Association Between Prescription Drug Monitoring Program Use Mandate and Opioid Prescribing and Patient-Reported Outcomes After Surgery.

OBJECTIVE: To evaluate changes in opioid prescribing and patient-reported outcomes after surgery following implementation of Michigan's prescription drug monitoring program (PDMP) use mandate in June 2018. BACKGROUND: Most states mandate clinicians to query prescription drug monitoring program (PDMP) databases before prescribing controlled substances. Whether these PDMP use mandates affect opioid prescribing and patient-reported outcomes after surgery is unclear, especially among patients with elevated "Narx" scores, a risk score for overdose death used in most PDMPs. METHODS: We conducted an interrupted time series analysis of a statewide surgical registry linked to Michigan's PDMP database. Analyses included adults undergoing general surgical procedures during January 2017-October 2019. Outcomes included monthly mean days supplied in dispensed opioid prescriptions (those filled within 3 days of discharge) and monthly mean scores for 3 patient-reported outcomes (pain in the week after surgery, care satisfaction, regret undergoing surgery). Segmented regression models were used to assess for level and slope changes in outcomes in June 2018. Analyses were repeated among patients with Narx scores ≥200, a threshold that defines the top quartile. RESULTS: Analyses included 21,897 patients. The mandate was associated with a -0.5 (95% CI: -0.8, -0.2) level decrease in mean days supplied in dispensed opioid prescriptions, but not with worsened patient-reported outcomes. Findings were similar among patients with Narx scores ≥200. CONCLUSIONS: Following implementation of Michigan's PDMP use mandate, the duration of opioid prescriptions decreased, but patient-reported outcomes did not worsen. Findings suggest PDMP use mandates may not be associated with worsened experience among general surgical patients.

Association Between Cost-Sharing and Buprenorphine Prescription Abandonment.

BACKGROUND: Prior studies suggest cost-sharing decreases buprenorphine dispensing. However, these studies used databases that only report prescriptions filled by patients, not those that were "abandoned." Consequently, the studies could not calculate the probability of buprenorphine prescription abandonment or evaluate whether cost-sharing is associated with abandonment. OBJECTIVE: To evaluate the association between cost-sharing and buprenorphine prescription abandonment. DESIGN: Cross-sectional analysis of the IQVIA Formulary Impact Analyzer, a pharmacy transaction database representing 63% of U.S. retail pharmacies. The database includes transaction records ("claims") for prescriptions even if they are not filled. PARTICIPANTS: Buprenorphine claims in 2022 among commercially insured and Medicare patients. MAIN MEASURES: We evaluated the association between cost-sharing per 30-day supply and abandonment using logistic regression, controlling for patient characteristics, product type, and buprenorphine use in the prior 180 days. We assessed for effect modification by prior buprenorphine use. KEY RESULTS: Analyses included 2,346,994 and 1,242,596 buprenorphine prescription claims for commercially insured and Medicare patients, respectively. Among these claims, mean (SD) cost-sharing per 30-day supply was $28.1 (46.4) and $8.4 (20.2), and 1.5% and 1.2% were abandoned. Each $10 increase in cost-sharing per 30-day supply was associated with a 0.09 (95% CI: 0.09, 0.10) and 0.09 (95% CI: 0.08, 0.10) percentage-point increase in abandonment among commercially insured and Medicare patients. Among commercially insured and Medicare patients without prior buprenorphine use, respectively, a $10 increase in cost-sharing per 30-day supply was associated with a 0.12 (95% CI: 0.11, 0.14) and 0.13 (95% CI: 0.07, 0.18) percentage-point higher increase in the probability of abandonment compared with patients with > 90 days of prior buprenorphine use. CONCLUSIONS: Among commercially insured and Medicare patients, buprenorphine prescription abandonment is rare and only minimally associated with cost-sharing. Findings suggest elimination of buprenorphine cost-sharing should only be one component of a larger, multi-faceted campaign to increase buprenorphine dispensing.

Association Between Cost Sharing and Naloxone Prescription Dispensing.

Importance: Increasing access to naloxone (an opioid antagonist that can reverse overdose) could slow the US opioid epidemic. Prior studies suggest cost sharing may be a barrier to dispensing of naloxone prescriptions, but these studies were limited by their cross-sectional designs and use of databases that do not capture prescriptions that are not filled (abandoned). Objective: To evaluate the association between cost sharing and naloxone prescription abandonment (nondispensing of naloxone prescriptions). Design, Setting, and Participants: This cross-sectional, regression discontinuity analysis exploited the fact that deductibles typically reset at the beginning of the year in commercial and Medicare plans. The included data were derived from the 2020-2021 IQVIA Formulary Impact Analyzer (a pharmacy transactions database that represents 63% of prescriptions at US pharmacies). The analysis included claims for naloxone nasal spray among commercially insured patients and Medicare patients that occurred during the 60 days before January 1, 2021, through 59 days after January 1, 2021. Exposure: Cost sharing, which is defined as the amount patients would have to pay to fill prescriptions. Main Outcomes and Measures: Local linear regression models were used to assess for abrupt changes in cost sharing and the probability of prescription abandonment on January 1, 2021. To estimate the association between cost sharing and prescription abandonment, a fuzzy regression discontinuity analysis was conducted. Results: These analyses included naloxone claims for 71 306 commercially insured patients and 101 706 Medicare patients (40 019 [56.1%] and 61 410 [60.4%], respectively, were female). The commercially insured patients and Medicare patients accounted for 73 311 and 106 076 naloxone claims, respectively. On January 1, 2021, the mean cost sharing per claim increased by $15.0 (95% CI, $13.8-$16.2) for commercially insured patients and increased by $12.3 (95% CI, $10.9-$13.6) for Medicare patients and the probability of abandonment increased by 4.7 (95% CI, 3.2-6.2) percentage points and 2.8 (95% CI, 1.6-4.1) percentage points, respectively. The results from the fuzzy regression discontinuity analysis suggest a decision by commercial and Medicare plans to increase naloxone cost sharing by $10 would be associated with percentage-point increases of 3.1 (95% CI, 2.2-4.1) and 2.3 (95% CI, 1.4-3.2), respectively, in the probability of abandonment. Conclusions: The elimination of cost sharing might be associated with increased naloxone dispensing to commercially insured and Medicare patients.

Naloxone and Buprenorphine Prescribing Following US Emergency Department Visits for Suspected Opioid Overdose: August 2019 to April 2021.

STUDY OBJECTIVE: Nonfatal emergency department (ED) visits for opioid overdose are important opportunities to prescribe naloxone and buprenorphine, both of which can prevent future overdose-related mortality. We assessed the rate of this prescribing using national data from August 2019 to April 2021, a period during which US opioid overdose deaths reached record levels. METHODS: We conducted a retrospective cohort analysis using Symphony Health's Integrated Dataverse, which includes data from 5,800 hospitals and 70,000 pharmacies. Of ED visits for opioid overdose between August 4, 2019, and April 3, 2021, we calculated the proportion with at least 1 naloxone prescription within 30 days and repeated this analysis for buprenorphine. To contextualize the naloxone prescribing rate, we calculated the proportion of ED visits for anaphylaxis with at least 1 prescription for epinephrine-another life-saving rescue medication-within 30 days. RESULTS: Analyses included 148,966 ED visits for opioid overdose. Mean weekly visits increased 23.6% during the period between April 26, 2020 and October 3, 2020 compared with the period between August 4, 2019 to April 25, 2020. Visits declined to prepandemic levels between October 4, 2020 and March 13, 2021, after which visits began to rise. Naloxone and buprenorphine were prescribed within 30 days at 7.4% and 8.5% of the 148,966 visits, respectively. The naloxone prescribing rate (7.4%) was substantially lower than the epinephrine prescribing rate (48.9%) after ED visits for anaphylaxis. CONCLUSION: Between August 4, 2019, and April 3, 2021, naloxone and buprenorphine were only prescribed after 1 in 13 and 1 in 12 ED visits for opioid overdose, respectively. Findings suggest that clinicians are missing critical opportunities to prevent opioid overdose-related mortality.

Comprehensive analysis of discharge reasons from methadone outpatient treatment programs.

BACKGROUND AND OBJECTIVES: Methadone treatment (MT) for opioid use disorder is only available in opioid treatment programs (OTPs) in the United States, with retention predictive of positive health outcomes. OTP discharge reason information is needed to develop interventions for facilitating MT retention. We sought to identify discharge reason frequencies and associations between discharge reasons and facility/county-level characteristics. METHODS: We examined annual OTP discharge reasons for all Florida OTPs from 2014 to 2017 (n = 44,774 discharges). We used multinomial logistic regression analysis to examine associations between patients' discharge reasons and (1) facility-level characteristics (e.g., size, funding type) and (2) county-level characteristics (e.g., race/ethnicity, overdose rates). RESULTS: Lost contact was the most common discharge reason (29%). Only 11% of patients were discharged for treatment completion, with the proportion one-third as low in privately versus publicly-funded OTPs (p < .001). Privately-funded OTPs had a patient share self-terminating treatment against medical advice about 3.5 times higher than publicly-funded OTPs. Inability to pay accounted for 7% of OTP discharges. Noncompliant discharges represented 6% and were more common in counties with larger proportions of Black residents (p < .01). Counties with higher drug overdose rates had significantly more discharges for noncompliance or self-terminating against medical advice (p < .01 and p < .05). DISCUSSION AND CONCLUSIONS: Statewide differences in discharge reasons exist between publicly and privately-funded OTPs, possibly reflecting differences in funding incentives and state oversight. State agencies should develop consistent approaches for collecting/reporting discharge reasons. SCIENTIFIC SIGNIFICANCE: Our study is the first to examine the relationship between OTP funding type and discharge reasons.

Interrater reproducibility of the 2016 American society of echocardiography left ventricular diastolic function guidelines.

BACKGROUND: Little data exist regarding interreader variability of diastolic measurements and their application by the 2016 American Society of Echocardiography left ventricular (LV) diastolic function guidelines. METHODS: Volunteers (n = 49) were recruited from an outpatient cardiology practice. The presence and grade of diastology dysfunction (DD) was determined by the 2016 LV diastology guideline algorithm. We determined the mean, standard deviation, coefficient of variation, and intraclass correlation coefficient (ICC) for each measurement and Fleiss K-statistic to define differences in grading DD. We determined predictors associated with disagreement of DD grade using odds ratios. RESULTS: The mean LVEF was 56%, LAVI 32 ml/m2 , and peak TR velocity was 2.3 m/s. The ICC for mitral inflow and tissue Doppler velocities were >.90, for LV volumes were .80-.86, and for LA volume was .56. The Fleiss K-value for the agreement of the presence of DD was .68 and for DD grade was .59. Variables with increased odds of disagreement were (1) at least one reader considering a TR signal uninterpretable (OR 12.0; 95% CI 1.3-109.6), (2) at least one reader assessing both LVEF 50%-55% and LAVI 29-39 ml/m2 (OR 9.3; 95% CI 1.0-87), and (3) at least one reader assessing LVEF 50-55% (OR 3.8; 95% CI 1.1-13.4). CONCLUSIONS: Using the 2016 ASE/EACVI diastology guidelines, we found excellent interrater reliability of Doppler measurements, moderate-good interrater reliability of volumetric measurements, and moderate-good but not excellent agreement for diastology grade.

Impacts of state COVID-19 reopening policy on human mobility and mixing behavior.

This study quantifies the effect of the 2020 state COVID economic activity reopening policies on daily mobility and mixing behavior, adding to the economic literature on individual responses to public health policy that addresses public contagion risks. We harness cellular device signal data and the timing of reopening plans to provide an assessment of the extent to which human mobility and physical proximity in the United States respond to the reversal of state closure policies. We observe substantial increases in mixing activities, 13.56% at 4 days and 48.65% at 4 weeks, following reopening events. Echoing a theme from the literature on the 2020 closures, mobility outside the home increased on average prior to these state actions. Furthermore, the largest increases in mobility occurred in states that were early adopters of closure measures and hard-hit by the pandemic, suggesting that psychological fatigue is an important barrier to implementation of closure policies extending for prolonged periods of time.

Trends in Buprenorphine Initiation and Retention in the United States, 2016-2022.

This study uses data from an all-payer database of prescriptions dispensed in US retail pharmacies to assess trends in buprenorphine initiation and retention during 2016-2022.

Association Between State Opioid Prescribing Limits and Duration of Opioid Prescriptions From Dentists.

Importance: In part to prevent the harms associated with dental opioid prescriptions, most states have enacted policies limiting the duration of opioid prescriptions for acute pain. Whether these limits are associated with changes in the duration of opioid prescriptions written by dentists is unclear. Objective: To evaluate the association between state opioid prescribing limits and the duration of opioid prescriptions from dentists. Design, Setting, and Participants: This difference-in-differences cross-sectional study used data from the IQVIA Longitudinal Prescription Database, an all-payer database reporting prescription dispensing from 92% of retail pharmacies in the US. The sample included opioid prescriptions from dentists dispensed to children aged 0 to 17 years and adults 18 years or older from January 2014 through February 2020. Treatment states were those that implemented limits between January 2016 and December 2018. Control states were those that did not implement limits during the study period. Data on opioid prescribing limits were derived from the Prescription Drug Abuse Policy System. Data were analyzed from January 1 to September 30, 2022. Exposures: State opioid prescribing limits. Main Outcomes and Measures: The outcome was opioid prescription duration, as measured by days' supply. The association between limits and duration was evaluated using a linear model with a 2-way fixed-effects specification. Covariates included patient characteristics, prescription characteristics, and indicators of implementation of prescription drug monitoring program use mandates. Separate analyses of data from adults and children were conducted owing to differences in the number of treatment states and restrictiveness of limits by age. Results: The adult analysis included 56 607 314 opioid prescriptions for 34 364 775 patients (18 448 788 females [53.7%]; mean [SD] age at the earliest fill, 44.0 [17.4] years) in 22 treatment states and 12 control states. The child analysis included 3 720 837 opioid prescriptions for 3 165 880 patients (1 740 449 females [55.0%]; mean [SD] age at the earliest fill, 14.4 [3.5] years) in 23 treatment states and 12 control states. In both analyses, the median (25th-75th percentile) duration of opioid prescriptions was 3.0 (2-5) days. Implementation of limits, most of which allowed up to a 7-day supply of opioids, was not associated with changes in the duration of opioid prescriptions for adults (mean days' supply: -0.06 days; 95% CI, -0.11 to <0.001 days) or children (mean days' supply: -0.07 days; 95% CI, -0.15 to 0.02 days). Conclusions and Relevance: In this study of national pharmacy dispensing data, opioid prescribing limits were not associated with changes in the duration of opioid prescriptions from dentists. Future research should investigate the potential role of alternative interventions in reducing opioid prescribing by dentists.

Changes in Surgical Opioid Prescribing and Patient-Reported Outcomes After Implementation of an Insurer Opioid Prescribing Limit.

Importance: Insurers are increasingly limiting the duration of opioid prescriptions for acute pain. Among patients undergoing surgery, it is unclear whether implementation of these limits is associated with changes in opioid prescribing and patient-reported outcomes, such as pain. Objective: To assess changes in surgical opioid prescribing and patient-reported outcomes after implementation of an opioid prescribing limit by a large commercial insurer in Michigan. Design, Setting, and Participants: This was a cross-sectional study with an interrupted time series analysis. Data analyses were conducted from October 1, 2022, to February 28, 2023. The primary data source was the Michigan Surgical Quality Collaborative, a statewide registry containing data on opioid prescribing and patient-reported outcomes from adults undergoing common general surgical procedures. This registry is linked to Michigan's prescription drug monitoring program database, allowing observation of opioid dispensing. The study included 6045 adults who were covered by the commercial insurer and underwent surgery from January 1, 2017, to October 31, 2019. Exposure: Policy limiting opioid prescriptions to a 5-day supply in February 2018. Main Outcomes and Measures: Among all patients, segmented regression models were used to assess for level or slope changes during February 2018 in 3 patient-reported outcomes: pain in the week after surgery (assessed on a scale of 1-4: 1 = none, 2 = minimal, 3 = moderate, and 4 = severe), satisfaction with surgical experience (scale of 0-10, with 10 being the highest satisfaction), and amount of regret regarding undergoing surgery (scale of 1-5, with 1 being the highest level of regret). Among patients with a discharge opioid prescription and a dispensed opioid prescription (prescription filled within 3 days of discharge), additional outcomes included total morphine milligram equivalents in these prescriptions, a standardized measure of opioid volume. Results: Among the 6045 patients included in the study, mean (SD) age was 48.7 (12.6) years and 3595 (59.5%) were female. Limit implementation was not associated with changes in patient-reported satisfaction or regret and was associated with only a slight level decrease in patient-reported pain score (-0.15 [95% CI, -0.26 to -0.03]). Among 4396 patients (72.7%) with a discharge and dispensed opioid prescription, limit implementation was associated with a -22.3 (95% CI, -32.8 to -11.9) and -26.1 (95% CI, -40.9 to -11.3) level decrease in monthly mean total morphine milligram equivalents of discharge and dispensed opioid prescriptions, respectively. These decreases corresponded approximately to 3 to 3.5 pills containing 5 mg of oxycodone. Conclusions: This cross-sectional analysis of data from adults undergoing general surgical procedures found that implementation of an insurer's limit was associated with modest reductions in opioid prescribing but not with worsened patient-reported outcomes. Whether these findings generalize to other procedures warrants further study.

Trends in Buprenorphine Coverage and Prior Authorization Requirements in US Commercial Formularies, 2017-2021.

This cross-sectional study assesses buprenorphine coverage and prior authorization requirements in US commercial formulary data from 2017 to 2021.

False positive pharmacologic myocardial perfusion SPECT study in the setting of a left bundle branch block.

We herein report a case of a false positive vasodilatory pharmacologic SPECT stress test in the setting of a left bundle branch block (LBBB). While this is more commonly seen with exercise stress testing, it can also occur with pharmacologic stress testing. In our SPECT exam, we illustrate the commonly mistaken septal/anteroseptal perfusion defects in those patients with a LBBB. PET stress testing may be more reliable for patients with LBBB.

The cumulative effects and clinical safety of repeat magnetic resonance imaging on an MRI-conditional pacemaker system at 1.5 tesla.

BACKGROUND: Studies have demonstrated magnetic resonance imaging (MRI) safety in the presence of MRI-conditional permanent pacemakers (PPM). However, since patients' care may require serial MRIs, it is necessary to evaluate device safety and performance after multiple scans. OBJECTIVES: We evaluated safety and performance of MRI-conditional PPMs after serial MRIs over various anatomic regions performed during a multicenter, prospective, single-arm study (ProMRI). METHODS: ProMRI was a multiphase observational study designed to evaluate PPM performance after MRI scans. Our study evaluated PPM function in a cohort of patients who underwent multiple 1.5-T MRI scans. Selected patients underwent separate head, chest, and lumbar spine MRIs. Pacing capture threshold (PCT), lead impedance (LI), sensing amplitude, and battery capacity were collected before and after scanning. Freedom from serious adverse device effects (SADE) through 1 month post MRI served as a primary endpoint. Changes in PPM function parameters, including threshold success rate and sensing attenuation, were analyzed for statistical significance and clinical relevance. RESULTS: In 81 patients no adverse events or SADE occurred. Statistically significant changes in ventricular PCT (0.034 ± 0.15 V) immediately after, ventricular LI immediately after (-18.7 ± 44.2 Ω) and 1 month post phase B (-19.8 ± 44.9 Ω), and atrial sensing attenuation immediately after (-0.27 ± 0.92 mV) and 1 month post phase B (-0.22 ± 0.92 mV) were noted. However, these changes were not clinically relevant in degree. CONCLUSION: These results demonstrate the safety and performance of the ProMRI PPM in patients undergoing 3 serial MRIs over various anatomic regions.

Precision Intravenous Immunoglobulin Dosing and Clinical Outcomes: A Retrospective Chart Review.

OBJECTIVES: Intravenous immunoglobulin (IVIg) is used for treatment of acute neurologic conditions such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy relapse, and myasthenia gravis exacerbation. Precision dosing (adjusted or ideal body weight) is proposed to conserve IVIg. There have been no published studies comparing clinical outcomes in traditional dosing (actual body weight) with precision dosing. In 2014, our institution began dosing patients with precision dosing. This decision was largely performed by administration rather than physicians' preference. We sought to analyze our retrospective data to understand the change in dosing methods with neurologic outcomes. METHODS: We performed a retrospective review of all patients hospitalized at a single center who received IVIg for myasthenia gravis, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyradiculoneuropathy from January 2010 to October 2017. We collected baseline information and clinical outcomes including mortality, readmission, need for second rescue treatment, length of stay, discharge disposition, treatment-related adverse events, and modified research council posttreatment sum score. RESULTS: Length of stay was significantly shorter with precision dosing. There was no statistically significant difference in discharge disposition, readmission, rescue treatment, or modified research council posttreatment sum score with precision dosing. CONCLUSION: Precision dosing did not adversely affect short-term neurologic outcomes.

Pharmaceutical payments to physicians may increase prescribing for opioids.

BACKGROUND AND AIMS: Given the recent complete suspension of opioid-related promotional activities aimed at physicians, interest has renewed in understanding the role of promotion in the US opioid crisis. The present analysis aimed to measure associations between such interactions and opioid prescribing. DESIGN: Data on all promotions by pharmaceutical companies directly to physicians were linked to physician-level data on opioid prescriptions filled in a federal insurance program and analyzed using multivariate regression. SETTING: United States. PARTICIPANTS: A total of 865 347 US physicians, with prescriptions filled in Medicare Part D, that might receive payments from pharmaceutical promotional activities from 2014 to 2016. MEASUREMENTS: The outcome variable was days' supply dispensed by each prescriber, by year, for all opioids (collectively) and separately for the following opioid classes: hydrocodone, oxycodone, fentanyl, tapentadol, morphine and a catch-all 'other opioids'. The independent variables were receipt of any payments and dollar amounts of payments received by each prescriber by year for all opioids and separately for opioid categories. FINDINGS: Prescribers who received opioid-specific payments prescribed 8784 opioid daily doses per year more than their peers who did not receive any such payments (P < 0.001). Recipient of hydrocodone-related payments was associated with 5161 additional daily doses of hydrocodone (P < 0.001). Recipient of oxycodone-related payments was associated with 3624 additional daily doses of oxycodone (P < 0.001). Prescribers receiving any fentanyl-specific payments prescribed 1124 daily doses per year more than their peers (P < 0.001). Among recipients of opioid-specific payments (63 062 physicians), a 1% increase in amount of payments was associated with 50 daily doses of opioid prescription (P < 0.001). CONCLUSIONS: In the United States, physicians who receive direct payments from providers for opioid prescribing tend to prescribe substantially larger quantities, particularly for hydrocodone and oxycodone.

Opioid Prescribing by US Surgeons, 2016-2022.

This cross-sectional study investigates the rate and dosing of opioid prescriptions among US surgeons from 2016 to 2022.

In vitro and in silico Evaluation of Non-Quaternary Reactivators of AChE as Antidotes of Organophosphorus Poisoning - a New Hope or a Blind Alley?

BACKGROUND: In the last decade, the concept of uncharged reactivators potentially able to penetrate the CNS has been introduced as an alternative to the classic charged oxime reactivators. However, this concept brings with it several associated drawbacks such as higher lipophilicity, difficulty in administration, lower affinity to cholinesterases, and higher toxicity risk. OBJECTIVE: In this study, we compare data obtained for a set of five classic charged reactivators and a set of three recently published uncharged oximes supplemented by two novel ones. METHODS: This time, we used only in silico prediction and in vitro approaches. RESULTS: Our data showed that tested uncharged oximes have low affinity for cholinesterases, do not possess high reactivation potency, and certainly represent a greater toxicity risk due to higher lipophilicity. We assume that balanced physicochemical properties will be required for the successful treatment of OP poisoning. Nevertheless, the compound meeting such criteria and pinpointed in silico (K1280) failed in this particular case. CONCLUSION: From the presented data, it seems that the concept of uncharged reactivators will have to be modified, at least to improve the bioavailability and to satisfy requirements for in vivo administration.