Chemical Resolution of an Epitope Recognized by Blood Group Antibodies Capable of Binding Both A and B Red Blood Cells.

The high specificity of human antibodies to blood group A and B antigens is impressive, especially when considering the structural difference between these antigens (tetrasaccharides) is a NHAc versus a hydroxyl group on the terminal monosaccharide residue. It is well established that in addition to anti-A and anti-B there is a third antibody, anti-A,B capable of recognizing both A and B antigens. To analyze this AB specificity, we synthesized a tetrasaccharide, where the NHAc of the A antigen was replaced with an NH2. This NH2 group was then used to attach the glycan to an affinity resin, creating an AB epitope (ABep) adsorbent where the critical site for recognition by A and B antibodies was not accessible, while the rest of the (conformationally compact) tetrasaccharide remained accessible. Anti-ABep antibodies were then isolated from blood group O donors and found to have expected A,B specificity against immobilized and red cell bound synthetic antigens, including ABep, and were able to agglutinate both A and B red cells. The amount of these anti-ABep (anti-A,B) antibodies found in the blood of group O donors was comparable to levels of anti-A and anti-B found in group B and A individuals. Using STD-NMR the location for the AB epitope on the tetrasaccharide was found.

Impact of 30-day prescribed opioid dose trajectory on fatal overdose risk: A population-based, statewide cohort study.

BACKGROUND: Both increases and decreases in patients' prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined. OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days. DESIGN: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors. PARTICIPANTS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients). MAIN MEASURES: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME). KEY RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk. CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.

A novel syphilis Treponema pallidum lipoprotein peptide antigen diagnostic assay using red cell kodecytes in routine blood centre column agglutination testing platforms.

BACKGROUND AND OBJECTIVES: The detection of treponemal antibodies, which are used to make a diagnosis of syphilis, is important both for diagnostic purposes and as a mandatory blood donor test in most countries. We evaluated the feasibility of using Kode Technology to make syphilis peptide red cell kodecytes for use in column agglutination serologic platforms. MATERIALS AND METHODS: Candidate Kode Technology function-spacer-lipid (FSL) constructs were made for the Treponema pallidum lipoprotein (TmpA) of T. pallidum, using the peptide and FSL selection algorithms, and then used to make kodecytes. Developmental kodecytes were evaluated against a large range of syphilis antibody reactive and non-reactive samples in column agglutination platforms and compared against established methodologies. Overall, 150 reactive and 2072 non-reactive Syphicheck assay (a modified T. pallidum particle agglutination) blood donor samples were used to evaluate the agreement rate of the developed kodecyte assay. RESULTS: From three FSL-peptide candidate constructs, one was found to be the most suitable for diagnostics. Of 150 Syphicheck assay reactive samples, 146 were TmpA-kodecyte reactive (97.3% agreement), compared with 58.0% with the rapid plasmin reagin (RPR) assay for the same samples. Against the 2072 expected syphilis non-reactive samples the agreement rate for TmpA-kodecytes was 98.8%. CONCLUSION: TmpA-kodecytes are viable for use as cost-effective serologic reagent red cells for the detection of treponemal antibodies to diagnose syphilis with a high level of specificity in blood centres. This kodecyte methodology also potentially allows for introduction of the reverse-algorithm testing into low-volume laboratories, by utilizing existing transfusion laboratory infrastructure.

Comparison of record linkage software for deduplicating patient identities in California's Prescription Drug Monitoring Program.

BACKGROUND: To help prevent overdose deaths involving prescription drugs, accurate linkage of prescription drug monitoring program (PDMP) records for individual patients is essential. OBJECTIVES: To compare the accuracy of the linkage program used by California's PDMP against various record linkage programs with respect to accuracy in deduplicating patient identities in the PDMP, with implications for identifying high-risk opioid use and outlier behaviors. RESEARCH DESIGN: We evaluated California's program, Link Plus, LinkSolv, and The Link King on 557 861 PDMP identity records with addresses in two 3-digit zip code areas for patients who filled a controlled substance prescription in 2013. Manual review was performed on a stratified sample of 720 paired records identified as matches by at least one program. MEASURES: We estimated sensitivity and positive predictive value, and computed PDMP patient alerts for the patient entities identified by each program. RESULTS: Sensitivity was 95% for LinkSolv and The Link King, 84% for Link Plus, and 73% for California's program; positive predictive value was ≥93% for all programs. The number of patient entities prompting a PDMP alert was similar among the programs for all alerts except multiple provider episodes (obtaining prescriptions from ≥6 prescribers or ≥6 pharmacies in the last 6 months), which were 10.9%, 26.6%, and 16.9% greater using The Link King, Link Plus, and LinkSolv, respectively, compared to California's program. CONCLUSIONS: PDMPs should assess the accuracy of record linkage algorithms and the impacts of these algorithms on patient safety alerts and develop national best practices for PDMP record linkage.

Surface Glycans of Microvesicles Derived from Endothelial Cells, as Probed Using Plant Lectins.

Glycans of MVs are proposed to be candidates for mediating targeting specificity or at least promoting it. In contrast to exosomes, glycomic studies of MVs are largely absent. We studied the glycoprofile of endothelial cell-derived MVs using 21 plant lectins, and the results show the dominance of oligolactosamines and their α2-6-sialylated forms as N-glycans and low levels of α2-3-sialylated glycans. The low levels of α2-3-sialosides could not be explained by the action of extracellular glycosidases. Additionally, the level of some Man-containing glycans was also decreased in MVs. Spatial masking as the causative relationship between these low level glycans (as glycosphingolipids) by integral proteins or proteoglycans (thus, their lack of interaction with lectins) seems unlikely. The results suggest that integral proteins do not pass randomly into MVs, but instead only some types, differing in terms of their specific glycosylation, are integrated into MVs.

Communicative Practices Clinicians Use to Correct Patient Misconceptions in Primary Care Visits.

To investigate how clinicians correct patient misconceptions, we analyzed 23 video recordings of primary care visits. Analysis focused on operationalizing, identifying, and characterizing clinician corrections, integrating two inductive approaches: microanalysis of clinical interaction and conversation analysis. According to our definition, patient misconception-clinician correction episodes met three essential criteria: (1) the clinician refuted something the patient had said, (2) which the patient had presented without uncertainty, and (3) which contained a proposition that was factually incorrect. We identified 59 such episodes; the patient misconceptions most commonly related to medication issues; fewer than half had foreseeable implications for patients' future actions. We identified seven clinician correction practices: Three direct practices (displaying surprise, marking disagreement, contradicting the patient) and four indirect practices (presenting the correct proposition, providing explanations, invoking an outside authority, demonstrating with evidence). We found an almost equal distribution of these direct and indirect practices.

Professional knowledge acquisition of dental students employed part-time as dental assistants.

INTRODUCTION: Whilst admission to dental school in many jurisdictions requires applicants to shadow dentists or undertake work experience at a dental practice, little is known about the impacts on professional learning when dental students work part-time as dental assistants whilst concurrently studying dentistry. This paper explores what, how and from whom dental students who work as dental assistants acquire professional knowledges during employment. METHODS: This study draws on a qualitative analysis of interviews with sixteen senior dental students who have extra-curricular part-time employment as dental assistants in private dental practices. RESULTS: Analysis produced four themes that relate to students learning in the professional environment: students learn about the responsibilities, rhythms and routines of practice, as well as patient communication and interactions. Students embedded in the dental team noticed and related to the dispositions and the work of dentistry. Students learned from all members of the dental team including clinical and non-clinical staff (reception, administration, laboratory and sterilisation). DISCUSSION: Students used their experiences in a practice setting to further their professional education. The ability to "read" a situation and formulate an appropriate response requires the integration of complex and actionable professional knowledges. CONCLUSION: This research study presents insight into the ways dental students employed as dental assistants are embedded in and learn from the dental team in a critically evaluative manner. Students professionally notice and make sense of complex practice environments whilst undertaking university studies to learn about practice routines, rhythms and responsibilities as well as advancing confidence in relating with patients. This study provides a stimulus for further research about the contribution of workplace experiences to dental education.

Visit Linearity in Primary Care Visits for Patients with Chronic Pain on Long-term Opioid Therapy.

BACKGROUND: Physicians and patients report frustration after primary care visits for chronic pain. The need to shift between multiple clinical topics to address competing demands during visits may contribute to this frustration. OBJECTIVE: This study creates a novel measure, "visit linearity," to assess visit organization and examines whether visits that require less shifting back and forth between topics are associated with better patient and physician visit experiences. It also explores whether visit linearity differs depending on the following: (1) whether or not pain is a major topic of the visit and (2) whether or not pain is the first topic raised. DESIGN: This study analyzed 41 video-recorded visits using inductive, qualitative analysis informed by conversation analysis. We used linear regression to evaluate associations between visit organization and post-visit measures of participant experience. PARTICIPANTS: Patients were established adult patients planning to discuss pain management during routine primary care. Physicians were internal or family medicine residents. MAIN MEASURES: Visit linearity, total topics, return topics, topic shifts, time per topic, visit duration, pain main topic, pain first topic, patient experience, and physician difficulty. KEY RESULTS: Visits had a mean of 8.1 total topics (standard deviation (SD)=3.46), 14.5 topic shifts (SD=6.28), and 1.9 topic shifts per topic (SD=0.62). Less linear visits (higher topic shifts to topic ratio) were associated with greater physician visit difficulty (ß=7.28, p<0.001) and worse patient experience (ß= -0.62, p=0.03). Visit linearity was not significantly impacted by pain as a major or first topic raised. CONCLUSIONS: In primary care visits for patients with chronic pain taking opioids, more linear visits were associated with better physician and patient experience. Frequent topic shifts may be disruptive. If confirmed in future research, this finding implies that reducing shifts between topics could help decrease mutual frustration related to discussions about pain.

Simulated RBC antibody identification training panels created using SARS-CoV-2 kodecytes and immune plasma.

BACKGROUND: Training is essential to develop and maintain skills required to be a competent serologist, yet samples required to achieve this are often difficult to obtain. We evaluated the feasibility of SARS-CoV-2 peptide modified RBCs (1144-kodecytes) to develop simulated antibody screening and identification panels of reagent RBCs suitable for practical training, recognition, and grading of serologic reactions. STUDY DESIGN AND METHODS: RBCs from a single donor were modified into kodecytes using Kode Technology function-spacer-lipid constructs bearing a short SARS-CoV-2 peptide. Kodecytes and unmodified cells were then arranged in patterns representative of RBC antibody profiles as simulated antibody screening and identification reagent cell panels (SASID), and then tested against immune donor plasma samples containing SARS-CoV-2 antibodies. Manual tube and two different gel card serologic platforms were evaluated by routine techniques. SASID exemplars were created for antibodies including D, Cw , f (ce), Jka (strong, weak, dosing), mixtures of D + E, Jka + K, Fya + E, high and low frequency antibodies and a warm IgG autoantibody. RESULTS: Kodecytes (positive reactions) and unmodified cells (negative) when arranged and tested in appropriate patterns in SASID panels were able to mimic IgG antibody reactions, and were capable of measuring both accuracy and precision in reaction grading. CONCLUSIONS: Kodecytes can be used to rapidly create in-house simulated yet realistic antibody screening and identification panels suitable for large scale training in the recognition and grading of serologic reactions.

The impact of California wildfires on patient access to prescription opioids.

BACKGROUND: Patients on long-term opioid therapy are particularly vulnerable to disruptions in medication access, especially during traumatic and chaotic events such as wildfires and other natural disasters. OBJECTIVES: To determine whether past highly destructive California wildfires were associated with disrupted access to prescription opioids for patients receiving long-term, and therefore physically dependent on, opioid medications. METHODS: Using California prescription drug monitoring program data, this retrospective study selected patients with long-term prescription opioid use episodes residing in ZIP code tabulation areas impacted by either the Camp Fire or Tubbs Fire. Autoregressive integrated moving average time series models were fit to pre-fire data to forecast post-fire expected values and then compared with observed post-fire data, specifically for weekly proportions of long-term episodes with early fills, late fills, changes in patients' prescriber and pharmacy, and fills within a different ZIP code tabulation area than the patient's residence. RESULTS: After the Camp Fire, there were significant spikes in the proportions of early fills (peak at 56% of total, week 1 after fire), late fills (peak at 29%, week 6), and immediate significant increases in prescriber (peak at 37%, week 3) and pharmacy changes (peak at 71%, week 1) in high-impact ZIP code tabulation areas. Low-impact ZIP code tabulation areas experienced no similar disruptions. Disruptions due to the Tubbs Fire were far less severe. CONCLUSION: Access to prescription opioids was greatly disrupted for patients living in areas most impacted by the Camp Fire. Future research should explore effectiveness of current state and federal controlled substance prescribing policies to determine what improvements are needed to minimize disruptions in medication access due to wildfires and other natural disasters.

Procedural Approach to Ultrasound-Guided Geniculate Nerve Blockade for Knee Pain in Patients with OA.

ABSTRACT: Ultrasound-guided genicular nerve block can provide excellent pain control for patients with knee OA. This procedure has the advantage of providing sensory blockade with concomitant sparing of motor compromise, which is observed when the femoral and its lateral femoral cutaneous branches are blocked. Once the geniculate nerve of interest is identified, the operator can use ultrasound guidance to surround nerve fascicles with an injectate mixture of anesthetic and corticosteroid, yielding decreased pain sensation at the joint capsule. Given the role of the geniculate nerve in providing sensory innervation to the joint capsule and knee ligaments, blockade of this nerve can serve as a useful tool for managing patients with acute knee pain secondary to OA.

SARS-CoV-2 Peptide Bioconjugates Designed for Antibody Diagnostics.

In the near future, the increase in the number of required tests for COVID-19 antibodies is expected to be many hundreds of millions. Obviously, this will be done using a variety of analytical methods and using different antigens, including peptides. In this work, we compare three method variations for detecting specific immunoglobulins directed against peptides of approximately 15-aa of the SARS-CoV-2 spike protein. These linear peptide epitopes were selected using antigenicity algorithms, and were synthesized with an additional terminal cysteine residue for their bioconjugation. In two of the methods, constructs were prepared where the peptide (F, function) is attached to a negatively charged hydrophilic spacer (S) linked to a dioleoylphosphatidyl ethanolamine residue (L, lipid) to create a function-spacer-lipid construct (FSL). These FSLs were easily and controllably incorporated into erythrocytes for serologic testing or in a lipid bilayer deposited on a polystyrene microplate for use in an enzyme immunoassays (EIA). The third method, also an EIA, used polyacrylamide conjugated peptides (peptide-PAA) prepared by controlled condensation of the cysteine residue of the peptide with the maleimide-derived PAA polymer which were immobilized on polystyrene microplates by physisorption of the polymer. In this work, we describe the synthesis of the PAA and FSL peptide bioconjugates, design of test systems, and comparison of the bioassays results, and discuss potential reasons for higher performance of the FSL conjugates, particularly in the erythrocyte-based serologic assay.

A Risk Prediction Model for Long-term Prescription Opioid Use.

BACKGROUND: Tools are needed to aid clinicians in estimating their patients' risk of transitioning to long-term opioid use and to inform prescribing decisions. OBJECTIVE: The objective of this study was to develop and validate a model that predicts previously opioid-naive patients' risk of transitioning to long-term use. RESEARCH DESIGN: This was a statewide population-based prognostic study. SUBJECTS: Opioid-naive (no prescriptions in previous 2 y) patients aged 12 years old and above who received a pill-form opioid analgesic in 2016-2018 and whose prescriptions were registered in the California Prescription Drug Monitoring Program (PDMP). MEASURES: A multiple logistic regression approach was used to construct a prediction model with long-term (ie, >90 d) opioid use as the outcome. Models were developed using 2016-2017 data and validated using 2018 data. Discrimination (c-statistic), calibration (calibration slope, intercept, and visual inspection of calibration plots), and clinical utility (decision curve analysis) were evaluated to assess performance. RESULTS: Development and validation cohorts included 7,175,885 and 2,788,837 opioid-naive patients with outcome rates of 5.0% and 4.7%, respectively. The model showed high discrimination (c-statistic: 0.904 for development, 0.913 for validation), was well-calibrated after intercept adjustment (intercept, -0.006; 95% confidence interval, -0.016 to 0.004; slope, 1.049; 95% confidence interval, 1.045-1.053), and had a net benefit over a wide range of probability thresholds. CONCLUSIONS: A model for the transition from opioid-naive status to long-term use had high discrimination and was well-calibrated. Given its high predictive performance, this model shows promise for future integration into PDMPs to aid clinicians in formulating opioid prescribing decisions at the point of care.

Using Prescription Drug Monitoring Program Data to Assess Likelihood of Incident Long-Term Opioid Use: a Statewide Cohort Study.

BACKGROUND: Limiting the incidence of opioid-naïve patients who transition to long-term opioid use (i.e., continual use for > 90 days) is a key strategy for reducing opioid-related harms. OBJECTIVE: To identify variables constructed from data routinely collected by prescription drug monitoring programs that are associated with opioid-naïve patients' likelihood of transitioning to long-term use after an initial opioid prescription. DESIGN: Statewide cohort study using prescription drug monitoring program data PARTICIPANTS: All opioid-naïve patients in California (no opioid prescriptions within the prior 2 years) age ≥ 12 years prescribed an initial oral opioid analgesic from 2010 to 2017. METHODS AND MAIN MEASURES: Multiple logistic regression models using variables constructed from prescription drug monitoring program data through the day of each patient's initial opioid prescription, and, alternatively, data available up to 30 and 60 days after the initial prescription were constructed to identify probability of transition to long-term use. Model fit was determined by the area under the receiver operating characteristic curve (C-statistic). KEY RESULTS: Among 30,569,125 episodes of patients receiving new opioid prescriptions, 1,809,750 (5.9%) resulted in long-term use. Variables with the highest adjusted odds ratios included concurrent benzodiazepine use, ≥ 2 unique prescribers, and receipt of non-pill, non-liquid formulations. C-statistics for the day 0, day 30, and day 60 models were 0.81, 0.88, and 0.94, respectively. Models assessing opioid dose using the number of pills prescribed had greater discriminative capacity than those using milligram morphine equivalents. CONCLUSIONS: Data routinely collected by prescription drug monitoring programs can be used to identify patients who are likely to develop long-term use. Guidelines for new opioid prescriptions based on pill counts may be simpler and more clinically useful than guidelines based on days' supply or milligram morphine equivalents.

COVID-19 antibody screening with SARS-CoV-2 red cell kodecytes using routine serologic diagnostic platforms.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic is having a major global impact, and the resultant response in the development of new diagnostics is unprecedented. The detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a role in managing the pandemic. We evaluated the feasibility of using SARS-CoV-2 peptide Kode Technology-modified red cells (C19-kodecytes) to develop an assay compatible with existing routine serologic platforms. STUDY DESIGN AND METHODS: A panel of eight unique red cells modified using Kode Technology function-spacer-lipid constructs and bearing short SARS-CoV-2 peptides was developed (C19-kodecyte assay). Kodecytes were tested against undiluted expected antibody-negative and -positive plasma samples in manual tube and three column agglutination technology (CAT) platforms. Parallel analysis with the same peptides in solid phase by enzyme immunoassays was performed. Evaluation samples included >120 expected negative blood donor samples and >140 COVID-19 convalescent plasma samples, with independent serologic analysis from two centers. RESULTS: Specificity (negative reaction rate against expected negative samples) in three different CAT platforms against novel C19-kodecytes was >91%, which correlated with published literature. Sensitivity (positive reaction rate against expected positive convalescent, PCR-confirmed samples) ranged from 82% to 97% compared to 77% with the Abbott Architect SARS-CoV-2 IgG assay. Manual tube serology was less sensitive than CAT. Enzyme immunoassay results with some Kode Technology constructs also had high sensitivity. CONCLUSIONS: C19-kodecytes are viable for use as serologic reagent red cells for the detection of SARS-CoV-2 antibody with routine blood antibody screening equipment.

Impacts of prescription drug monitoring program policy changes and county opioid safety coalitions on prescribing and overdose outcomes in California, 2015-2018.

In 2015, California received funding to implement the Prescription Drug Overdose Prevention Initiative, a 4-year program to reduce deaths involving prescription opioids by 1) leveraging improvements to California's prescription drug monitoring program (PDMP) (i.e., mandatory PDMP registration for prescribers and pharmacists), and 2) supporting county opioid safety coalitions. We used statewide data from 2011 to 2018 to evaluate the Initiative's impact on opioid prescribing and overdose rates. Prescribing data were obtained from California's PDMP; fatal and non-fatal overdose data were obtained from the California Department of Public Health. Outcomes were monthly opioid prescribing rates and opioid overdose rates, modeled using generalized linear mixed models. Exposures were mandatory PDMP registration, presence of county coalitions, and Initiative support for county coalitions. Mandatory PDMP registration was associated with a 25% decrease (95%CI, 0.71-0.79) in opioid prescribing rates after 24 months. Having a county coalition was associated with a 2% decrease (95%CI, 0.96-0.99) in the opioid prescribing rate; receiving Initiative support was associated with an additional 2% decrease (95%CI, 0.97-0.98). Mandatory PDMP registration and county coalitions were associated with a 35% decrease (95%CI, 0.43-0.97) and a 21% decrease (95% CI, 0.70-0.90), respectively in prescription opioid overdose deaths. Both interventions were also associated with significantly fewer deaths involving any opioid but had no significant association with non-fatal overdose rates. Findings add to the knowledge available to guide policy to prevent high-risk prescribing and opioid overdoses. While further study is needed, coalitions and mandatory PDMP registration may be important components in such efforts.

Longitudinal Dose Trajectory Among Patients Tapering Long-Term Opioids.

OBJECTIVE: To evaluate the dose trajectory of new opioid tapers and estimate the percentage of patients with sustained tapers at long-term follow-up. DESIGN: Retrospective cohort study. SETTING: Data from the OptumLabs Data Warehouse® which includes de-identified medical and pharmacy claims and enrollment records for commercial and Medicare Advantage enrollees, representing a diverse mixture of ages, ethnicities, and geographical regions across the United States. SUBJECTS: Patients prescribed stable, higher-dose opioids for ≥12 months from 2008 to 2018. METHODS: Tapering was defined as ≥15% relative reduction in average MME/day during any of six overlapping 60-day periods in the initial 7 months of follow-up after the period of stable baseline dosing. Average monthly dose was ascertained during consecutive 60-day periods up to 16 months of follow-up. Linear regression estimated the geometric mean relative dose by tapering status and follow-up duration. Poisson regression estimated the percentage of tapered patients with sustained dose reductions at follow-up and patient-level predictors of failing to sustain tapers. RESULTS: The sample included 113,618 patients with 203,920 periods of stable baseline dosing (mean follow-up = 13.7 months). Tapering was initiated during 37,170 follow-up periods (18.2%). After taper initiation, patients had a substantial initial mean dose reduction (geometric mean relative dose .73 [95% CI: .72-.74]) that was sustained through 16 months of follow-up; at which point, 69.8% (95% CI: 69.1%-70.4%) of patients who initiated tapers had a relative dose reduction ≥15%, and 14.2% (95% CI: 13.7%-14.7%) had discontinued opioids. Failure to sustain tapers was significantly less likely among patients with overdose events during follow-up (adjusted incidence rate ratio [aIRR]: .56 [95% CI: .48-.67]) and during more recent years (aIRR: .93 per year after 2008 [95% CI: .92-.94]). CONCLUSIONS: In an insured and Medicare Advantage population, over two-thirds of patients who initiated opioid dose tapering sustained long-term dose reductions, and the likelihood of sustaining tapers increased substantially from 2008 to 2018.

Responding to the Opioid Epidemic: Educational Competencies for Pain and Substance Use Disorder from the Medical Schools of the University of California.

OBJECTIVE: The University of California (UC) leadership sought to develop a robust educational response to the epidemic of opioid-related deaths. Because the contributors to this current crisis are multifactorial, a comprehensive response requires educating future physicians about safe and effective management of pain, safer opioid prescribing, and identification and treatment of substance use disorder (SUD). METHODS: The six UC medical schools appointed an opioid crisis workgroup to develop educational strategies and a coordinated response to the opioid epidemic. The workgroup had diverse specialty and disciplinary representation. This workgroup focused on developing a foundational set of educational competencies for adoption across all UC medical schools that address pain, SUD, and public health concerns related to the opioid crisis. RESULTS: The UC pain and SUD competencies were either newly created or adapted from existing competencies that addressed pain, SUD, and opioid and other prescription drug misuse. The final competencies covered three domains: pain, SUD, and public health issues related to the opioid crisis. CONCLUSIONS: The authors present a novel set of educational competencies as a response to the opioid crisis. These competencies emphasize the subject areas that are fundamental to the opioid crisis: pain management, the safe use of opioids, and understanding and treating SUD.

The story vs the storyteller: Factors associated with the effectiveness of brief video-recorded patient stories for promoting opioid tapering.

BACKGROUND: Narrative communication is often more persuasive for promoting health behaviour change than communication using facts and figures; the extent to which narrative persuasiveness is due to patients' identification with the storyteller vs engagement with the story is unclear. OBJECTIVE: To examine the relative impacts of patient engagement, age concordance and gender concordance on perceived persuasiveness of video-recorded narrative clips about opioid tapering. METHODS: Patient raters watched and rated 48 brief video-recorded clips featuring 1 of 7 different storytellers describing their experiences with opioid tapering. The dependent variable was clips' perceived persuasiveness for encouraging patients to consider opioid tapering. Independent variables were rater engagement with the clip, rater-storyteller gender concordance and rater-storyteller age concordance (<60 vs ≥60). Covariates were rater beliefs about opioids and opioid tapering, clip duration and clip theme. Mixed-effects models accounted for raters viewing multiple clips and clips nested within storytellers. RESULTS: In multivariable models, higher rater engagement with the clip was associated with higher perceived persuasiveness (coefficient = 0.46, 95% CI 0.39-0.53, P < .001). Neither age concordance nor gender concordance significantly predicted perceived persuasiveness. The theme Problems with opioids also predicted perceived persuasiveness. CONCLUSION: Highly engaging, clinically relevant stories are likely persuasive to patients regardless of the match between patient and storyteller age and gender. When using patient stories in tools to promote health behaviour change, stories that are clinically relevant and engaging are likely to be persuasive regardless of storytellers' demographics. PATIENT OR PUBLIC CONTRIBUTION: Patients were involved as storytellers (in each clip) and assessed the key study variables.

Agenda setting and visit openings in primary care visits involving patients taking opioids for chronic pain.

BACKGROUND: Agenda setting is associated with more efficient care and better patient experience. This study develops a taxonomy of visit opening styles to assess use of agenda and non-agenda setting visit openings and their effects on participant experience. METHODS: This observational study analyzed 83 video recorded US primary care visits at a single academic medical center in California involving family medicine and internal medicine resident physicians (n = 49) and patients (n = 83) with chronic pain on opioids. Using conversation analysis, we developed a coding scheme that assessed the presence of agenda setting, distinct visit opening styles, and the number of total topics, major topics, surprise patient topics, and returns to prior topics discussed. Exploratory quantitative analyses were conducted to assess the relationship of agenda setting and visit opening styles with post-visit measures of both patient experience and physician perception of visit difficulty. RESULTS: We identified 2 visit opening styles representing agenda setting (agenda eliciting, agenda reframing) and 3 non-agenda setting opening styles (open-ended question, patient launch, physician launch). Agenda setting was only performed in 11% of visits and was associated with fewer surprise patient topics than visits without agenda setting (mean (SD) 2.67 (1.66) versus 4.28 (3.23), p = 0.03). CONCLUSIONS: In this study of patients with chronic pain, resident physicians rarely performed agenda setting, whether defined in terms of "agenda eliciting" or "agenda re-framing." Agenda setting was associated with fewer surprise topics. Understanding the communication context and outcomes of agenda setting may inform better use of this communication tool in primary care  practice.