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.

KDM4A lysine demethylase induces site-specific copy gain and rereplication of regions amplified in tumors.

Acquired chromosomal instability and copy number alterations are hallmarks of cancer. Enzymes capable of promoting site-specific copy number changes have yet to be identified. Here, we demonstrate that H3K9/36me3 lysine demethylase KDM4A/JMJD2A overexpression leads to localized copy gain of 1q12, 1q21, and Xq13.1 without global chromosome instability. KDM4A-amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase, and is not stable but is regenerated each cell division. Sites with increased copy number are rereplicated and have increased KDM4A, MCM, and DNA polymerase occupancy. Suv39h1/KMT1A or HP1γ overexpression suppresses the copy gain, whereas H3K9/K36 methylation interference promotes gain. Our results demonstrate that overexpression of a chromatin modifier results in site-specific copy gains. This begins to establish how copy number changes could originate during tumorigenesis and demonstrates that transient overexpression of specific chromatin modulators could promote these events.

H3 K27M and EZHIP Impede H3K27-Methylation Spreading by Inhibiting Allosterically Stimulated PRC2.

Diffuse midline gliomas and posterior fossa type A ependymomas contain the recurrent histone H3 lysine 27 (H3 K27M) mutation and express the H3 K27M-mimic EZHIP (CXorf67), respectively. H3 K27M and EZHIP are competitive inhibitors of Polycomb Repressive Complex 2 (PRC2) lysine methyltransferase activity. In vivo, these proteins reduce overall H3 lysine 27 trimethylation (H3K27me3) levels; however, residual peaks of H3K27me3 remain at CpG islands (CGIs) through an unknown mechanism. Here, we report that EZHIP and H3 K27M preferentially interact with PRC2 that is allosterically activated by H3K27me3 at CGIs and impede its spreading. Moreover, H3 K27M oncohistones reduce H3K27me3 in trans, independent of their incorporation into the chromatin. Although EZHIP is not found outside placental mammals, expression of human EZHIP reduces H3K27me3 in Drosophila melanogaster through a conserved mechanism. Our results provide mechanistic insights for the retention of residual H3K27me3 in tumors driven by H3 K27M and EZHIP.

Continued Activity of the Pioneer Factor Zelda Is Required to Drive Zygotic Genome Activation.

Reprogramming cell fate during the first stages of embryogenesis requires that transcriptional activators gain access to the genome and remodel the zygotic transcriptome. Nonetheless, it is not clear whether the continued activity of these pioneering factors is required throughout zygotic genome activation or whether they are only required early to establish cis-regulatory regions. To address this question, we developed an optogenetic strategy to rapidly and reversibly inactivate the master regulator of genome activation in Drosophila, Zelda. Using this strategy, we demonstrate that continued Zelda activity is required throughout genome activation. We show that Zelda binds DNA in the context of nucleosomes and suggest that this allows Zelda to occupy the genome despite the rapid division cycles in the early embryo. These data identify a powerful strategy to inactivate transcription factor function during development and suggest that reprogramming in the embryo may require specific, continuous pioneering functions to activate the genome.

An AI-guided screen identifies probucol as an enhancer of mitophagy through modulation of lipid droplets.

Failures in mitophagy, a process by which damaged mitochondria are cleared, results in neurodegeneration, while enhancing mitophagy promotes the survival of dopaminergic neurons. Using an artificial intelligence platform, we employed a natural language processing approach to evaluate the semantic similarity of candidate molecules to a set of well-established mitophagy enhancers. Top candidates were screened in a cell-based mitochondrial clearance assay. Probucol, a lipid-lowering drug, was validated across several orthogonal mitophagy assays. In vivo, probucol improved survival, locomotor function, and dopaminergic neuron loss in zebrafish and fly models of mitochondrial damage. Probucol functioned independently of PINK1/Parkin, but its effects on mitophagy and in vivo depended on ABCA1, which negatively regulated mitophagy following mitochondrial damage. Autophagosome and lysosomal markers were elevated by probucol treatment in addition to increased contact between lipid droplets (LDs) and mitochondria. Conversely, LD expansion, which occurs following mitochondrial damage, was suppressed by probucol and probucol-mediated mitophagy enhancement required LDs. Probucol-mediated LD dynamics changes may prime the cell for a more efficient mitophagic response to mitochondrial damage.

Distinct factors control histone variant H3.3 localization at specific genomic regions.

The incorporation of histone H3 variants has been implicated in the epigenetic memory of cellular state. Using genome editing with zinc-finger nucleases to tag endogenous H3.3, we report genome-wide profiles of H3 variants in mammalian embryonic stem cells and neuronal precursor cells. Genome-wide patterns of H3.3 are dependent on amino acid sequence and change with cellular differentiation at developmentally regulated loci. The H3.3 chaperone Hira is required for H3.3 enrichment at active and repressed genes. Strikingly, Hira is not essential for localization of H3.3 at telomeres and many transcription factor binding sites. Immunoaffinity purification and mass spectrometry reveal that the proteins Atrx and Daxx associate with H3.3 in a Hira-independent manner. Atrx is required for Hira-independent localization of H3.3 at telomeres and for the repression of telomeric RNA. Our data demonstrate that multiple and distinct factors are responsible for H3.3 localization at specific genomic locations in mammalian cells.

Mechanism of transcription modulation by the transcription-repair coupling factor.

Elongation by RNA polymerase is dynamically modulated by accessory factors. The transcription-repair coupling factor (TRCF) recognizes paused/stalled RNAPs and either rescues transcription or initiates transcription termination. Precisely how TRCFs choose to execute either outcome remains unclear. With Escherichia coli as a model, we used single-molecule assays to study dynamic modulation of elongation by Mfd, the bacterial TRCF. We found that nucleotide-bound Mfd converts the elongation complex (EC) into a catalytically poised state, presenting the EC with an opportunity to restart transcription. After long-lived residence in this catalytically poised state, ATP hydrolysis by Mfd remodels the EC through an irreversible process leading to loss of the RNA transcript. Further, biophysical studies revealed that the motor domain of Mfd binds and partially melts DNA containing a template strand overhang. The results explain pathway choice determining the fate of the EC and provide a molecular mechanism for transcription modulation by TRCF.

Evolution of RND efflux pumps in the development of a successful pathogen.

AIMS: This study examined the origins and evolution of the AdeABC, AdeFGH and AdeIJK efflux pumps in the Acinetobacter genus, including human and animal pathogens and species from non-clinical environments. METHODS: Comparative genome analyses were performed using the reference sequences for 70 Acinetobacter species to identify putative orthologs of AdeABC, AdeFGH and AdeIJK and their regulators. Sequence similarities and the genomic locations of coding sequences were correlated with phylogeny to infer modes of evolution. Intraspecies variation was assessed in species of interest using up to 236 complete genome sequences. Mutants overproducing adeIJK in A. baylyi were examined to identify regulators of this system in a non A. baumannii species. RESULTS: The results indicate that adeIJK has been a stable part of Acinetobacter genomes since the genesis of this genus, whereas adeABC and adeFGH were carried by less than half of the species, but showed some lineage specificity. The organisation and local genetic contexts of adeABC loci were particularly variable to the sub-species level, suggesting frequent recombination. Cognate regulatory systems were almost always found in the genomes of species encoding pumps. Mutations in adeN, which encodes a repressor of adeIJK, were selected by antibiotic exposure in A. baylyi, similar to previous findings in pathogenic lineages. CONCLUSIONS: The multidrug efflux capacity of clinical Acinetobacter strains stems from accessory and core genetic features. AdeIJK is likely to have ancient core function(s) that have promoted its maintenance, whereas recent antibiotic use may be driving the evolution of the AdeABC pump.

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.

Nurse experiences of partnership nursing when caring for children with long-term conditions and their families: A qualitative systematic review.

AIM: To explore the experiences of partnership nursing among nurses when caring for children and young people with long-term conditions, and their families. BACKGROUND: Partnership nursing is promoted as a positive model of care among paediatric nurses, where shared roles and decision-making, parental participation, mutual trust and respect, communication and negotiation are valued to create positive care experiences and enhance patient outcomes. Little is known about how nurses use partnership with both the patient and the parents in this triad to deliver partnership nursing. DESIGN: A qualitative systematic review followed Joanna Briggs Institute meta-aggregation approach and has been reported according to PRISMA guidelines. METHODS: A comprehensive systematic search was conducted in seven electronic databases. Studies were assessed according to a pre-determined inclusion criteria. Qualitative findings with illustrative participant quotes were extracted from included studies and grouped into categories to inform overall synthesised findings. Methodological quality assessment was conducted. FINDINGS: A total of 5837 publications were screened, and 41 qualitative studies were included. Three overarching synthesised findings were identified: (1) Using education to promote feelings of safety and support, (2) Partnering to develop a strong therapeutic relationship and (3) Optimising communication underpinned by shared decision-making principles to deliver individualised care. CONCLUSION: Nurses demonstrated successful partnership in their practice, but focused on developing dyadic nurse-parent and dyadic nurse-child partnerships. Future practice development that creates a three-way triadic partnership may aid therapeutic relationships and shared decision-making. IMPLICATIONS FOR CLINICAL PRACTICE: Clinicians can reflect on how dyadic partnerships (focusing on the child or the parent) may exclude opportunities for coherent care. Further exploration in practice, policy and research as to how nurses determine child competency and child and parent level of engagement in triadic partnership may improve the potential of meaningful shared decision-making.

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.

Human spliceosomal snRNA sequence variants generate variant spliceosomes.

Human pre-mRNA splicing is primarily catalyzed by the major spliceosome, comprising five small nuclear ribonucleoprotein complexes, U1, U2, U4, U5, and U6 snRNPs, each of which contains the corresponding U-rich snRNA. These snRNAs are encoded by large gene families exhibiting significant sequence variation, but it remains unknown if most human snRNA genes are untranscribed pseudogenes or produce variant snRNAs with the potential to differentially influence splicing. Since gene duplication and variation are powerful mechanisms of evolutionary adaptation, we sought to address this knowledge gap by systematically profiling human U1, U2, U4, and U5 snRNA variant gene transcripts. We identified 55 transcripts that are detectably expressed in human cells, 38 of which incorporate into snRNPs and spliceosomes in 293T cells. All U1 snRNA variants are more than 1000-fold less abundant in spliceosomes than the canonical U1, whereas at least 1% of spliceosomes contain a variant of U2 or U4. In contrast, eight U5 snRNA sequence variants occupy spliceosomes at levels of 1% to 46%. Furthermore, snRNA variants display distinct expression patterns across five human cell lines and adult and fetal tissues. Different RNA degradation rates contribute to the diverse steady state levels of snRNA variants. Our findings suggest that variant spliceosomes containing noncanonical snRNAs may contribute to different tissue- and cell-type-specific alternative splicing patterns.

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.

Histone H3.3 G34 mutations promote aberrant PRC2 activity and drive tumor progression.

A high percentage of pediatric gliomas and bone tumors reportedly harbor missense mutations at glycine 34 in genes encoding histone variant H3.3. We find that these H3.3 G34 mutations directly alter the enhancer chromatin landscape of mesenchymal stem cells by impeding methylation at lysine 36 on histone H3 (H3K36) by SETD2, but not by the NSD1/2 enzymes. The reduction of H3K36 methylation by G34 mutations promotes an aberrant gain of PRC2-mediated H3K27me2/3 and loss of H3K27ac at active enhancers containing SETD2 activity. This altered histone modification profile promotes a unique gene expression profile that supports enhanced tumor development in vivo. Our findings are mirrored in G34W-containing giant cell tumors of bone where patient-derived stromal cells exhibit gene expression profiles associated with early osteoblastic differentiation. Overall, we demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors.

Developing a model of neonatal nurse-controlled analgesia: A Delphi study.

AIM: To develop a nurse-led model of analgesia to manage post-operative pain in the surgical neonate. DESIGN: A four-round e-Delphi study was conducted from March to December 2022. METHODS: An e-Delphi method was used seeking a consensus of 70% or greater. Fifty-one experts were invited to join the panel. Members consisted of multi-disciplinary healthcare professionals who work in areas associated with neonatal care. In round 1, 49 statements relative to neonatal pain assessment and management were distributed to the panel. Panel members were asked to rate their level of agreeance on a Likert scale from 1 to 5 (1 = strongly disagree to 5 = strongly agree). Ratings equal to or greater than 4 represented agreement, 3 indicated uncertainty and 2 or less disagreement with the proposed statement. An opportunity for free-text responses after each statement was provided. This iterative process continued for three rounds. In the fourth and final round, the completed model of neonatal nurse-controlled analgesia was presented along with a further opportunity to provide feedback on the final version. RESULTS: Four rounds of statements and voting were required to reach consensus on a model of neonatal nurse-controlled analgesia. The model consists of criteria for use, over-arching guidelines and three separate pathways based on an individual baby's pain assessment scores, need for pain relieving interventions and time-lapsed post-surgical procedure. CONCLUSION: A comprehensive model of neonatal nurse-controlled analgesia, applicable to the Australasian context, was developed in collaboration with a group of neonatal experts. IMPACT: This study provides a multi-modal family-integrated model to manage neonatal post-operative pain. By providing nurses with increased autonomy to assess and manage acute pain, this model has the potential to not only provide a more responsive and individualized approach to alleviate discomfort, but highlights the integral role of parent partnerships in the neonatal intensive care. REPORTING METHOD: This study was reported in line with the Conducting and REporting of DElphi studies (CREDE) guidance on Delphi studies. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was utilized for this study.

Practical advice for refugees aspiring to become registered nurses in Australia.

AIMS: This paper describes practical advice for refugees aspiring to become Registered Nurses (RNs) in Australia. DESIGN: Qualitative description using a naturalistic inquiry framework. METHODS: Between February 2018 and September 2019, the lead author conducted semi-structured interviews with employed RNs that are former refugees that speak English. Interviews were 45-90 min in duration and digitally recorded. Participants provided voluntary informed consent and were sent questions beforehand. All transcription data were thematically analysed for key themes until no further themes were identified. This paper covers practical advice provided by the participants at the conclusion of their interviews. RESULTS: Twelve participants provided practical advice. Six themes were identified: (1) Find your purpose and set goals; (2) Work hard and never give up; (3) Seek support; (4) Capitalize on opportunities; (5) Be optimistic; (6) Give back. The last theme, give back, was salient across all interviews and was an inherent motivator for some participants once their RN status was achieved. CONCLUSION: Each participant set the goal of becoming a fully registered nurse and made it a life goal that provided meaning for them. Despite their experiences, the participants provided practical advice that could guide younger people aspiring to become successfully qualified RNs. IMPACT: The findings in this study are unique as they are derived from people with experiences as refugees who, despite their adversity, became RNs. The practical advice provides a framework not only for younger people from refugee backgrounds seeking to achieve their professional goals, but others looking to succeed in other workforce sectors. The practical advice for success will be useful in informing nursing authorities, tertiary institutions and private and public health organizations to develop effective approaches to guide the next generation of would-be RNs set to contribute to nursing practice in Australia. There were no patient or public contributions as the focus was the personal and professional lives of nurses with refugee backgrounds.

Perception of Perioperative Risk for Arthroplasty Patients: A Poll of Australian Orthopedic Surgeons.

BACKGROUND: There is growing interest in the perioperative management of patients who have indications for hip and knee arthroplasty in the setting of modifiable risk factors such as morbid obesity, poorly controlled diabetes, and smoking. A recent survey of the American Association of Hip and Knee Surgeons (AAHKS) found that 95% of respondents address modifiable risk factors prior to surgery. The aim of this study was to poll Australian arthroplasty surgeons regarding their approach to patients who have modifiable risk factors. METHODS: The survey tool used in the AAHKS study was adapted for use in the Australian context and distributed to the membership of the Arthroplasty Society of Australia via SurveyMonkey. There were 77 responses received, representing a response rate of 64%. RESULTS: The majority of respondents were experienced, high volume arthroplasty surgeons. Overall, 91% of respondents restricted access to arthroplasty for patients who have modifiable risk factors. There were 72% restricting access for excessive body mass index, 85% for poor diabetic control, and 46% for smoking. Most respondents made decisions based on personal experience or literature review rather than hospital or departmental pressures. While 49% of surgeons believed that current payment systems did not impair their ability to achieve good outcomes, 58% believed that certain arthroplasty patients would benefit from additional intervention, based on their socioeconomic status. CONCLUSION: Over 90% of surgeons who responded address modifiable risk factors prior to surgery. This finding aligns with the practice patterns of AAHKS members, despite differences in healthcare systems.

Hip Arthroplasty Outcomes in the Presence of Kidney Failure: A National Data Linkage Study.

BACKGROUND: Patients who have kidney failure are at higher risk of requiring total hip arthroplasty (THA) and are at higher risk of complications. This study compared the rate of revision surgery and mortality following THA between patients who have kidney failure receiving long term dialysis or who had a kidney transplant and those who did not have kidney failure. METHODS: A data linkage study was performed using data from 2 national registries: a registry of dialysis and kidney transplant patients and a registry of THA procedures. Both registries had coverage of almost all procedures or treatments in Australia. Data from September 1999 to December 2016 were used. Mortality and revision surgery were compared between patients receiving dialysis, those who had a functioning kidney transplant, and patients who did not have kidney failure using Cox and Fine-Gray (competing risk) regression models. A total of 383,478 primary THA procedures were identified as people receiving dialysis (n = 490), who had a functioning kidney transplant (n = 459), or who did not have kidney failure (n = 382,529). RESULTS: There was no significant difference in the overall rate of revision surgery between the groups (dialysis versus no kidney failure HR = 1.20; 95% CI 0.76, 1.88, transplant versus no kidney failure (hazard ratio) HR = 1.01; 95% (confidence interval) CI 0.66, 1.53). The risk for death after surgery was significantly higher in the dialysis group compared to both the functioning transplant group (HR = 3.44; 95%CI 1.58, 7.5), and in those without kidney failure (HR = 4.13; 95%CI 3.25, 5.25). CONCLUSION: The rate of mortality after THA in patients on dialysis is higher than in patients who have a functioning transplant or those who do not have kidney failure, but there is no early excess mortality to suggest a difference in this metric due to the surgery.

Short-stem hip arthroplasty in Australia and the Netherlands: a comparison of 12,680 cases between the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and the Dutch Arthroplasty Register (LROI).

BACKGROUND AND PURPOSE: We compared the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and the Dutch Arthroplasty Register (LROI) regarding patient, prosthesis, and procedure characteristics as well as revision rates for uncemented short-stem total hip arthroplasties (THAs). PATIENTS AND METHODS: All THAs with an uncemented short-stemmed femoral component performed between 2009 and 2021 were included from the AOANJRR (n = 9,328) and the LROI (n = 3,352). Kaplan-Meier survival analyses and multivariable Schemper's weighted Cox regression analyses with data from 2009-2021 and 2015-2021 were performed with overall revision as endpoint. RESULTS: In Australia, the proportion of male patients (51% vs. 40%), patients with ASA III-IV score (30% vs. 3.7%), BMI ≥ 30.0 (39% vs. 19%), and femoral heads of 36 mm (58% vs. 20%) were higher than in the Netherlands. Short-stem THAs in Australia and the Netherlands had comparable 10-year revision rates (3.4%, 95% confidence interval [CI] 2.9-4.0 vs. 4.8%, CI 3.7-6.3). Multivariable Cox regression analyses with data from 2009-2021 showed a higher risk for revision of short-stem THAs performed in the Netherlands (HR 1.8, CI 1.1-2.8), whereas the risk for revision was comparable (HR 0.9, CI 0.5-1.7) when adjusted for more potential confounders using data from 2015-2021. CONCLUSION: Short-stem THAs in Australia and the Netherlands have similar crude and adjusted revision rates, which are acceptable at 10 years of follow-up.

Becoming a non-resident father: Marginalised through distress, disadvantage and disempowerment.

ISSUE ADDRESSED: Becoming a non-resident father through divorce is stressful and this often results in compromised mental health and well-being. Non-resident fathers' mental well-being has been measured at very low levels which may require clinical treatment, especially when correlated with child access and family court issues. A United Nations report highlighted how non-resident fathers may be marginalised, but to date, limited literature considers the lives of non-resident fathers from their own perspective and reflecting their own voice and it has been claimed that as fathers are often absent from parenting research, this absence, they are not heard. The aim of this paper was to identify how non-resident fathers' interactions with legal and welfare services and ex-partners may result in their marginalisation and affect their mental health. METHODS: In-depth interviews with open-ended questions were conducted with 19 non-resident fathers, both long term, newly divorced or in the divorce process, so as to capture a long range view of their experiences. Thematic Analysis was used for data analysis and the generation of the themes. RESULTS: Three themes emerged from the data: (1) Becoming a non-resident father with two sub themes; (2) Being in a state of distress, with three sub-themes and (3) Managing distress and seeking help, with two sub-themes. Participants reported a lack of agency, lack of power in decision making and a lack of social and financial resources all contributing to the deterioration in their self-reported experiences of mental health. This impact was highlighted by the number of participants who undertook counselling or psychological assistance to deal with their perceived marginalisation, feeling of invisibility and disempowerment. CONCLUSIONS: The implications of marginalisation for non-resident fathers' mental health, as outlined by the participants, are discussed regarding the impact of becoming a non-resident father, legal aspects, welfare service experiences and relationship with ex-partner. The chronic stress experienced by non-resident fathers who often find themselves in a situation which is difficult to resolve without major compromises to their desired outcomes must be recognised. SO WHAT: One means of achieving better mental health for non-resident fathers is to address the impact of marginalisation and lack of agency and that court processes are resolved swiftly with a view to increasing non-resident father's agency in post-divorce decision making.