Single-Cell Transcription Mapping of Murine and Human Mammary Organoids Responses to Female Hormones.

During female adolescence and pregnancy, rising levels of hormones result in a cyclic source of signals that control the development of mammary tissue. While such alterations are well understood from a whole-gland perspective, the alterations that such hormones bring to organoid cultures derived from mammary glands have yet to be fully mapped. This is of special importance given that organoids are considered suitable systems to understand cross species breast development. Here we utilized single-cell transcriptional profiling to delineate responses of murine and human normal breast organoid systems to female hormones across evolutionary distinct species. Collectively, our study represents a molecular atlas of epithelial dynamics in response to estrogen and pregnancy hormones.

General neurology: Current challenges and future implications.

BACKGROUND AND PURPOSE: In the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future. METHODS: The European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN. RESULTS: The TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future. CONCLUSIONS: GN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost-effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN.

Innate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88.

RBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs before transfusion increases RBC immunogenicity through an unknown mechanism. We previously reported that sterile, stored mouse RBCs activate splenic dendritic cells (DCs), which are required for alloimmunization. Here we transfused mice with allogeneic RBCs to test whether stored RBCs activate pattern recognition receptors (PRRs) on recipient DCs to induce adaptive immunity. TLRs are a class of PRRs that regulate DC activation, which signal through two adapter molecules: MyD88 and TRIF. We show that the inflammatory cytokine response, DC activation and migration, and the subsequent alloantibody response to transfused RBCs require MyD88 but not TRIF, suggesting that a restricted set of PRRs are responsible for sensing RBCs and triggering alloimmunization.

Association of COVID-19 and the Prevalence of In-person Versus Telehealth Primary Care Visits and Subsequent Impacts on Tobacco Use Assessment and Referral for Cessation Assistance.

INTRODUCTION: The COVID-19 pandemic dramatically altered patterns of healthcare delivery. Smoking remains an important risk factor for multiple chronic conditions and may exacerbate more severe symptoms of COVID-19. Thus, it is important to understand how pandemic-induced changes in primary care practice patterns affected smoking assessment and cessation assistance. AIMS AND METHODS: Electronic health record data from eight community health centers were examined from March 1, 2019 to February 28, 2022. Data include both telehealth (phone and video) and in-person office visits and represent 310 388 visits by adult patients. Rates of smoking assessment, provision of referral to counseling, and orders for smoking cessation medications were calculated. Comparisons by visit mode and time period were examined using generalized estimating equations and logistic regression. RESULTS: The proportion of telehealth visits was < 0.1% 1 year prior to COVID-19 onset and, 54.5% and 34.1% 1 and 2 years after. The odds of asking about smoking status and offering a referral to smoking cessation counseling were significantly higher during in-person versus telehealth visits; adjusted odds ratios (AOR) (95% CI) = 15.0 (14.7 to 15.4) and AOR (95% CI) = 6.5 (3.0 to 13.9), respectively. The interaction effect of visit type * time period was significant for ordering smoking cessation medications. CONCLUSIONS: Telehealth visits were significantly less likely to include smoking status assessment and referral to smoking cessation counseling compared to in-person visits. Given that smoking assessment and cessation assistance do not require face-to-face interactions with health care providers, continued efforts are needed to ensure provision at all visits, regardless of modality. IMPLICATIONS: The COVID-19 pandemic dramatically altered patterns of healthcare-seeking and delivery with a considerable rise in telehealth visits. This study examined 1 year prior to the onset of COVID-19 and 2 years after to evaluate the assessment of tobacco use and assistance with tobacco cessation and differences during in-person versus telehealth visits. Tobacco assessment was 15 times more likely during in-person versus telehealth visits in the 2 years post onset of COVID-19. Given that telehealth visits are likely to continue, ensuring that patients are regularly assessed for tobacco regardless of visit modality is an important concern for health systems.

Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates.

Degradation by the ubiquitin-proteasome system requires assembly of a polyubiquitin chain upon substrate. However, the structural and mechanistic features that enable template-independent processive chain synthesis are unknown. We show that chain assembly by ubiquitin ligase SCF and ubiquitin-conjugating enzyme Cdc34 is facilitated by the unusual nature of Cdc34-SCF transactions: Cdc34 binds SCF with nanomolar affinity, nevertheless the complex is extremely dynamic. These properties are enabled by rapid association driven by electrostatic interactions between the acidic tail of Cdc34 and a basic 'canyon' in the Cul1 subunit of SCF. Ab initio docking between Cdc34 and Cul1 predicts intimate contact between the tail and the basic canyon, an arrangement confirmed by crosslinking and kinetic analysis of mutants. Basic canyon residues are conserved in both Cul1 paralogs and orthologs, suggesting that the same mechanism underlies processivity for all cullin-RING ubiquitin ligases. We discuss different strategies by which processive ubiquitin chain synthesis may be achieved.

Functional and radiographic results of anatomic total shoulder arthroplasty in the setting of subscapularis dysfunction: 5-year outcomes analysis.

BACKGROUND: Subscapularis management is a critical component to the success of anatomic total shoulder arthroplasty (TSA). Failure to heal the subscapularis can result in pain, weakness, loss of function, and revision. However, not all patients have poor outcomes. The purpose of this study is to compare patients with normal and dysfunctional subscapularis function following TSA in regard to (1) patient-reported outcome measures (PROMs); (2) range of motion (ROM) and strength; (3) achievement of minimal clinically important differences (MCIDs); and (4) specific functional internal rotation tasks. METHODS: A retrospective review of patients treated with TSA for osteoarthritis with a minimum 2-year follow-up was performed to identify patients with subscapularis dysfunction. Subscapularis dysfunction was diagnosed when any degree of weakness in internal rotation was detected on physical examination (positive belly press sign). These patients were case controlled matched on a 1:3 ratio to patients with normal subscapularis function based on age and sex. PROMs, measured active motion, revision rates, patient satisfaction, and postoperative radiographic findings were compared. Population-specific institutional anchor-based MCID values were used to compare the improvement in PROM. RESULTS: Of the 668 patients included, 34 patients (5.1%) demonstrated evidence of subscapularis dysfunction. Mean follow-up for the normal subscapularis function cohort was 63.4 ± 29.7 and 58.7 ± 26.8 for the dysfunctional subscapularis cohort. Patients with subscapularis dysfunction demonstrated significantly worse postoperative Simple Shoulder Test, Single Assessment Numerical Evaluation, visual analog scale (VAS) function, VAS pain, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores with higher rates of unsatisfactory results when compared to patients with normal subscapularis function. Abduction, elevation, internal rotation ROM, along with supraspinatus and external rotation strength were also significantly worse in the dysfunctional group. Similarly, these patients were more likely to have decreased ability to perform functional internal rotation tasks, with only 47% of the patients being able to reach the small of their back compared to 85% with normal subscapularis function. Radiographically, the dysfunctional cohort demonstrated higher rates of anterior subluxation (56% vs. 7%; P < .001) and glenoid loosening (24% vs. 5%; P = .004). Similarly, revision rates were significantly higher for patients with subscapularis dysfunction (8 patients, 23.5%). Nonetheless, the dysfunctional subscapularis cohort demonstrated improvements in VAS pain (4.0 ± 3.7) and ASES (46.4 ± 35.9) scores that exceeded MCID thresholds. CONCLUSION: Patients who develop subscapularis dysfunction after TSA have significantly worse PROMs, ROM, functional tasks of internal rotation, and radiographic outcomes, as well as increased rates of revision. Although patients show worse outcomes and high revision rates compared with their normal-functioning counterparts, these patients maintained improvement above MCID thresholds for pain and function at a mean 5-year follow-up.

Impact of humeral stem length on calcar resorption in anatomic total shoulder arthroplasty.

BACKGROUND: Use of standard-length anatomic total shoulder (TSA) humeral stems has been associated with high rates of medial calcar bone loss. Calcar bone loss has been attributed to stress shielding, debris-induced osteolysis, and undiagnosed infection. Short stem and canal-sparing humeral components may provide more optimal stress distribution and thus lower rates of calcar bone loss related to stress shielding. The purpose of this study is to determine whether implant length will affect the rate and severity of medial calcar resorption. METHODS: A retrospective review was performed on TSA patients treated with three different-length humeral implants (canal-sparing, short, and standard-length designs). Patients were matched 1:1:1 based on both gender and age (±4 years), resulting in 40 patients per cohort. Radiographic changes in medial calcar bone were evaluated and graded on a 4-point scale, from the initial postoperative radiographs to those at 3 months, 6 months, and 12 months. RESULTS: The presence of any degree of medial calcar resorption demonstrated an overall rate of 73.3% at one year. At 3 months, calcar resorption was observed in 20% of the canal-sparing cohort, while the short and standard designs demonstrated resorption in 55% and 52.5%, respectively (P = .002). At 12 months, calcar resorption was seen in 65% of the canal-sparing design, while both the short and standard designs had a 77.5% rate of resorption (P = .345). The severity of calcar resorption for the canal-sparing cohort was significantly lower at all time points when compared to the short stem (3 months, P = .004; 6 months, P = .003; 12 months, P = .004) and at 3 months when compared to the standard-length stem (P = .009). CONCLUSION: Patients treated with canal-sparing TSA humeral components have significantly lower rates of early calcar resorption with less severe bone loss when compared to patients treated using short and standard-length designs.

Macromolecular modeling and design in Rosetta: recent methods and frameworks.

The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities. Here we review tools developed in the last 5 years, including over 80 methods. We discuss improvements to the score function, user interfaces and usability. Rosetta is available at http://www.rosettacommons.org.

Coaxial Placement of Balloon-Expandable and Self-Expanding Stents: Impact on Crush Resistance and Luminal Recovery in a Benchtop Model.

During endovascular interventions, coaxial deployment of stents may be required to preserve luminal gain. This study characterized in vitro the effect on crush resistance and postcompression recovery when 316L stainless steel balloon-expandable (BE) and laser-cut nitinol self-expanding (SE) venous stents were deployed coaxially. Various stent configurations were parallel-plate compressed from a fully expanded state to 50% diameter reduction (Criterion, Model 42; MTS, Eden Prairie, Minnesota) in a 37 °C ± 1 water bath. Coaxial deployments of SE stent inside BE stent and BE stent inside SE stent demonstrated higher crush resistances compared with each stent individually or their mathematical summation (analysis of variance P < .0001; pairwise comparison P < .01). The configuration of SE stent inside BE stent showed higher postcompression luminal recovery at 48.7% compared with that of BE stent inside SE stent at 27.5% (P = .0001). Coaxial deployment of SE stent inside BE stent may improve crush resistance and luminal recovery after compression in the appropriate clinical context.

Twelve tips for the pre-brief to promote psychological safety in simulation-based education.

It is recognised that simulation-based education can be stressful, and this can impact negatively on learning. A fundamental aspect of facilitating simulation is creating a safe educational environment. Edmondson's seminal work on creating psychological safety among interpersonal teams has been embraced by the healthcare simulation community. Psychological safety is an underpinning philosophy for creating simulation experiences in which learners can develop within a stimulating and challenging yet supportive social atmosphere. Through careful design and thoughtful delivery, the introductory phase of simulation, the pre-briefing, can effectively prepare learners for simulation, reduce learner anxiety, and promote psychological safety, to enhance learning experiences. These twelve tips provide guidance for conducting a pre-brief and promoting a psychologically safe environment for simulation-based education.

Comparison of reverse shoulder arthroplasty and total shoulder arthroplasty for patients with inflammatory arthritis.

BACKGROUND: End-stage glenohumeral joint arthritis is common in patients with inflammatory arthritis. Reverse shoulder arthroplasty (RSA) and anatomic total shoulder arthroplasty (TSA) are both indicated in this setting. RSA is often considered based on the impacts of long-standing inflammatory arthritis including glenoid and humeral bone erosion and rotator cuff insufficiency. However, acromial and scapular spine fractures following RSA have been reported more commonly in these patients, which can have a significant impact on outcomes. Currently, no study has directly compared the efficacy and complication rates of RSA vs. TSA in patients with inflammatory arthritis. This study aimed to investigate differences in clinical outcomes and complications in patients undergoing RSA vs. TSA with glenohumeral inflammatory arthritis. METHODS: We performed a retrospective review of 86 patients with inflammatory arthritis treated with primary RSA (n = 43) or TSA (n = 43) with a minimum of 2 years' follow-up. American Shoulder and Elbow Surgeons scores, Simple Shoulder Test scores, visual analog scale scores for pain and function, active range of motion, and patient self-ratings of upper-extremity normality (Subjective Assessment of Normal Evaluation [SANE]) were collected preoperatively and at minimum 2-year follow-up. Radiographic classification of preoperative glenoid and humeral bone loss was performed, and postoperative complications were observed. Revision and complication details were compared. RESULTS: The study cohort had an average age of 72.1 years (range, 31-92 years) and average follow-up period of 51.6 months (range, 22-159 months). Both the RSA and TSA cohorts demonstrated improvements in patient-reported outcome measures and ranges of motion; however, patients treated with TSA showed a greater postoperative final Simple Shoulder Test score (P < .001), visual analog scale score for function (P = .0347), active elevation (P = .0331), active external rotation (P < .001), active internal rotation (P = .005), and Single Assessment Numeric Evaluation (SANE) score (P = .0161). Analysis of complication rates demonstrated no statistically significant difference between cohorts. Four acromial fractures occurred in the RSA group. When RSA patients who sustained acromial fractures were removed from the analysis, there were minimal differences in outcomes between the RSA and TSA cohorts. CONCLUSION: TSA in patients with inflammatory arthritis leads to improved clinical outcomes but higher early revision rates when compared with RSA. RSA outcomes are negatively impacted by a high rate of postoperative acromial fractures.

Isolated effect of filler particle size on surface properties of experimental resin composites before and after toothbrush abrasion.

OBJECTIVE: This study aimed to isolate the relationship between filler size and the surface properties of roughness and gloss before and after toothbrush abrasion for experimental resin-based composites (RBCs) containing uniform spherical fillers. MATERIALS AND METHODS: Five experimental light-cured RBCs with different spherical filler sizes and three commercial RBCs were studied. Forty specimens were polished using silicon carbide papers. Gloss was measured after 0, 90, 180, and 360 min of simulated toothbrushing, and surface roughness was measured before and after 360 min of toothbrushing. Two-way ANOVA/Tukey's multiple comparison tests were used to compare the RBCs, and the correlation between particle size and surface roughness or gloss was also determined. RESULTS: After polishing and toothbrushing, RBCs with smaller fillers exhibited significantly higher gloss and lower surface roughness, and RBCs with larger fillers exhibited lower gloss and higher surface roughness. A significant correlation was found between filler particle size and gloss and surface roughness both before and after toothbrush abrasion. CONCLUSIONS: Gloss of RBCs containing fillers with larger particle sizes was significantly reduced. After toothbrushing abrasion, the surface roughness increased for all RBCs, except those containing the finest-sized fillers. The particle size of the filler is a critical determinant of the surface roughness and gloss of RBCs, after polishing and after toothbrushing. CLINICAL SIGNIFICANCE: Increased surface roughness caused by toothbrush abrasion reduces the gloss of resin-based composites. Resin-based composites containing finer fillers best maintain glossiness after routine tooth brushing.

Endovascular Venous Stenosis and Thrombosis Large Animal Model: Angiographic, Histological, and Biomechanical Characterizations.

PURPOSE: To characterize an ovine endovascular radiofrequency (RF) ablation-based venous stenosis and thrombosis model for studying venous biomechanics and response to intervention. MATERIALS AND METHODS: Unilateral short-segment (n = 2) or long-segment (n = 6) iliac vein stenoses were created in 8 adult sheep using an endovenous RF ablation technique. Angiographic assessment was performed at baseline, immediately after venous stenosis creation, and after 2-week (n = 6) or 3-month (n = 2) survival. Stenosed iliac veins and the contralateral healthy controls were harvested for histological and biomechanical assessment. RESULTS: At follow-up, the short-segment RF ablation group showed stable stenosis without occlusion. The long-segment group showed complete venous occlusion/thrombosis with the formation of collateral veins. Stenosed veins showed significant wall thickening (0.28 vs 0.16 mm, P = .0175) and confluent collagen deposition compared with the healthy controls. Subacute nonadherent thrombi were apparent at 2 weeks, which were replaced by fibrous luminal obliteration with channels of recanalization at 3 months. Stenosed veins demonstrated increased longitudinal stiffness (448.5 ± 5.4 vs 314.6 ± 1.5 kPa, P < .0001) and decreased circumferential stiffness (140.8 ± 2.6 vs 246.0 ± 1.6 kPa, P < .0001) compared with the healthy controls. CONCLUSION: Endovenous RF ablation is a reliable technique for creating venous stenosis and thrombosis in a large animal model with histological and biomechanical attributes similar to those seen in humans. This platform can facilitate understanding of venous biomechanics and testing of venous-specific devices and interventions.

Impact of Postthrombotic Vein Wall Biomechanics on Luminal Flow during Venous Angioplasty and Stent Placement: Computational Modeling Results.

This study characterized the impact of vein wall biomechanics on inflow diameter and luminal flow during venous angioplasty and stent placement, using postthrombotic and healthy biomechanical properties from an ovine venous stenosis and thrombosis model. Finite element analysis demonstrated more pronounced inflow channel narrowing in the postthrombotic vein compared with the healthy control vein during angioplasty and stent placement (relative inflow diameter reduction of 42% versus 13%, P < .0001). Computational fluid dynamics modeling showed increased relative areas of low wall shear rate in the postthrombotic vein compared with the normal vein (0.46 vs 0.24 for shear rate < 50 s-1; 0.13 vs 0.07 for shear rate < 15 s-1; P < .05), with flow stagnation and recirculation. Since inflow narrowing and low wall shear rate are associated with in-stent restenosis and reintervention, these computational results based on experimentally obtained biomechanical values highlight the significance of postthrombotic venous properties in optimizing venous intervention outcomes.

Development and Results of the First Certification Examination in the American Board of Medical Specialties Neurocritical Care Subspecialty.

This article reviews the development of the American Board of Medical Specialties subspecialty in neurocritical care (NCC) and describes the requirements for certification and the results of the first certification examination administered in October 2021. The American Board of Psychiatry and Neurology (ABPN) is the administrative board, and the sponsoring boards are the American Board of Anesthesiology (ABA), American Board of Emergency Medicine (ABEM), American Board of Internal Medicine (ABIM), and American Board of Neurological Surgery. The American Board of Medical Specialties approved the subspecialty in 2018, and the Accreditation Council for Graduate Medical Education developed and approved the training requirements in 2021. The fellowship programs are either 12 or 24 months in length and may become available in Academic Year 2022-2023. The first NCC examination was developed by a multispecialty group of subject matter experts following established test development procedures and was successfully administered to 1,011 candidates in October 2021. There were 406 (40.2%) ABIM candidates, 356 (35.2%) ABPN candidates, 208 (20.6%) ABA candidates, and 41 (4.1%) ABEM candidates. The end-of-test survey indicated that most examinees were satisfied with their test taking experience, and the .92 reliability index indicated that the test scores were reliable. An established process was also followed to set the criterion-referenced passing standard, and the resulting pass rate of 72.7% was judged to be reasonable. In summary, the combined efforts of representatives from the ABPN, ABA, ABEM, ABIM, and American Board of Neurological Surgery yielded a quality assessment instrument to identify physicians who possess the expertise required to be certified in NCC. The test development committee will continue to expand and improve the pool of test questions for the next examination, which is scheduled for October 2022.

Functional internal rotation is similar between lesser tuberosity osteotomy and subscapularis peel in total shoulder arthroplasty: short-term follow-up.

INTRODUCTION: Lesser tuberosity osteotomy (LTO) and subscapularis peel (Peel) are 2 common techniques used to mobilize the subscapularis tendon during anatomic total shoulder arthroplasty (TSA). The literature is inconclusive over which technique is optimal; thus, controversy exists over which technique should be performed. The purpose of this study was to compare specific functional internal rotation tasks and general outcome scores in TSA patients who received either an LTO or Peel. METHODS: A retrospective review of 563 patients treated with primary TSA using either an LTO (n = 358) or Peel (n = 205) with a minimum 2-year follow-up was performed. Subjective internal rotation, active internal rotation, and specific questions related to functional internal rotation isolated from the Simple Shoulder Test (SST) and American Shoulder and Elbow Surgeons functional questionnaires were reviewed. Other outcome scores including visual analog scale pain and function, Single Assessment Numerical Evaluation, SST, American Shoulder and Elbow Surgeons, and revision rates were compared between the 2 groups. RESULTS: The study found no difference in postoperative functional internal rotation and range of motion between LTO and Peel. Patients who received a Peel were shown to have a slightly greater improvement in the ability to perform toileting and a higher average change in SST score that did not reach clinical significance. There was no difference in the percentage of maximal improvement, revision rate, or need for revision between the 2 groups. CONCLUSION: No difference was found between the LTO and Peel techniques in regard to functional tasks of internal rotation at short-term follow-up.

A comparison of patient same-day discharge selection after shoulder arthroplasty before and after the COVID-19 pandemic.

Background: Early discharge has been a target of cost control efforts, given the growing demand for joint replacement surgery. Select patients are given the choice for same-day discharge (SDD) or overnight stay after shoulder arthroplasty. The COVID-19 pandemic changed patient perspectives regarding hospital visitation and admission. The purpose of this study was to determine if the COVID-19 pandemic impacted the utilization of SDD after shoulder arthroplasty. We hypothesize that patients undergoing shoulder arthroplasty after the start of the COVID-19 pandemic will have higher rates of SDD. Methods: A retrospective continuous review was performed on 370 patients who underwent a primary anatomic (total shoulder arthroplasty) or reverse shoulder arthroplasty between August 2019 and December 2020 by a single surgeon. This group of patients represent the 185 arthroplasty cases completed before the COVID-19 pandemic and the first 185 patients after the start of the pandemic. April 1, 2020, was chosen as the cutoff for pre-COVID patients, as this represents the date a statewide ban on elective surgery was declared. All patients were counseled preoperatively regarding SDD and given the choice to stay overnight, unless medically contraindicated. Demographics, medical history, length of stay, 30- and 90-day readmissions, and 90-day emergency room (ER) and urgent care visits were obtained from medical records and compared. Two-tailed student t-tests, chi-square tests, and Fischer's exact were performed where appropriate. Results: The 2 groups were similar in age, body mass index, gender distribution, and Outpatient Arthroplasty Risk Assessment score. During the collection period, there were more anatomic shoulder arthroplasties performed after (54%) than before (44%) the COVID-19 pandemic (P = .029). Patients treated after the start of the COVID-19 pandemic were almost 3 times more likely to have an SDD (P < .001), with 85.4% (158/185) of patients being discharged the same day after COVID-19, compared with 34.6% (64/185) before COVID-19. Discharge disposition (location of discharge) was significantly different, as 99% (183/185) of patients undergoing surgery after the start of the COVID-19 pandemic were discharged home, compared with 94% (174/185) of patients before COVID-19. There was no difference in 30-day readmissions, 90-day readmissions, and 90-day (ER) and urgent care visits between the 2 groups. Conclusion: Our study suggests that the COVID-19 pandemic has dramatically impacted patient choices for SDD within a single surgeon's practice, with nearly 3 times as many patients electing for SDD. Readmissions and ER visits were similar, indicating that SDD remains a safe alternative for patients after total shoulder arthroplasty and reverse shoulder arthroplasty. Level of evidence: Level III; Retrospective Comparative Study.

Improving Regional Blood Pressure Control: a Positive Deviance Tiered Intensity Approach.

BACKGROUND: Accelerated translation of real-world interventions for hypertension management is critical to improving cardiovascular outcomes and reducing disparities. OBJECTIVE: To determine whether a positive deviance approach would improve blood pressure (BP) control across diverse health systems. DESIGN: Quality improvement study using 1-year cross sections of electronic health record data over 5 years (2013-2017). PARTICIPANTS: Adults ≥ 18 with hypertension with two visits in 2 years with at least one primary care visit in the last year (N = 114,950 at baseline) to a primary care practice in Better Health Partnership, a regional health improvement collaborative. INTERVENTIONS: Identification of a "positive deviant" and dissemination of this system's best practices for control of hypertension (i.e., accurate/repeat BP measurement; timely follow-up; outreach; standard treatment algorithm; and communication curriculum) using 3 different intensities (low: Learning Collaborative events describing the best practices; moderate: Learning Collaborative events plus consultation when requested; and high: Learning Collaborative events plus practice coaching). MAIN MEASURES: We used a weighted linear model to estimate the pre- to post-intervention average change in BP control (< 140/90 mmHg) for 35 continuously participating clinics. KEY RESULTS: BP control post-intervention improved by 7.6% [95% confidence interval (CI) 6.0-9.1], from 67% in 2013 to 74% in 2017. Subgroups with the greatest absolute improvement in BP control included Medicaid (12.0%, CI 10.5-13.5), Hispanic (10.5%, 95% CI 8.4-12.5), and African American (9.0%, 95% CI 7.7-10.4). Implementation intensity was associated with improvement in BP control (high: 14.9%, 95% CI 0.2-19.5; moderate: 5.2%, 95% CI 0.8-9.5; low: 0.2%, 95% CI-3.9 to 4.3). CONCLUSIONS: Employing a positive deviance approach can accelerate translation of real-world best practices into care across diverse health systems in the context of a regional health improvement collaborative (RHIC). Using this approach within RHICs nationwide could translate to meaningful improvements in cardiovascular morbidity and mortality.

Better together: Elements of successful scientific software development in a distributed collaborative community.

Many scientific disciplines rely on computational methods for data analysis, model generation, and prediction. Implementing these methods is often accomplished by researchers with domain expertise but without formal training in software engineering or computer science. This arrangement has led to underappreciation of sustainability and maintainability of scientific software tools developed in academic environments. Some software tools have avoided this fate, including the scientific library Rosetta. We use this software and its community as a case study to show how modern software development can be accomplished successfully, irrespective of subject area. Rosetta is one of the largest software suites for macromolecular modeling, with 3.1 million lines of code and many state-of-the-art applications. Since the mid 1990s, the software has been developed collaboratively by the RosettaCommons, a community of academics from over 60 institutions worldwide with diverse backgrounds including chemistry, biology, physiology, physics, engineering, mathematics, and computer science. Developing this software suite has provided us with more than two decades of experience in how to effectively develop advanced scientific software in a global community with hundreds of contributors. Here we illustrate the functioning of this development community by addressing technical aspects (like version control, testing, and maintenance), community-building strategies, diversity efforts, software dissemination, and user support. We demonstrate how modern computational research can thrive in a distributed collaborative community. The practices described here are independent of subject area and can be readily adopted by other software development communities.

A cluster randomized trial evaluating a teachable moment communication process for tobacco cessation support.

INTRODUCTION: This study examines the uptake of a clinician-focused teachable moment communication process (TMCP) and its impact on patient receipt of tobacco cessation support. The TMCP is a counseling method that uses patient concerns to help clinicians guide behavior change discussions about tobacco. We evaluate the added value of the TMCP training in a health system that implemented an Ask-Advise-Connect (AAC) systems-based approach. METHODS: A stepped wedge cluster randomized trial included eight community health centers. Training involved a web module and onsite skill development with standardized patients and coaching. Main outcome measures included contact and enrollment in cessation services among patients referred for counseling, prescription of cessation medications and quit attempts. RESULTS: Forty-four of 60 eligible clinicians received the TMCP training. Among TMCP-trained clinicians 68% used a TMCP approach (documented by flowsheet use) one or more times, with the median number of uses being 15 (IQR 2-33). Overall, the TMCP was used in 661 out of 8198 visits by smokers (8%). There was no improvement in any of the tobacco cessation assistance outcomes for the AAC + TMCP vs. the AAC only period. Visits where clinicians used the TMCP approach were associated with increased ordering of tobacco cessation medications, (OR = 2.6; 95% CI = 1.9, 3.5) and providing advice to quit OR 3.2 (95% CI 2.2, 4.7). CONCLUSIONS: Despite high fidelity to the training, uptake of the TMCP approach in routine practice was poor, making it difficult to evaluate the impact on patient outcomes. When the TMCP approach was used, ordering tobacco cessation medications increased. IMPLICATIONS: Tobacco cessation strategies in primary care have the potential to reach a large portion of the population and deliver advice tailored to the patient. The poor uptake of the approach despite high training fidelity suggests that additional implementation support strategies, are needed to increase sustainable adoption of the TMCP approach. TRIAL REGISTRATION: clinicaltrials.gov #NCT02764385 , registration date 06/05/2016.