Flexed elbow, abducted shoulder, forearm supinated (FABS) reconstruction from three-dimensional elbow MRI: diagnostic performance assessment in biceps head anatomy and pathology.

AIM: To determine inter-reader analysis and diagnostic performance on digitally reconstructed virtual flexed, abducted, supinated (FABS) imaging from three-dimensional (3D) isotropic elbow magnetic resonance imaging (MRI). MATERIALS AND METHODS: Six musculoskeletal radiologists independently evaluated elbow MRI images with virtual FABS reconstructions, blinded to clinical findings and final diagnoses. Each radiologist recorded a binary result as to whether the tendon was intact and if both heads were visible, along with a categorical value to the type of tear and extent of retraction in centimetres where applicable. Kappa and interclass correlation (ICC) were reported with 95% confidence intervals. Areas under the receiver operating curve (AUC) were reported. RESULTS: FABS reconstructions were obtained successfully in all 48 cases. With respect to tendon intactness, visibility of both heads, and type of tear, the Kappa values were 0.66 (0.53-0.78), 0.24 (0.12-0.37), and 0.55 (0.43-0.66), respectively. For the extent of retraction, the ICC was 0.85 (0.79-0.91) when including the tendons with and without retraction and 0.78 (0.61-0.91) when only including tendons with retraction. For tear versus no tear, AUC values were 0.82 (0.74-0.89) to 0.96 (0.91-1.01). CONCLUSION: Digital reconstruction of FABS positioning is feasible and allows good assessment of individual tendon head tears and retraction with high diagnostic performance.

ProsTAV, a novel blood-based test for biopsy decision management in significant prostate cancer.

BACKGROUND: Current pathways in early diagnosis of prostate cancer (PCa) can lead to unnecessary biopsy procedures. Here, we used telomere analysis to develop and evaluate ProsTAV®, a risk model for significant PCa (Gleason score >6), with the objective of improving the PCa diagnosis pathway. METHODS: This retrospective, multicentric study analyzed telomeres from patients with serum PSA 3-10 ng/mL. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate telomere-associated variables (TAVs) in peripheral blood mononucleated cells. ProsTAV® was developed by multivariate logistics regression based on three clinical variables and six TAVs. The predictive capacity and accuracy of ProsTAV® were summarized by receiver operating characteristic (ROC) curves and its clinical benefit with decision curves analysis. RESULTS: Telomeres from 1043 patients were analyzed. The median age of the patients was 63 years, with a median PSA of 5.2 ng/mL and a percentage of significant PCa of 23.9%. A total of 874 patients were selected for model training and 169 patients for model validation. The area under the ROC curve of ProsTAV® was 0.71 (95% confidence interval [CI], 0.62-0.79), with a sensitivity of 0.90 (95% CI, 0.88-1.0) and specificity of 0.33 (95% CI, 0.24-0.40). The positive predictive value was 0.29 (95% CI, 0.21-0.37) and the negative predictive value was 0.91 (95% CI, 0.83-0.99). ProsTAV® would make it possible to avoid 33% of biopsies. CONCLUSIONS: ProsTAV®, a predictive model based on telomere analysis through TAV, could be used to increase the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/mL.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

All-Optical, Air-Coupled Ultrasonic Detection of Low-Pressure Gas Leaks and Observation of Jet Tones in the MHz Range.

We used an ultrasensitive, broadband optomechanical ultrasound sensor to study the acoustic signals produced by pressurized nitrogen escaping from a variety of small syringes. Harmonically related jet tones extending into the MHz region were observed for a certain range of flow (i.e., Reynolds number), which is in qualitative agreement with historical studies on gas jets emitted from pipes and orifices of much larger dimensions. For higher turbulent flow rates, we observed broadband ultrasonic emission in the ~0-5 MHz range, which was likely limited on the upper end due to attenuation in air. These observations are made possible by the broadband, ultrasensitive response (for air-coupled ultrasound) of our optomechanical devices. Aside from being of theoretical interest, our results could have practical implications for the non-contact monitoring and detection of early-stage leaks in pressured fluid systems.

Complex 10-nm resolution nanogap and nanowire geometries for plasmonic metasurface miniaturization.

Emerging electromagnetic inverse design methods have pushed nanofabrication methods to their limits to extract maximum performance from plasmonic aperture-based metasurfaces. Using plasmonic metamaterial-lined apertures as an example, we demonstrate the importance of fine nanowire and nanogap features for achieving strong miniaturization of plasmonic nanoapertures. Metamaterial-lined nanoapertures are miniaturized over bowtie nanoapertures with identical minimum feature sizes by a factor of 25% without loss of field enhancement. We show that features as small as 10 nm can be reliably patterned over the wide areas required of metasurfaces using the helium focused ion beam microscope. Under imperfect fabrication conditions, we achieve 11-nm-wide nanogaps and 12-nm-wide nanowires over an area of 13 µm2, and successfully validate our results with optical characterization and comparable full-wave simulations.

Visible-Light Switching of Metallosupramolecular Assemblies.

A photoswitchable ligand and palladium(II) ions form a dynamic mixture of self-assembled metallosupramolecular structures. The photoswitching ligand is an ortho-fluoroazobenzene with appended pyridyl groups. Combining the E-isomer with palladium(II) salts affords a double-walled triangle with composition [Pd3 L6 ]6+ and a distorted tetrahedron [Pd4 L8 ]8+ (1 : 2 ratio at 298 K). Irradiation with 410 nm light generates a photostationary state with approximately 80 % of the E-isomer of the ligand and results in the selective disassembly of the tetrahedron, the more thermodynamically stable structure, and the formation of the triangle, the more kinetically inert product. The triangle is then slowly transformed back into the tetrahedron over 2 days at 333 K. The Z-isomer of the ligand does not form any well-defined structures and has a thermal half-life of 25 days at 298 K. This approach shows how a thermodynamically preferred self-assembled structure can be reversibly pumped to a kinetic trap by small perturbations of the isomer distribution using non-destructive visible light.

Antibiotic prescribing across age groups in the Kaiser Permanente Northern California population in association with different diagnoses, and with influenza incidence, 2010-2018.

There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis and otitis media). Here, we estimated age/diagnosis-specific proportions of antibiotic prescriptions (fills) for the Kaiser Permanente Northern California population during 2010-2018 that were influenza-associated. The proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was higher in children aged 5-17 years compared to children aged under 5 years, ranging from 1.4% [95% CI (0.7-2.1)] in aged <1 year to 2.7% (1.9-3.4) in aged 15-17 years. For adults aged over 20 years, the proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was lower, ranging from 0.7% (0.5-1) for aged 25-29 years to 1.6% (1.2-1.9) for aged 60-64 years. Most of the influenza-associated antibiotic prescribing in children aged under 10 years was for ear infections, while for age groups over 25 years, 45-84% of influenza-associated antibiotic prescribing was for respiratory diagnoses without a bacterial indication. This suggests a modest benefit of increasing influenza vaccination coverage for reducing antibiotic prescribing, as well as the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication in persons aged over 25 years, both of which may further contribute to the mitigation of antimicrobial resistance.

Prescribing for different antibiotic classes across age groups in the Kaiser Permanente Northern California population in association with influenza incidence, 2010-2018.

There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis). We estimated that for the Kaiser Permanente Northern California population during 2010-2018, 3.4% (2.8%-4%) of all macrolide prescriptions (fills), 2.7% (2.3%-3.2%) of all aminopenicillin prescriptions, 3.1% (2.4%-3.9%) of all 3rd generation cephalosporins prescriptions, 2.2% (1.8%-2.6%) of all protected aminopenicillin prescriptions and 1.3% (1%-1.6%) of all quinolone prescriptions were influenza-associated. The corresponding proportions were higher for select age groups, e.g. 4.3% of macrolide prescribing in ages over 50 years, 5.1% (3.3%-6.8%) of aminopenicillin prescribing in ages 5-17 years and 3.3% (1.9%-4.6%) in ages <5 years was influenza-associated. The relative contribution of influenza to antibiotic prescribing for respiratory diagnoses without a bacterial indication in ages over 5 years was higher than the corresponding relative contribution to prescribing for all diagnoses. Our results suggest a modest benefit of increasing influenza vaccination coverage for reducing prescribing for the five studied antibiotic classes, particularly for macrolides in ages over 50 years and aminopenicillins in ages <18 years, and the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication, both of which may contribute to the mitigation of antimicrobial resistance.

Racial Disparities in COVID-19 Testing and Outcomes : Retrospective Cohort Study in an Integrated Health System.

BACKGROUND: Racial disparities exist in outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE: To evaluate the contribution of race/ethnicity in SARS-CoV-2 testing, infection, and outcomes. DESIGN: Retrospective cohort study (1 February 2020 to 31 May 2020). SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: Adult health plan members. MEASUREMENTS: Age, sex, neighborhood deprivation index, comorbid conditions, acute physiology indices, and race/ethnicity; SARS-CoV-2 testing and incidence of positive test results; and hospitalization, illness severity, and mortality. RESULTS: Among 3 481 716 eligible members, 42.0% were White, 6.4% African American, 19.9% Hispanic, and 18.6% Asian; 13.0% were of other or unknown race. Of eligible members, 91 212 (2.6%) were tested for SARS-CoV-2 infection and 3686 had positive results (overall incidence, 105.9 per 100 000 persons; by racial group, White, 55.1; African American, 123.1; Hispanic, 219.6; Asian, 111.7; other/unknown, 79.3). African American persons had the highest unadjusted testing and mortality rates, White persons had the lowest testing rates, and those with other or unknown race had the lowest mortality rates. Compared with White persons, adjusted testing rates among non-White persons were marginally higher, but infection rates were significantly higher; adjusted odds ratios [aORs] for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 2.01 (95% CI, 1.75 to 2.31), 3.93 (CI, 3.59 to 4.30), 2.19 (CI, 1.98 to 2.42), and 1.57 (CI, 1.38 to 1.78), respectively. Geographic analyses showed that infections clustered in areas with higher proportions of non-White persons. Compared with White persons, adjusted hospitalization rates for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 1.47 (CI, 1.03 to 2.09), 1.42 (CI, 1.11 to 1.82), 1.47 (CI, 1.13 to 1.92), and 1.03 (CI, 0.72 to 1.46), respectively. Adjusted analyses showed no racial differences in inpatient mortality or total mortality during the study period. For testing, comorbid conditions made the greatest relative contribution to model explanatory power (77.9%); race only accounted for 8.1%. Likelihood of infection was largely due to race (80.3%). For other outcomes, age was most important; race only contributed 4.5% for hospitalization, 12.8% for admission illness severity, 2.3% for in-hospital death, and 0.4% for any death. LIMITATION: The study involved an insured population in a highly integrated health system. CONCLUSION: Race was the most important predictor of SARS-CoV-2 infection. After infection, race was associated with increased hospitalization risk but not mortality. PRIMARY FUNDING SOURCE: The Permanente Medical Group, Inc.

Visible-Light-Responsive Self-Assembled Complexes: Improved Photoswitching Properties by Metal Ion Coordination.

A photoswitchable ligand based on azobenzene is self-assembled with palladium(II) ions to form a [Pd2 (E-L)4 ]4+ cage. Irradiation with 470 nm light results in the near-quantitative switching to a monomeric species [Pd(Z-L)2 ]2+ , which can be reversed by irradiation with 405 nm light, or heat. The photoswitching selectivity towards the metastable isomer is significantly improved upon self-assembly, and the thermal half-life is extended from 40 days to 850 days, a promising approach for tuning photoswitching properties.

The qNMR Summit 5.0: Proceedings and Status of qNMR Technology.

The goal of the qNMR Summit is to take stock of the status quo and the recent developments in qNMR research and applications in a timely and accurate manner. It provides a platform for both advanced and novice qNMR practitioners to receive a well-rounded update and discuss potential qNMR-related applications and collaborations. For over a decade, scientists from academia, industry, nonprofit institutions, and governmental bodies have focused on the standardization of qNMR methodology, as well as its metrological and pharmacopeial utility. This paper reviews key content of qNMR Summits 1.0 to 4.0 and puts into perspective the outcomes and available transcripts of the October 2019 Summit 5.0, with attendees from the United States, Canada, Japan, Korea, and several European countries. Summit presentations focused on qNMR methodology in the pharmaceutical industry, advanced quantitation algorithms, and promising developments.

Prenylated Coumaric Acids from Artemisia scoparia Beneficially Modulate Adipogenesis.

Two new diprenylated coumaric acid isomers (1a and 1b) and two known congeners, capillartemisin A (2) and B (3), were isolated from Artemisia scoparia as bioactive markers using bioactivity-guided HPLC fractionation. Their structures were determined by spectroscopic means, including 1D and 2D NMR methods and LC-MS, with their purity assessed by 1D 1H pure shift qNMR spectroscopic analysis. The bioactivity of compounds was evaluated by enhanced accumulation of lipids, as measured using Oil Red O staining, and by increased expression of several adipocyte marker genes, including adiponectin in 3T3-L1 adipocytes relative to untreated negative controls. Compared to the plant's 80% EtOH extract, these purified compounds showed significant but still weaker inhibition of TNFα-induced lipolysis in 3T3-L1 adipocytes. This suggests that additional bioactive substances are responsible for the multiple metabolically favorable effects on adipocytes observed with Artemisia scoparia extract.

Depletion-of-susceptibles Bias in Analyses of Intra-season Waning of Influenza Vaccine Effectiveness.

Bias arises in studies of waning vaccine effectiveness when higher-risk individuals are depleted from the at-risk population at different rates between study groups. We examined how this bias arises and how to avoid it. A reanalysis of data from California confirmed a finding of intra-season waning of influenza vaccine effectiveness.

Individual and Neighborhood Factors Associated With Failure to Vaccinate Against Influenza During Pregnancy.

Uptake of influenza vaccine among pregnant women remains low. We investigated whether unvaccinated pregnant women were clustered geographically and determined factors associated with failure to vaccinate using spatial and multivariate logistic regression analyses. Pregnant women who were members of Kaiser Permanente Northern California in 2015 or 2016 were included in the study. More than half (53%) of the 77,607 included pregnant women were unvaccinated. Spatial analysis identified 5 clusters with a high prevalence of unvaccinated pregnant women. The proportion of unvaccinated women ranged from 57% to 75% within clusters as compared with 51% outside clusters. In covariate-adjusted analyses, residence in a cluster was associated with a 41% increase in the odds of being unvaccinated (odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.36, 1.46). The odds of being unvaccinated were greater for Black women (OR = 1.58, 95% CI: 1.49, 1.69), Hispanic women (OR = 1.15, 95% CI: 1.05, 1.25), women with subsidized health insurance (OR = 1.18, 95% CI: 1.11, 1.24), women with fewer than 5 prenatal-care visits (OR = 1.85, 95% CI: 1.60, 2.16), and neighborhoods with a high deprivation index (fourth quartile vs. first: OR = 1.14, 95% CI: 1.07, 1.21). In conclusion, unvaccinated pregnant women were clustered geographically and by key sociodemographic factors. These findings suggest that interventions to increase influenza vaccine coverage among pregnant women are needed, particularly in vulnerable populations.

Intraseason Waning of Influenza Vaccine Effectiveness.

BACKGROUND: In the United States, it is recommended that healthcare providers offer influenza vaccination by October, if possible. However, if the vaccine's effectiveness soon begins to wane, the optimal time for vaccination may be somewhat later. We examined whether the effectiveness of influenza vaccine wanes during the influenza season with increasing time since vaccination. METHODS: We identified persons who were vaccinated with inactivated influenza vaccine from 1 September 2010 to 31 March 2017 and who were subsequently tested for influenza and respiratory syncytial virus (RSV) by a polymerase chain reaction test. Test-confirmed influenza was the primary outcome and days-since-vaccination was the predictor of interest in conditional logistic regression. Models were adjusted for age and conditioned on calendar day and geographic area. RSV was used as a negative-control outcome. RESULTS: Compared with persons vaccinated 14 to 41 days prior to being tested, persons vaccinated 42 to 69 days prior to being tested had 1.32 (95% confidence interval [CI], 1.11 to 1.55) times the odds of testing positive for any influenza. The odds ratio (OR) increased linearly by approximately 16% for each additional 28 days since vaccination. The OR was 2.06 (95% CI, 1.69 to 2.51) for persons vaccinated 154 or more days prior to being tested. No evidence of waning was found for RSV. CONCLUSIONS: Our results suggest that effectiveness of inactivated influenza vaccine wanes during the course of a single season. These results may lead to reconsideration of the optimal timing of seasonal influenza vaccination.

Depletion-of-susceptibles bias in influenza vaccine waning studies: how to ensure robust results.

Vaccine effectiveness studies are subject to biases due to depletion-of-persons at risk of infection, or at especially high risk of infection, at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination to assess waning in vaccine protection as a function of vaccination time (namely whether earlier vaccination would result in lower subsequent protection compared to later vaccination). Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomised trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable to depletion-of-susceptibles bias in its inference of waning as a function of vaccination time under the null hypothesis that none exists, and will - if waning does actually occur - underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomised.

Large Carrier Mobilities in ErMnO3 Conducting Domain Walls Revealed by Quantitative Hall-Effect Measurements.

Kelvin probe force microscopy (KPFM) has been used to directly and quantitatively measure Hall voltages, developed at conducting tail-to-tail domain walls in ErMnO3 single crystals, when current is driven in the presence of an approximately perpendicular magnetic field. Measurements across a number of walls, taken using two different atomic force microscope platforms, consistently suggest that the active p-type carriers have unusually large room temperature mobilities of the order of hundreds of square centimeters per volt second. Associated carrier densities were estimated to be of the order of 1013 cm-3. Such mobilities, at room temperature, are high in comparison with both bulk oxide conductors and LaAlO3-SrTiO3 sheet conductors. High carrier mobilities are encouraging for the future of domain-wall nanoelectronics and, significantly, also suggest the feasibility of meaningful investigations into dimensional confinement effects in these novel domain-wall systems.

Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial.

Many cigarette smokers express a desire to quit smoking, but ~85% of cessation attempts fail. In our attempt to delineate genetic modulators of smoking persistence, we have earlier shown that a locus within an ~250 kb haplotype block spanning the 5' untranslated region region of insulin-degrading enzyme is associated with serum cotinine levels; the study's measure of smoking quantity. Based on our findings, and coupled with recent preclinical studies showing the importance of multiple neuropeptides in reinstatement of drug use, we formulated intranasal insulin to evaluate its efficacy during acute abstinence from smoking. Our original study was a crossover trial including 19 otherwise healthy smokers who abstained from smoking for 36 h. The morning following their second night of abstinence, in random order, study participants received intranasal insulin (60 IU) or placebo (8.7% sodium chloride). The goal of our second study was to replicate the craving findings from the original trial and expand this research by including additional stress-related measures. Thirty-seven study participants abstained from smoking overnight. The next day, they were administered either intranasal insulin (60 IU) or placebo, following which they participated in the Trier Social Stress Test Task. This was a parallel design study focusing on the standard stress subjective, hormonal and cardiovascular measures. We also evaluated any changes in circulating glucose, insulin and c-peptide (a marker of endogenous insulin). In the original study, intranasal insulin significantly reduced morning nicotine craving (b=3.65, P⩽0.05). Similarly, in the second study, intranasal insulin reduced nicotine cravings over time (b=0.065, P⩽0.05) and the effect lasted through the psychosocial stress period. Intranasal insulin also increased circulating cortisol levels (F=12.78, P⩽0.001). No changes in insulin or c-peptide were detected. A significant treatment × time interaction (P⩽0.05) was detected for glucose, but subjects remained well within the euglycemic range. Previous studies have shown that heightened nicotine cravings and blunted response to stress are independent and significant predictors of relapse to smoking. In our study, intranasal insulin normalized the subjective and hormonal response to stress. As such, intranasal insulin should further be studied in a larger clinical trial of smoking cessation. In support of this, we provide evidence that the treatment is safe and effective and, based on absence of peripheral insulin changes, conclude that the pharmacodynamic effect is centrally driven.

Use of a prescription opioid registry to examine opioid misuse and overdose in an integrated health system.

Strategies are needed to identify at-risk patients for adverse events associated with prescription opioids. This study identified prescription opioid misuse in an integrated health system using electronic health record (EHR) data, and examined predictors of misuse and overdose. The sample included patients from an EHR-based registry of adults who used prescription opioids in 2011 in Kaiser Permanente Northern California, a large integrated health care system. We characterized time-at-risk for opioid misuse and overdose, and used Cox proportional hazard models to model predictors of these events from 2011 to 2014. Among 396,452 patients, 2.7% were identified with opioid misuse and 1044 had an overdose event. Older patients were less likely to meet misuse criteria or have an overdose. Whites were more likely to be identified with misuse, but not to have an overdose. Alcohol and drug disorders were related to higher risk of misuse and overdose, with the exception that marijuana disorder was not related to opioid misuse. Higher daily opioid dosages and benzodiazepine use increased the risk of both opioid misuse and overdose. We characterized several risk factors associated with misuse and overdose using EHR-based data, which can be leveraged relatively quickly to inform preventive strategies to address the opioid crisis.

Oncologist and organizational factors associated with variation in breast cancer multigene testing.

PURPOSE: Multigene testing for breast cancer recurrence risk became available in 2007, yet many eligible patients remain untested. This study evaluated variation in testing rates, and oncologist and organizational factors associated with variation, in a setting without financial influences on testing. METHODS: We conducted a retrospective cohort study using electronic data and oncologist surveys within Kaiser Permanente Northern California, a large integrated health care system. Analyses included all 2974 test eligible patients from 2013 to 2015, 113 oncologists, and 15 practice groups. Receipt of multigene testing was evaluated with generalized linear mixed models. RESULTS: Overall, 39% of eligible patients had multigene testing, but rates varied widely among practice groups, ranging from 24 to 48% after case mix adjustment. This 24% difference among practices was greater than the variation associated with most patient characteristics, including comorbidities and race/ethnicity, and similar to that associated with tumor size. Practice group and oncologist factors were statistically significant contributors to the variation in testing after adjusting for patient factors. Patients were more likely to be tested if they had a female oncologist (aOR 1.60, 95% CI 1.21-2.12) or were in a practice whose chief had a high testing rate (aOR 1.20, 95% CI 1.12-1.29 per 10% increase in the percent tested). CONCLUSIONS: Oncologist and leadership practices play a key role in the variation in genomic test use for cancer recurrence risk even in a healthcare system without financial barriers to testing and could be a leverage point for implementing desired practice changes for new genomic advances.