternative to casts in the treatment of distal radius fractures that do not require manipulation.
The Skeletal Ciliopathies
Within the broad and growing spectrum of human ciliopathies is a range of linked and overlapping disorders that present with skeletal features. These have been coined the skeletal ciliopathies. The syndromes have, to this point, been largely attributed to alterations in cellular Hedgehog signalling during development. However, a huge surge in fundamental discovery and clinical research has unveiled a plethora of roles for cilia in biology. This implicates a range of molecular and cell processes in the pathogenesis of skeletal ciliopathies. Our understanding of bi-directional interactions between cilia and the extracellular matrix remains in its infancy. The identification of genes and causal mutations defines skeletal ciliopathies. Some of these genes, and the proteins they encode, are now being explored further, by means of cell, animal, and other model approaches, seeking to understand the molecular underpinnings of disease. However, given the relatively recent appreciation of links between cilia biology and human disease, there is much work to be done. This chapter will briefly introduce the primary cilium and its associated ‘ciliome’, before describing the ciliary-associated skeletal disorders and the genes with which they are associated. Where possible, it will expand upon our current mechanistic understanding.
Impact of pandemic service changes on ethnic inequalities in maternal and perinatal outcomes in England: a population-based study.
OBJECTIVE: In the UK and worldwide, there are substantial ethnic inequalities in maternal and perinatal care and outcomes. We aim to assess the impact of the unprecedented change in care provision during the COVID-19 pandemic on inequalities in adverse maternity outcomes. DESIGN: Retrospective cohort study using structured electronic health record data. SETTING: English hospital trusts providing maternity care. PARTICIPANTS: Women giving birth and babies born in the National Health Service (NHS) in England between 1 April 2018 and 31 March 2021, in three time groups: prepandemic, the first pandemic wave (26 March 2020 to 30 June 2020) and second pandemic wave (1 July 2020 to 31 March 2021). Self-reported ethnicity was grouped into White, South-Asian, Black, Mixed and Other. MAIN OUTCOME MEASURES: Composite and component measures of maternal (emergency caesarean section, obstetric anal sphincter injury, hysterectomy, sepsis, anaesthetic complications and prolonged hospital stay) and perinatal (stillbirth, neonatal death, preterm birth, brain injury, small for gestational age and prolonged hospital stay). Poisson regression was used to compare relative risks between different ethnic groups. FINDINGS: 1.54 million maternal and 1.43 million neonatal records were included. The overall incidence of adverse outcomes per 1000 births initially decreased maternal: from 308.0 (95% CI 307.0 to 309.0) to 291.0 (95% CI 311.4 to 314.9) (p<0.001); perinatal: from 133.0 (95% CI 132.3 to 133.7) to 111.9 (95% CI 110.1 to 113.7) (p<0.001)), but then increased in the second pandemic period (maternal: 313.2 (95% CI 311.4 to 314.9) (p<0.001); perinatal 118.9 (95% CI 117.7 to 120.0) (p<0.001)). The risk of adverse outcomes was higher in women and babies from all ethnic minority groups compared with White women in both pandemic periods. Black and South-Asian women and babies were approximately 25% more likely to sustain adverse outcomes. While similar overall changes in adverse outcomes were seen in all groups, existing inequalities were sustained throughout the pandemic periods. INTERPRETATION: Existing inequalities in adverse maternal and perinatal/neonatal outcomes were maintained, not tempered, during the pandemic, despite substantial changes to maternity services and care. Further research on possible interventions to reduce inequality is needed.
Association between socioeconomic status and patient-reported outcome at 1 year after shoulder arthroplasty for osteoarthritis or cuff-tear arthropathy: a nationwide cohort study of 2,292 arthroplasties.
PURPOSE: We aimed to evaluate the association between socioeconomic factors and patient-reported Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 1 year after hemiarthroplasty, reverse, or anatomical total shoulder arthroplasty for osteoarthritis or cuff-tear arthropathy. METHODS: Eligible patients were identified using linked national data from the Danish Shoulder Arthroplasty Registry and Statistics Denmark between April 2012 and April 2019. Univariable and multivariable linear regression was used to identify the association between socioeconomic factors and the WOOS index at 1 year following primary shoulder arthroplasty adjusted for age, sex, underlying diagnosis, implant design, and comorbidities. We examined socioeconomic factors including employment status, marital status, education, and income. Estimates were provided with 95% confidence intervals (CI). RESULTS: 2,292 patients were identified with a mean WOOS index of 76 (standard deviation 24). In the adjusted analysis, unemployed patients had a significantly lower WOOS index compared with patients with low-level jobs (14, CI 7.0-21), patients with high-level jobs (19, CI 12-25), and retired patients (14, CI 8.3-21). Low education level was associated with a lower WOOS index compared with medium education (4.8, CI 2.6-7.0) and high education level (7.7, CI 5.0-10). There was no association between WOOS index and income or marital status. CONCLUSION: Unemployment and low education level were associated with worse WOOS index 1 year after shoulder arthroplasty for osteoarthritis or cuff-tear arthropathy. This highlights a potential inequity in patient-reported outcomes after shoulder arthroplasty.
Rapid assessment of the osteogenic capacity of hydroxyapatite/aragonite using a murine tibial periosteal ossification model.
Biomaterials are widely used as orthopaedic implants and bone graft substitutes. We aimed to develop a rapid osteogenic assessment method using a murine tibial periosteal ossification model to evaluate the bone formation/remodelling potential of a biomaterial within 2-4 weeks. A novel hydroxyapatite/aragonite (HAA) biomaterial was implanted into C57BL/6 mice juxtaskeletally between the tibia and tibialis anterior muscle. Rapid intramembranous bone formation was observed at 14 days, with 4- to 8-fold increases in bone thickness and callus volume in comparison with sham-operated animals (p
In vitro and in vivo effects of zoledronic acid on senescence and senescence-associated secretory phenotype markers.
In addition to reducing fracture risk, zoledronic acid has been found in some studies to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple co-morbidities, the non-skeletal actions of zoledronic acid could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype [SASP]) actions. To test this, we first performed in vitro senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronic acid killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronic acid or vehicle for 8 weeks, zoledronic acid significantly reduced circulating SASP factors, including CCL7, IL-1β, TNFRSF1A, and TGFβ1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronic acid demonstrated a significant downregulation of senescence/SASP genes (SenMayo). To establish that these cells are potential senolytic/senomorphic targets of zoledronic acid, we used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronic acid significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. Collectively, our findings demonstrate that zoledronic acid has senolytic effects in vitro and modulates senescence/SASP biomarkers in vivo. These data point to the need for additional studies testing zoledronic acid and/or other bisphosphonate derivatives for senotherapeutic efficacy.
Real-Time Impedance-Based Monitoring of the Growth and Inhibition of Osteomyelitis Biofilm Pathogen Staphylococcus aureus Treated with Novel Bisphosphonate-Fluoroquinolone Antimicrobial Conjugates.
Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.
Bisphosphonates in dentistry: Historical perspectives, adverse effects, and novel applications.
Studies of the potential role of bisphosphonates in dentistry date back to physical chemical research in the 1960s, and the genesis of the discovery of bisphosphonate pharmacology in part can be linked to some of this work. Since that time, parallel research on the effects of bisphosphonates on bone metabolism continued, while efforts in the dental field included studies of bisphosphonate effects on dental calculus, caries, and alveolar bone loss. While some utility of this drug class in the dental field was identified, leading to their experimental use in various dentrifice formulations and in some dental applications clinically, adverse effects of bisphosphonates in the jaws have also received attention. Most recently, certain bisphosphonates, particularly those with strong bone targeting properties, but limited biochemical effects (low potency bisphosphonates), are being studied as a local remedy for the concerns of adverse effects associated with other more potent members of this drug class. Additionally, low potency bisphosphonate analogs are under study as vectors to target active drugs to the mineral surfaces of the jawbones. These latter efforts have been devised for the prevention and treatment of oral problems, such as infections associated with oral surgery and implants. Advances in the utility and mechanistic understanding of the bisphosphonate class may enable additional oral therapeutic options for the management of multiple aspects of dental health.
Bisphosphonates for delivering drugs to bone.
Advances in the design of potential bone-selective drugs for the treatment of various bone-related diseases are creating exciting new directions for multiple unmet medical needs. For bone-related cancers, off-target/non-bone toxicities with current drugs represent a significant barrier to the quality of life of affected patients. For bone infections and osteomyelitis, bacterial biofilms on infected bones limit the efficacy of antibiotics because it is hard to access the bacteria with current approaches. Promising new experimental approaches to therapy, based on bone-targeting of drugs, have been used in animal models of these conditions and demonstrate improved efficacy and safety. The success of these drug-design strategies bodes well for the development of therapies with improved efficacy for the treatment of diseases affecting the skeleton. LINKED ARTICLES: This article is part of a themed issue on The molecular pharmacology of bone and cancer-related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc.