Changes in the Appropriateness of US Outpatient Antibiotic Prescribing After the COVID-19 Outbreak: An Interrupted Time Series Analysis of 2016-2021 Data.

BACKGROUND: No national study has evaluated changes in the appropriateness of US outpatient antibiotic prescribing across all conditions and age groups after the coronavirus disease 2019 (COVID-19) outbreak in March 2020. METHODS: This was an interrupted time series analysis of Optum's de-identified Clinformatics Data Mart Database, a national commercial and Medicare Advantage claims database. Analyses included prescriptions for antibiotics dispensed to children and adults enrolled during each month during 2017-2021. For each prescription, we applied our previously developed antibiotic appropriateness classification scheme to International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes on medical claims occurring on or during the 3 days prior to dispensing. Outcomes included the monthly proportion of antibiotic prescriptions that were inappropriate and the monthly proportion of enrollees with ≥1 inappropriate prescription. Using segmented regression models, we assessed for level and slope changes in outcomes in March 2020. RESULTS: Analyses included 37 566 581 enrollees, of whom 19 154 059 (51.0%) were female. The proportion of enrollees with ≥1 inappropriate prescription decreased in March 2020 (level decrease: -0.80 percentage points [95% confidence interval {CI}, -1.09% to -.51%]) and subsequently increased (slope increase: 0.02 percentage points per month [95% CI, .01%-.03%]), partly because overall antibiotic dispensing rebounded and partly because the proportion of antibiotic prescriptions that were inappropriate increased (slope increase: 0.11 percentage points per month [95% CI, .04%-.18%]). In December 2021, the proportion of enrollees with ≥1 inappropriate prescription equaled the corresponding proportion in December 2019. CONCLUSIONS: Despite an initial decline, the proportion of enrollees exposed to inappropriate antibiotics returned to baseline levels by December 2021. Findings underscore the continued importance of outpatient antibiotic stewardship initiatives.

Prevalence of Inappropriate Antibiotic Prescribing with or without a Plausible Antibiotic Indication among Safety-Net and Non-Safety Net Populations.

BACKGROUND: Clinicians can prescribe antibiotics inappropriately without coding the indication for antibiotics. Whether the prevalence of inappropriate antibiotic prescribing with or without a plausible indication differs between safety-net and non-safety-net populations is unknown. OBJECTIVE: To assess differences in inappropriate antibiotic prescribing with or without a plausible indication between safety-net and non-safety net populations. DESIGN: Cross-sectional. PARTICIPANTS: Office visits in the 2016, 2018, 2019 National Ambulatory Medical Care Survey with ≥ 1 antibiotic prescription among children (0-17 years) and adults (18-64 years). MAIN MEASURES: Inappropriate antibiotic prescribing with a plausible indication (visits with infection-related diagnosis codes that do not warrant antibiotics, e.g., acute bronchitis); inappropriate prescribing without a plausible indication (visits with codes that are not antibiotic indications, e.g., hypertension). By age group, we used linear regression to assess differences between safety-net (public/no insurance) and non-safety net populations (privately insured), controlling for patient and visit characteristics. KEY RESULTS: Analyses included 67,065,108 and 122,731,809 weighted visits for children and adults, respectively. Among visits for children in the safety-net and non-safety populations, the prevalence of inappropriate antibiotic prescribing with a plausible indication was 11.7% and 22.0% (adjusted difference: -8.0%, 95% CI: -17.1%, 1.0%); the prevalence of inappropriate prescribing without a plausible indication was 11.8% and 8.6% (adjusted difference: -2.0%, 95% CI: -4.6%, 0.6%). Among visits for adults in the safety-net and non-safety populations, the prevalence of inappropriate antibiotic prescribing with a plausible indication was 12.1% and 14.3% (adjusted difference: -0.1%, 95% CI -9.4%, 9.1%); the prevalence of inappropriate prescribing without a plausible indication was 48.2% and 32.3% (adjusted difference: 12.5%, 95% CI: 3.6%, 21.4%). CONCLUSIONS: Inappropriate antibiotic prescribing with or without a plausible antibiotic indication is common in all populations, highlighting the importance of broad-based antibiotic stewardship initiatives. However, targeted initiatives focused on improving coding quality in adult safety-net settings may be warranted.

Successful implementation of a stakeholder engagement program for pharmacoepidemiologic research.

PURPOSE: Rigorously conducted pharmacoepidemiologic research requires methodologically complex study designs and analysis yet evaluates problems of high importance to patients and clinicians. Despite this, participation in and mechanisms for stakeholder engagement in pharmacoepidemiologic research are not well-described. Here, we describe our approach and lessons learned from engaging stakeholders, of varying familiarity with research methods, in a rigorous multi-year pharmacoepidemiologic research program evaluating the comparative effectiveness of diabetes medications. METHODS: We recruited 5 patient and 4 clinician stakeholders; each was compensated for their time. Stakeholders received initial formal training in observational research and pharmacoepidemiologic methods sufficient to enable contribution to the research project. After onboarding, stakeholder engagement meetings were held virtually, in the evening, 2-3 times annually. Each was approximately 90 min and focused on 1-2 specific questions about the project, with preparatory materials sent in advance. RESULTS: Stakeholder meeting attendance was high (89%-100%), and all stakeholders engaged with the research project, both during and between meetings. Stakeholders reported positive experiences with meetings, satisfaction, and interest in the research project and its findings, and dedication to the success of the project's goals. They affirmed the value of receiving materials to review in advance and the effectiveness of a virtual platform. Their contributions included prioritizing and suggesting research questions, optimizing written evidence briefs for a lay audience, and guidance on broader topics such as research audience and methods of dissemination. CONCLUSIONS: Stakeholder engagement in pharmacoepidemiologic research using complex study designs and analysis is feasible, acceptable, and positively impacts the research project.

Disagreement between pharmacy claims and direct interview to identify patients with non-adherence to chronic cardiometabolic medications.

BACKGROUND: Accurate methods of identifying patients with suboptimal adherence to cardiometabolic medications are needed, and each approach has benefits and tradeoffs. METHODS: We used data from a large trial of patients with poorly controlled cardiometabolic disease and evidence of medication non-adherence measured using pharmacy claims data whose adherence was subsequently assessed during a telephone consultation with a clinical pharmacist. We then evaluated if the pharmacist assessment agreed with the non-adherence measured using claims. When pharmacist and claims assessments disagreed, we identified reasons why claims were insufficient and used multivariable modified Poisson regression to identify patient characteristics associated with disagreement. RESULTS: Of 1,069 patients identified as non-adherent using claims (proportion of days covered [PDC] <80%), 646 (60.4%) were confirmed as non-adherent on pharmacist interview. For the 423 patients (39.6%) where the interview disagreed with the claims, the most common reasons were paying cash or using an alternate insurance (36.6%), medication discontinuation or regimen change (32.8%), and recently becoming adherent (26.7%). Compared to patients whose claims and interview both showed non-adherence, patients whose interview disagreed with claims were less likely to miss outpatient office visits (RR:0.91, 95%CI:0.85-0.97) and more likely to have a baseline PDC above the median (RR:1.35, 95%CI:1.10-1.64). CONCLUSIONS: Among patients identified as non-adherent by claims, 39.6% were observed to be adherent when assessed during pharmacist consultation. This discrepancy was largely driven by paying out-of-pocket, using alternative insurance, or medication discontinuation or change. These findings have important implications for using pharmacy claims to identify and intervene upon medication non-adherence.

Getting to 100%: Research Priorities and Unanswered Questions to Inform the US Debate on Universal Health Insurance Coverage.

A majority of Americans favor universal health insurance, but there is uncertainty over how best to achieve this goal. Whatever the insurance design that is implemented, additional details that must be considered include breadth of services covered, restrictions and limits on volumes of services, cost-sharing for individuals, and pricing. In the hopes that research can inform this ongoing debate, we review evidence supporting different models for achieving universal coverage in the US and identify areas where additional research and stakeholder input is needed. Key areas in need of further research include how care should be organized, how costs can be reduced, and what healthcare services universal insurance should cover.

A Comparison of Individuals with Diabetes and EMPA-REG Trial Participants: Exploring Aspects of External Validity.

BACKGROUND: There is increasing use of sodium glucose co-transporter 2 (SGLT2) inhibitors to treat diabetes. Since trials apply specific entry and exclusion criteria to ensure internal validity, comparisons of trial populations with nationally representative samples can inform the applicability of study findings to practice. OBJECTIVE: To compare individuals with diabetes from a nationally representative sample to patients who underwent randomization in the EMPA-REG trial. A secondary aim was to characterize what proportion of individuals prescribed an SGLT2 inhibitor in a nationally representative sample would have been included in the EMPA-REG trial. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Adults with diabetes who took part in the National Health and Nutrition Examination Survey (NHANES) between 2011-2014 (primary analysis corresponding to EMPA-REG enrollment) and 2015-2018 (secondary analysis corresponding to contemporary sample). MAIN MEASURES: The primary outcome was a comparison of demographic (age, sex, ethnicity, and pregnancy status), clinical (comorbidities and medication use), examination (weight, body mass index, and systolic and diastolic blood pressure), and laboratory (hgba1c, low- and high-density lipoprotein cholesterol, triglycerides, and estimated glomerular filtration rate) characteristics of NHANES respondents versus EMPA-REG trial participants. The secondary outcome was the proportion of NHANES respondents who had been prescribed an SGLT2 inhibitor that would have met inclusion criteria for the EMPA-REG trial. KEY RESULTS: There were 655 and 48 respondents, representing a weighted sample of 21,849,775 and 1,062,573 individuals, included in the primary and secondary analyses, respectively. Overall, 7.6% (95% CI 4.8-10.6%) of 2011-2014 NHANES respondents would have met all EMPA-REG trial inclusion criteria. NHANES respondents and EMPA-REG participants differed across demographic, clinical, examination, and laboratory domains. Of NHANES respondents from 2015 to 2018 who were prescribed an SGLT2 inhibitor, 10.6% (95% CI <1-24.7%) would have met all inclusion criteria for the EMPA-REG trial. CONCLUSIONS: The EMPA-REG population differed from a nationally representative sample, which could affect generalizability.

Incidence and Predictors of Primary Nonadherence to Sodium Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Agonists in a Large Integrated Healthcare System.

BACKGROUND: Newer glucose-lowering drugs, including sodium glucose co-transporter 2 inhibitors (SGLT2i) and GLP-1 agonists, have a key role in the pharmacologic management of type 2 diabetes. No studies have measured primary nonadherence for these two drug classes, defined as when a medication is prescribed for a patient but ultimately not dispensed to them. OBJECTIVE: To describe the incidence and predictors of primary nonadherence to SGLT2i (canagliflozin, empagliflozin) or GLP-1 agonists (dulaglutide, liraglutide, semaglutide) using a dataset that links electronic prescribing with health insurance claims. DESIGN AND PARTICIPANTS: A retrospective cohort design using data of adult patients from a large health system who had at least one prescription order for a SGLT2i or GLP-1 agonist between 2012 and 2019. We used mixed-effects multivariable logistic regression to determine associations between sociodemographic, clinical, and provider variables and primary nonadherence. MAIN MEASURES: Primary medication nonadherence, defined as no dispensed claim within 30 days of an electronic prescription order for any drug within each medication class. KEY RESULTS: The cohort included 5146 patients newly prescribed a SGLT2i or GLP-1 agonist. The overall incidence of 30-day primary medication nonadherence was 31.8% (1637/5146). This incidence rate was 29.8% (n = 726) and 33.6% (n = 911) among those initiating a GLP-1 agonist and SGLT2i, respectively. Age ≥ 65 (aOR 1.37 (95% CI 1.09 to 1.72)), Black race vs White (aOR 1.29 (95% CI 1.02 to 1.62)), diabetic nephropathy (aOR 1.31 (95% CI 1.02 to 1.68)), and hyperlipidemia (aOR 1.18 (95% CI 1.01 to 1.39)) were associated with a higher odds of primary nonadherence. Female sex (aOR 0.86 (95% CI 0.75 to 0.99)), peripheral artery disease (aOR 0.73 (95% CI 0.56 to 0.94)), and having the index prescription ordered by an endocrinologist vs a primary care provider (aOR 0.76 (95% CI 0.61 to 0.95)) were associated with lower odds of primary nonadherence. CONCLUSIONS: One third of patients prescribed SGLT2i or GLP-1 agonists in this sample did not fill their prescription within 30 days. Black race, male sex, older age, having greater baseline comorbidities, and having a primary care provider vs endocrinologist prescribe the index drug were associated with higher odds of primary nonadherence. Interventions targeting medication adherence for these newer drugs must consider primary nonadherence as a barrier to optimal clinical care.

Associations Between Copays, Coverage Limits for Opioid Use Disorder Medications, and Prescribing in Medicaid, 2018.

BACKGROUND: Opioid use disorder (OUD) affects millions of Americans, but only a fraction receive treatment. Many patients with OUD are enrolled in Medicaid, but elements of different state Medicaid programs' drug benefit designs may impact patients' access to life-saving care. OBJECTIVE: To describe medication for OUD (mOUD) use in Medicaid and examine the relationship between mOUD use and state drug benefit design plans. DESIGN/SUBJECTS: Cross-sectional study using Medicaid State Drug Utilization Data from 2018 to quantify office-based mOUD and the Medicaid Behavioral Health Services Database to extract copay amounts and coverage limits for mOUD. We excluded states with <5% coverage and assessed for associations between copays or coverage limits and mOUD dispensing using simple linear regression. MEASURES: Proportion of mOUD prescriptions relative to all prescriptions, opioid prescriptions, and the state-level prevalence of pain reliever use disorder and association between copays, coverage limits and these proportions. RESULTS: There was substantial variability in mOUD use. Although state Medicaid drug benefit designs also varied, we found no significant relationship between copay requirements (yes/no), coverage limits (yes/no), copay amount ($0-$0.99 vs. $1 or more), and mOUD utilization measures. CONCLUSIONS: Substantial state-level variation exists in mOUD use, but we did not find a significant association between copays or coverage limits and use in Medicaid. Further research is needed to assess other potential impacts of mOUD drug benefit design elements in Medicaid.

Secondary effects of an opioid-focused academic detailing program on non-opioid controlled substance prescribing in primary care.

Background: Educational outreach programs that focus on safe opioid prescribing and awareness of state prescription monitoring programs may modify clinicians' prescribing behavior. The objective of this study was to evaluate the secondary effects of an opioid-focused academic detailing (AD) program on non-opioid controlled substance prescribing in primary care. Methods: A quasi-experimental pre-post study of primary care clinicians exposed and unexposed to the AD program was conducted using data from the Illinois Prescription Monitoring Program from December 2017 to February 2019. Outcomes were mean monthly prescriptions for benzodiazepines (BZD), non-BZD sedative-hypnotics, and carisoprodol, per clinician. A difference-in-differences (DID) approach utilizing repeated-measures mixed-effects linear regression models was used to compare changes in outcomes six-months before and after the program. Results: Mean monthly BZD prescriptions declined in both groups of clinicians (AD-exposed n = 151; controls n = 399) after implementation of the AD program. Although the mean monthly number of BZD prescriptions decreased in both groups after the AD program, BZD prescribing in the AD-exposed group declined at a slower rate following the AD program (DID = 0.73; 95% CI: 0.14, 1.31). The AD-exposed group had a 0.06 (95% CI: -0.11, -0.01) lower rate of mean monthly carisoprodol prescriptions compared to the control group following the AD program. There was no change in the rate of mean monthly non-BZD sedative-hypnotic prescriptions between the two groups. Conclusions: The higher relative rate of BZD prescribing in the AD-exposed group compared to the control group following the AD program may be reflective of an unintended consequence of opioid-focused AD programs as clinicians learn to be cautious about opioid prescribing. Our findings may suggest the need for incorporation of targeted education on appropriate BZD prescribing into opioid-focused AD programs as a featured component. These findings warrant further consideration and investigation before large-scale implementation of opioid-focused educational outreach programs.

Comparison of a new 3-item self-reported measure of adherence to medication with pharmacy claims data in patients with cardiometabolic disease.

BACKGROUND: Less than half of patients with cardiometabolic disease consistently take prescribed medications. While health insurers and some delivery organizations use claims to measure adherence, most clinicians do not have access during routine interactions. Self-reported scales exist, but their practical utility is often limited by length or cost. By contrast, the accuracy of a new 3-item self-reported measure has been demonstrated in individuals with HIV. We evaluated its concordance with claims-based adherence measures in cardiometabolic disease. METHODS: We used data from a recently-completed pragmatic trial of patients with cardiometabolic conditions. After 12 months of follow-up, intervention subjects were mailed a survey with the 3-item measure that queries about medication use in the prior 30 days. Responses were linearly transformed and averaged. Adherence was also measured in claims in month 12 and months 1-12 of the trial using proportion of days covered (PDC) metrics. We compared validation metrics for non-adherence for self-report (average <0.80) compared with claims (PDC <0.80). RESULTS: Of 459 patients returning the survey (response rate: 43.5%), 50.1% were non-adherent in claims in month 12 while 20.9% were non-adherent based on the survey. Specificity of the 3-item metric for non-adherence was high (month 12: 0.83). Sensitivity was relatively poor (month 12: 0.25). Month 12 positive and negative predictive values were 0.59 and 0.52, respectively. CONCLUSIONS: A 3-item self-reported measure has high specificity but poor sensitivity for non-adherence versus claims in cardiometabolic disease. Despite this, the tool could help target those needing adherence support, particularly in the absence of claims data.

Does quantitative assessment of arterial phase hyperenhancement and washout improve LI-RADS v2018-based classification of liver lesions?

OBJECTIVES: To compare interreader agreement and diagnostic accuracy of LI-RADS v2018 categorization using quantitative versus qualitative MRI assessment of arterial phase hyperenhancement (APHE) and washout (WO) of focal liver lesions. METHODS: Sixty patients (19 female; mean age, 56 years) at risk for HCC with 71 liver lesions (28 HCCs, 43 benign) who underwent contrast-enhanced MRI were included in this retrospective study. Four blinded radiologists independently assigned a qualitative LI-RADS score per lesion. Two other radiologists placed ROIs within the lesion, adjacent liver parenchyma, and paraspinal musculature on pre- and post-contrast MR images. The percentage of arterial enhancement and the liver-to-lesion contrast ratio were calculated for quantification of APHE and WO. Using these quantitative parameters, a quantitative LI-RADS score was assigned. Interreader agreement and AUCs were calculated. RESULTS: Interreader agreement was similar for qualitative and quantitative LI-RADS (κ = 0.38 vs. 0.40-0.47) with a tendency towards improved agreement for quantitatively assessed APHE (κ = 0.65 vs. 0.81) and WO (κ = 0.53 vs. 0.78). Qualitative LI-RADS showed an AUC of 0.86, 0.94, 0.94, and 0.91 for readers 1, 2, 3, and 4, respectively. The quantitative LI-RADS score where APHE/WO/or both were replaced showed an AUC of 0.89/0.84/0.89, 0.95/0.92/0.92, 0.93/0.91/0.89, and 0.91/0.86/0.88 for readers 1, 2, 3, and 4, respectively. Sensitivity of LR-4/5 slightly increased, while specificity slightly decreased using quantitative APHE. CONCLUSION: Qualitative and quantitative LI-RADS showed similar performance. Quantitatively assessed APHE showed the potential to increase interreader agreement and sensitivity of HCC diagnosis, whereas quantitatively assessed WO had the opposite effect and needs to be redefined. KEY POINTS: • Quantitative assessment of arterial phase hyperenhancement shows the potential to increase interreader agreement and sensitivity to diagnose hepatocellular carcinoma. • Adding quantitative measurements of major LI-RADS features does not improve accuracy over qualitative assessment alone according to the LI-RADS v2018 algorithm.

Practice change intentions after academic detailing align with subsequent opioid prescribing.

OBJECTIVE: Self-reported behavior change is used to evaluate the effectiveness of educational outreach interventions delivered to clinicians, such as academic detailing (AD). However, self-reported changes in behavior are often not corroborated with data on actual behavior change. To assess alignment between self-reported practice change intentions and actual opioid prescribing behavior among primary care clinicians after an AD intervention. METHODS: We used a difference-in-differences approach to compare pre-post changes in opioid prescribing using data from the Illinois Prescription Monitoring Program. An opioid-focused AD intervention was delivered to primary care clinicians from a large health system in the Chicago metropolitan area from June 2018 to August 2018. Immediately after the AD intervention, clinicians were administered a single-item self-reported practice change measure. Clinicians were categorized into 2 groups on the basis of their responses: (1) intention to change and (2) no-to-moderate intention to change. Outcomes were mean total opioid prescriptions and high-dose opioid prescriptions (≥ 90 morphine milligram equivalents) per clinician per month. Repeated measures linear regression models were used to compare changes in opioid prescribing outcomes between the 2 groups in the 6 months before and after the AD intervention. RESULTS: A total of 149 clinicians were included for analysis. An intention to change was reported by 72 clinicians and no-to-moderate intention to change was reported by 77 clinicians. In the 6 months after the AD intervention, there were 1.48 (95% CI -2.48 to -0.47) fewer total opioid prescriptions and 0.50 (-0.69 to -0.31) fewer high-dose opioid prescriptions per clinician per month in the intention to change group than in the no-to-moderate intention to change group. CONCLUSION: This study showed considerable alignment between self-reported practice change intentions and actual changes in opioid prescribing behavior. Future opioid-focused educational outreach interventions should consider using standardized single-item practice change measures as an immediate indicator of future behavior change.

Comparative effectiveness of generic and brand-name medication use: A database study of US health insurance claims.

BACKGROUND: To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications. METHODS AND FINDINGS: For commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004-2013) and (2) Truven MarketScan (years: 2003-2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88-0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84-0.99] and 0.84 [0.76-0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01-1.10] and 1.07 [1.01-1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98-1.13] and 1.11 [1.05-1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by either residual confounding or generic perception bias. Limitations of this study include potential residual confounding due to the unavailability of certain clinical parameters in administrative claims data and the inability to evaluate surrogate outcomes, such as immediate changes in blood pressure, upon switching from brand products to generics. CONCLUSIONS: In this study, we observed that use of generics was associated with comparable clinical outcomes to use of brand-name products. These results could help in promoting educational interventions aimed at increasing patient and provider confidence in the ability of generic medicines to manage chronic diseases.

Academic Detailing in the New Era of Diabetes Medication Management.

PURPOSE OF REVIEW: Educating clinicians on how to improve the medical management of type 2 diabetes in the modern pharmacologic era represents an enormous challenge given the number of medications available and the diversity across guideline recommendations. Academic detailing uses active social marketing techniques to deliver in-office, face-to-face educational encounters between a trained clinical educator (academic detailer) and a primary care clinician and can improve the quality of prescribing and management decisions, leading to better patient outcomes. RECENT FINDINGS: This updated review provides context on how academic detailing programs can improve diabetes-related clinical knowledge and practice among primary care providers, incorporating the perspective of a field-based academic detailer. It also profiles 4 diabetes-specific academic detailing programs varying in geographic scope and detailing approach, based in Massachusetts, Pennsylvania, Vermont, and Saskatchewan Province (Canada). Academic detailing can effectively overcome challenges to increasing the evidence-based use of newer glucose-lowering medications in primary care settings.

Vertebral body insufficiency fractures: detection of vertebrae at risk on standard CT images using texture analysis and machine learning.

PURPOSE: To evaluate the diagnostic performance of bone texture analysis (TA) combined with machine learning (ML) algorithms in standard CT scans to identify patients with vertebrae at risk for insufficiency fractures. MATERIALS AND METHODS: Standard CT scans of 58 patients with insufficiency fractures of the spine, performed between 2006 and 2013, were analyzed retrospectively. Every included patient had at least two CT scans. Intact vertebrae in a first scan that either fractured ("unstable") or remained intact ("stable") in the consecutive scan were manually segmented on mid-sagittal reformations. TA features for all vertebrae were extracted using open-source software (MaZda). In a paired control study, all vertebrae of the study cohort "cases" and matched controls were classified using ROC analysis of Hounsfield unit (HU) measurements and supervised ML techniques. In a within-subject vertebra comparison, vertebrae of the cases were classified into "unstable" and "stable" using identical techniques. RESULTS: One hundred twenty vertebrae were included. Classification of cases/controls using ROC analysis of HU measurements showed an AUC of 0.83 (95% confidence interval [CI], 0.77-0.88), and ML-based classification showed an AUC of 0.97 (CI, 0.97-0.98). Classification of unstable/stable vertebrae using ROC analysis showed an AUC of 0.52 (CI, 0.42-0.63), and ML-based classification showed an AUC of 0.64 (CI, 0.61-0.67). CONCLUSION: TA combined with ML allows to identifying patients who will suffer from vertebral insufficiency fractures in standard CT scans with high accuracy. However, identification of single vertebra at risk remains challenging. KEY POINTS: • Bone texture analysis combined with machine learning allows to identify patients at risk for vertebral body insufficiency fractures on standard CT scans with high accuracy. • Compared to mere Hounsfield unit measurements on CT scans, application of bone texture analysis combined with machine learning improve fracture risk prediction. • This analysis has the potential to identify vertebrae at risk for insufficiency fracture and may thus increase diagnostic value of standard CT scans.

Computed tomography volumetry of esophageal cancer - the role of semiautomatic assessment.

BACKGROUND: The clinical and research value of Computed Tomography (CT) volumetry of esophageal cancer tumor size remains controversial. Development in CT technique and image analysis has made CT volumetry less cumbersome and it has gained renewed attention. The aim of this study was to assess esophageal tumor volume by semi-automatic measurements as compared to manual. METHODS: A total of 23 esophageal cancer patients (median age 65, range 51-71), undergoing CT in the portal-venous phase for tumor staging, were retrospectively included between 2007 and 2012. One radiology resident and one consultant radiologist measured the tumor volume by semiautomatic segmentation and manual segmentation. Reproducibility of the respective measurements was assessed by intraclass correlation coefficients (ICC) and by average deviation from mean. RESULTS: Mean tumor volume was 46 ml (range 5-137 ml) using manual segmentation and 42 ml (range 3-111 ml) using semiautomatic segmentation. Semiautomatic measurement provided better inter-observer agreement than traditional manual segmentation. The ICC was significantly higher for semiautomatic segmentation in comparison to manual segmentation (0.86, 0.56, p < 0.01). The average absolute percentage difference from mean was reduced from 24 to 14% (p < 0.001) when using semiautomatic segmentation. CONCLUSIONS: Semiautomatic analysis outperforms manual analysis for assessment of esophageal tumor volume, improving reproducibility.

Dual source abdominal computed tomography: the effect of reduced X-ray tube voltage and intravenous contrast media dosage in patients with reduced renal function.

BACKGROUND: X-ray tube voltage (kVp) reduction increases intravenous contrast medium (CM) attenuation at computed tomography (CT), but tube output limits its use in large patients. PURPOSE: To evaluate the feasibility and image quality of reducing CM dose by low kVp and using dual X-ray source at liver CT. MATERIAL AND METHODS: Patients with estimated glomerular filtration rate (eGFR) < 45 mL/min (n = 43) aged 60-91 years (75 ± 7.7), weighing 42-114 kg (75 ± 15) were prospectively scanned using a reduced CM dose of 0.25 or 0.3 g iodine (I)/kg with 70 or 80 kVp respectively, using either single-source or dual-source CT depending on patient size. Liver contrast-to-noise ratio (CNR), liver noise, and muscle noise were quantitatively compared with those of 43 consecutive patients aged > 65 years with eGFR > 45 mL/min scanned using a standard abdominal protocol at 120 kVp after receiving 0.5 gI/kg. RESULTS: There was no statistically significant difference in CNR, liver noise, or muscle noise at reduced CM protocols compared to the standard protocol: CNR was 4.6 (95% CI = 4.2-5.0) vs. 5.0 (95% CI = 4.5-5.5), liver noise was 11.1 (95% CI = 10.7-11.6) vs. 11.0 (95% CI = 10.5-11.6), muscle noise was 11.7 (95% CI = 11.2-12.1) vs. 10.8 (95% CI = 10.1-11.4). The mean SSDE was 70% higher with the reduced CM protocol. CONCLUSION: CM dosage can be reduced by 40-50% with maintained measured noise and CNR in patients with BMIs of 15-36 kg/m2 by lowering the tube voltage and dual-source CT scanning of the liver.

Triple Arterial Phase CT of the Liver with Radiation Dose Equivalent to That of Single Arterial Phase CT: Initial Experience.

Purpose To develop and evaluate a triple arterial phase CT liver protocol with a similar radiation dose to that of standard single arterial phase CT in study subjects suspected of having hepatocellular carcinoma (HCC). Materials and Methods The study consisted of a retrospective part A for protocol development (n = 15) and a prospective part B to evaluate diagnostic accuracy (n = 38). All 53 participants underwent perfusion CT with 50 mL contrast material between August 2013 and September 2014. Group B underwent an additional standard multiphasic liver CT examination with 120 mL of contrast material (range, 70-143 mL). Image sets from triple arterial phase imaging were reconstructed from perfusion CT by fusing images from three dedicated arterial time points. Triple arterial phase CT and standard single arterial phase CT were compared by two readers, who assessed subjective image quality and HCC detection rate. A third reader served as reference reader and assessed objective image quality. The paired Student t test, Wilcoxon signed rank test, jackknife alternative free-response receiver operating characteristic (JAFROC), and JAFROC curve were applied. Results The mean volume CT dose index was 11.6 mGy for triple arterial phase CT and 11.9 mGy for standard single arterial phase CT (P = .73). Triple arterial phase CT showed lower image noise and better contrast-to-noise ratio compared with standard single arterial phase CT (P < .001 and P = .032, respectively); however, there was no significant difference in lesion-to-liver-contrast ratio (P = .31). Subjective image quality was good for both protocols. The detection rate of the 65 HCC lesions was 82% for reader 1 and 83% for reader 2 at triple arterial phase CT and 80% for reader 1 and 77% for reader 2 at standard single arterial phase CT (P = .4). Conclusion Triple arterial phase imaging is feasible at the same radiation dose as that used for standard single arterial phase CT. Triple arterial phase imaging provides equivalent to superior image quality and equal HCC detection rate despite the use of less than half the contrast material dose used at standard single arterial phase CT. © RSNA, 2018.

Whole-body adipose tissue and lean muscle volumes and their distribution across gender and age: MR-derived normative values in a normal-weight Swiss population.

PURPOSE: To determine age- and gender-dependent whole-body adipose tissue and muscle volumes in healthy Swiss volunteers in Dixon MRI in comparison with anthropometric and bioelectrical impedance (BIA) measurements. METHODS: Fat-water-separated whole-body 3 Tesla MRI of 80 healthy volunteers (ages 20 to 62 years) with a body mass index (BMI) of 17.5 to 26.2 kg/m2 (10 men, 10 women per decade). Age and gender-dependent volumes of total adipose tissue (TAT), visceral adipose tissue (VAT), total abdominal subcutaneous adipose tissue (ASAT) and total abdominal adipose tissue (TAAT), and the total lean muscle tissue (TLMT) normalized for body height were determined by semi-automatic segmentation, and correlated with anthropometric and BIA measurements as well as lifestyle parameters. RESULTS: The TAT, ASAT, VAT, and TLMT indexes (TATi, ASATi, VATi, and TLMTi, respectively) (L/m2 ± standard deviation) for women/men were 6.4 ± 1.8/5.3 ± 1.7, 1.6 ± 0.7/1.2 ± 0.5, 0.4 ± 0.2/0.8 ± 0.5, and 5.6 ± 0.6/7.1 ± 0.7, respectively. The TATi correlated strongly with ASATi (r > 0.93), VATi, BMI and BIA (r > 0.70), and TAATi (r > 0.96), and weak with TLMTi for both genders (r > -0.34). The VAT was the only parameter showing an age dependency (r > 0.32). The BMI and BIA showed strong correlation with all MR-derived adipose tissue volumes. The TAT mass was estimated significantly lower from BIA than from MRI (both genders P < .001; mean bias -5 kg). CONCLUSIONS: The reported gender-specific MRI-based adipose tissue and muscle volumes might serve as normative values. The estimation of adipose tissue volumes was significantly lower from anthropometric and BIA measurements than from MRI. Magn Reson Med 79:449-458, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Association of Medicare's Bundled Payment Reform With Changes in Use of Vitamin D Among Patients Receiving Maintenance Hemodialysis: An Interrupted Time-Series Analysis.

BACKGROUND & RATIONALE: Medicare's 2011 prospective payment system (PPS) was introduced to curb overuse of separately billable injectable drugs. After epoietin, intravenous (IV) vitamin D analogues are the biggest drug cost drivers in hemodialysis (HD) patients, but the association between PPS introduction and vitamin D therapy has been scarcely investigated. STUDY DESIGN: Interrupted time-series analyses. SETTING & PARTICIPANTS: Adult US HD patients represented in the US Renal Data System between 2008 and 2013. EXPOSURES: PPS implementation. OUTCOMES: The cumulative dose of IV vitamin D analogues (paricalcitol equivalents) per patient per calendar quarter in prevalent HD patients. The average starting dose of IV vitamin D analogues and quarterly rates of new vitamin D use (initiations/100 person-months) in incident HD patients within 90 days of beginning HD therapy. ANALYTICAL APPROACH: Segmented linear regression models of the immediate change and slope change over time of vitamin D use after PPS implementation. RESULTS: Among 359,600 prevalent HD patients, IV vitamin D analogues accounted for 99% of the total use, and this trend was unchanged over time. PPS resulted in an immediate 7% decline in the average dose of IV vitamin D analogues (average baseline dose = 186.5 µg per quarter; immediate change = -13.5 µg [P < 0.001]; slope change = 0.43 per quarter [P = 0.3]) and in the starting dose of IV vitamin D analogues in incident HD patients (average baseline starting dose = 5.22 µg; immediate change = -0.40 µg [P < 0.001]; slope change = -0.03 per quarter [P = 0.03]). The baseline rate of vitamin D therapy initiation among 99,970 incident HD patients was 44.9/100 person-months and decreased over time, even before PPS implementation (pre-PPS ß = -0.46/100 person-months [P < 0.001]; slope change = -0.19/100 person-months [P = 0.2]). PPS implementation was associated with an immediate change in initiation levels (by -4.5/100 person-months; P < 0.001). LIMITATIONS: Incident HD patients were restricted to those 65 years or older. CONCLUSION: PPS implementation was associated with a 7% reduction in the average dose and starting dose of IV vitamin D analogues and a 10% reduction in the rate of vitamin D therapy initiation.