Efficacy and safety of pentosan polysulfate sodium in people with symptomatic knee osteoarthritis and dyslipidaemia: protocol of the MaRVeL trial.

INTRODUCTION: Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia. METHODS AND ANALYSIS: MaRVeL is a phase II, single-centre, parallel, superiority trial which will be conducted at Royal North Shore Hospital, Sydney, Australia. 92 participants (46 per arm) aged 40 and over with painful knee OA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) will be recruited from the community and randomly allocated to receive two cycles of either oral PPS or placebo for 5 weeks starting at baseline and week 11. Primary outcome will be the 16-week change in overall average knee pain severity measured using an 11-point Numeric Rating Scale. Main secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life and other structural changes. A biostatistician blinded to allocation groups will perform the statistical analysis according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The protocol has been approved by the NSLHD Human Research Ethics Committee (HREC) (2021/ETH00315). All participants will provide written informed consent online. Study results will be disseminated through conferences, social media and academic publications. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trial Registry (ACTRN12621000654853); U1111-1265-3750.

Hypofractionated re-irradiation with bevacizumab for relapsed chemorefractory glioblastoma after prior high dose radiotherapy: a feasible option for patients with large-volume relapse.

PURPOSE: There remains no standard of care for patients with recurrent and chemorefractory glioblastoma. Re-irradiation (reRT) provides an additional management option. However, published series predominantly focus on small reRT volumes utilizing stereotactic hypofractionated regimens. Concerns regarding toxicity have limited utilisation of reRT for larger recurrences, however this may be mitigated with use of bevacizumab (BEV). METHODS AND MATERIALS: A prospective database of patients managed with the EORTC-NCIC (Stupp) protocol 60 Gy chemoradiotherapy protocol for glioblastoma between 2007 and 2021 was reviewed for those patients receiving reRT for chemorefractory relapse. Serial MRI and PET were used to establish true progression and exclude patients with pseudoprogression or radionecrosis from reRT. The primary endpoint was overall survival (OS) from date of reRT. Prognostic factors were also assessed. RESULTS: 447 patients managed for glioblastoma under the Stupp protocol were identified, of which 372 had relapsed and were thus eligible for reRT. 71 patients underwent reRT. Median relapse-free survival from diagnosis for the reRT and overall cohorts were similar at 11.6 months (95%CI:9.4-14.2) and 11.8 months (95%CI:9.4-14.2) respectively. 60/71 (85%) reRT patients had received BEV prior to reRT and continued concurrent BEV during reRT. Of the 11 patients not managed with BEV during reRT, 10 required subsequent salvage BEV. ReRT patients were younger (median 53 vs. 59 years, p < 0.001), had better performance status (86% vs. 69% ECOG 0-1, p = 0.002) and more commonly had MGMT promoter-methylated tumours (54% vs. 40%, p = 0.083) compared to non-reRT patients. Median reRT PTV volume was 135cm3 (IQR: 69-207cm3). Median OS from reRT to death was 7.1 months (95%CI:6.3-7.9). Patients aged < 50, 50-70 and > 70 years had post-reRT median OS of 7.7, 6.4 and 6.0 months respectively (p = 0.021). Median post-reRT survival was longer for patients with ECOG performance status 0-1 compared to 2-3 (8.1 vs. 6.3 months, p = 0.039). PTV volume, site of relapse, MGMT promoter-methylation status and extent of initial surgical resection were not associated with post-reRT survival. ReRT was well-tolerated. Out of the 6 patients (8%) admitted to hospital after reRT, only one was for reRT toxicity. This was a CTCAE grade 3 radiation necrosis event in a patient managed without prior BEV. CONCLUSION: Patients with recurrent glioblastoma who have been previously treated with 60 Gy radiotherapy have a meaningful survival benefit from large volume re-irradiation which is well tolerated. ReRT should not be ignored as a salvage treatment option in patients with chemorefractory progressive disease.

Clinician perspectives on voluntary assisted dying and willingness to be involved: a multisite, cross-sectional survey during implementation in New South Wales, Australia.

BACKGROUND: In the context of nationwide law reform, New South Wales (NSW) became the last state in Australia to legalise voluntary assisted dying (VAD) - commencing 28 November 2023. Clinicians have divergent views regarding VAD, with varying levels of understanding, support, and willingness to be involved, and these may have a significant impact on the successful implementation. AIMS: To understand levels of support, understanding and willingness to be involved in VAD among clinical staff across NSW during implementation of VAD. METHODS: A multisite, cross-sectional online survey of clinicians across four local health districts, assessing relevant demographics, awareness of and support for VAD legislation and willingness to be involved in different levels of VAD-related clinical activities. RESULTS: A total of 3010 clinical staff completed the survey. A majority of participants were aware of VAD legislation in NSW (86.35%) and supportive of it (76%), with nursing and allied health clinicians significantly more likely than medical specialists to express support. Among medical specialists, support was statistically more likely in those who did not care for patients at the end of life and those with limited knowledge of the legislation. Willingness of medical specialists to perform key roles was significantly lower, with 41.49% willing to act in coordinating or consulting roles, and only 23.21% as administering practitioners. CONCLUSIONS: The majority of clinical staff surveyed across NSW supported VAD legislation. While many eligible clinicians were reluctant to be actively involved, sufficient numbers appear willing to provide VAD services, indicating that successful implementation should be possible.

Patient outcomes following arthroscopic distal clavicle excision: a prospective case series.

Background: Distal clavicle excision for acromioclavicular joint (ACJ) pathology is currently the mainstay of surgical management in patients with symptoms refractory to nonoperative treatment. There have been few high quality studies outlining the efficacy of arthroscopic excision of the distal clavicle as a single procedure in patients with isolated disease. Aim: To characterize function and pain outcomes in patients undergoing arthroscopic distal clavicle excision by utilizing stringent inclusion criteria to isolate ACJ pathology. Methods: Prospective data collection was undertaken with a minimum two year follow-up of 59 patients undergoing arthroscopic distal clavicle excision for ACJ osteoarthritis or distal clavicle osteolysis. Stringent eligibility criteria were applied to each patient. Data collection consisted of demographic data, clinical assessment of range of motion, and patient-reported outcome measures (PROMs), utilizing the standardized Shoulder Pain and Disability Index (SPADI) and the Visual Analogue (VAS) score to characterize pain. Furthermore, time to return to work and sport and a subjective measure of how 'normal' the shoulder felt were assessed. Data was recorded preoperatively, and at six, 12, and 24 months postoperatively. Statistical analysis was conducted utilizing institutional support. Results: Statistically significant improvements in range of motion measurements (abduction, forward elevation and external rotation), and PROMs (SPADI and VAS scores) were reported. VAS scores reduced from an average of 8.20 preoperatively to 3.39 (P < .001), 2.13 (P < .001) and 1.36 (P < .001) at 6, 12, and 24 month follow-up, respectively. Similarly, SPADI scores reduced from an average of 62.65 preoperatively to 19.96 (P < .001), 12.6 (P < .001), and 6.13 (P < .001) at 6, 12, and 24 months, respectively. The majority of patients were able to return to sport and work, within an average time of 1.72 and 3.02 months. Conclusion: In patients who presented with isolated ACJ pathology, arthroscopic distal clavicle excision, as a single procedure, results in statistically significant improvements in PROMs and functional outcomes.

Combined Digital Interventions for Pain Reduction in Patients Undergoing Knee Replacement: A Randomized Clinical Trial.

Importance: Digital technology represents an opportunity to improve outcomes following total knee replacement (TKR). Digitally delivered interventions have been shown to be similar to face-to-face interventions and to increase participation levels in people with osteoarthritis. Objective: To assess the effect of a digital technology package in reducing pain compared with usual care following TKR. Design, Setting, and Participants: This randomized clinical trial recruited 102 adults after they received TKR in 3 rehabilitation hospitals in Sydney, Australia, between June 2020 and July 2021. Interventions: All participants underwent usual care. In addition to usual care, 51 participants received a digital technology package consisting of an exercise app, fitness tracker, and online health coaching. In the usual care group, 51 participants received a fitness tracker but with all notifications turned off and goals for step count, sleep, and active hours removed. Participants were followed up for 12 months (June 2021 to July 2022). Main Outcome and Measures: The primary outcome was mean knee pain during the past week assessed using a numerical rating scale (range, 0-10, with 10 indicating worst possible pain) at 3 months. In unadjusted analyses, considered primary and based on multiple imputations, independent t tests were used to compare means between groups. Secondary outcomes, including measures of function, activity participation, and quality of life, were analyzed using a generalized estimating equation model that accounted for repeated measurements. Results: Of 102 participants (mean [SD] age, 67.9 [7.2] years; 68 [67%] female; and 92 [90%] White) randomly assigned to intervention or usual care groups, 47 (92%) in each group completed the 3-month follow up. At 3 months, participants in the intervention group demonstrated small but not clinically meaningful improvements in pain compared with the usual care group in the unadjusted intention-to-treat analysis (mean difference, -0.84; 95% CI, -1.59 to -0.10; P = .03). Secondary outcomes indicated a statistically significant reduction in pain intensity, (mean difference, -0.94; 95% CI, -1.82 to -0.06), pain disability (mean difference, -5.42; 95% CI, -10.00 to -0.83), and sedentary behavior (mean difference, -9.76; 95% CI, -19.17 to -0.34) favoring the intervention from baseline to 3, 6, and 12 months. Conclusions and Relevance: In this randomized clinical trial, a combined digital technology program provided small but not clinically meaningful improvements in pain at 3 months and other longer-term favorable outcomes following TKR compared with usual care. Future studies should tailor digital interventions based on participants' abilities and preferences to ensure that the intervention is appropriate and fosters long-term self-management. Trial Registration: Anzctr.org.au Identifier: ACTRN12618001448235.

The OA Trial Bank: Update of individual patient data meta-analysis of intra-articular glucocorticoids in persons with knee and hip osteoarthritis.

Objective: To evaluate the efficacy of intra--articular (IA) glucocorticoid for knee or hip osteoarthritis (OA) in specific subgroups of patients according to the baseline severity of pain and inflammatory signs using individual patient data (IPD) from existing trials. Furthermore, this study aims to assess if a baseline pain cut-off was associated with clinically important effectiveness of IA glucocorticoid. This is an update of an IA glucocorticoid IPD meta-analysis by the OA Trial Bank. Method: Randomized trials evaluating one or more IA glucocorticoid preparations in hip and knee OA, published to May 2018 were selected. IPD of patient and disease characteristics and outcome measures were acquired. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). Potential interaction effect of severe pain (≥70 points, 0-100 scale) and signs of inflammation at baseline were studied using a two-stage approach with general liner model followed by random effects model. Analysis of trend was conducted, assessing if a baseline pain cut-off was associated with the threshold for clinically important treatment effect of IA glucocorticoid compared to placebo. Results: Four out of 16 eligible randomized clinical trials (n â€‹= â€‹641) were combined with the existing OA Trial Bank studies (n â€‹= â€‹620), yielding 1261 participants from eleven studies. Participants with severe baseline pain compared to those with less severe pain had greater pain reduction at mid-term (around 12 weeks) (mean reduction: -6.90 (95%CI -10.91; -2.90)), but not at short- and long-term. No interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo at all follow-up time-points. Analysis of trend demonstrated treatment response to IA glucocorticoid from baseline pain levels >50 (0-100 scale) and above. Conclusion: This updated IPD meta-analysis demonstrated that participants with severe pain compared to those with less severe pain at baseline experienced significantly more pain relief with IA glucocorticoid compared with placebo at mid-term.

A retrospective review of immunology patients with primary and/or secondary immunodeficiency, demonstrating the benefits of the rapid transitioning from intravenous immunoglobulin to subcutaneous immunoglobulin at the onset of the COVID-19 pandemic.

Forty-four of 50 immunology patients with primary or secondary immunodeficiency receiving intravenous immunoglobulin at a hospital in New South Wales, Australia, were rapidly enrolled in the subcutaneous immunoglobulin (SCIg) programme at the onset of the 2020 COVID-19 pandemic. Health and economic outcomes demonstrated that SCIg provides clinical efficacy as evidenced by the number of infections and maintenance of IgG levels, and also facilitates cost reduction in immunoglobulin maintenance programmes.

Do patients with femoroacetabular impingement syndrome who undergo hip arthroscopy display improved alpha angle (magnetic resonance imaging) and radiographic hip morphology?

AIMS: To compare (a) the change in radiological bony morphology between participants with femoroacetabular impingement (FAI) syndrome who underwent arthroscopic hip surgery compared to physiotherapist-led non-surgical care and (b) the change in radiological bony morphology between participants with FAI syndrome who underwent arthroscopic hip surgery involving cam resection or acetabular rim trimming or combined cam resection and acetabular rim trimming. METHODS: Maximum alpha angle measurements on magnetic resonance imaging and Hip2 Norm standardized hip measurements on radiographs were recorded at baseline and at 12 months postoperatively. One-way analysis of covariance and independent T tests were conducted between participants who underwent arthroscopic hip surgery and physiotherapist-led non-surgical care. Independent T tests and analysis of variance were conducted between participants who underwent the 3 different arthroscopic hip procedures. RESULTS: Arthroscopic hip surgery resulted in significant improvements to mean alpha angle measurements (decreased from 70.8° to 62.1°) (P value < .001, 95% CI -11.776, -4.772), lateral center edge angle (LCEA) (P value = .030, 95% CI -3.403, -0.180) and extrusion index (P value = 0.002, 95% CI 0.882, 3.968) compared to physiotherapist-led management. Mean maximum 1-year postoperative alpha angle was 59.0° (P value = .003, 95% CI 4.845, 18.768) for participants who underwent isolated cam resection. Measurements comparing the 3 different arthroscopic hip procedures only differed in total femoral head coverage (F[2,37] = 3.470, P = .042). CONCLUSION: Arthroscopic hip surgery resulted in statistically significant improvements to LCEA, extrusion index and alpha angle as compared to physiotherapist-led management. Measured outcomes between participants who underwent cam resection and/or acetabular rim trimming only differed in total femoral head coverage.

Determinants of quality of life and hand function among people with hand osteoarthritis.

OBJECTIVE: The objectives of this study are to ascertain the determinants of quality of life (QoL) and hand function among persons with hand osteoarthritis (OA) and to assess the influence of hand function on QoL among persons with OA. METHODOLOGY: Two hundred and four participants in a clinical trial completed the baseline assessment. Demographic, socioeconomic, QoL (AqoL-4D), hand function (Functional Index for Hand Osteoarthritis, FIHOA), pain assessment, radiographic and clinical characteristics of participants were measured using standard methods. Univariate and multivariate analyses were performed to evaluate potential associations. RESULTS: We studied 204 participants (76% female, age 65.63 ± 8.13 years, body mass index 28.7 ± 6.5 kg/m2 ) with hand OA. The mean pain score of the participants on a visual analog scale was 57.8 (SD ±13.6). There was a significant, negative moderate correlation between hand function and QoL scores except for the sense domain score. Global assessment, household income and serious illness were associated with QoL (P < .001) and explained 18% of the variance of the QoL. Pain scale, Patient Global Assessment, Mental Health Score, grip strength and cyst index were associated with hand function score and explained 26% of the variance of hand function. CONCLUSION: The results indicate increasing impairment in hand function decreases the QoL of persons with hand OA. Some determinants were significantly associated with hand function and QoL. Determinants related to hand functions may be modifiable. In future, appropriate intervention strategies should be implemented, and further studies should be conducted to identify the effectiveness of those interventions.