Researching professional practice: The integrated practice perspectives model and continuing education.

The Integrated Practice Perspectives model reframes previous efforts to link education with professional practice by using theories of situated cognition and learning. Reframing allows other variables in professional performance to be identified, performance to be more thoroughly linked to social and cultural contexts, and a more integrative and deeper conceptualization of professional practice and context to be developed

Chemotherapeutic impact on pain and global health-related quality of life in hormone-refractory prostate cancer: Dynamically Modified Outcomes (DYNAMO) analysis of a randomized controlled trial.

PURPOSE: This paper applies the Dynamically Modified Outcomes (DYNAMO) model to a clinical trial of two chemotherapeutic regimens on global health-related quality of life (GHRQL) in hormone-refractory prostate cancer. METHODS: DYNAMO identifies the causal influences operating in a clinical trial and their mediation, moderation, and modulation by uncontrolled variables. The Southwest Oncology Group trial S9916 randomized assignment to mitoxantrone plus prednisone (M + P) versus docetaxel plus estramustine (D + E) treatments. In this application, we examine baseline-adjusted impacts of worst pain (McGill Pain Questionnaire) on GHRQL (EORTC Quality of Life Questionnaire-C30) at 10 weeks. RESULTS: The average treatment levels of pain did not differ, hence, the average mediated effect of treatment on GHRQL was zero. Nonetheless, M + P reduced the impact (the relational outcome) of pain on GHRQL by 54% relative to D + E. Individual variation in the relational outcome (modulation) was of the same magnitude as the average difference between the groups. Performance status moderated the direct effects of treatment, with D + E being more effective in good, but not poor, performance strata. CONCLUSIONS: The DYNAMO approach comprehensively accounted for treatment effects. Rather than a single average effect, there were three distinct treatment effects: one direct effect for each performance status level and a direct effect on the relationship between pain and GHRQL

Postoperative Pain Trajectories in Cardiac Surgery Patients

Poorly controlled postoperative pain is a longstanding and costly problem in medicine. The purposes of this study were to characterize the acute pain trajectories over the first four postoperative days in 83 cardiac surgery patients with a mixed effects model of linear growth to determine whether statistically significant individual differences exist in these pain trajectories, and to compare the quality of measurement by trajectory with conventional pain measurement practices. The data conformed to a linear model that provided slope (rate of change) as a basis for comparing patients. Slopes varied significantly across patients, indicating that the direction and rate of change in pain during the first four days of recovery from surgery differed systematically across individuals. Of the 83 patients, 24 had decreasing pain after surgery, 24 had increasing pain, and the remaining 35 had approximately constant levels of pain over the four postoperative days

Mindfulness-Oriented Recovery Enhancement vs Supportive Group Therapy for Co-occurring Opioid Misuse and Chronic Pain in Primary Care: A Randomized Clinical Trial

Importance: Successful treatment of opioid misuse among people with chronic pain has proven elusive. Guidelines recommend nonopioid therapies, but the efficacy of mindfulness-based interventions for opioid misuse is uncertain. Objective: To evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement (MORE) for the reduction of opioid misuse and chronic pain. Design, Setting, and Participants: This interviewer-blinded randomized clinical trial enrolled patients from primary care clinics in Utah between January 4, 2016, and January 16, 2020. The study included 250 adults with chronic pain receiving long-term opioid therapy who were misusing opioid medications. Interventions: Treatment with MORE (comprising training in mindfulness, reappraisal, and savoring positive experiences) or supportive group psychotherapy (control condition) across 8 weekly 2-hour group sessions. Main Outcomes and Measures: Primary outcomes were (1) opioid misuse assessed by the Drug Misuse Index (self-report, interview, and urine screen) and (2) pain severity and pain-related functional interference, assessed by subscale scores on the Brief Pain Inventory through 9 months of follow-up. Secondary outcomes were opioid dose, emotional distress, and ecological momentary assessments of opioid craving. The minimum intervention dose was defined as 4 or more completed sessions of MORE or supportive group psychotherapy. Results: Among 250 participants (159 women [63.6%]; mean [SD] age, 51.8 [11.9] years), 129 were randomized to the MORE group and 121 to the supportive psychotherapy group. Overall, 17 participants (6.8%) were Hispanic or Latino, 218 (87.2%) were White, and 15 (6.0%) were of other races and/or ethnicities (2 American Indian, 3 Asian, 1 Black, 2 Pacific Islander, and 7 did not specify). At baseline, the mean duration of pain was 14.7 years (range, 1-60 years), and the mean (SD) morphine-equivalent opioid dose was 101.0 (266.3) mg (IQR, 16.0-90.0 mg). A total of 203 participants (81.2%) received the minimum intervention dose (mean [SD], 5.7 [2.2] sessions); at 9 months, 92 of 250 participants (36.8%) discontinued the study. The overall odds ratio for reduction in opioid misuse through the 9-month follow-up period in the MORE group compared with the supportive psychotherapy group was 2.06 (95% CI, 1.17-3.61; P = .01). At 9 months, 36 of 80 participants (45.0%) in the MORE group were no longer misusing opioids compared with 19 of 78 participants (24.4%) in the supportive psychotherapy group. Mixed models demonstrated that MORE was superior to supportive psychotherapy through 9 months of follow-up for pain severity (between-group effect: 0.49; 95% CI, 0.17-0.81; P = .003) and pain-related functional interference (between-group effect: 1.07; 95% CI, 0.64-1.50; P < .001). Participants in the MORE group reduced their opioid dose to a greater extent than those in the supportive psychotherapy group. The MORE group also had lower emotional distress and opioid craving. Conclusions and Relevance: In this randomized clinical trial, among adult participants in a primary care setting, the MORE intervention led to sustained improvements in opioid misuse and chronic pain symptoms and reductions in opioid dosing, emotional distress, and opioid craving compared with supportive group psychotherapy. Despite attrition caused by the COVID-19 pandemic and the vulnerability of the sample, MORE appeared to be efficacious for reducing opioid misuse among adults with chronic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT0260253

Confirmatory Factor Analysis of the Pain Care Quality Surveys (Pain CQ © )

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/1/hesr12014-sup-0001-Author_matrix.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/2/hesr12014.pd

The challenge of measuring intra-individual change in fatigue during cancer treatment

Evaluate how well three different patient-reported outcomes (PROs) measure individual change

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice