The incidence of subsequent hip arthroscopy after rectus-sparing periacetabular osteotomy.

Aims: Periacetabular osteotomy (PAO) is the preferred treatment for symptomatic acetabular dysplasia in adolescents and young adults. There remains a lack of consensus regarding whether intra-articular procedures such as labral repair or improvement of femoral offset should be performed at the time of PAO or addressed subsequent to PAO if symptoms warrant. The purpose was to determine the rate of subsequent hip arthroscopy (HA) in a contemporary cohort of patients, who underwent PAO in isolation without any intra-articular procedures. Methods: From June 2012 to March 2022, 349 rectus-sparing PAOs were performed and followed for a minimum of one year (mean 6.2 years (1 to 11)). The mean age was 24 years (14 to 46) and 88.8% were female (n = 310). Patients were evaluated at final follow-up for patient-reported outcome measures (PROMs). Clinical records were reviewed for complications or subsequent surgery. Radiographs were reviewed for the following acetabular parameters: lateral centre-edge angle, anterior centre-edge angle, acetabular index, and the alpha-angle (AA). Patients were cross-referenced from the two largest hospital systems in our area to determine if subsequent HA was performed. Descriptive statistics were used to analyze risk factors for HA. Results: A total of 16 hips (15 patients; 4.6%) underwent subsequent HA with labral repair and femoral osteochondroplasty, the most common interventions. For those with a minimum of two years of follow-up, 5.3% (n = 14) underwent subsequent HA. No hips underwent total hip arthroplasty and one revision PAO was performed. Overall, 17 hips (4.9%) experienced a complication and 99 (26.9%) underwent hardware removal. All PROMs improved significantly postoperatively. Radiologically, 80% of hips (n = 279) reached the goal for acetabular correction (77% for acetbular index and 93% for LCEA), with no significant differences between those who underwent subsequent HA and those who did not. Conclusion: Rectus-sparing PAO is associated with a low rate of subsequent HA for intra-articular pathology at a mean of 6.2 years' follow-up (1 to 11). Acetabular correction alone may be sufficient as the primary intervention for the majority of patients with symptomatic acetabular dysplasia.

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.

BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Factors associated with interobserver variation amongst pathologists in the diagnosis of endometrial hyperplasia: A systematic review.

OBJECTIVE: Reproducible diagnoses of endometrial hyperplasia (EH) remains challenging and has potential implications for patient management. This systematic review aimed to identify pathologist-specific factors associated with interobserver variation in the diagnosis and reporting of EH. METHODS: Three electronic databases, namely MEDLINE, Embase and Web of Science, were searched from 1st January 2000 to 25th March 2023, using relevant key words and subject headings. Eligible studies reported on pathologist-specific factors or working practices influencing interobserver variation in the diagnosis of EH, using either the World Health Organisation (WHO) 2014 or 2020 classification or the endometrioid intraepithelial neoplasia (EIN) classification system. Quality assessment was undertaken using the QUADAS-2 tool, and findings were narratively synthesised. RESULTS: Eight studies were identified. Interobserver variation was shown to be significant even amongst specialist gynaecological pathologists in most studies. Few studies investigated pathologist-specific characteristics, but pathologists were shown to have different diagnostic styles, with some more likely to under-diagnose and others likely to over-diagnose EH. Some novel working practices were identified, such as grading the "degree" of nuclear atypia and the incorporation of objective methods of diagnosis such as semi-automated quantitative image analysis/deep learning models. CONCLUSIONS: This review highlighted the impact of pathologist-specific factors and working practices in the accurate diagnosis of EH, although few studies have been conducted. Further research is warranted in the development of more objective criteria that could improve reproducibility in EH diagnostic reporting, as well as determining the applicability of novel methods such as grading the degree of nuclear atypia in clinical settings.

Editorial Commentary: High Tibial Osteotomy and Distal Femoral Osteotomy Address Biologics and Biomechanics.

Osteotomies were historically a common treatment for knee osteoarthritis. This has given way to arthroplasty in many patients. However, osteotomies are still an excellent treatment for younger patients with malignment and joint pain. High tibial and distal femoral osteotomy are both mechanical and biological surgeries. Osteotomies about the knee result in both mechanical correction and modulation of the inflammatory environment in the joint resulting from correction of malalignment. This reinforces their importance in the treatment of the knee joint as an organ in which a complex interplay of factors is required for homeostasis. Osteotomy is a critical part of comprehensive treatment of young patients with knee pain, malignment, and cartilage disorders.

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol.

BACKGROUND: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. METHODS: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). FINDINGS: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8-86·9) in the abiraterone group versus 45·7 months (41·6-52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53-0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9-81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3-59·0) in the standard of care group (HR 0·65 [0·55-0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83-1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). INTERPRETATION: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

Technical development and validation of a clinically applicable microenvironment classifier as a biomarker of tumour hypoxia for soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS) are rare, heterogeneous tumours and biomarkers are needed to inform management. We previously derived a prognostic tumour microenvironment classifier (24-gene hypoxia signature). Here, we developed/validated an assay for clinical application. METHODS: Technical performance of targeted assays (Taqman low-density array, nanoString) was compared in 28 prospectively collected formalin-fixed, paraffin-embedded (FFPE) biopsies. The nanoString assay was biologically validated by comparing to HIF-1α/CAIX immunohistochemistry (IHC) in clinical samples. The Manchester (n = 165) and VORTEX Phase III trial (n = 203) cohorts were used for clinical validation. The primary outcome was overall survival (OS). RESULTS: Both assays demonstrated excellent reproducibility. The nanoString assay detected upregulation of the 24-gene signature under hypoxia in vitro, and 16/24 hypoxia genes were upregulated in tumours with high CAIX expression in vivo. Patients with hypoxia-high tumours had worse OS in the Manchester (HR 3.05, 95% CI 1.54-5.19, P = 0.0005) and VORTEX (HR 2.13, 95% CI 1.19-3.77, P = 0.009) cohorts. In the combined cohort, it was independently prognostic for OS (HR 2.24, 95% CI 1.42-3.53, P = 0.00096) and associated with worse local recurrence-free survival (HR 2.17, 95% CI 1.01-4.68, P = 0.04). CONCLUSIONS: This study comprehensively validates a microenvironment classifier befitting FFPE STS biopsies. Future uses include: (1) selecting high-risk patients for perioperative chemotherapy; and (2) biomarker-driven trials of hypoxia-targeted therapies.

Epidemiology of open limb fractures attended by ambulance clinicians in the out-of-hospital setting: A retrospective analysis.

BACKGROUND: Open limb fractures are a time-critical orthopaedic emergency that present to jurisdictional ambulance services. This study describes the demographic characteristics and epidemiological profile of these patients METHODS: We undertook a retrospective analysis of all patients that presented to Queensland Ambulance Service with an open limb fracture (fracture to the humerus, radius/ulna, tibia/fibula or femur) over a two-year period (January 2018 - December 2019). RESULTS: Overall, 1020 patients were included. Patients were mainly male (65.9%) and middle-aged (age 41 years, IQR 22-59). Fractures predominately occurred in the lower extremities (64.9%) with transport crashes the primary mechanism of injury (47.8%). The location of the fracture varied depending on the cause of injury, with femur fractures associated with motorcycle crashes, and fractures to the radius/ulna attributed to falls of greater than one metre (p = 0.001). The median prehospital episode of care was 83 min (IQR 62-144) with aeromedical air ambulance involvement and the attendance of a critical care paramedic or emergency physician, both independent factors that increased this time interval. CONCLUSION: Open limb fractures are a relatively infrequent injury presentation encountered by ambulance clinicians. The characteristics of these patients is consistent with previously described national and international out-of-hospital trauma cohorts.

Combined Borderline Acetabular Dysplasia and Increased Femoral Anteversion Is Associated With Worse Outcomes in Female Patients Undergoing Hip Arthroscopy for Femoroacetabular Impingement.

PURPOSE: To determine the relationship of increased femoral anteversion and borderline acetabular dysplasia on the outcomes of hip arthroscopy for femoroacetabular impingement in a female cohort of patients. METHODS: This is a retrospective study of female patients undergoing hip arthroscopy for femoroacetabular impingement. All patients had preoperative radiographs and computed tomography scans from which lateral center edge angle (LCEA) and femoral anteversion were measured. Patient outcome was quantified by preoperative and postoperative International Hip Outcome Tool 12-item instrument (iHOT-12). All patients had follow-up at 2 to 4 years postoperatively. Published values for minimum clinically important difference, substantial clinical benefit (SCB), patient acceptable symptomatic state (PASS), and a normal or abnormal hip were used to determine outcome as well as the final score and delta of the iHOT-12. RESULTS: There were 243 female patients included in the cohort (83% follow-up) who had iHOT-12 scores at 2- to 4-year follow-up (mean 36.9 months). Female patients with combined LCEA ≤25° and femoral anteversion >20° had lower final IHOT-12 scores (P = .001) and delta iHOT-12 (P = .010) and were less likely to achieve a normal hip (P = .013), minimum clinically important difference (P = .018), SCB (P < .001), or PASS (P < .001) and more likely to have an abnormal hip (P = .002). In addition, patients with an LCEA ≤25° and normal femoral version were less likely to achieve a normal hip (P = .013), SCB (P < .001), and PASS (P < .001) compared with those with normal acetabular coverage (all P < .05). There was no difference in these outcome measures between the groups with an LCEA >25° with or without increased femoral version. CONCLUSIONS: Female patients with femoral anteversion >20° and borderline acetabular dysplasia did poorly after hip arthroscopy. However, those with increased femoral anteversion and normal acetabular coverage had outcomes similar to control hips. LEVEL OF EVIDENCE: Level IV, case series.

Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.

BACKGROUND: STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival. METHODS: Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression). RESULTS: Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity. CONCLUSIONS: There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.

Cost-utility analysis of adding abiraterone acetate plus prednisone/prednisolone to long-term hormone therapy in newly diagnosed advanced prostate cancer in England: Lifetime decision model based on STAMPEDE trial data.

Adding abiraterone acetate (AA) plus prednisolone (P) to standard of care (SOC) improves survival in newly diagnosed advanced prostate cancer (PC) patients starting hormone therapy. Our objective was to determine the value for money to the English National Health Service (NHS) of adding AAP to SOC. We used a decision analytic model to evaluate cost-effectiveness of providing AAP in the English NHS. Between 2011-2014, the STAMPEDE trial recruited 1917 men with high-risk localised, locally advanced, recurrent or metastatic PC starting first-line androgen-deprivation therapy (ADT), and they were randomised to receive SOC plus AAP, or SOC alone. Lifetime costs and quality-adjusted life-years (QALYs) were estimated using STAMPEDE trial data supplemented with literature data where necessary, adjusting for baseline patient and disease characteristics. British National Formulary (BNF) prices (£98/day) were applied for AAP. Costs and outcomes were discounted at 3.5%/year. AAP was not cost-effective. The incremental cost-effectiveness ratio (ICER) was £149,748/QALY gained in the non-metastatic (M0) subgroup, with 2.4% probability of being cost-effective at NICE's £30,000/QALY threshold; and the metastatic (M1) subgroup had an ICER of £47,503/QALY gained, with 12.0% probability of being cost-effective. Scenario analysis suggested AAP could be cost-effective in M1 patients if priced below £62/day, or below £28/day in the M0 subgroup. AAP could dominate SOC in the M0 subgroup with price below £11/day. AAP is effective for non-metastatic and metastatic disease but is not cost-effective when using the BNF price. AAP currently only has UK approval for use in a subset of M1 patients. The actual price currently paid by the English NHS for abiraterone acetate is unknown. Broadening AAP's indication and having a daily cost below the thresholds described above is recommended, given AAP improves survival in both subgroups and its cost-saving potential in M0 subgroup.

Survival outcomes in endometrial cancer patients according to diabetes: a systematic review and meta-analysis.

BACKGROUND: Diabetes is an established risk factor for endometrial cancer development but its impact on prognosis is unclear and epidemiological studies to date have produced inconsistent results. We aimed to conduct the first systematic review and meta-analysis to compare survival outcomes in endometrial cancer patients with and without pre-existing diabetes. METHODS: We conducted a systematic search of MEDLINE, EMBASE and Web of Science databases up to February 2022 for observational studies that investigated the association between pre-existing diabetes and cancer-specific survival in endometrial cancer patients. Secondary outcomes included overall survival and progression or recurrence-free survival. Quality assessment of included studies was undertaken using the Newcastle-Ottawa Scale and a random-effects model was used to produce pooled hazard ratios (HRs) and 95% confidence intervals (CIs). (PROSPERO 2020 CRD42020196088). RESULTS: In total, 31 studies were identified comprising 55,475 endometrial cancer patients. Pooled results suggested a worse cancer-specific survival in patients with compared to patients without diabetes (n = 17 studies, HR 1.15, 95% CI 1.00-1.32, I2 = 62%). Similar results were observed for progression or recurrence-free survival (n = 6 studies, HR 1.23, 95% CI 1.02-1.47, I2 = 0%) and for overall survival (n = 24 studies, HR 1.42, 95% CI 1.31-1.54, I2 = 46%). CONCLUSION: In this systematic review and meta-analysis, we show that diabetes is associated with a worse cancer-specific and overall survival in endometrial cancer patients.

Association of Radiographic Markers of Hip Instability and Worse Outcomes 2 to 4 Years After Hip Arthroscopy for Femoroacetabular Impingement in Female Patients.

BACKGROUND: Reported outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement (FAI) with underlying borderline acetabular dysplasia are mixed. This may in part be the result of mixed-sex reporting. PURPOSE: To determine the effect of radiographic measures of acetabular dysplasia and hip instability on outcomes of female patients undergoing hip arthroscopy for FAI. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: This was a retrospective study of female patients undergoing arthroscopic surgery for FAI. All patients had preoperative radiographs including a standing anteroposterior pelvic view on which lateral center-edge angle (LCEA), anterior wall index (AWI), posterior wall index (PWI), and femoroepiphyseal acetabular roof (FEAR) index were measured. Patient outcomes were quantified by preoperative and postoperative 12-Item International Hip Outcome Tool (iHOT-12) scores. All patients had follow-up at 2 to 4 years postoperatively. Published values for minimal clinically important difference (MCID), substantial clinical benefit (SCB), Patient Acceptable Symptom State (PASS), and a normal (iHOT-12 > 86 points) or abnormal (iHOT-12 < 56 points) hip were used to determine outcome, as well as the final iHOT-12 score and iHOT-12 preoperative to postoperative difference. RESULTS: The cohort consisted of 249 female patients (83% follow-up) with iHOT-12 scores at 2 to 4 years after surgery (mean, 34.6 months). Female patients with combined LCEA ≤25° and AWI <0.35 had lower final iHOT-12 score and iHOT-12 difference and were less likely to meet MCID, SCB, and PASS and have a normal hip and were more likely to have an abnormal hip as determined by iHOT-12 cutoffs when compared with those patients who had an LCEA >25° and an AWI ≥0.35 (all P < .05). There was no effect of PWI on outcomes. Similarly, female patients with combined LCEA ≤25° and a laterally oriented (positive) FEAR index were less likely to meet MCID, SCB, and PASS and have a normal hip and were more likely to have an abnormal hip compared with those patients who had an LCEA >25° and a negative (medial) FEAR index (all P < .05). In multivariate regression, an LCEA between 18° and 25° was an independent predictor of worse outcomes. CONCLUSION: An LCEA of 18° to 25°, in combination with an AWI of <0.35 or a laterally opening FEAR index, was predictive of worse outcomes in female patients undergoing hip arthroscopy for FAI.

The Impacts of Car-Free Days and Events on the Environment and Human Health.

PURPOSE OF REVIEW: In this paper, we seek to elucidate the impact of car-free days and events on human health. Car-free days and events are often designed to alleviate the impact of transportation-related air pollution, noise, physical inactivity, traffic congestion, or other detrimental externalities of private motor vehicle travel. We reviewed existing peer-reviewed and gray literature to understand the variety of potential public health impacts that have been measured as a result of car-free days or events and associated changes in environmental exposures and lifestyles. RECENT FINDINGS: The impacts of car-free days and events are highly variable and seem to depend on the scope (frequency, duration, and geographic size) and goals of each car-free day and event. Most of the existing literature measures impacts in terms of air and noise pollution and some studies focus on physical activity metrics. In some cases, car-free days and events were successful in reducing the concentration of certain air pollutants but had little or adverse impacts on the concentration of others. Often, traffic is diverted from cordoned areas to surrounding streets, displacing traffic congestion and adverse environmental exposures to other areas of a city, with potential understudied implications to environmental justice. Car-free days and events are often an attractive policy option; however, they require intensive planning to be successful. The organization and execution of car-free days and events, as well as public support and stakeholder engagement, greatly influence the level of success and the sustainability of such initiatives. Health benefits may be a palatable and convincing argument to the general public. However, very few studies focus on actual health impacts associated with car-free days and events. Future research could be most useful if it focused on measuring health outcomes associated with car-free days and events through longitudinal studies.

Estimating the percentage of patients who might benefit from proton beam therapy instead of X-ray radiotherapy.

OBJECTIVES: High-energy Proton Beam Therapy (PBT) commenced in England in 2018 and NHS England commissions PBT for 1.5% of patients receiving radical radiotherapy. We sought expert opinion on the level of provision. METHODS: Invitations were sent to 41 colleagues working in PBT, most at one UK centre, to contribute by completing a spreadsheet. 39 responded: 23 (59%) completed the spreadsheet; 16 (41%) declined, arguing that clinical outcome data are lacking, but joined six additional site-specialist oncologists for two consensus meetings. The spreadsheet was pre-populated with incidence data from Cancer Research UK and radiotherapy use data from the National Cancer Registration and Analysis Service. 'Mechanisms of Benefit' of reduced growth impairment, reduced toxicity, dose escalation and reduced second cancer risk were examined. RESULTS: The most reliable figure for percentage of radical radiotherapy patients likely to benefit from PBT was that agreed by 95% of the 23 respondents at 4.3%, slightly larger than current provision. The median was 15% (range 4-92%) and consensus median 13%. The biggest estimated potential benefit was from reducing toxicity, median benefit to 15% (range 4-92%), followed by dose escalation median 3% (range 0 to 47%); consensus values were 12 and 3%. Reduced growth impairment and reduced second cancer risk were calculated to benefit 0.5% and 0.1%. CONCLUSIONS: The most secure estimate of percentage benefit was 4.3% but insufficient clinical outcome data exist for confident estimates. The study supports the NHS approach of using the evidence base and developing it through randomised trials, non-randomised studies and outcomes tracking. ADVANCES IN KNOWLEDGE: Less is known about the percentage of patients who may benefit from PBT than is generally acknowledged. Expert opinion varies widely. Insufficient clinical outcome data exist to provide robust estimates. Considerable further work is needed to address this, including international collaboration; much is already underway but will take time to provide mature data.

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

BACKGROUND: Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS: These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS: Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION: Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

Asymmetrically increased femoral version with high prevalence of moderate and severe femoral anteversion in unilateral Legg-Calvé-Perthes disease.

PURPOSE: To determine and stratify femoral version in Legg-Calvé-Perthes disease (LCPD), and to compare the femoral version between the LCPD hip and the contralateral unaffected hip. METHODS: We performed a retrospective review of 45 patients with unilateral LCPD who had available CT scan through the hips and knees between January 2000 and June 2017. There were 34 (76%) male cases with a mean age of 14 years (sd 4.69). Two independent readers measured femoral version on the affected and the unaffected contralateral femur. Femoral version was classified as follows: severely decreased version (< 10°); moderately decreased (10° to 14°); normal femoral version range (15° to 20°); moderately increased (21° to 25°); and severely increased version (> 25°). RESULTS: LCPD hips had predominantly increased femoral version (38% severely increased anteversion, 24% moderately increased anteversion), while 51% of the contralateral unaffected hips had normal femoral version (p < 0.001). LCPD hips had higher mean femoral version than the contralateral, unaffected side (mean difference = 13o; 95% confidence iterval 10o to 16o; p < 0.001). As the version of the affected hip increased, so did the discrepancy between sides. No effect of sex on the LCPD femoral version was detected (p = 0.34). CONCLUSION: This study included a selected group of patients with unilateral LCPD and available CT scans obtained for surgical planning. The femoral version was asymmetric, with a high proportion of excessive anteversion observed at later stages of disease in the affected hips. Future studies will be necessary to determine the pathogenesis of increased femoral version associated with LCPD. LEVEL OF EVIDENCE: Level IV, retrospective study.

Editorial Commentary: Complete Capsular Closure During Hip Arthroscopy Provides the Most Reliable and Durable Outcome . . . Capsule Closed . . . Case Closed!

The management of the hip capsule has been a recent area of controversy in hip arthroscopy. Over the past 5 years, there has been mounting biomechanical and clinical evidence that complete capsular closure is an important step to achieve the best and most durable outcome from hip arthroscopy. Numerous studies in the laboratory have shown that repairing the capsulotomy during simulated hip arthroscopy establishes normal hip biomechanics. Multiple studies have also reported improved clinical outcomes and less conversion to total hip arthroplasty in patients undergoing capsular repair. We have published that patients improve after revision hip arthroscopy for repair of capsular defects. I think it is safe to say that complete capsular closure after hip arthroscopy is becoming the standard of care in our field.

Standardizing the Diagnostic Evaluation of Nonarthritic Hip Pain Through the Delphi Method.

BACKGROUND: Femoroacetabular impingement and acetabular dysplasia have gained increased attention as nonarthritic sources of pain and dysfunction in young, active patients. To date, no standardized approach to the diagnostic evaluation of nonarthritic hip pain has been identified, as previous work has focused on the diagnostic evaluation and management of patients with femoroacetabular impingement undergoing hip arthroscopy. PURPOSE: To explore the standard diagnostic evaluation practice of experts in the field of hip preservation surgery and combine their expertise through the Delphi method to form a standardized approach to the diagnostic evaluation of patients with nonarthritic hip pain. STUDY DESIGN: Consensus statement. METHODS: An expert panel made up of 18 orthopaedic surgeons with extensive experience in the treatment of nonarthritic hip disorders participated in this Delphi study. The Delphi panelists were presented with 4 clinical vignettes representing a spectrum of patients with nonarthritic hip pain. Three iterative survey rounds were presented to the panelists based on these clinical vignettes, and a 3-step classic Delphi method was used to establish consensus techniques in the diagnostic evaluation of nonarthritic hip pain. RESULTS: Total (100%) participation was gained, with all 18 experts completing all 3 Delphi survey rounds. Consensus (≥75% support) was achieved for some, if not all, vignettes for each of the following diagnostic domains: historical features, physical examination, radiographic sequences, radiographic interpretation, cross-sectional imaging, and ancillary diagnostics. CONCLUSION: In this Delphi study, we identified standardized diagnostic treatment approaches as derived from expert opinion for patients with nonarthritic hip pathomorphologies.

Transition to Telehealth Physical Therapy After Hip Arthroscopy for Femoroacetabular Impingement: A Pilot Study With Retrospective Matched-Cohort Analysis.

BACKGROUND: Telehealth use has increased significantly of late. However, outside of total hip and knee arthroplasty, there is minimal evidence regarding its efficacy in orthopaedics and postoperative rehabilitation. PURPOSE: To determine the efficacy and cost-effectiveness of a transition to postoperative telehealth physical therapy in patients undergoing hip arthroscopy for femoroacetabular impingement (FAI). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included were 51 patients undergoing postoperative physical therapy after hip arthroscopy for FAI. The intervention group consisted of patients undergoing initial in-person visits followed by a transition to telehealth physical therapy for 3 months postoperatively (group 1; n = 17). Comparison groups included patients undergoing in-person physical therapy with the same physical therapy team as the telehealth group (group 2; n = 17) and patients undergoing in-person therapy with a different therapy team at the same facility (group 3; n = 17). All groups were matched 1-to-1 by patient age and sex. All patients completed the short version of the International Hip Outcome Tool (iHOT-12) both preoperatively and at 3 months postoperatively. At 3 months postoperatively, it was determined whether patients met the minimally clinically important difference (MCID; ≥13 points) or substantial clinical benefit (SCB; ≥28 points) or whether they reached a Patient Acceptable Symptomatic State (PASS; ≥64 points). Billed charges were recorded as a measure of cost. RESULTS: The overall mean age of the study patients ranged from 33 to 34 years. Among the 3 groups, there was no significant difference in the preoperative, postoperative, or pre- to postoperative change in iHOT-12 scores or in the percentage of patients meeting MCID, SCB, or PASS at 3 months. Group 1 had significantly lower mean costs ($1015.67) compared with group 2 ($1555.62; P = .011) or group 3 ($1896.38; P < .001). CONCLUSION: In this pilot study, telehealth physical therapy after hip arthroscopy was found to lead to similar short-term outcomes and was cost-effective compared with in-person physical therapy.