Ultrasound-Guided Transfemoral Access for Coronary Procedures: A Pooled Learning Curve Analysis From the FAUST and UNIVERSAL Trials.

BACKGROUND: The learning curve for new operators performing ultrasound-guided transfemoral access (TFA) remains uncertain. METHODS: We performed a pooled analysis of the FAUST (Femoral Arterial Access With Ultrasound Trial) and UNIVERSAL (Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures) trials, both multicenter randomized controlled trials of 1:1 ultrasound-guided versus non-ultrasound-guided TFA for coronary procedures. Outcomes included the composite of major bleeding or vascular complications and successful common femoral artery cannulation. Participants were stratified by the operators' accrued case volume. We used adjusted repeated-measurement logistic regression, with random intercepts for operator clustering, for comparison against the non-ultrasound-guided TFA group and to model the learning curve. RESULTS: The FAUST and UNIVERSAL trials randomized a total of 1624 patients, of which 810 were randomized to non-ultrasound-guided TFA and 814 to ultrasound-guided TFA (cases 1-10, 391; 11-20, 183; and >20, 240). Participants who had operators who performed >20 ultrasound-guided TFAs had a decreased risk for the primary end point (5/240 [2.1%] versus 64/810 [7.9%]; adjusted odds ratio, 0.26 [95% CI, 0.09-0.61]) compared with non-ultrasound-guided TFA. Operators who performed >20 ultrasound-guided procedures had increased odds of successfully cannulating the common femoral artery (224/246 [91.1%] versus 327/382 [85.6%]; adjusted odds ratio, 1.76 [95% CI, 1.08-2.89]) compared with non-ultrasound-guided TFA. The learning curve plots demonstrated growing competence with increasing accrued cases. CONCLUSIONS: New operators should perform at least 20 ultrasound-guided TFA to decrease access site complications and increase proper cannulation compared with non-ultrasound-guided TFA. Additional accrued cases may lead to increased proficiency. Training programs should consider these findings in the transradial era.

Knee braces and foot orthoses multimodal 3-month treatment of medial knee osteoarthritis in a randomised crossover trial.

PURPOSE: Immediate biomechanical and functional benefits of knee braces and lateral wedge foot orthoses (FO) are often reported on patients with medial knee osteoarthritis. However, the effectiveness of their combined use in a longer-term orthotic treatment remains unclear. The aim was to evaluate pain, function, comfort and knee adduction moment (KAM) during the stance phase of gait with three modalities of orthotic treatment. METHODS: Twenty-two patients with knee osteoarthritis were analysed in a randomised crossover trial including a knee brace with valgus and external rotation functions (VER), FO and their combined use (VER + FO). Western Ontario and McMaster Universities scale (WOMAC) and Knee injury and Osteoarthritis Outcome Scores and KAM during gait were obtained before and after each orthotic treatment of 3 months. Repeated measures analyses of variance contrasted the factors orthosis (VER, FO, VER + FO), treatment (pre and post) and wear (without and with) on pain, function, comfort and KAM. RESULTS: An interaction between orthosis and treatment on the WOMAC pain (effect size [ES] = 0.17) and a main effect on the pain visual analogue score (ES = 0.24) indicated that VER and VER + FO were more alleviating than FO. The three modalities of orthotic treatment significantly improved functional scores (ES > 0.2) and reduced discomfort (ES = 0.25). A significant multivariate interaction between orthosis and wear (ES = 0.73) showed that the KAM reduction while wearing the orthoses was more pronounced with the VER and VER + FO than the FO. CONCLUSION: The VER-brace obtained more effectiveness than FO on pain and KAM after 3 months for medial knee osteoarthritis and the combined treatment did not substantially improve biomechanical and functional outcomes. LEVEL OF EVIDENCE: Therapeutic study level I randomised crossover trial.

The Otto Aufranc Award: Does Hip Arthroscopy at the Time of Periacetabular Osteotomy Improve the Clinical Outcome for the Treatment of Hip Dysplasia? A Multicenter Randomized Clinical Trial.

BACKGROUND: A periacetabular osteotomy (PAO) is often sufficient to treat the symptoms and improve quality of life for symptomatic hip dysplasia. However, acetabular cartilage and labral pathologies are very commonly present, and there is a lack of evidence examining the benefits of adjunct arthroscopy to treat these. The goal of this study was to compare the clinical outcome of patients undergoing PAO with and without arthroscopy, with the primary end point being the International Hip Outcome Tool-33 at 1 year. METHODS: In a multicenter study, 203 patients who had symptomatic hip dysplasia were randomized: 97 patients undergoing an isolated PAO (mean age 27 years [range, 16 to 44]; mean body mass index of 25.1 [range, 18.3 to 37.2]; 86% women) and 91 patients undergoing PAO who had an arthroscopy (mean age 27 years [range, 16 to 49]; mean body mass index of 25.1 [17.5 to 25.1]; 90% women). RESULTS: At a mean follow-up of 2.3 years (range, 1 to 5), all patients exhibited improvements in their functional score, with no significant differences between PAO plus arthroscopy versus PAO alone at 12 months postsurgery on all scores: preoperative International Hip Outcome Tool-33 score of 31.2 (standard deviation [SD] 16.0) versus 36.4 (SD 15.9), and 12 months postoperative score of 72.4 (SD 23.4) versus 73.7 (SD 22.6). The preoperative Hip disability and Osteoarthritis Outcome pain score was 60.3 (SD 19.6) versus 66.1 (SD 20.0) and 12 months postoperative 88.2 (SD 15.8) versus 88.4 (SD 18.3). The mean preoperative physical health Patient-Reported Outcomes Measurement Information System score was 42.5 (SD 8.0) versus 44.2 (SD 8.8) and 12 months postoperative 48.7 (SD 8.5) versus 52.0 (SD 10.6). There were 4 patients with PAO without arthroscopy who required an arthroscopy later to resolve persistent symptoms, and 1 patient from the PAO plus arthroscopy group required an additional arthroscopy. CONCLUSIONS: This randomized controlled trial has failed to show any significant clinical benefit in performing hip arthroscopy at the time of the PAO at 1-year follow-up. Longer follow-up will be required to determine if hip arthroscopy provides added value to a PAO for symptomatic hip dysplasia.

Lower limbs biomechanical deficits associated with stage 1 and 2 posterior tibialis tendon dysfunction during walking.

BACKGROUND: Posterior tibialis tendon dysfunction (PTTD) is a chronic degenerative musculoskeletal disorder causing a progressive ankle complex and arch collapse altering lower limb biomechanics. However, biomechanical changes associated with stage 1 and 2 PTTD need to be better characterized during walking to guide clinical recommendations and improve non-operative treatments. RESEARCH QUESTION: What are the lower limb kinematic and kinetic differences between individuals with stage 1 (PTTD1), individuals with stage 2 PTTD (PTTD2) and healthy counterparts during gait? METHODS: Sixteen PTTD1, 11 PTTD2 and 20 healthy controls were included in this multicentric case-control study to compare their lower limb gait biomechanics. Kinematic and kinetic data were recorded using a three-dimensional motion capture system and a force plate. One-dimensional statistical parametric mapping was used to compare lower limb joint motion and moments between groups during the stance phase. RESULTS: PTTD1 had minimal biomechanical differences compared with the control group. In contrast, PTTD2 presented significant differences compared with controls and PTTD1. At the ankle, PTTD2 exhibited greater plantarflexion and eversion angles and midfoot dorsiflexion and inversion angles throughout stance compared with controls and PTTD1. PTTD2 presented lower midfoot abduction moments compared with controls. These changes led PTTD2 to exhibit knee and hip adaptative biomechanical mechanisms in the frontal and transverse planes in late stance. PTTD2 had greater knee internal rotation angles and smaller knee external rotation moments compared to controls. PTTD2 had smaller hip internal rotation angles compared with PTTD1 and smaller hip adduction moments compared with controls. SIGNIFICANCE: PTTD1 showed minimal biomechanical differences compared to controls and important differences compared to PTTD2. The lower limb biomechanical deficits accentuate as the pathology advances from stage 1 to stage 2. PTTD is a progressive condition needing early clinical management at stage 1 to avoid successive biomechanical changes associated with stage 2.

Sleep Apnea is Not an Obstacle for Outpatient Hip and Knee Arthroplasty.

BACKGROUND: Up to 25% of patients requiring hip or knee arthroplasty have sleep apnea (SA), and these patients have historically been excluded from outpatient programs. The objectives of this study were to evaluate same-day discharge failure as well as 30-day complications, readmissions, and unexpected visits. METHODS: A retrospective case-control study comparing patients who have and do not have SA matched for age, sex and arthroplasty type (total hip arthroplasty, total knee arthroplasty, unicompartimental knee arthroplasty) who underwent primary outpatient surgery between February 2019 and December 2022 in 2 academic hospitals was conducted. Cases with mild SA, moderate SA with a body mass index (BMI) <35, and SA of all severity treated by continuous positive airway pressure machines were eligible. There were 156 patients included (78 cases). Complications were assessed according to the Clavien-Dindo Classification and the Comprehensive Complication Index. Continuous variables were evaluated by Student's T or Mann-Whitney tests, while categorical data were analyzed by Chi-square or Fisher tests. Univariate analyses were performed to determine discharge failure risk factors. RESULTS: There were 6 cases (7.7%) and 5 controls (6.4%) who failed to be discharged on surgery day (P = .754), with postoperative hypoxemia (6, [3.8%]) and apnea periods (3, [1.9%]) being the most common causes. Higher BMI (odds ratio = 1.19, P = .013) and general anesthesia (odds ratio = 11.97, P = .004) were found to be risk factors for discharge failure. No difference was observed on 30-day readmissions (P = .497), unexpected visits (P = 1.000), and complications on the Clavien-Dindo Classification (P > .269) and Comprehensive Complication Index (P > .334) scales. CONCLUSIONS: Selected patients who have SA can safely undergo outpatient hip or knee arthroplasty. Higher BMI and general anesthesia increased the odds of same-day discharge failure. LEVEL OF EVIDENCE: Level III, Case-control Study.

Extrasynaptic localization is essential for α5GABAA receptor modulation of dopamine system function.

Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting Gamma-Aminobutyric Acid type A receptors (GABAAR) containing the α5, but not α1, subunit in the ventral hippocampus (vHipp). The reason for this discrepancy in efficacy remains elusive; however, one key difference is that α1GABAARs are primarily located in the synapse, whereas α5GABAARs are mostly extrasynaptic. To test whether receptor location is responsible for this difference in efficacy, we injected a small interfering ribonucleic acid (siRNA) into the vHipp to knock down radixin, a scaffolding protein that holds α5GABAARs in the extrasynaptic space. We then administered GL-II-73, a positive allosteric modulator of α5GABAARs (α5-PAM) known to reverse shock-induced deficits in dopamine system function, to determine if shifting α5GABAARs from the extrasynaptic space to the synapse would prevent the effects of α5-PAM on dopamine system function. As expected, knockdown of radixin significantly decreased radixin-associated α5GABAARs and increased the proportion of synaptic α5GABAARs, without changing the overall expression of α5GABAARs. Importantly, GL-II-73 was no longer able to modulate dopamine neuron activity in radixin-knockdown rats, indicating that the extrasynaptic localization of α5GABAARs is critical for hippocampal modulation of the dopamine system. These results may have important implications for clinical use of GL-II-73, as periods of high hippocampal activity appear to favor synaptic α5GABAARs, thus efficacy may be diminished in conditions where aberrant hippocampal activity is present.Significance Statement Currently available treatments for psychosis, a debilitating symptom linked with several brain disorders, are inadequate. While they can help manage symptoms in some patients, they do so imperfectly. They are also associated with severe side effects that can cause discontinuation of medication. This study provides preclinical evidence that the drug, GL-II-73, possesses the ability to modulate dopamine activity, a key player in psychosis symptoms, and further provides some mechanistic details regarding these effects. Overall, this work contributes to the growing body of literature suggesting that GL-II-73 and similar compounds may possess antipsychotic efficacy.

Gait pattern analysis before and after periacetabular osteotomy in unilaterally affected dysplastic patients.

BACKGROUND: Patients with acetabular dysplasia have an abnormal acetabular geometry which results in insufficient coverage of the femoral head. This coverage deficiency reduces contact surfaces within the joint, accelerating the wear of the articular cartilage and predisposing patients to early osteoarthritis. Periacetabular osteotomy is a surgical treatment of acetabular dysplasia that aims to reorient the acetabulum relative to the femoral head, increasing coverage. METHODS: Pelvic kinematics and lower limbs joint kinematics and kinetics during the stance phase of gait were recorded using a 3D motion capture system and force plates, then compared pre- to post- and between limbs with a repeated measures 2-way ANOVA. Radiographic measurements and gait parameters were compared pre- to post-surgery using a t-test for dependant samples. To identify predictors of pelvic symmetry improvements during gait, a multivariate analysis was performed using a forward stepwise linear regression. FINDINGS: Radiographic measurements improved for all participants while gait parameters remained unchanged. Hip flexion symmetry was improved following surgery. The external rotation moment of the healthy hip was reduced after surgery (-29%) resulting in increased asymmetry. Pelvic tilt was significantly greater on the affected side (+0.5°) during the loading response, and the difference tended to be greater after surgery (+0.8°). INTERPRETATION: Unilaterally affected dysplastic patients have an asymmetrical gait pattern that is only partially corrected by periacetabular osteotomy even when radiographic and clinical targets are met. Differences between the limbs could be explained in part by a learned antalgic pattern and muscle weaknesses leading to complex compensation mechanisms.

Lateral knee laxity increases the risk of excessive joint line obliquity after medial opening-wedge high tibial osteotomy.

BACKGROUND: Medial opening-wedge high tibial osteotomy (HTO) is a well-recognized treatment for patient with varus knee osteoarthritis. Joint line obliquity has recently been suggested to negatively impact clinical outcomes following HTO, but little is known about what factors lead to increased joint line obliquity. The purpose of the current study was (1) to evaluate whether increased preoperative lateral knee laxity, represented by the joint line convergence angle, results in increased joint line obliquity in a consecutive series of patients treated with HTO and (2) to determine the effect of advanced arthritic changes on joint line obliquity. HYPOTHESIS: Increased joint line convergence angle would be associated with increased joint line obliquity. PATIENTS AND METHODS: All HTOs performed at our center between 2010-2017 were retrospectively reviewed. Patients were excluded if pre- and postoperative standing alignment radiographs were not available. Varus-producing osteotomies were excluded. Patients were subdivided according to their preoperative joint line convergence angle (≤3° or >3°) and the degree of radiographic arthritic change. The primary outcome measure was the postoperative joint line obliquity. Categorical variables were compared using the paired samples t-test. Survival analysis was performed for failure and overall rate of reoperation. RESULTS: During the study period, 90 HTO were performed, and 38 patients (42 knees; M/F: 32/6; mean age: 41.6; mean follow-up: 4.72 years) met the inclusion criteria. The most common surgical indications were varus knee osteoarthritis (n=27, 64.3%) and osteochondritis dissecans (n=7, 8.2%). Patients with a preoperative joint line convergence angle >3° demonstrated significantly greater joint line obliquity postoperatively as compared to those with a joint line convergence angle ≤3° (6.4°±4.6° vs. 2.5°±5.7°, respectively; p=0.02). Patients with advanced arthritic changes had significantly lower preoperative (-3°±3.4° vs. -5.6°±4.1°; p=0.03) and greater postoperative (5.8°±4° vs. 2.2°±6.4°; p=0.04) joint line obliquity as compared to those with minimal arthritic changes. There were 12 complications among the 42 procedures: one conversion to total knee replacement (TKR), one hardware failure (fixation revised), one infection, and 9 hardware removals. Overall survival using conversion to TKR was 96.23% (95% CI 0.92-1.0) at 10 years. DISCUSSION: Lateral knee laxity, as defined by a preoperative joint line convergence angle >3°, and advanced arthritic changes are associated with increased postoperative joint line obliquity following medial opening-wedge high tibial osteotomy. Soft-tissue adaptation should be accounted for in order to avoid excessive joint line obliquity following high tibial osteotomy, and the planned correction should be reduced by 25% in patients with a preoperative joint line convergence angle >3° when templating using standing alignment radiographs. LEVEL OF EVIDENCE: IV.

Level of implementation of pain management and early mobilization strategies to prevent delirium in geriatric trauma patients: A mixed-methods study.

BACKGROUND: Pain management and early mobilization strategies are recommended in clinical practice guidelines for the prevention of delirium in older adults. However, available data on the implementation of these strategies in trauma are limited. AIMS: To describe the use of pain management and early mobilization strategies in older adults at a level I trauma center, as well as the facilitators and barriers to their implementation. METHODS: A convergent mixed methods study was used. Quantitative data were collected from sixty medical records. Qualitative data was collected through a focus group with healthcare providers to explore their perspectives regarding the use of the target practices and on barriers and facilitators to their implementation. Descriptive statistics were calculated, and a thematic analysis using an inductive and deductive interpretative descriptive approach was undertaken. RESULTS: A question on the presence/absence of pain was the most frequently documented pain assessment method. Pain assessment was poorly documented. Frequencies of non-opioid and opioid administrations were similar, but non-pharmacological strategies were not widely used. The first mobilization was performed quickly and was most commonly to a chair. The focus group discussion confirmed many of the data collected in the medical records. Barriers to implementing the targeted strategies were primarily related to organizational context and facilitation processes. CONCLUSIONS: Areas for improvement were identified including pain assessment, the use of non-pharmacological pain management strategies and ambulation as a mobilization strategy. Our findings will serve as a starting point for optimizing and adapting practices for geriatric trauma patients and evaluating their impact.

Ultrasound guidance for transfemoral access in coronary procedures: an individual participant-level data metaanalysis from the femoral ultrasound trialist collaboration.

BACKGROUND: Randomised controlled trials of ultrasound (US)-guided transfemoral access (TFA) for coronary procedures have shown mixed results. AIMS: We aimed to compare US-guided versus non-US-guided TFA from randomised data in an individual participant-level data (IPD) meta-analysis. METHODS: We completed a systematic review and an IPD meta-analysis of all randomised controlled trials comparing US-guided versus non-US-guided TFA for coronary procedures. We performed a one-stage mixed-model meta-analysis using the intention-to-treat population from included trials. The primary outcome was a composite of major vascular complications or major bleeding within 30 days. RESULTS: A total of 2,441 participants (1,208 US-guided, 1,233 non-US-guided) from 4 randomised clinical trials were included. The mean age was 65.5 years, 27.0% were female, and 34.5% underwent a percutaneous coronary intervention. The incidence of major vascular complications or major bleeding (34/1,208 [2.8%] vs 55/1,233 [4.5%]; odds ratio [OR] 0.61, 95% confidence interval [CI]: 0.39-0.94; p=0.026) was lower in the US-guided TFA group. In the prespecified subgroup of participants who received a vascular closure device, those randomised to US-guided TFA experienced a reduction in the primary outcome (2.1% vs 5.6%; OR 0.36, 95% CI: 0.19-0.69), while no benefit for US guidance was observed in the subgroup without vascular closure devices (4.1% vs 3.3%; OR 1.21, 95% CI: 0.65-2.26; interaction p=0.009). CONCLUSIONS: In participants undergoing coronary procedures by TFA, US guidance decreased the composite outcome of major vascular complications or bleeding and may be especially helpful when using vascular closure devices.

The impact of Canadian-produced research on the global orthopedic literature: a bibliometric analysis.

BACKGROUND: Little is known about the quality and impact of Canadian-produced research relative to that of other developed nations. The purpose of this study was to determine the contribution of Canadian authors to the orthopedic literature globally and nationally as well as Canada's research productivity in orthopedics. We hypothesized that Canada ranks among the most impactful countries in terms of orthopedic research productivity. METHODS: We performed a bibliometric analysis to identify articles published between 2001 and 2020 in the category of orthopedics. We identified Canada's global rank in terms of overall productivity and assessed the contributions of individual Canadian authors. We also examined the quality of publications as determined by category normalized citation impact (CNCI) and publication in the top quartile of journals (%Q1) in terms of impact factor. In addition, we calculated the percentage of Canadian publications that were in orthopedics. RESULTS: We identified 10 821 orthopedic publications from 2001 to 2020. Canada placed sixth globally in terms of productivity in orthopedic research. The annual productivity of Canadian orthopedic researchers increased over the study period by a factor of 3.2. In terms of research quality, with a %Q1 of 36.5% and a CNCI of 1.22, Canada outperformed Asian countries and the United States; the latter country had a %Q1 of 35.3% and a CNCI of 1.14 over the study period. CONCLUSION: The body of Canadian orthopedic literature has grown consistently over the past 20 years. Despite the overall leadership of the United States and other developed nations such as China and Japan, Canada ranks among the most influential countries in terms of the quality and quantity of orthopedic research.

Bibliometric evaluation of negative publications from orthopedics and traumatology from the ten most influential journals of 2009-2010 and 2019-2020: A comparative study with the "Orthopedics & Traumatology: Surgery & Research" journal, using the same analysis of submitted and accepted articles.

BACKGROUND: There is a paucity of data in the literature regarding negative articles concerning surgery in orthopedics and trauma. Knowledge pertaining to treatments or techniques which confer a beneficial effect remains important, as does knowledge regarding those which have a null or pejorative effect. Thus, this study was carried out on negative articles in order to: (1) determine their proportion in the ten predominant journals concerning orthopedic and trauma surgery; (2) assess variability in their publication rate depending on the journal and the year, and compare their citation rate to that of positive articles; (3) specify whether a positive article was more likely to be cited compared to a negative article; (4) carry out the same bibliometric analysis with the "Orthopedics & Traumatology: Surgery & Research (OTSR)" journal, and detect possible selection bias for negative articles during the review. HYPOTHESIS: There are fewer negative articles than positive articles in the literature relating to orthopedic and trauma surgery. MATERIAL AND METHOD: The study was carried out using the ten orthopedic and trauma surgery journals with the highest impact factors for the year 2021. Two periods were compared, 2009-2010 and 2019-2020. Among the 17,812 publications obtained, 11,962 publications were retained to carry out the analysis (technical notes, meta-analyses, editorials and letters to the editor were all excluded). An analysis using the same method was carried out on the 3,727 articles submitted to OTSR from 2015 to 2021, which made it possible to compare the rejected articles to the accepted articles. RESULTS: Negative articles represented 11% (1,342/12,023) of the literature relating to orthopedic and trauma surgery. There were differences in the rate of publication of negative articles depending on the journals (from 4.04% to 17.14%) (p<0.0001). The negative article publication rate did not change between the two periods studied: 534/4963 articles (10.76%) in 2009-2010 versus 802/6999 (11.46%) in 2019-2020 (p=0.23). Positive articles were not cited more often than negative ones: no significant difference between the Category Normalized Citation Impact (CNCI) classes (respectively for classes 0;1[/[1;2[/≥ 2 with 45.66% 28.22% and 26.12% for negative articles versus 44.90% 27.46% and 27.64% for positive articles [p=0.4]) and the Top10% (with 18.86% for negative articles versus 20.10% for positive ones [p=0.28]). The OTSR journal had a rate of negative articles of 9.46% which was within the average range of the journals studied. A selection bias (p<0.02) for negative articles during the review of the OTSR journal was identified with fewer negative articles accepted (115/1216 [9.46%]) than positive articles (164/1330 [12.33%]). DISCUSSION: The publication of negative articles varies according to the journals and although it is modest, at only 11%, it is essential because it allows us not to repeat errors but also not to bias the carrying out of meta-analyses, and among other things to avoid useless studies. LEVEL OF EVIDENCE: III; case control study from the literature.

Validation of the French version of the Non-Arthritic Hip Score (NAHS) in 113 hip arthroscopy procedures.

BACKGROUND: The Non-Arthritic Hip Score (NAHS) used to evaluate the hip in younger patients is a self-administered questionnaire with 20 items in four sections: pain, symptoms, function, and activities. Although used in France, no transcultural version had been validated. The objective of this study was to translate the NAHS into French then assess the validity, reliability, and sensitivity to change of the French-language version (NAHS-Fr) in younger patients with hip conditions other than osteoarthritis. HYPOTHESIS: The NAHS-Fr demonstrates good validity and reliability when used in younger French-speaking patients with hip pain. MATERIAL AND METHODS: We conducted a prospective observational study in 105 patients (62 males and 43 females) scheduled for surgery on one or both hips (113 hips in total) to treat cam-type femoro-acetabular impingement or labral lesions. Before and 6 months after surgery, each patient completed the NAHS-Fr and Western Ontario and McMaster Osteoarthritis Index (WOMAC). Statistical tests were done to evaluate validity, reliability, and sensitivity to change, as recommended by the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN). RESULTS: The response rate was 100%, confirming that the NAHS-Fr was easy to use. The NAHS-Fr was both valid and reliable. No ceiling or floor effect was detected for the total NAHS-Fr score. All items had Cronbach alpha coefficients greater than 0.8, indicating good internal consistency. External consistency between the NAHS-Fr and WOMAC was negative (-0.676) due to inversely proportional score indexing. Before surgery, the NAHS-Fr and WOMAC scores were strongly and significantly correlated (p<0.0001). The effect size was greater than 0.8, indicating good sensitivity to the change induced by surgery. DISCUSSION: These results confirm the study hypothesis: the NAHS-Fr has the same good psychometric characteristics as does the original version and versions in other languages. The NAHS-Fr is useful for evaluating younger patients with non-osteoarthritic hip pain and can be used by French-speaking surgeons in everyday clinical practice. LEVEL OF EVIDENCE: IV, prospective observational non-comparative cohort study.

Extrasynaptic localization is essential for α5GABA A receptor modulation of dopamine system function.

Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting Gamma-Aminobutyric Acid type A receptors (GABA A R) containing the α5, but not α1, subunit in the ventral hippocampus (vHipp). The reason for this discrepancy in efficacy remains elusive; however, one key difference is that α1GABA A Rs are primarily located in the synapse, whereas α5GABA A Rs are mostly extrasynaptic. To test whether receptor location is responsible for this difference in efficacy, we injected a small interfering ribonucleic acid (siRNA) into the vHipp to knock down radixin, a scaffolding protein that holds α5GABA A Rs in the extrasynaptic space. We then administered GL-II-73, a positive allosteric modulator of α5GABA A Rs (α5-PAM) known to reverse shock-induced deficits in dopamine system function, to determine if shifting α5GABA A Rs from the extrasynaptic space to the synapse would prevent the effects of α5-PAM on dopamine system function. As expected, knockdown of radixin significantly decreased radixin-associated α5GABA A Rs and increased the proportion of synaptic α5GABA A Rs, without changing the overall expression of α5GABA A Rs. Importantly, GL-II-73 was no longer able to modulate dopamine neuron activity in radixin-knockdown rats, indicating that the extrasynaptic localization of α5GABA A Rs is critical for hippocampal modulation of the dopamine system. These results may have important implications for clinical use of GL-II-73, as periods of high hippocampal activity appear to favor synaptic α5GABA A Rs, thus efficacy may be diminished in conditions where aberrant hippocampal activity is present. Significance Statement: Dopamine activity is known to be altered in both psychosis patients and in animal models, with promising new antipsychotics restoring normal dopamine system function. One such drug is GL-II-73, a positive allosteric modulator of α5GABA A Rs (α5-PAM). Interestingly, previous research has shown that a positive allosteric modulator of α1GABA A Rs (α1-PAM) does not share this ability, even when directly given to the ventral hippocampus, a region known to modulate dopamine activity. One potential explanation for this difference we examined in this study is that α1GABA A Rs are primarily located in the synapse, whereas α5GABA A Rs are mostly extrasynaptic. Determining the mechanism of this differential efficacy could lead to the refinement of antipsychotic treatment and improve patient outcomes overall.

The Impact of Age on Clinical Outcomes of Acetabular Microfracture During FAI Surgery.

BACKGROUND: Full-thickness acetabular cartilage lesions are common findings during primary surgical treatment of femoroacetabular impingement (FAI). PURPOSE: To evaluate clinical outcomes after acetabular microfracture performed during FAI surgery in a prospective, multicenter cohort. STUDY DESIGN: Cohort Study; Level of evidence, 3. METHODS: Patients with FAI who had failed nonoperative management were prospectively enrolled in a multicenter cohort. Preoperative and postoperative (mean follow-up, 4.3 years) patient-reported outcome measures were obtained with a follow-up rate of 81.6% (621/761 hips), including 54 patients who underwent acetabular microfracture. Patient characteristics, radiographic parameters, intraoperative disease severity, and operative procedures were analyzed. Propensity matching using linear regression was used to match 54 hips with microfracture to 162 control hips (1:3) to control for confounding variables. Subanalyses of hips ≤35 and >35 years of age with propensity matching were also performed. RESULTS: Patients who underwent acetabular microfracture were more likely to be male (81.8% vs 40.9%; P < .001), be older in age (35.0 vs 29.9 years; P = .001), have a higher body mass index (27.2 vs 25.0; P = .001), and have a greater alpha angle (69.6° vs 62.3°; P < .001) compared with the nonmicrofracture cohort (n = 533). After propensity matching to control for covariates, patients treated with microfracture displayed no differences in the modified Harris Hip Score or Hip Disability and Osteoarthritis Outcome Score (P = .22-.95) but were more likely to undergo total hip arthroplasty (THA) (13% [7/54] compared with 4% [6/162] in the control group; P = .002), and age >35 years was associated with conversion to THA after microfracture. Microfracture performed at or before 35 years of age portended good outcomes with no significant risk of conversion to THA at the most recent follow-up. CONCLUSION: Microfracture of acetabular cartilage defects appears to be safe and associated with reliably improved short- to mid-term results in younger patients; modified expectations should be realized when full-thickness chondral lesions are identified in patients >35 years of age.

GL-II-73, a Positive Allosteric Modulator of α5GABAA Receptors, Reverses Dopamine System Dysfunction Associated with Pilocarpine-Induced Temporal Lobe Epilepsy.

Although seizures are a hallmark feature of temporal lobe epilepsy (TLE), psychiatric comorbidities, including psychosis, are frequently associated with TLE and contribute to decreased quality of life. Currently, there are no defined therapeutic protocols to manage psychosis in TLE patients, as antipsychotic agents may induce epileptic seizures and are associated with severe side effects and pharmacokinetic and pharmacodynamic interactions with antiepileptic drugs. Thus, novel treatment strategies are necessary. Several lines of evidence suggest that hippocampal hyperactivity is central to the pathology of both TLE and psychosis; therefore, restoring hippocampal activity back to normal levels may be a novel therapeutic approach for treating psychosis in TLE. In rodent models, increased activity in the ventral hippocampus (vHipp) results in aberrant dopamine system function, which is thought to underlie symptoms of psychosis. Indeed, we have previously demonstrated that targeting α5-containing γ-aminobutyric acid receptors (α5GABAARs), an inhibitory receptor abundant in the hippocampus, with positive allosteric modulators (PAMs), can restore dopamine system function in rodent models displaying hippocampal hyperactivity. Thus, we posited that α5-PAMs may be beneficial in a model used to study TLE. Here, we demonstrate that pilocarpine-induced TLE is associated with increased VTA dopamine neuron activity, an effect that was completely reversed by intra-vHipp administration of GL-II-73, a selective α5-PAM. Further, pilocarpine did not alter the hippocampal α5GABAAR expression or synaptic localization that may affect the efficacy of α5-PAMs. Taken together, these results suggest augmenting α5GABAAR function as a novel therapeutic modality for the treatment of psychosis in TLE.

No-reflow after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: an angiographic core laboratory analysis of the TOTAL Trial.

BACKGROUND: The optimal strategy to prevent no-reflow in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) is unknown. AIMS: We aimed to examine the effect of thrombectomy on the outcome of no-reflow in key subgroups and the adverse clinical outcomes associated with no-reflow. METHODS: We performed a post hoc analysis of the TOTAL Trial, a randomised trial of 10,732 patients comparing thrombectomy versus PCI alone. This analysis utilised the angiographic data of 1,800 randomly selected patients. RESULTS: No-reflow was diagnosed in 196 of 1,800 eligible patients (10.9%). No-reflow occurred in 95/891 (10.7%) patients randomised to thrombectomy compared with 101/909 (11.1%) in the PCI-alone arm (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.71-1.28; p-value=0.76). In the subgroup of patients who underwent direct stenting, those randomised to thrombectomy compared with PCI alone experienced less no-reflow (19/371 [5.1%] vs 21/216 [9.7%], OR 0.50, 95% CI: 0.26-0.96). In patients who did not undergo direct stenting, there was no difference between the groups (64/504 [12.7%] vs 75/686 [10.9%)], OR 1.18, 95% CI: 0.82-1.69; interaction p-value=0.02). No-reflow patients had a significantly increased risk of experiencing the primary composite outcome (cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA Class IV heart failure) at 1 year (adjusted hazard ratio 1.70, 95% CI: 1.13-2.56; p-value=0.01). CONCLUSIONS: In patients with STEMI treated by PCI, thrombectomy did not reduce no-reflow in all patients but may be synergistic with direct stenting. No-reflow is associated with increased adverse clinical outcomes.

Interdisciplinary strategies to prevent long-term and detrimental opioid use following trauma: a stakeholder consensus study.

OBJECTIVE: Prolonged opioid use is common following traumatic injuries. Although preventive strategies have been recommended, the evidence supporting their use is low. The objectives of this study were to select interdisciplinary strategies to prevent long-term, detrimental opioid use in trauma patients for further evaluation and to identify implementation considerations. DESIGN: A consensus study using the nominal group technique. SETTING: Four trauma systems in Canada. SUBJECTS: Participants included expert clinicians and decision makers, and people with lived experience. METHODS: Participants had to discuss the relevance and implementation of 15 strategies and then rank them using a 7-point Likert scale. Implementation considerations were identified through a synthesis of discussions. RESULTS: A total of 41 expert stakeholders formed the nominal groups. Overall, eight strategies were favored: 1) using multimodal approach for pain management, 2) professional follow-up in physical health, 3) assessment of risk factors for opioid misuse, 4) physical stimulation, 5) downward adjustment of opioids based on patient recovery, 6) educational intervention for patients, 7) training offered to professionals on how to prescribe opioids, and 8) optimizing communication between professionals working in different settings. Discussions with expert stakeholders revealed the rationale for the selected strategies and identified issues to consider when implementing them. CONCLUSION: This stakeholder consensus study identified, for further scientific study, a set of interdisciplinary strategies to promote appropriate opioid use following traumatic injuries. These strategies could ultimately decrease the burden associated with long-term opioid use.