Survivorship of primary NexGen knee replacement: comparing cementless trabecular metal to other designs of tibial component.

PURPOSE: The impact of cementless trabecular metal (TM) implants on implant survivorship are not well delineated. This study compares primary total knee arthroplasty (TKA) revision rates of cemented knee replacements to two cementless knee replacement designs-cementless TM and another cementless design. METHOD: Data from a national registry queried TKA procedures performed for osteoarthritis from 1999 to 2020. The risk of revision of Zimmer NexGen TKA using cementless TM, cementless non-TM, and cemented non-TM were compared. Analyses included Kaplan-Meier estimates of survivorship and Cox hazard ratios (HR), stratified by age and gender. RESULTS: Cementless TM components had higher risks of revision compared to cementless non-TM implants (HR = 1.49; p = < 0.001). Cementless TM implants showed higher risks of revision compared to cemented non-TM prostheses for the first 2 years (HR = 1.75, p < 0.001). Non-TM prostheses posed equal risk of revision for cementless and cemented fixations (HR = 0.95, p = 0.522). Patients aged 55-64 years and 65-74 years had a higher risk of revision for cementless TM compared to cementless non-TM (HR = 1.40, p = 0.033 and HR = 1.79, p <0.001, respectively) and cemented non-TM implants (HR = 1.51, p < 0.001 and HR = 1.54, p <0.001, respectively). CONCLUSION: The study shows there is an increased risk of revision with TM cementless implants for patients aged 55-74 years. These results do not support the use of TM tibial implants for patients of this age group for primary TKA.

Barriers and enablers to the implementation and sustainability of short-stay arthroplasty programs for elective primary total hip and knee replacement: A systematic review with qualitative evidence synthesis.

INTRODUCTION: We aimed to systematically review contemporary evidence on the barriers and enablers to implementing and sustaining short-stay arthroplasty programs for elective primary total hip and knee replacement from the perspectives of patients, health professionals, carers, healthcare administrators, funders and policymakers and to map the findings to the Theoretical Domains Framework (TDF). METHODS: Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and the Cochrane Central Register of Controlled Trials were searched (up to 19 August 2023). Primary qualitative or mixed-methods studies reporting on perspectives relating to the review aims that utilised a short-stay programme were eligible for inclusion. Study quality was assessed using the qualitative critical appraisal tool from the Joanna Briggs Institute. Data were analysed inductively. The final themes were mapped to the TDF. The confidence in the findings was assessed using GRADE CERQual. RESULTS: Fifteen studies were included. Twelve barrier themes and twelve enabler themes were identified. Three themes were graded with high confidence, 10 were graded with moderate confidence, three were graded with low confidence, and eight were graded with very low confidence. The most pertinent domains that the themes were mapped to for patients were beliefs about capabilities, reinforcement, and the environmental context and resources. Health professionals identified knowledge, environmental context and resources as important domains. Two domains were identified for carers: (1) social/professional role and identity and (2) memory, attention, and decision processes. CONCLUSION: We identified key barrier and enabler themes linked to the TDF that can be used to guide implementation initiatives and promote the sustainability of short-stay arthroplasty programs.

How Does the New Australian EQ-5D-5L Value Set Impact Utility Scores? Analysis of Data from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: With advances in health state valuation methods, new value sets may be developed for some countries. Quantifying the impact of moving between existing and new value sets is critical for guiding decisions around utility score interpretation, reporting and comparison with published scores. OBJECTIVES: The aim of this study is to examine, using large-scale national registry data, how the new Australian EQ-5D-5L value set impacts utility scores for patients undergoing joint replacement. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. All primary total hip (THR), knee (TKR), and shoulder replacement (TSR) procedures between 2018 and 2022 with pre-operative and 6-month post-operative EQ-5D-5L data were included. Utility scores were generated using the 2013 and 2023 Australian value sets ('previous' and 'new' value sets, respectively) and analysed descriptively for each joint replacement cohort. Agreement between the two utility score sets was evaluated using concordance correlation coefficients and Bland-Altman plots. RESULTS: EQ-5D-5L data were available for 17,576 THR, 23,010 TKR, and 1667 TSR procedures. The new value set produced a lowest possible EQ-5D-5L utility score of -0.30 (compared with -0.68 previously) and fewer patients had 'worse-than-dead' quality of life (score < 0.00) before surgery. Mean pre-operative scores were 0.21 (THR), 0.19 (TKR), and 0.17 (TSR) units higher with the new value set, and mean post-operative scores were 0.11-0.14 units higher. The new value set resulted in smaller effect sizes for the THR (1.08 versus 1.23) and TKR cohorts (0.86 versus 0.92). There was moderate-to-good overall agreement (coefficients: 0.70-0.80), but concordance varied by time point. CONCLUSION: Although acceptable agreement was evident, the new Australian value set produces less extreme negative utility scores and markedly higher group-level scores. Transition to reporting new EQ-5D-5L utility scores will require accompanying explanation to signal measurement modifications rather than better quality of life.

Collared Cementless Femoral Components Reduce the Revision Rates in Primary Total Hip Arthroplasty Using the Direct Anterior Approach: An Australian Orthopaedic Association National Joint Replacement Registry Study.

BACKGROUND: An increased risk of periprosthetic fracture and aseptic loosening is reported when the direct anterior approach (DAA) is used for total hip arthroplasty (THA), especially with cementless implants. We assessed the rate of revision comparing collared and collarless femoral stems when using the DAA for THA. METHODS: We used data from the Australian Orthopaedic Association National Joint Replacement Registry for primary THA for osteoarthritis inserted with the DAA between January 2015 and December 2022. There were 48,567 THAs that used the DAA (26,690 collarless cementless, 10,161 collared cementless, and 11,716 cemented). Cumulative percent revision was calculated for all-cause revision, revision for periprosthetic femoral fractures, and aseptic femoral stem loosening. Cox proportional hazard ratios [HRs] were used to compare the revision of collared and collarless cementless stems. We also compared collared cementless stems and cemented stems. RESULTS: A higher rate of all-cause revision within 3 months of surgery was observed with collarless compared to collared cementless implants (HR: 1.99 [95% confidence interval (CI), 1.56 to 2.54]; P < .001). Similarly, collarless cementless implants were associated with a greater rate of revision for fracture in the first 6 months (HR: 2.90 [95% CI, 1.89 to 4.45]; P < .001) and after 6 months (HR 10.04 [95% CI 1.38 to 73.21]; P = .02), as well as an increased rate of revision for aseptic loosening after 2 years (HR: 5.76 [95% CI, 1.81 to 18.28], P = .003). Collared cementless and cemented stems performed similarly. CONCLUSION: Collared stems were associated with a reduced rate of all-cause revision for cementless THA performed via the DAA. The reduction in risk may be due to protection from periprosthetic femoral fracture and aseptic loosening.

Cardiopulmonary resuscitation and basic life support guidelines for people with disability: a scoping review.

PURPOSE: To explore literature, policies or procedures available to care providers on how to deliver CPR and BLS to people with a disability, for whom the current standard guidelines are not fit for purpose. MATERIAL AND METHODS: A scoping review was conducted using four databases, namely, CINHAL, PubMed, Scopus, Medline and Google Scholar. Keywords used included, disab*, wheelchairs, cardiopulmonary, resuscitation, "basic life support", life support care, and bystander CPR. 1119 papers were retrieved and 1043 were screened following removal of 76 for duplication. 18 full text articles were reviewed and 5 met the inclusion criteria. RESULTS: The five articles were from three counties and included one case study, three expert opinion papers and one intervention study. Four of the papers advocated in favour of improved CPR and BLS guidelines and three of the papers discussed techniques and ideas for supplementation of standard CPR and BLS. CONCLUSION: The scoping review has uncovered a paucity of evidence explaining delivery of CPR and BLS for people with disability and highlights the need for further research. In the absence of further evidence, it is reasonable for educators to provide ideas and discussion about supplementing CPR and BLS for people with disability to carers.

People with disability and wheelchair users are at a high risk for premature or preventable deaths.Improved first aid responses are proposed to be a mitigating factor for premature and preventable deaths.Improved first aid responses will afford people with disability and wheelchair users the same opportunities for care and rehabilitation as people without disability.Formal and informal carers do not currently have prescriptive guidelines to improve their knowledge on responding to emergency events for people with disabilities.Development of improved guidelines is recommended to reduce fear and anxiety for formal and informal carers whilst also increasing their confidence to respond to emergency situations.

Skeletal stability of inter-molar mandibular distraction osteogenesis in growing patients.

INTRODUCTION: The aim of this retrospective study was to firstly assess the stability of surgical advancement using inter-molar mandibular distraction osteogenesis (IMDO) and secondly to assess the impact of the surgical intervention on subsequent mandibular growth in patients with residual growth. METHODS: The sample consisted of 17 (13F and 4M) consecutively treated patients who underwent IMDO and orthodontic treatment. Cephalometric analysis was performed at three time points: T0 prior to distraction; T1 post-distraction immediately prior to surgical removal of the distractors; and T2 following completion of orthodontic treatment when the final lateral cephalogram was taken (0.86-4.37 years after T1). Statistical comparison of lower facial height, mandibular length, growth, condylar position and anterior mandibular rotation was performed. RESULTS: No association was found between changes in any of the cephalometric measurements and the length of the follow-up interval. The anterior mandibular segment underwent clockwise rotation during distraction and recovered to near its pre-distraction angulation during remodelling. An increase in the lower facial height of 1.88 ± 2.81mm also occurred during distraction (T0-T1) and was maintained during the follow-up period (T1-T2). Post-distraction (T1-T2) growth of lower facial height (p value 0.872) and mandibular length (p value 0.251) showed no association when compared to an untreated control group and an overall reduction in growth was reported. CONCLUSIONS: IMDO was highly stable within a follow-up period of 2.3 ± 0.9 years; however, growth appears to have been inhibited.

Interplay between Two Paralogous Human Silencing Hub (HuSH) Complexes in Regulating LINE-1 Element Silencing.

The Human Silencing Hub (HuSH) complex is composed of TASOR, MPP8, and PPHLN1 subunits and serves as a conserved protein complex responsible for silencing transposable elements in vertebrate animals. Despite its importance, the regulatory mechanisms and recruitment dynamics governing this complex remain poorly understood. In this study, we have identified a second HuSH complex, termed HuSH2, centered around TASOR2, a paralog of the core TASOR protein in HuSH. Our findings indicate that every subunit in both HuSH and HuSH2 has an important role in achieving precise genomic localization to distinct, non-overlapping genomic loci. We utilized in silico protein structure prediction to simulate the interactions between MPP8 and both TASOR paralogs. Drawing on the insights gained from these predictions, we implemented amino acid substitutions that interfered with the binding of MPP8 to each HuSH complex. Leveraging these MPP8 transgenes and other constructs, we identified an important role played by the relative quantities of HuSH complexes in controlling the activity of LINE-1 elements. Furthermore, our results suggest that dynamic changes in TASOR and TASOR2 expression enable cells to finely tune the extent of HuSH-mediated silencing. Our study provides insights into the intricate interplay between HuSH complexes, illuminating their important role in the regulation of retrotransposon silencing.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCCs) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3. The former group exhibits reduced proliferation, genome instability, and heightened sensitivity to genotoxic agents like PARP1/2 inhibitors. Conversely, H3K36M HNSCC models with constant H3K27me3 levels lack these characteristics unless H3K27me3 is elevated by DNA hypomethylating agents or inhibiting H3K27me3 demethylases KDM6A/B. Mechanistically, H3K36M reduces H3K36me by directly impeding the activities of the histone methyltransferase NSD3 and the histone demethylase LSD2. Notably, aberrant H3K27me3 levels induced by H3K36M expression are not a bona fide epigenetic mark because they require continuous expression of H3K36M to be inherited. Moreover, increased sensitivity to PARP1/2 inhibitors in H3K36M HNSCC models depends solely on elevated H3K27me3 levels and diminishing BRCA1- and FANCD2-dependent DNA repair. Finally, a PARP1/2 inhibitor alone reduces tumor burden in a H3K36M HNSCC xenograft model with elevated H3K27me3, whereas in a model with consistent H3K27me3, a combination of PARP1/2 inhibitors and agents that up-regulate H3K27me3 proves to be successful. These findings underscore the crucial balance between H3K36 and H3K27 methylation in maintaining genome instability, offering new therapeutic options for patients with H3K36me-deficient tumors.

A systematic review and meta-analysis of short-stay programmes for total hip and knee replacement, focusing on safety and optimal patient selection.

BACKGROUND: Short-stay joint replacement programmes are used in many countries but there has been little scrutiny of safety outcomes in the literature. We aimed to systematically review evidence on the safety of short-stay programmes versus usual care for total hip (THR) and knee replacement (KR), and optimal patient selection. METHODS: A systematic review and meta-analysis. Randomised controlled trials (RCTs) and quasi-experimental studies including a comparator group reporting on 14 safety outcomes (hospital readmissions, reoperations, blood loss, emergency department visits, infection, mortality, neurovascular injury, other complications, periprosthetic fractures, postoperative falls, venous thromboembolism, wound complications, dislocation, stiffness) within 90 days postoperatively in adults ≥ 18 years undergoing primary THR or KR were included. Secondary outcomes were associations between patient demographics or clinical characteristics and patient outcomes. Four databases were searched between January 2000 and May 2023. Risk of bias and certainty of the evidence were assessed. RESULTS: Forty-nine studies were included. Based upon low certainty RCT evidence, short-stay programmes may not reduce readmission (OR 0.95, 95% CI 0.12-7.43); blood transfusion requirements (OR 1.75, 95% CI 0.27-11.36); neurovascular injury (OR 0.31, 95% CI 0.01-7.92); other complications (OR 0.63, 95% CI 0.26-1.53); or stiffness (OR 1.04, 95% CI 0.53-2.05). For registry studies, there was no difference in readmission, infection, neurovascular injury, other complications, venous thromboembolism, or wound complications but there were reductions in mortality and dislocations. For interrupted time series studies, there was no difference in readmissions, reoperations, blood loss volume, emergency department visits, infection, mortality, or neurovascular injury; reduced odds of blood transfusion and other complications, but increased odds of periprosthetic fracture. For other observational studies, there was an increased risk of readmission, no difference in blood loss volume, infection, other complications, or wound complications, reduced odds of requiring blood transfusion, reduced mortality, and reduced venous thromboembolism. One study examined an outcome relevant to optimal patient selection; it reported comparable blood loss for short-stay male and female participants (p = 0.814). CONCLUSIONS: There is low certainty evidence that short-stay programmes for THR and KR may have non-inferior 90-day safety outcomes. There is little evidence on factors informing optimal patient selection; this remains an important knowledge gap.

Stakeholder perspectives on short-stay joint replacement programs: results from a national cross-sectional study.

BACKGROUND: The capacity to meet anticipated growth in joint replacement demand requires safe, efficient models of care. While short-stay joint replacement programs are being used internationally, they have not been widely implemented in many countries. Importantly, the critical challenges that need to be addressed ahead of large-scale program implementation remain unclear. This study aimed to investigate stakeholder perspectives on short-stay joint replacement programs, including perceived barriers and enablers to implementation and sustainability, and understand current practices in Australia. METHODS: Four key stakeholder groups were invited to participate in this national study: (1) health professionals who provide joint replacement care; (2) hospital administrators involved in joint replacement provision; (3) patients with recent joint replacement; and (4) carers of people with recent joint replacement. Data on perceived feasibility (0 (not at all feasible) - 10 (highly feasible), appeal (0 (not at all appealing) - 10 (highly appealing), current practices, and barriers and enablers were collected using visual analogue scales, multiple response option and open-ended questions, via an online platform. Descriptive analysis and free-text content analysis was undertaken. RESULTS: Data were available from 1,445 participants including 360 health professionals, 20 hospital administrators, 1,034 patients, and 31 carers. Short-stay program implementation was considered moderately feasible by health professionals (median 6, interquartile range (IQR) 3-8) and hospital administrators (median 5, IQR 5-6). Short-stay programs were moderately appealing to patients (median 7, IQR 2-9) but of little appeal to carers (median 3, IQR 1-7). Prominent implementation barriers included perceived limited appropriateness of short-stay programs, inadequate home supports, and issues around reimbursement models or program funding. Not having daily physiotherapy access and concerns about pain and mobility at home were common barriers for patients. Concern about patients' ability to manage daily activities was the most common barrier for carers. Access to post-discharge services, better funding models, improved staffing, and consistent protocols and national care standards were prominent enablers. CONCLUSIONS: This national study has uniquely captured multiple stakeholder perspectives on short-stay joint replacement programs. The findings can guide future quality improvement and implementation initiatives and the development of resources to best support patients, carers, clinicians, and hospitals.

Drug epidemiology in Trinidad and Tobago

This study traces the problem of substance abuse (alcohol,cocaine) in Trinidad and Tobago.