An interrupted time series evaluation of the effect of cannabis legalization on intentional self-harm in two Canadian provinces: Ontario and Alberta. / Évaluation, à l'aide de séries chronologiques interrompues, de l'effet de la légalisation du cannabis sur les lésions auto-infligées dans deux provinces canadiennes : Ontario et Alberta.

INTRODUCTION: Despite the association between cannabis use and higher prevalence of suicidal ideation and attempt, the effect of cannabis legalization and regulation in Canada on intentional self-harm has not been determined. METHODS: We used an interrupted time series of population-based rates of emergency department (ED) visits and hospitalizations for intentional self-harm per 100 000 in Ontario and Alberta from January/April 2010 to February 2020. Aggregate monthly counts of ED visits and hospitalizations for intentional self-harm (ICD-10 codes X60-X84, R45.8) were obtained from the National Ambulatory Care Reporting System and Discharge Abstract Database, respectively. RESULTS: The legalization and regulation of cannabis in Canada was not significantly associated with a change in rates of ED visits for intentional self-harm in Ontario (level = 0.58, 95% CI: -1.14 to 2.31; trend = -0.17, 95% CI: -0.35 to 0.01) or Alberta (level = -0.06, 95% CI: -2.25 to 2.12; trend = -0.07, 95% CI: -0.27 to 0.13). Hospitalizations for intentional self-harm also remained unchanged in Ontario (level = -0.14, 95% CI: -0.48 to 0.20; trend = 0.01, 95% CI: -0.03 to 0.04) and Alberta (level = -0.41, 95% CI: -1.03 to 0.21; trend = -0.03, 95% CI: -0.08 to 0.03). CONCLUSION: Legalization and regulation of cannabis in Canada has not increased rates of ED visits or hospitalizations for intentional self-harm in Ontario and Alberta. Individual-level analyses that account for demographic characteristics and include other provinces and territories are needed.

Differences in Microbial Community Composition between Uterine Horns Ipsilateral and Contralateral to the Corpus Luteum in Beef Cows on Day 15 of the Estrous Cycle.

This study evaluated differences in uterine microbiota composition between uterine horns ipsilateral and contralateral to the corpus luteum of beef cows on day 15 of the estrous cycle. Cows (n = 23) were exposed to an estrus synchronization protocol to exogenously induce synchronized ovulation. Cows were then euthanized on day 15 of the estrous cycle, and individual swabs were collected from uterine horns ipsilateral and contralateral to the corpus luteum using aseptic techniques. DNA was extracted, and the entire (V1-V9 hypervariable regions) 16s rRNA gene was sequenced. Sequences were analyzed, and amplicon sequence variants (ASVs) were determined. Across all samples, 2 bacterial domains, 24 phyla, and 265 genera were identified. Butyribirio, Cutibacterium, BD7-11, Bacteroidales BS11 gut group, Ruminococcus, Bacteroidales RF16 group, and Clostridia UCG-014 differed in relative abundances between uterine horns. Rikenellaceae RC9 gut group, Bacteroidales UCG-001, Lachnospiraceae AC2044 group, Burkholderia-Caballeronia-Paraburkholderia, Psudobutyribibrio, and an unidentified genus of the family Chitinophagaceae and dgA-11 gut group differed between cows that expressed estrus and those that did not. The composition of the microbial community differed between the ipsilateral and contralateral horns and between cows that expressed estrus and cows that failed to express estrus, indicating that the uterine microbiota might play a role in cow fertility.

Using audit and feedback to guide tailored implementations of measurement-based care in community mental health: a multiple case study.

BACKGROUND: Audit and feedback (A&F) is an implementation strategy that can facilitate implementation tailoring by identifying gaps between desired and actual clinical care. While there are several theory-based propositions on which A&F components lead to better implementation outcomes, many have not been empirically investigated, and there is limited guidance for stakeholders when applying A&F in practice. The current study aims to illustrate A&F procedures in six community mental health clinics, with an emphasis on reporting A&F components that are relevant to theories of how feedback elicits behavior change. METHODS: Six clinics from a larger trial using a tailored approach to implement measurement-based care (MBC) were analyzed for feedback content, delivery mechanisms, barriers to feedback, and outcomes of feedback using archival data. Pattern analysis was conducted to examine relations between A&F components and changes in MBC use. RESULTS: Several sites utilized both aggregate and individualized data summaries, and data accuracy concerns were common. Feedback cycles featuring individual-level clinician data, data relevant to MBC barriers, and information requested by data recipients were related to patterns of increased MBC use. CONCLUSIONS: These findings support extant theory, such as Feedback Intervention Theory. Mental health professionals wishing to apply A&F should consider establishing reciprocal feedback mechanisms on the quality and amount of data being received and adopting specific roles communicating and addressing data quality concerns. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02266134.

GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade.

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. Here we show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous Hh pathway activation in the primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction. Reconstitution studies reveal that GRK2 phosphorylation enables active SMO to bind PKA-C directly. Lastly, the SMO-GRK2-PKA pathway underlies Hh signal transduction in a range of cellular and in vivo models. Thus, GRK2 phosphorylation of ciliary SMO, and the ensuing PKA-C binding and inactivation, are critical initiating events for the intracellular steps in Hh signaling. More broadly, our study suggests an expanded role for GRKs in enabling direct GPCR interactions with diverse intracellular effectors.

The effect of recreational cannabis legalization on rates of traffic injury in Canada.

AIMS: To measure the impact of Canada's recreational cannabis legalization (RCL) in October 2018 and the subsequent impact of the coronavirus disease 2019 (COVID-19) lockdowns from March 2020 on rates of emergency department (ED) visits and hospitalizations for traffic injury. DESIGN: An interrupted time series analysis of rates of ED visits and hospitalizations in Canada recorded in population-based databases from January/April 2010 to March 2021. SETTING: ED visits in Ontario and Alberta and hospitalizations in Ontario, Alberta, British Columbia, the Prairies (Manitoba and Saskatchewan) and the Maritimes (Nova Scotia, New Brunswick, Newfoundland and Prince Edward Island). PARTICIPANTS: Monthly counts of presentations to the ED or hospital for motor vehicle injury or pedestrian/cyclist injury, used to calculate monthly rates per 100 000 population. MEASUREMENTS: An occurrence of one or more International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada (ICD-10-CA) code for motor vehicle injury (V20-V29, V40-V79, V30-V39 and V86) and pedestrian/cyclist injury (V01-V09 and V10-V19) within the National Ambulatory Care Reporting System and Discharge Abstract Database. FINDINGS: There were no statistically significant changes in rates of ED visits and hospitalizations for motor vehicle or pedestrian/cyclist injury after RCL after accounting for multiple testing. After COVID-19, there was an immediate decrease in the rate of ED visits for motor vehicle injury that was statistically significant only in Ontario (level change ß = -16.07 in Ontario, 95% CI = -20.55 to -11.60, P = 0.000; ß = -10.34 in Alberta, 95% CI = -17.80 to -2.89, P = 0.008; α of 0.004) and no changes in rates of hospitalizations. CONCLUSIONS: Canada's recreational cannabis legalization did not notably impact motor vehicle and pedestrian/cyclist injury. The rate of emergency department visits for motor vehicle injury decreased immediately after COVID-19 lockdowns, resulting in rates below post-recreational cannabis legalization levels in the year after COVID-19.

Taking a Magnifying Glass to Measurement-Based Care Consultation Sessions: with What Issues Do Mental Health Clinicians Struggle?

PURPOSE: Ongoing consultation following initial training is one of the most commonly deployed implementation strategies to facilitate uptake of evidence-based practices, such as measurement-based care (MBC). Group consultation provides an interactive experience with an expert and colleagues to get feedback on actual issues faced, yet there is little research that unpacks the questions raised in consultation and what types of issues are important to address. METHODS: The current study characterized the questions and concerns raised by community mental health clinicians (N = 38 across six clinics) during group consultation sessions completed as part of an MBC implementation trial. We conducted a qualitative content analysis of consultation forms completed by clinicians before each MBC consultation session. RESULTS: Clinicians sought MBC consultation for clients across a range of ages and levels of depression severity. Qualitative results revealed five main questions and concerns in consultation sessions: (1) how to administer the PHQ-9, (2) how to review PHQ-9 scores, (3) how to respond to PHQ-9 score, (4) the types of clients for whom MBC would be appropriate, and (5) how MBC could impact a clinician's usual care. CONCLUSION: Findings highlight the need for ongoing consultation and limitations of workshop training alone. Practical recommendations for addressing the common questions and concerns identified are presented to support MBC use.

Using a most significant change approach to evaluate learner-centric outcomes of clinical scholars leadership training program.

BACKGROUND: Most significant change (MSC) analysis is an evaluative method used to supplement outcome and impact program evaluations. MSC stories provide mini-narratives contextualizing the effect a program had on an individual. The Clinical Scholars program evaluation team used MSC to explore learner-centric leadership outcomes of the Clinical Scholars leadership training program. PURPOSE OF THE RESEARCH: To identify thematic outcomes of trainees during the three years of their leadership training in the Clinical Scholars program. RESULTS: We identified three central thematic areas of most significant change: (1) leadership in practice, (2) self-awareness, and (3) equity, diversity, and inclusion. Other present themes included stakeholder engagement, effective leadership, collaboration, impact, expanded influence, innovation, networking, community engagement, evidence-based, implementation science, organizational development, hope, and advocating within organizations, teams, and the community. A total of 25 mid- and advanced-career level participants represented a diverse array of disciplines within the healthcare sector. CONCLUSIONS: MSC stories represented leaders' individual and team growth due to participating in the Clinical Scholars program. Results confirmed fidelity of program implementation to the original program goals, as outlined in the grant proposal. They highlighted three critical areas of development for this cohort of Fellows.

Standardized Versus Tailored Implementation of Measurement-Based Care for Depression in Community Mental Health Clinics.

Objective: Measurement-based care (MBC) is an evidence-based practice that is rarely integrated into psychotherapy. The authors sought to determine whether tailored MBC implementation can improve clinician fidelity and depression outcomes compared with standardized implementation. Methods: This cluster-randomized trial enrolled 12 community behavioral health clinics to receive 5 months of implementation support. Clinics randomized to the standardized implementation received electronic health record data captured with the nine-item Patient Health Questionnaire (PHQ-9), a needs assessment, clinical training, guidelines, and group consultation in MBC fidelity. Tailored implementation support included these strategies, but the training content was tailored to clinics' barriers to MBC, and group consultation centered on overcoming these barriers. Clinicians (N=83, tailored; N=71, standardized) delivering individual psychotherapy to 4,025 adults participated. Adult patients (N=87, tailored; N=141, standardized) contributed data for depression outcome analyses. Results: The odds of PHQ-9 completion were lower in the tailored group at baseline (odds ratio [OR]=0.28, 95% CI=0.08­0.96) but greater at 5 months (OR=3.39, 95% CI=1.00­11.48). The two implementation groups did not differ in full MBC fidelity. PHQ-9 scores decreased significantly from baseline (mean±SD=17.6±4.4) to 12 weeks (mean=12.6±5.9) (p<0.001), but neither implementation group nor MBC fidelity significantly predicted PHQ-9 scores at week 12. Conclusions: Tailored MBC implementation outperformed standardized implementation with respect to PHQ-9 completion, but discussion of PHQ-9 scores in clinician-patient sessions remained suboptimal. MBC fidelity did not predict week-12 depression severity. MBC can critically inform collaborative adjustments to session or treatment plans, but more strategic system-level implementation support or longer implementation periods may be needed.

Femoral tunnel malposition is the most common indication for revision medial patellofemoral ligament reconstruction with promising early outcomes following revision reconstruction: a systematic review.

PURPOSE: The purpose of this study was to identify the causes of failure of previous medial patellofemoral ligament reconstruction (MPFL-R), and to furthermore report the surgical techniques available for MPFL revision surgery. METHODS: Four databases [PubMed, Ovid (MEDLINE), Cochrane Database, and EMBASE] were searched until September 29, 2020 for human studies pertaining to revision MPFL. Two reviewers screened the literature independently and in duplicate. Methodological quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria, or the CAse REport guidelines (CARE), where appropriate. RESULTS: Fourteen studies (one level II, one level III, two level IV, ten level V) were identified. This search resulted in a total of 76 patients with a mean age (range) of 22 (14-39) years. The patients were 75% female with a mean (range) time to revision of 24.1 (1-60) months and mean (range) follow-up of 36.2 (2-48) months. The most common indication for revision surgery was malpositioning of the femoral tunnel (38.1%), unaddressed trochlear dysplasia (18.4%), patellar fracture (11.8%). Femoral tunnel malposition was typically treated via revision MPFL-R with quadriceps tendon or semitendinosus autograft and may retain the primary graft if fixation points were altered. Unaddressed trochlear dysplasia was treated with deepening trochleoplasty with or without revision MPFL-R, and patella fracture according to the nature of the fracture pattern and bone quality. Though generally, outcomes in the revision scenario across all indications were inferior to those post-primary procedure, overall, revision patients demonstrated positive improvements in pain and instability symptoms. Transverse patella fractures treated with debridement and filling with demineralized bone matrix if required with further fixation according to the fracture pattern. CONCLUSION: The most common causes of MPFL failure in literature published to date, in order of decreasing frequency, are: malposition of the femoral tunnel, unaddressed trochlear dysplasia, and patellar fracture. Although surgical techniques of revision MPFL-R to manage these failures were varied, promising outcomes have been reported to date. Larger prospective comparative studies would be useful to clarify optimal surgical management of MPFL-R failure at long-term follow-up. LEVEL OF EVIDENCE: IV.

Rapid, Direct SMOOTHENED Activity Assays in Live Cells Using cAMP-Based Conformational Sensors.

Communication between PATCHED1 (PTCH1) and SMOOTHENED (SMO) is fundamental to Hedgehog (Hh) signal transduction in development and disease. We describe a real-time cell-based SMO functional assay based on SMO activity-dependent changes in cellular cAMP concentrations. This assay is capable of detecting changes in SMO conformation within minutes of PTCH1 inactivation by Hh ligands. As a result, it expands the range of experimental perturbations that can be used to dissect PTCH1-SMO communication, enabling a deeper mechanistic understanding of a longstanding mystery in Hh signal transduction.

Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.

The Hedgehog (Hh) pathway is essential for organ development, homeostasis, and regeneration. Dysfunction of this cascade drives several cancers. To control expression of pathway target genes, the G protein-coupled receptor (GPCR) Smoothened (SMO) activates glioma-associated (GLI) transcription factors via an unknown mechanism. Here, we show that, rather than conforming to traditional GPCR signaling paradigms, SMO activates GLI by binding and sequestering protein kinase A (PKA) catalytic subunits at the membrane. This sequestration, triggered by GPCR kinase (GRK)-mediated phosphorylation of SMO intracellular domains, prevents PKA from phosphorylating soluble substrates, releasing GLI from PKA-mediated inhibition. Our work provides a mechanism directly linking Hh signal transduction at the membrane to GLI transcription in the nucleus. This process is more fundamentally similar between species than prevailing hypotheses suggest. The mechanism described here may apply broadly to other GPCR- and PKA-containing cascades in diverse areas of biology.

Training "Pivots" from the Pandemic: Lessons Learned Transitioning from In-Person to Virtual Synchronous Training in the Clinical Scholars Leadership Program.

INTRODUCTION: Since the inception of distance-based teaching modalities, a debate has ensued over the quality of online versus in-person instruction. Due to the COVID-19 pandemic, a number of teaching environments-including leadership development trainings for post-graduate learners-have been thrust into exploring the virtual learning environment more thoroughly. One three-year leadership development program for interdisciplinary healthcare professionals transitioned three simultaneous leadership intensives from in-person to online in the spring of 2020. METHODS: Documented changes in overall training length, session length, and session format are described. Further, evaluative data were collected from participants at both retreats via post-session surveys. Ninety-three participants attended the 2019 retreat, and 92 participants attended the 2020 virtual retreat. Quantitative data of three rating questions per session are reported: 1) overall session satisfaction, 2) participants' reported knowledge gain, and 3) participants' reported ability gain. Qualitative data were obtained via two open-ended feedback questions per session. RESULTS: In comparing pre/post scores for knowledge and ability, participants had meaningful (and in some cases higher) self-reported gains in knowledge and ability measures in the online environment, as compared to the in-person environment. Participants reported statistically significant gains in all sessions for both knowledge and ability. Qualitative data of participant feedback identified a number of positive themes similar across the in-person and virtual settings. Negative or constructive feedback of the virtual setting included time constraint issues (eg too much content in one session, a desire for more sessions overall), technical difficulties, and the loss of social connection and networking with fellow participants as compared to in-person trainings. DISCUSSION: While meaningful shifts in knowledge and ability ratings indicate that the transition to successful online learning is possible, several disadvantages remain. The preparation time for both faculty and participants was considerable, there is a need to reduce overall content in each session due to time restraints, and participants indicated feeling the loss of one-on-one connections with their peers in the training. Lessons learned of transitioning leadership training from in-person to an online experience are highlighted.

Association between perceived risk of harm and self-reported binge drinking, cigarette smoking, and marijuana smoking in young adults.

OBJECTIVES: Evaluate the association between perceived risk of harm and self-reported binge drinking, cigarette smoking, and marijuana smoking among college students. PARTICIPANTS: Participants were 599 students (ages 19-28) at a large Midwestern university recruited from October 2015 to December 2017. METHODS: Hurdle regression was used to test the relationship between perceived risk of harm from substance use (i.e., binge drinking, cigarette smoking, and marijuana smoking), and self-reported use. Demographic characteristics were tested as moderators of this relationship. RESULTS: Engagement in all three substance use behaviors was less likely when perceived risk was high. Age moderated the association between perceived risk and self-reported marijuana smoking with younger participants demonstrating a stronger relationship between perceived risk of smoking marijuana and self-reported marijuana smoking. CONCLUSION: Intervention programs will be most effective when perceived risk of substance use is high. Therefore, intervention programs should aim to increase college students' perceived risk of substance use.

In Search of Reliability: Expert-Informed Training Methods for Conducting Observational Coding of Cognitive Behavioral Therapy Fidelity.

BACKGROUND: Observational coding is the gold standard for measuring treatment fidelity; however, the intensive training needed for reliable and valid measurement has not been carefully scrutinized. A systematic review concluded there is a lack of information in published studies on how to approach training raters, and the available content suggests widely variable approaches are taken across research teams. The quality and comparability of the data produced from these treatment fidelity measures is undermined by heterogeneous training approaches occurring both within and between coding teams. No guidance for training teams to do observational coding for fidelity is currently available. The aims of the current study were to: (a) characterize expert-informed processes for observational coding regarding training, coding, and achieving reliability, and (b) generate expert recommendations for training and conducting observational coding. METHOD: A semi-structured interview was used to explore international CBT expert's (N = 11) perspectives and experiences regarding observational coding training processes. A qualitative content analysis approach was used to analyze the data. RESULTS: Experts in the study provided information about their training, coding, and reliability processes. CONCLUSION: Results from this study informed recommendations on how to: (a) introduce scale items, (b) anchor ratings, and (c) drift prevention.

The dimensions of the hip labrum can be reliably measured using magnetic resonance and computed tomography which can be used to develop a standardized definition of the hypoplastic labrum.

PURPOSE: The purpose of this study was to examine the existing literature to determine the dimensions of the acetabular labrum, with a focus on hypotrophic labra, including the modalities and accuracy of measurement, factors associated with smaller labra, and any impacts on surgical management. METHODS: Four databases (PubMed, Ovid [MEDLINE], Cochrane Database, and EMBASE) were searched from database inception to January 2020. Two reviewers screened the literature independently and in duplicate. Methodological quality of included papers was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Where possible, data on labral size were combined using a random effects model. RESULTS: Twenty-one studies (5 level II, 9 level III, 7 level IV) were identified. This resulted in 6,159 patients (6,436 hips) with a mean age of 34.3 years (range 8.4-85). The patients were 67.3% female with an average follow-up of 57.3 months. There was no consistent definition of labral size quoted throughout the literature. The mean width on MRI/MRA was 7.3 mm (95% CI 6.9-7.8 mm), on computed tomography arthrography was 8.7 mm (95% CI 8.0-9.3), and during arthroscopy was 5.0 mm (95% CI 4.9-5.2). Inter-observer reliability was good to excellent in all modalities. Labral hypotrophy may be associated with increased acetabular coverage. Hypertrophic labra were highly associated with acetabular dysplasia (r = - 0.706, - 0.596, - 0.504, respectively; P < 0.001). CONCLUSION: Labral width can reliably be measured utilizing imaging techniques including magnetic resonance and computed tomography. The pooled mean labral width was 6.2 mm, and height 4.6 mm. The establishment of a gold-standard of measurement on arthroscopy and advanced imaging would aid in clinical decision-making regarding treatment options for patients presenting with a painful hip, particularly those with hypoplastic labra, and provide radiological guidelines for standardized labrum size classifications. LEVEL OF EVIDENCE: Level IV.

The use of virtual training to support insertion of advanced technology at remote military locations.

Effective training in advanced medical technologies is essential for military healthcare providers to support the far forward battlefield. The use of modern video communication technologies and novel medical devices can be utilized for meeting this challenge. This study demonstrates the combined use of video conferencing equipment and videolaryngoscopy in the virtual training of a novice in videolaryngoscopy, nasal intubation and airway foreign body removal.