Establishing minimal clinically important differences and patient acceptable symptom state thresholds following birmingham hip resurfacing.

INTRODUCTION: Birmingham Hip Resurfacing (BHR) has emerged as a compelling and innovative alternative to total hip arthroplasty (THA), especially among young, active patients. However, the Minimal Clinically Important Difference (MCID) and the Patient Acceptable Symptom State (PASS) thresholds have not yet been determined for patients undergoing BHR. Therefore, the current study aimed to (1) determine the MCID and PASS thresholds for both the Hip disability and Osteoarthritis Outcome Score (HOOS)-Pain and HOOS physical function shortform (PS), for patients who underwent BHR; and (2) identify factors influencing the achievement of MCID and PASS for HOOS-Pain and HOOS-PS. METHODS: Prospectively collected data from patients undergoing BHR was analyzed. Patients with osteoarthritis and completed preoperative and 1-year postoperative PROMs were included. Distribution-based and anchored-based approaches were used to estimate MCID and PASS, respectively. The optimal cut-off point for PASS thresholds was calculated using the Youden index. RESULTS: MCID for HOOS-Pain and PS were calculated to be 9.2 and 9.3, respectively. The PASS threshold for HOOS-Pain and PS were ≥ 77.7 and ≥ 87.3, respectively. The current study identified several factors affecting postoperative achievement of thresholds. Baseline Mental Component Summary (MCS) scores were a predictor for achieving MCID for postoperative HOOS-Pain, achieving MCID for postoperative HOOS-PS, achieving PASS for postoperative HOOS-Pain, and achieving PASS for postoperative HOOS-PS. Furthermore, baseline HOOS-Pain was a significant predictor for achieving MCID for postoperative HOOS-PS, achieving PASS for postoperative HOOS-Pain, and achieving PASS for postoperative HOOS-PS. CONCLUSIONS: MCID and PASS thresholds were established for HOOS-Pain and PS domains following BHR with most patients achieving these clinically meaningful benchmarks. Additionally, several factors affecting achievement of MCID and PASS were identified, including modifiable risk factors that may allow clinicians to implement optimization strategies and further improve outcomes.

Assessing the impact of health-care access on the severity of low back pain by country: a case study within the GBD framework.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS). We present a novel approach to estimate the effect of exposure to health interventions on the severity of low back pain by country and over time. METHODS: We extracted treatment effects for ten low back pain interventions from the Cochrane Database, combining these with coverage data from the MEPS to estimate the hypothetical severity in the absence of treatment in the USA. Severity across countries was then graded using the Health Access and Quality Index, allowing estimates of averted and avoidable burden under various treatment scenarios. FINDINGS: We included 210 trials from 36 Cochrane systematic reviews in the network analysis. The pooled effect sizes (measured as a standardised mean difference) for the most effective intervention classes were -0·460 (95% uncertainty interval -0·606 to -0·309) for a combination of psychological and physical interventions and -0·366 (-0·525 to -0·207) for surgery. Globally, access to treatment averted an estimated 17·6% (14·8 to 23·8) of the low back pain burden in 2020. If all countries had provided access to treatment at a level estimated for Iceland with the highest Health Access and Quality Index score, an extra 9·1% (6·4 to 11·2) of the burden of low back pain could be avoided. Even with full coverage of optimal treatment, a large proportion (65·9% [56·9 to 70·4]) of the low back pain burden is unavoidable. INTERPRETATION: This methodology fills an important shortcoming in the GBD by accounting for low back pain severity variations over time and between countries. Assumptions of unequal treatment access increased YLD estimates in resource-poor settings, with a modest decrease in countries with higher Health Access and Quality Index scores. Nonetheless, the large proportion of unavoidable burden indicates poor intervention efficacy. This method, applicable to other GBD conditions, provides policy makers with insights into health gains from improved treatment and underscores the importance of investing in research for new interventions. FUNDING: Bill and Melinda Gates Foundation and Queensland Health.

Conversion Birmingham Hip Resurfacing in Managing Post-traumatic Arthritis With Retained Femoral Hardware: A Case Report.

CASE: A 70-year-old man with a year-long history of arthritic pain in his left hip presented to our clinic. He had a left intertrochanteric hip fracture 6 years ago, fixed with an open reduction internal fixation with a cephalomedullary nail. He underwent a conversion Birmingham Hip Resurfacing (BHR) with removal of the proximal helicoidal blade and retention of the intramedullary nail. At 7-year follow-up, the patient reported satisfactory clinical outcomes and excellent radiographic fixation. CONCLUSION: This case highlights using conversion BHR in patients with post-traumatic arthritis with retained femoral hardware as an alternative to conventional total hip arthroplasty.

Long-term stability and the physical and chemical factors predictive for antimicrobial activity in Australian honey.

The growing burden of expired medicines contributes to environmental contamination and landfill waste accumulation. Medicinal honey, with its non-toxic nature and potentially long shelf-life, represents a promising and underutilised therapeutic that avoids some of these issues. However, limited knowledge on how its antimicrobial properties change over time combined with a lack of reliable processes in the honey industry for measuring antimicrobial potential, hinder its clinical adoption. Using a diverse selection of 30 Australian honey samples collected between 2005 and 2007, we comprehensively evaluated their antibacterial and antifungal activity and pertinent physical and chemical properties with the aims of assessing the effect of long-term storage on activity, pinpointing factors associated with antimicrobial efficacy, and establishing robust assessment methods. Minimum inhibitory concentration (MIC) assays proved superior to the standard phenol equivalence assay in capturing the full range of antimicrobial activity present in honey. Correlations between activity and a range of physical and chemical properties uncovered significant associations, with hydrogen peroxide, antioxidant content, and water activity emerging as key indicators in non-Leptospermum honey. However, the complex nature and the diverse composition of honey samples precludes the use of high-throughput chemical tests for accurately assessing this activity, and direct assessment using live microorganisms remains the most economical and reliable method. We provide recommendations for different methods of assaying various honey properties, taking into account their accuracy along with technical difficulty and safety considerations. All Leptospermum and fourteen of seventeen non-Leptospermum honey samples retained at least some antimicrobial properties after 15-17 years of storage, suggesting that honey can remain active for extended periods. Overall, the results of this study will help industry meet the growing demand for high-quality, medicinally active honey while ensuring accurate assessment of its antimicrobial potential.

Consensus on the definitions and descriptions of the domains of the OMERACT Core Outcome Set for shared decision making interventions in rheumatology trials.

OBJECTIVE: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions. METHODS: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains. RESULTS: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains. CONCLUSION: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set for trials of SDM interventions.

Stakeholder endorsement advancing the implementation of a patient-reported domain for harms in rheumatology clinical trials: Outcome of the OMERACT Safety Working Group.

OBJECTIVES: To develop an understanding of the concept of safety/harms experienced by patients involved in clinical trials for their rheumatic and musculoskeletal diseases (RMDs) and to seek input from the OMERACT community before moving forward to developing or selecting an outcome measurement instrument. METHODS: OMERACT 2023 presented and discussed interview results from 34 patients indicating that up to 171 items might be important for patients' harm-reporting. RESULTS: Domain was defined in detail and supported by qualitative work. Participants in the Special-Interest-Group endorsed (96 %) that enough qualitative data are available to start Delphi survey(s). CONCLUSION: We present a definition of safety/harms that represents the patient voice (i.e., patients' perception of safety) evaluating the symptomatic treatment-related adverse events for people with RMDs enrolled in clinical trials.

Metal-on-metal (MoM) hip implants and pregnancy: are MoM implants good for mom?-a systematic review.

Metal-on-metal (MoM) bearing surfaces were historically used for young patients undergoing total hip arthroplasty (THA), and remain commonplace in modern hip resurfacing. A substantial number of female patients with MoM bearings subsequently gave birth following implantation of the bearings before a full understanding of metal ions exposure in these patients was established. In theory, it has been postulated that metal ions released from such implants may cross the placental barrier and cause harm to the fetus. In light of this potential risk, recommendations against the use of MoM components in women of child-bearing age have been advocated. The purpose of this systematic review was to evaluate: (I) the MoM bearing types and ion levels found; (II) the concentrations of metals in maternal circulation and the umbilical cord; and (III) the presence of abnormalities in the fetus or delivered child. A comprehensive literature review was conducted of studies published between January 1st, 1975 and April 1st, 2019 using specific keywords. We defined the inclusion criteria for qualifying studies for this review as follows: (I) studies that reported on the women who experienced pregnancy and who had a MoM hip implant; (II) studies that reported on maternal metal ions blood and umbilical cord levels; and (III) studies that reported on the occurrence of fetal complications. Data on cobalt and chromium ion levels in the maternal blood and umbilical cord blood, as well as the presence of adverse effects in the infant were collected. Age at parturition and time from MoM implant to parturition were also collected. A total of six studies were included in the final analysis that reported on a total of 21 females and 21 infants born. The mean age at parturition was 31 years (range, 24 to 41 years), and the mean time from MoM implantation to parturition was 47 months (range, 11 to 119 months). Maternal blood cobalt levels were found as a weighted average of 34.09 µg/L (0.425 to 138 µg/L), while umbilical cord blood cobalt levels were found to be 22.61 µg/L (0.52 to 51.11 µg/L). Cobalt levels were reduced by an average of 34% between maternal and umbilical cord blood. Maternal cord blood chromium levels were found as a weighted average of 18.18 µg/L (0.225 to 75 µg/L), while umbilical cord chromium levels were found to be 3.96 µg/L (0.14 to 11.96 µg/L). Chromium levels were reduced by an average of 78% between maternal and umbilical cord blood. No cobalt or chromium was detected in the umbilical cord blood of three patients. Out of the 21 infants born to women with MoM implants, 20 were born healthy with no adverse effects or complications. Only one complication was recorded in single infant that did not appear to be related to the maternal MoM implant. To date, there is a lack of consensus as to whether MoM hip arthroplasty implants are to be avoided in the child-bearing female population and whether they constitute a hazard to the fetus in utero. Both chromium and cobalt ions were markedly reduced in levels when transitioning from maternal to cord blood. In particular, chromium showed a greater reduction on average than cobalt (78% vs. 34%). Based on the current evidence, there appears to be no correlation between the presence of metal ions in umbilical cord blood and complications, as none of the infants experienced abnormalities uniquely attributable to the presence of metal ions.

Dihydroxyacetone in the Floral Nectar of Ericomyrtus serpyllifolia (Turcz.) Rye (Myrtaceae) and Verticordia chrysantha Endl. (Myrtaceae) Demonstrates That This Precursor to Bioactive Honey Is Not Restricted to the Genus Leptospermum (Myrtaceae).

Ma̅nuka honey is known for its strong bioactivity, which arises from the autocatalytic conversion of 1,3-dihydroxyacetone (dihydroxyacetone, DHA) in the floral nectar of Leptospermum scoparium (Myrtaceae) to the non-peroxide antibacterial compound methylglyoxal during honey maturation. DHA is also a minor constituent of the nectar of several other Leptospermum species. This study used high-performance liquid chromatography to test whether DHA was present in the floral nectar of five species in other genera of the family Myrtaceae: Ericomyrtus serpyllifolia (Turcz.) Rye, Chamelaucium sp. Bendering (T.J. Alford 110), Kunzea pulchella (Lindl.) A.S. George, Verticordia chrysantha Endl., and Verticordia picta Endl. DHA was found in the floral nectar of two of the five species: E. serpyllifolia and V. chrysantha. The average amount of DHA detected was 0.08 and 0.64 µg per flower, respectively. These findings suggest that the accumulation of DHA in floral nectar is a shared trait among several genera within the family Myrtaceae. Consequently, non-peroxide-based bioactive honey may be sourced from floral nectar outside the genus Leptospermum.

Hip resurfacing arthroplasty as an alternative to total hip arthroplasty in patients aged under 40 years.

Aims: The aims of the study were to report for a cohort aged younger than 40 years: 1) indications for HRA; 2) patient-reported outcomes in terms of the modified Harris Hip Score (HHS); 3) dislocation rate; and 4) revision rate. Methods: This retrospective analysis identified 267 hips from 224 patients who underwent an hip resurfacing arthroplasty (HRA) from a single fellowship-trained surgeon using the direct lateral approach between 2007 and 2019. Inclusion criteria was minimum two-year follow-up, and age younger than 40 years. Patients were followed using a prospectively maintained institutional database. Results: A total of 217 hips (81%) were included for follow-up analysis at a mean of 3.8 years. Of the 23 females who underwent HRA, none were revised, and the median head size was 46 mm (compared to 50 mm for males). The most common indication for HRA was femoroacetabular impingement syndrome (n = 133), and avascular necrosis ( (n = 53). Mean postoperative HHS was 100 at two and five years. No dislocations occurred. A total of four hips (1.8%) required reoperation for resection of heterotopic ossification, removal of components for infection, and subsidence with loosening. The overall revision rate was 0.9%. Conclusion: For younger patients with higher functional expectations and increased lifetime risk for revision, HRA is an excellent bone preserving intervention carrying low complication rates, revision rates, and excellent patient outcomes without lifetime restrictions allowing these patients to return to activity and sport. Thus, in younger male patients with end-stage hip disease and higher demands, referral to a high-volume HRA surgeon should be considered.

Pandemic planning: data, information and evidence.

In this article, we examine the role and effectiveness of the Centers for Disease Control and Prevention in the USA and Europe and consider possible lessons for future pandemic planning in Australia. We also 'map' the interjurisdictional communication pathways that have been secured since the election of the new Commonwealth government. We suggest a number of steps that could be taken to upgrade the collection, distribution, accessibility and timelines of key information required to improve pandemic management and national health outcomes. While it may be hard to contemplate a move to a fully integrated National capacity when we are only just emerging from the pandemic, we do have a unique opportunity to at least start the process of review. We should use the lessons we have learned to transform our systems, rather than 'tinker' with them and ensure we are better prepared for next time.

Targeting the secreted RGDKGE collagen fragment reduces PD­L1 by a proteasome­dependent mechanism and inhibits tumor growth.

Structural alterations of collagen impact signaling that helps control tumor progression and the responses to therapeutic intervention. Integrins represent a class of receptors that include members that mediate collagen signaling. However, a strategy of directly targeting integrins to control tumor growth has demonstrated limited activity in the clinical setting. New molecular understanding of integrins have revealed that these receptors can regulate both pro­ and anti­tumorigenic functions in a cell type­dependent manner. Therefore, designing strategies that block pro­tumorigenic signaling, without impeding anti­tumorigenic functions, may lead to development of more effective therapies. In the present study, evidence was provided for a novel signaling cascade in which ß3­integrin­mediated binding to a secreted RGDKGE­containing collagen fragment stimulates an autocrine­like signaling pathway that differentially governs the activity of both YAP and (protein kinase­A) PKA, ultimately leading to alterations in the levels of immune checkpoint molecule PD­L1 by a proteasome dependent mechanism. Selectively targeting this collagen fragment, reduced nuclear YAP levels, and enhanced PKA and proteasome activity, while also exhibiting significant antitumor activity in vivo. The present findings not only provided new mechanistic insight into a previously unknown autocrine­like signaling pathway that may provide tumor cells with the ability to regulate PD­L1, but our findings may also help in the development of more effective strategies to control pro­tumorigenic ß3­integrin signaling without disrupting its tumor suppressive functions in other cellular compartments.

Do patient-reported outcome measures improve after aseptic revision total hip arthroplasty?

BACKGROUND: The purpose of this study was to determine patient-reported outcome measures (PROMs) changes in: (1) pain, function and global health; and (2) predictors of PROMs in patients undergoing aseptic revision total hip arthroplasty (rTHA) using a multilevel model with patients nested within surgeon. METHODS: A prospective cohort of 216 patients with baseline and 1-year PROMs who underwent aseptic rTHA between January 2016 and December 2017 were analysed. The most common indication for rTHA was aseptic loosening, instability, and implant failure. The PROMs included in this study were HOOS Pain and HOOS Physical Function Short-form (PS), Veterans RAND-12 Physical Component Score (VR-12 PCS), and VR-12 Mental Component Score (MCS). Multivariable linear regression models were constructed for predicting 1-year PROMs. RESULTS: Mean 1-year PROMs improvement for aseptic revisions were 30.4 points for HOOS Pain and 22.1 points for HOOS PS. Predictors of better pain relief were patients with higher baseline pain scores. Predictors of better 1-year function were patients with higher baseline function and patients with a posterolateral hip surgical approach during revision. Although VR-12 PCS scores had an overall improvement, nearly 50% of patients saw no improvement or had worse physical component scores. Only 30.7% of patients reported improvements in VR-12 MCS. CONCLUSIONS: Overall, patients undergoing aseptic rTHA improved in pain and function PROMs at 1 year. Although global health assessment improved overall, nearly half of aseptic rTHA patients reported no change in physical/mental health status. The associations highlighted in this study can help guide the shared decision-making process by setting expectations before aseptic revision THA.

Telehealth in cancer care during the COVID-19 pandemic.

INTRODUCTION: The Victorian COVID-19 Cancer Network (VCCN) Telehealth Expert Working Group aimed to evaluate the telehealth (TH) experience for cancer patients, carers and clinicians with the rapid uptake of TH in early 2020 during the COVID-19 pandemic. METHODS: We conducted a prospective multi-centre cross-sectional survey involving eight Victorian regional and metropolitan cancer services and three consumer advocacy groups. Patients or their carers and clinicians who had TH consultations between 1 July 2020 and 31 December 2020 were invited to participate in patient and clinician surveys, respectively. These surveys were opened from September to December 2020. RESULTS: The acceptability of TH via both video (82.9%) and phone (70.4%) were high though acceptability appeared to decrease in older phone TH users. Video was associated with higher satisfaction compared to phone (87.1% vs 79.7%) even though phone was more commonly used. Various themes from the qualitative surveys highlighted barriers and enablers to rapid TH implementation. DISCUSSION: The high TH acceptability supports this as a safe and effective strategy for continued care and should persist beyond the pandemic environment, where patient preferences are considered and clinically appropriate. Ongoing support to health services for infrastructure and resources, as well as expansion of reimbursement eligibility criteria for patients and health professionals, including allied health and nursing, are crucial for sustainability.

Multiscale anisotropy analysis of second-harmonic generation collagen imaging of human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a minority (< 10%) of patients surviving five years past diagnosis. This could be improved with the development of new imaging modalities for early differentiation of benign and cancerous fibrosis. This study intends to explore the application of a two-photon microscopy technique known as second harmonic generation to PDAC using the 2D Wavelet Transform Modulus Maxima (WTMM) Anisotropy method to quantify collagen organization in fibrotic pancreatic tissue. Forty slides from PDAC patients were obtained and eight images were captured per each tissue category on each slide. Brownian surface motion and white noise images were generated for calibration and testing of a new variable binning approach to the 2D WTMM Anisotropy method. The variable binning method had greater resistance to wavelet scaling effects and white noise images were found to have the lowest anisotropy factor. Cancer and fibrosis had greater anisotropy factors (Fa) at small wavelet scales than normal and normal adjacent tissue. At a larger scale of 21 µm this relationship changed with normal tissue having a higher Fa than all other tissue groups. White noise is the best representative image for isotropy and the 2D WTMM anisotropy method is sensitive to changes induced in collagen by PDAC.

Quality assessment and chemical diversity of Australian propolis from Apis mellifera bees.

The propolis industry is well established in European, South American and East Asian countries. Within Australia, this industry is beginning to emerge with a few small-scale producers. To contribute to the development of the Australian propolis industry, the present study aimed to examine the quality and chemical diversity of propolis collected from various regions across Australia. The results of testing 158 samples indicated that Australian propolis had pure resin yielding from 2 to 81% by weight, total phenolic content and total flavonoid content in one gram of dry extract ranging from a few up to 181 mg of gallic acid equivalent and 145 mg of quercetin equivalent, respectively. Some Australian propolis showed more potent antioxidant activity than the well-known Brazilian green, Brazilian red, and Uruguayan and New Zealand poplar-type propolis in an in vitro DPPH assay. In addition, an HPLC-UV analysis resulted in the identification of 16 Australian propolis types which can be considered as high-grade propolis owing to their high total phenolic content. Chemometric analysis of their 1H NMR spectra revealed that propolis originating from the eastern and western coasts of Australia could be significantly discriminated based on their chemical composition.

Anti-Fibrotic Potential of Tomentosenol A, a Constituent of Cerumen from the Australian Native Stingless Bee, Tetragonula carbonaria.

Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and immortalised keratinocytes (HaCaTs). Tomentosenol A (1), inhibited NFF and HaCaT cell proliferation and prevented NFF and HaCaT scratch wound repopulation at 12.5-25 µM concentrations. These inhibitory effects were associated with reduced cell viability, determined by tetrazolium dye (MTT) and sulforhodamine B (SRB) assays. Compound 1 further inhibited transforming growth factor-ß1 (TGF-ß1)-stimulated, NFF-myofibroblast differentiation and soluble collagen production; and was an effective scavenger of the model oxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH·), with an EC50 value of 44.7 ± 3.1 µM. These findings reveal significant anti-fibrotic potential for cerumen-derived tomentosenol A (1).

COVID-19 revisited – is a national pandemic plan possible?

As we review health governance during the COVID-19 pandemic, we have an opportunity to reflect on these processes and ensure that future challenges might be managed in a more collaborative and whole of system response. This 'Perspective' reviews COVID-19 responses in Australia, reflects on a number of potential solutions that have been developed by organisations over the past two decades and proffers a governance framework for a Communicable Disease and Pandemic Management Authority that might assist health responses to future challenges.