Total Prescriptions Research Articles

Opioid prescribing among aged care residents during the first year of the COVID-19 pandemic: an analysis using general practice health records in Australia

BackgroundOpioid use is common among adults 65 years and older, while long-term use of opioids remains controversial and poses risks of drug dependence and other adverse events. The acute disease caused by the SARS-CoV-2 (COVID-19) pandemic has created new challenges and barriers to healthcare access, particularly for long-term care residents. Australia had a relatively low incidence and deaths due to COVID-19 during the first year of the pandemic compared to most OECD countries. In this context, we examined opioid prescribing rates and their dosage in residential aged care facilities (RACFs) before (2019) and during the COVID-19 pandemic (2020) from March to December in Australia.MethodsWe conducted a retrospective cohort analysis using general practice electronic health records. This includes 17,304 RACF residents aged 65 years and over from 361 general practices in New South Wales and Victoria. Number of opioid prescriptions and percentage of opioids over 50 mg/day of oral morphine equivalent (OME) were described. Multivariate generalized estimating equations were applied to estimate odds ratios [aORs (95% confidence intervals)] for 1) opioids prescribed per consultation and 2) prescription opioids over 50 mg/day OME.ResultsIn 2020 among 11,154 residents, 22.8% of 90,897 total prescriptions were opioids, and of the opioids, 11.3% were over 50 mg/day OME. In 2019 among 10,506 residents, 18.8% of 71,829 total prescriptions were opioids, of which 10.3% were over 50 mg/day OME. Year [2020 vs. 2019: aOR (95% CI):1.50 (1.44, 1.56); 1.29 (1.15, 1.46)] and regionality [rural/regional vs. metropolitan: 1.37 (1.26, 1.49); 1.40 (1.14, 1.71)] were associated with higher odds of prescription opioids and OME > 50 mg/day, respectively. Similar results were found when limited to the same residents (n = 7,340) recorded in both years.ConclusionsHigher prescription rates of opioids were observed during the COVID-19 pandemic in 2020 than in 2019 in Australian RACFs. The higher odds of prescription opioids and higher dosing in rural/regional than metropolitan areas indicate a widening of the gap in the quality of pain management during the pandemic. Our findings contribute to the limited data that indicate increased opioid prescriptions in long-term care facilities, which is likely to continue while COVID-19 pandemic restrictions remain.

The use of Chinese herbal medicines throughout the pregnancy life course and their safety profiles: a population-based cohort study

Chinese herbal medicines (CHM) have been long used among pregnant populations in China. However, despite the high susceptibility of this population to drug exposure, it continued to remain unclear about how often they were used, to what extent they were used at different pregnancy stages, and whether their use was based on sound safety profiles particularly when used in combination with pharmaceutical drugs. The aim of this descriptive cohort study was to systematically investigate the use of CHM throughout the pregnancy and their safety profiles. We developed a large medication use cohort by linking a population-based pregnancy registry and a population-based pharmacy database, which documented all prescriptions both at outpatients and inpatients from conception to 7 days after delivery, including pharmaceutical drugs and processed CHM formula that were approved by regulatory authority and prepared under the guidance of national quality standards. We investigated the prevalence of CHM formula use, prescription pattern and combination use of pharmaceutical drugs throughout the pregnancy life course. Multivariable log-binomial regression was conducted to assess temporal trend, and further explore the potential characteristics associated with the CHM use. Two authors independently conducted a qualitative systematic review of patientpackageinserts (PPI) of top 100 CHM formula use to identify their safety profiles. Our study included 199,710 pregnancies; of those, 65.71% (131,235/199,710) were administered with CHM formula, including 26.13% during pregnancy (corresponding to 14.00%, 8.91% and 8.26% in the first, second, and third trimesters), and 55.63% at post-delivery. The peak uses of CHM occurred between the 5th and 10th weeks. The use of CHM significantly increased over the years (63.28% in 2014 to 69.59% in 2018, adjusted relative risk [aRR]: 1.11, 95% CI: 1.10-1.13), which was particularly great during pregnancy (18.47% to 32.46%, 1.84, 95% CI: 1.77-1.90). Our study observed 291,836 prescriptions involving 469 CHM formula, and the 100 mostly used CHM accounted for 98.28% of the total prescriptions. Of those, a third (33.39%) were dispensed at outpatient visits; 6.79% were external use and 0.29% were injections. However, CHM were very often prescribed in combination with pharmaceutical drugs (overall 94.96%), involving 1,175 pharmaceutical drugs with 1,667,459 prescriptions. A median of 10 (IQR: 5-18) pharmaceutical drugs was prescribed in combination with CHM per pregnancy. The systematic review of drug patient package inserts found that the 100 most frequently prescribed CHM contained a total of 240 herb constituents (median 4.5); 7% were explicitly indicated for pregnancy or postpartum conditions; 43.00% were reported with efficacy or safety data from randomized controlled trials. Information was lacking about whether the medication has any reproductive toxicity, is excreted in human milk or may cross the placenta. The use of CHM was prevalent throughout the pregnancy and increased over years. The CHM use peaked at the first trimester and was very often used in combination with pharmaceutical drugs. However, their safety profiles were mostly unclear or incomplete, warranting a strong need for post-approval surveillance for CHM use during pregnancy life course.

Observational Analysis of the Costs Associated with Acute Treatment of Breakthrough Migraine Attacks in Medicaid Patients Using Preventive Therapies.

Medications for preventive treatment of migraine reduce migraine frequency, usually measured by a reduction in monthly migraine days (MMD), but generally do not eliminate the need for acute treatment. To assess the economic impact of treatment-related reductions in frequency, methodological guidance recommends capturing cost differences along the spectrum of MMD. Characterize monthly migraine medication costs along the spectrum of MMD for patients using calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) for prevention. Medicaid State Drug Utilization Data (SDUD) were used to identify formulations and per-unit costs for oral, intranasal, and parenteral migraine-specific medications for acute and preventive treatment used by fee-for-service (FFS) Medicaid enrollees in 2020. National drug codes of relevant therapies were used to match SDUD to formulation characteristics including substance, route of administration, and branded/generic marketing status. Mean per-unit cost and the formulation's share of total prescriptions were estimated. Monthly medication costs were modeled based on formulations' per-unit costs and frequency of acute medication use during clinical trials of CGRP mAbs. In the SDUD, there were 563,338 prescriptions for migraine-specific acute medications; triptans accounted for 97.37%. Triptan formulations prescribed were 83.78% oral tablet, 10.89% orally disintegrating tablet, 2.60% intranasal, and 2.73% parenteral. Dihydroergotamine accounted for < 1% of total prescriptions and had the highest per-unit cost ($443.50, branded intranasal). There were 97,119 prescriptions for CGRP mAbs, the majority for erenumab (45.73%) or galcanezumab (45.24%). Modeled monthly acute and preventive medication costs ranged from approximately $550 in patients with the fewest MMD treated with oral triptans to > $1500 in patients with the most MMD treated with dihydroergotamine. In consideration of the migraine-specific acute medications used in FFS Medicaid 2020, for patients using CGRP mAbs for prevention, medication costs may vary significantly with the number of breakthrough attacks treated per month and the type of migraine-specific acute therapy used.

Use of prophylactic perioperative antibiotics for lumbar spinal fusions: A nationwide population-based cohort study

BackgroundPerioperative prophylactic antibiotic (PPA) use in spine surgery is known to reduce the rate of surgical site infections. In the past decade, several evidence-based guidelines have been published and surveillance systems to monitor the proper use of antimicrobials had been adapted by many institutes. ObjectiveTo report the trends of PPA prescription in lumbar fusion surgeries nationwide in the Republic of Korea. MethodsThis is a nationwide registry study. Using the population-based data from the Republic of Korea provided by the Korean Health Insurance Review and Assessment Service, data of all lumbar spinal fusion surgeries performed between 2010 and 2018 in adult patients (age ≥19 years) were reviewed. ResultsThe most frequently used antibiotics were first-generation cephalosporins, which accounted for 38.2 % of total PPA prescriptions and were prescribed in 58.96 % of lumbar fusion surgeries. A gradual increase in prescription trends was observed. The second most frequently used PPAs were second-generation cephalosporins, which showed decrease in use from 2016. The frequency of vancomycin prescriptions gradually increased over the observation period and showed an almost four-fold increase in 2018 compared to 2010. First- and second-generation cephalosporins were prescribed less frequently to patients with renal disease. ConclusionThe pattern of PPA use has changed remarkably over the observation period. Furthermore, specific differences in PPA prescriptions were observed among patients with certain co-morbidities.

Point prevalence survey on antibiotic use in the hospitals of Mauritius

BackgroundThis study aims at determining the antibiotic prescribing pattern in admitted patients in the regional public hospitals of Mauritius.MethodsA Point Prevalence Survey (PPS) on antibiotic use according to the World Health Organization Methodology for PPS on antibiotic use in hospitals, was carried out in 3 secondary public hospitals. Data was collected in February 2018 for Hospital 1 and in April-May 2019 for Hospital 2 and Hospital 3. Eligible inpatients were those who were hospitalized in the ward at 8.00 a.m. on the day of the survey.ResultsAmong 915 inpatients, 482 (53%) were treated with 753 therapies or prescriptions of antibiotics, averaging 1.6 therapies or prescriptions per patient. Among those treated with antibiotics, an average of 88 patients (55%), 58 patients (36%) and 15 patients (9%) were given 1, 2 and 3 or more antibiotics respectively. The highest proportion of inpatients treated with antibiotics was among those with community acquired infections (n=243, 50%) followed by surgical prophylaxis (n=191, 40%). In the three hospitals, it was observed that third generation cephalosporins (ceftriaxone, cefotaxime), amoxicillin, metronidazole (parenteral) and ciprofloxacin accounted for more than 75% of total prescriptions and sixteen per cent (16%) of patients had an Antibiotic Susceptibility Testing report before prescription of antibiotics.ConclusionThis study provides valuable information on antibiotic use in the country. Several misuses have been identified such as the excessive use of antibiotics for surgical prophylaxis, the high use of third generation cephalosporins and of the WATCH category of antibiotics. It also demonstrates a low percentage of Antibiotic Susceptibility Testing prior to prescription of antibiotics. This investigation shows that there is now a pressing need to repeat the Point Prevalence Survey on antibiotic use in hospitals in future whilst extending the survey to the private healthcare system to get a complete picture concerning antibiotic use in Mauritius.

Association of a State Prescribing Limits Policy with Opioid Prescribing and Long-term Use: an Interrupted Time Series Analysis.

Prescription opioids were a major initial driver of the opioid crisis. States have attempted to reduce overprescribing by enacting policies that limit opioid prescriptions, but the impacts of such policies on new prescribing and subsequent transitions to long-term use are not fully understood. To examine the association of implementation of a state prescribing limits policy with opioid prescribing and transitions to long-term opioid use. Interrupted time series analyses assessing trends in new opioid prescriptions and long-term use before and after policy implementation. A total of 130,591 New Jersey Medicaid enrollees ages 18-64 who received an initial opioid prescription from January 2014 to December 2019. New Jersey's opioid prescribing limit policy implemented in March 2017. Total new opioid prescriptions, percentage of new prescriptions with >5 days' supply, and transition to long-term opioid use, defined as having opioid supply on day 90 after the initial prescription. Policy implementation was associated with a significant monthly increase in new opioid prescriptions of 0.86 per 10,000 enrollees, halving the pre-policy decline in the prescribing rate. Among new opioid prescriptions, the percentage with >5 days' supply decreased by about 1 percentage point (-0.76 percentage points, 95% CI -0.89, -0.62) following policy implementation. However, policy implementation was associated with a significant monthly increase in the rate of initial prescriptions with supply on day 90 (9.95 per 10,000 new prescriptions, 95% CI 4.80, 15.11) that reversed the downward pre-implementation trend. The New Jersey policy was associated with a reduction in initial prescriptions with >5 days' supply, but not with an overall decline in new opioid prescriptions or in the rate at which initial prescriptions led to long-term use. Given their only modest benefits, policymakers and clinicians should carefully weigh potential unintended consequences of strict prescribing limits.

Evidence-Based Opioid Prescribing Guidelines and New Persistent Opioid Use After Surgery.

Evaluate the association of evidence-based opioid prescribing guidelines with new persistent opioid use after surgery. Patients exposed to opioids after surgery are at risk of new persistent opioid use, which is associated with opioid use disorder and overdose. It is unknown whether evidence-based opioid prescribing guidelines mitigate this risk. Using Medicare claims, we performed a difference-in-differences study of opioid-naive patients who underwent 1 of 6 common surgical procedures for which evidence-based postoperative opioid prescribing guidelines were released and disseminated through a statewide quality collaborative in Michigan in October 2017. The primary outcome was the incidence of new persistent opioid use, and the secondary outcome was total postoperative opioid prescription quantity in oral morphine equivalents (OME). We identified 24,908 patients who underwent surgery in Michigan and 118,665 patients who underwent surgery outside of Michigan. Following the release of prescribing guidelines in Michigan, the adjusted incidence of new persistent opioid use decreased from 3.29% (95% CI 3.15-3.43%) to 2.51% (95% CI 2.35-2.67%) in Michigan, which was an additional 0.53 (95% CI 0.36-0.69) percentage point decrease compared with patients outside of Michigan. Simultaneously, adjusted opioid prescription quantity decreased from 199.5 (95% CI 198.3-200.6) mg OME to 88.6 (95% CI 78.7-98.5) mg OME in Michigan, which was an additional 55.7 (95% CI 46.5-65.4) mg OME decrease compared with patients outside of Michigan. Evidence-based opioid prescribing guidelines were associated with a significant reduction in the incidence of new persistent opioid use and the quantity of opioids prescribed after surgery.

Prescription Analysis and Evaluation of Potential Drug–Drug Interactions among Patients Attending the Geriatric Unit at a Tertiary Care Hospital

Abstract Background: The elderly stand a greater risk of drug-drug interactions (DDIs). This study was an earnest attempt at in-depth prescriptions analysis and evaluating the potential DDIs (pDDIs) among patients in the geriatric outpatient department (OPD). Aims and Objectives: The aim is to conduct prescriptions analysis of patients and to evaluate the pDDIs among patients in the geriatric OPD. Materials and Methods: A retrospective observational study began after Institutional Review Board approval. Demographic details, clinical profile, and drugs prescribed were recorded. The prescription analysis was done by prespecified criteria and pDDIs were identified using various tools. Results: Prescriptions of 202 patients with a mean age of 68.76 years were collected. Mean drugs prescribed were 6.07. Total number of fixed-dose combinations (FDCs) and over-the-counter drugs were 669 (40.50%) and 430 (26.03%), respectively. 129 (63.9%) prescriptions were incomplete in terms of dose, duration, frequency, or dosage form. Maximum interactions - 367 (34.42%) were found with aspirin followed by cardiovascular drugs. Total prescriptions with pDDIs were 137 (67.82%) Out of 34 (3.82%) serious interactions, pharmacodynamic pDDIs were seen with aspirin and enalapril/ramipril and pharmacokinetic were between omeprazole/rabeprazole and clopidogrel. Consequences of common pDDIs were identified as deterioration in renal function and hyperkalemia. The number of interactions was positively correlated with number of FDCs and number of drugs prescribed (r = 0.427, P = 0.0001 and r = 0.189, P = 0.0001, respectively). Conclusion: Prespecified prescription analysis criteria were one of the most useful tools to improve prescribing patterns. Drug interactions can be reduced by prescribing minimum drugs in elderly, alteration in time of dosing and fractionation of dose along with amalgamating the use of online DDI checker in hospital information system. Training of prescribers especially in geriatric patients is the need of the hour.

WHO-Point Prevalence Survey of Antibiotic Use Among Inpatients at a Core National Antimicrobial Consumption Network Site in North India: Findings and Implications.

Data on Point Prevalence Surveys (PPSs) in India are limited yet. We report findings of a PPS conducted in a core "National Antimicrobial Consumption Network site" under National Centre for Disease Control - WHO project "Point prevalence survey of antimicrobial consumption at healthcare facilities." A cross-sectional survey was conducted as per the "WHO methodology for PPS on antibiotic use in hospitals" in a tertiary care hospital in India in December 2021. Data were collected using predesigned and pretested questionnaire in separate hospital, ward, and patient forms. Eight hundred two inpatients (excluding ICUs) were covered out of whom 299 (37.3%) were on antibiotics with 11.7% receiving 3 or more antibiotics. Surgical prophylaxis (SP) (42.5%) and community acquired infections (32.8%) were the most common indications for antibiotic use. Of the patients, 92.5% received SP for more than 24 hrs. Most commonly prescribed antibiotics were penicillins with beta-lactamase inhibitors (22.3%). Of the total antibiotic prescriptions, 81.5% were from WHO essential medicines list and 12% from "not recommended" WHO AWaRe classification. Of the antibiotic prescriptions, 84.6% were parenteral. Few prescriptions complied with standard treatment guidelines (1.9%), documented indication for antibiotic use (11.6%), and stop/review date (4.4%) in notes. Double anaerobic cover accounted for 6.8% of the total prescriptions. Some identified areas for improvement were: formulation of hospital antibiotic guidelines, promoting culture of sending cultures, improvement in surgical antibiotic prophylaxis, decreasing use of antibiotic combinations and double anaerobic cover, fostering IV to oral switch of antibiotics, and ensuring effective communication among health care workers by documenting adequate information in medical notes.

Antibiotic treatment of respiratory tract infections in adults in Norwegian general practice.

To analyse the prevalence of respiratory tract infection (RTI) episodes with and without antibiotic prescriptions in adult patients in Norwegian general practice during the period 2012-2019. Observational study linking data from the Norwegian Control and Payment for Health Reimbursements Database and the Norwegian Prescription Database. Episodes of acute RTIs in patients aged 18 years or older were identified and linked to antibiotic prescriptions dispensed within 7 days after diagnosis. We analysed annual infection rates and antibiotic prescription rates and antibiotics prescribed for the different RTI conditions. RTI episode rate per 1000 inhabitants was 312 in 2012 and 277 in 2019, but showed no linear trend of change during the study period (P = 0.205). Antibiotic prescription rate decreased from 37% of RTI episodes in 2012 to 23% in 2019 (P < 0.001). The reduction in prescribing was most pronounced for episodes coded with ICPC-2 symptom diagnoses, as well as upper RTIs, influenza, acute bronchitis and sinusitis. Prescriptions for phenoxymethylpenicillin decreased from 178 746 in 2012 to 143 095 in 2019, but increased as proportion of total antibiotic prescriptions from 40% in 2012 to 53% in 2019 (P < 0.001). This study demonstrates stable RTI episode rates and reduced antibiotic prescription rates for RTIs for adults in Norwegian general practice 2012-2019. We also observed a shift towards relatively more use of phenoxymethylpenicillin and less broad-spectrum antibiotics. These changes are in line with the aims of the Norwegian strategy against antibiotic resistance.

Prescription of Choreito, a Japanese Kampo Medicine, with Antimicrobials for Treatment of Acute Cystitis: A Retrospective Cohort Study.

Choreito, a Japanese Kampo medicine, is used to treat Japanese female patients for the quick relief of inflammatory symptoms associated with acute cystitis. We evaluated whether Choreito is effective in reducing antibiotic use and the number of clinic visits for these patients. Females aged 18-49 years who had acute cystitis for the first time, with no history of medical insurance use within 90 days prior to their visit, and no hospitalizations within the 30 days after their first visit were identified from the JMDC Claims Database between April 2018 and March 2021. For the 30 days after their first visit, patients who were given their first antimicrobial prescriptions with or without Choreito were compared regarding (i) the number of clinic visits, (ii) total antimicrobial prescription days, and (iii) the number of antimicrobial prescriptions adjusted for their age, Charlson comorbidity index, and the COVID-19 pandemic period (after April 2020). For the 319 and 8515 patients with or without a Choreito prescription, respectively, multivariable Poisson regression analyses showed that Choreito was significantly associated with a 5% shortening of a patient's total antimicrobial prescription days (Beta, 0.950; p = 0.038), whereas no significant difference was observed in the number of clinic visits and antimicrobial prescriptions (p = 0.624 and p = 0.732, respectively). The prescription of Choreito in combination with antimicrobials was associated with a slight reduction in total antimicrobial use for acute cystitis among females.

1788. COVID-19 and Antibiotic Prescriptions in the United States: A County-level Analysis

Abstract Background Declines in outpatient antibiotic prescribing were reported during the beginning of the COVID-19 pandemic in the United States; however, the overall impact of COVID-19 cases on antibiotic prescribing remains unclear. Methods We conducted an observational, ecological study to assess the impact of COVID-19 cases and pandemic-related, non-pharmaceutical interventions (NPIs) (e.g., school closures and facemasks) on antibiotic prescribing from February to December 2020 in the US. A random effects panel regression of county-level monthly reported COVID-19 case data and corresponding systemic antibiotic prescription data from IQVIA was used. The model controlled for county demographics, NPIs, and prior years’ prescribing. Results Total antibiotic prescriptions fell 26.1% between March and December 2020 compared to this period from 2017 to 2019. Prescribing rates dropped most among children (Figure 1). A 1% increase in county-level monthly COVID-19 cases was associated with a 0.9% increase (95% CI 0.7%, 1.1%; p&amp;lt; 0.01) in monthly prescriptions dispensed to adults and a 1.2% decrease (95% CI -1.7%, -0.8%; p&amp;lt; 0.01) in prescriptions dispensed to children (Table 1). Counties with schools open for in-person instruction were associated with a 4.4% increase (95% CI 2.3%, 6.4%; p&amp;lt; 0.01) in prescriptions among children compared to counties that closed schools. Internal movement restrictions and requiring facemasks were also associated with lower prescribing among children. Figure 1A) Total prescriptions per 100,000 population by month (2017-2020). B) Mean prescriptions per 100,000 population for seven age groups (2017-2019 vs 2020).Table 1 Conclusion Though the number of antibiotic prescriptions in 2020 was lower than previous years, the positive association of COVID-19 cases with prescribing for adults and the negative association for children indicates increases in prescribing occurred primarily among adults. The rarity of bacterial co-infection in COVID-19 patients suggests a large fraction of these prescriptions may have been inappropriate. Facemasks and school closures were correlated with reductions in prescribing among children, likely due to the prevention of other upper respiratory infections (e.g., the cold and influenza). Despite reductions, the strongest predictors of prescribing were prior years’ prescribing trends, suggesting the possibility that behavioral norms are an important driver of prescribing practices. Disclosures Sara E. Cosgrove, MD, Basilea: Member of Infection Adjudication Committee Ramanan Laxminarayan, PhD, HealthCubed: Board Member|HealthCubed: Ownership Interest.

Medication non-adherence and associated factors among older adult stroke survivors in China.

Aim: Medication non-adherence has remained a common and costly global health issue of growing importance among older adults. This study aims to determine the prevalence and associated factors related to medication non-adherence among older adult stroke survivors in China. Methods and results: In this cross-sectional study, a total of 402 older adult stroke survivors were recruited from three tertiary hospitals in China. The results of the survey showed that 61.4% exhibited medication non-adherence. The chances of medication non-adherence among older adult stroke survivors who had primary school or less educational levels were higher than those who had senior secondary and junior college educational levels [OR (95% CI) = 0.440(0.249, 0.778)] as well as those who had a bachelor's degree or above educational levels [OR (95%CI) = 0.367(0.202, 0.667)]. Moreover, the probability of medication non-adherence with 4-5 and ≥6 types of total prescription medications per day increased by 1.993 times [OR (95% CI) = 1.993(1.190, 3.339))] and 2.233 times [OR (95%CI) = 2.233(1.159, 4.300)], respectively, as compared to when there were ≤3 types. Furthermore, medication non-adherence decreased with the increase in health literacy scores (β = -0.641 (95% CI; (0.913, 0.965)) and BMQ specific-necessity scores (β = -0.131 (95% CI; 0.806, 0.995)). On the other hand, when the BMQ specific-concerns score increased by one unit, medication non-adherence increased by 11.1% [OR (95% CI) = 1.111(1.044, 1.182)]. Conclusion: The present study found that patient medication adherence among older adult stroke survivors in China is problematic and associated with educational levels, total prescribed drugs per day, beliefs about medication, and health literacy scores. This indicates that measures should be taken to enhance medication adherence among such higher-risk populations.

Intersection of atrial fibrillation and heart failure with mildly reduced and preserved ejection fraction in >400 000 participants in the Get With The Guidelines-Heart Failure Registry.

Although atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), few data are available evaluating AF-specific care patterns and post-discharge outcomes in patients hospitalized for HFpEF. We evaluated AF-specific medical therapies and post-discharge outcomes among patients hospitalized for heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF by AF history. Trends in AF prevalence were evaluated among patients hospitalized for HFmrEF or HFpEF in the Get With The Guidelines-Heart Failure Registry from 2014 to 2020. Among those with linked Centers for Medicare & Medicaid Services post-discharge data, we assessed associations of AF with 12-month outcomes and determined trends in post-discharge prescriptions. Among 429 464 patients (median age 76 years [interquartile range 65-85], 57% women), 216 486 (50%) had a history of AF. Over time, the proportion of patients with AF increased slightly. Among the 79 895 patients with post-discharge data, AF was independently associated with higher risk of mortality and all-cause readmissions at 12 months, with stronger associations in HFpEF than in HFmrEF (mortality hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.09-1.16 vs. HR 1.03, 95% CI 0.97-1.10; pinteraction =0.009). Anti-arrhythmic drug use after heart failure hospitalization was low (18%) and increased modestly over time. Amiodarone accounted for 71% of total anti-arrhythmic drug prescriptions. Overall use of anticoagulants after heart failure hospitalization has significantly increased from 52% in 2014 to 61% in 2019, but remained modest. Prevalence of AF is rising among patients hospitalized with HFpEF. Those with comorbid AF face elevated post-discharge risks of death and rehospitalization. Current use of pharmacological rhythm control is low.

Pronounced Declines in Meperidine in the US: Is the End Imminent?

Background: Once a widely used analgesic in the United States (US), meperidine offered an alternative opioid to other opioids as a pain reliever and was widely assumed to be safer with acute pancreatitis. However, within the last two decades meperidine, has gone from a frequently used drug to being used only when patients exhibit atypical reactions to opioids (e.g., morphine and hydromorphone), to being taken off the World Health Organization List of Essential Medications and receiving strong recommendations for overall avoidance. The aim of this study was to identify changes in meperidine distribution in the US, and regional disparities as reported to the Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (DEA ARCOS) and Medicaid. Methods: Data related to meperidine distribution was obtained through ARCOS (2001-2021) and Medicaid public use files (2016-2021). Heat maps were used to visualize regional disparities in distribution by state. States outside a 95% confidence interval were statistically significant. Results: Meperidine distribution between 2001 and 2021 decreased by 97.4% (R = -0.97, p &lt; 0.0001). There was a 34-fold state-level difference in meperidine distribution between Arkansas (16.8 mg/10 persons) and Connecticut (0.5 mg/10 persons) in 2020. Meperidine distribution in 2020 was elevated in Arkansas, Mississippi, and Alabama. In 2021, meperidine distribution was highest in Arkansas (16.7 mg/10 persons) and lowest in Connecticut (0.8 mg/10 persons). Total prescriptions of meperidine as reported by Medicaid decreased by 73.8% (R = -0.67, p = 0.045) between 2016 and 2021. Conclusion: We observed a decrease in the overall distribution of meperidine in the past two decades, with a similar recent decline in prescribing it to Medicaid enrollees. The shortage of some parenteral formulations is an important contributor to these declines, however, the most likely explanation for this global decline in use is related to an increased recognition of safety concerns related to important drug interactions and a neurotoxic metabolite. This data may reflect plans to phase out the use of this opioid, especially in the many situations where safer and more preferred opioids are available.

Prediction of High Acute Care Utilization in Children with Sickle Cell Disease

Background: A small percentage of patients with sickle cell disease (SCD) account for a high percentage of acute care utilization and painful vaso-occlusive episodes (VOEs) requiring hospitalization. Chronic pain may develop in patients with SCD who experience frequent VOEs. Little is known about the mechanisms mediating the development of chronic pain in SCD, and there are no reliable clinical predictors for the development of a chronic pain phenotype. We aimed to determine the factors associated with the development of chronic pain phenotype characterized by high acute care utilization, in children and adolescents with SCD. Methods: We performed a single-institution, retrospective case-control study of all patients aged 10-25 years old who received SCD care at our institution from 2016-2020. Patients were identified using ICD-10 codes for SCD. For patients meeting inclusion/exclusion criteria, we extracted demographic, laboratory, and opioid prescription data. ED visits and hospitalization encounters during which parenteral opioids were administered were identified in the electronic medical record. Distribution of acute care encounters among all included patients was used to establish cases who met criteria for high acute care utilization, defined as > 85th percentile for all patients. Laboratory data were collected from the index year, defined as the first year a case met criteria for high acute care utilization, or from the matched year within 1-2 year window, for controls, as well as from the year prior. Chi-square and student t test were used to compare categorical and continuous variables, respectively, between cases and controls using SAS (Cary, NC). ROC curves were created to determine the discriminatory ability of using opioid prescription data to identify patients meeting criteria for high acute care utilization. Results: A total of 200 patients with SCD (all genotypes) met inclusion/exclusion criteria for the study. The 85thpercentile cut point corresponded to ≥4 acute care encounters in one year. Using this definition, 36/200 (18%) patients who were considered "high acute care utilizers" and had ≥4 acute care visits during any 1-year period during 2016-2020 were chosen as cases. Matching 2:1 by genotype and calendar year, 72 "low-utilizers" were randomly selected as controls among the 127 patients who had ≤1 acute care visit during each year of inclusion. Age, sex, and hydroxyurea use did not differ among cases vs controls. We found a higher proportion of patients with Medicaid insurance (83% vs 62%, p=0.03), as well as asthma (33% vs 11%, p=0.008) and anxiety or depression (39% vs 2%, p<0.001), among cases vs controls. Steady-state laboratory variables did not differ significantly among cases vs controls. Total opioid prescriptions were significantly higher in both index year [7.7 (95% CI: 5.2-10.2) vs 1.3 (0.9-1.7), p<0.001] and in the year prior [4.6 (95% CI: 1.9-7.2) vs 1.0 (0.7-1.3), p=0.01] among cases vs controls. Total morphine equivalents during the index year utilizers [3540 (95% CI: 1010-6060) vs 554 (355-753), p=0.02] and in the year prior [1386 mg (95% CI: 597-2170) vs 448 mg (249-648), p=0.01] were significantly higher among high acute care utilizers. ROC curves for average total opioid prescriptions and total morphine equivalents prescribed in the year prior to meeting criteria for high acute care utilization demonstrated AUCs of 0.80 and 0.81, respectively. Using these ROC curves, a cutpoint of ≥2 opioid prescriptions in the prior year was associated with a maximal sensitivity of 75% and a specificity of 76%. A cutpoint of ≥400mg of total morphine equivalents in the year prior was associated with a maximal sensitivity of 81% and a maximal specificity of 71%. Conclusions: We found no relationship between laboratory variables and high acute care utilization in children and young adults with SCD. Demographic and clinical factors associated with high acute care utilization include Medicaid insurance status, asthma and mood disorders as well as number of opioid prescriptions in the year prior to meeting our criterion for high acute care utilization. Future studies should be conducted to prospectively identify predictors of high acute care utilization and the development of chronic pain in SCD. The role of opioids for the treatment of chronic pain in SCD and the relationship of opioid to the development of high acute care utilization and chronic pain should also be further studied.

PO13: Development of a Risk-Based Workflow to Identify Dosimetric Relevance of Implanted Cardiac Devices (ICDs) for Brachytherapy Patients

<h3>Objective</h3> To develop a risk-based workflow for assessing dosimetric relevance of ICDs (i.e pacemaker/defibrillators) in patients undergoing brachytherapy in our department. <h3>Materials and Methods</h3> In order to conservatively assess possible dose to ICD in clinical brachytherapy situations, worst-case scenarios were generated for brachytherapy procedures performed at our institution. Cases were organized by site and technique: Pelvic HDR [prostate HDR, gynecologic HDR, rectum HDR, pelvic intraoperative (IORT)], pelvic permanent implantations (prostate and other pelvic seed implantations with I-125 and Pd-103), upper abdomen/chestwall/H&N HDR (Esophagus HDR, upper body HDR IORT). Twenty patients were randomly selected among recently treated cases; prescription doses, treatment images (when available) and treatment plan dose distributions (TG43) were used to develop worst-case scenario geometries for each application. Patients did not have ICDs, and theoretical ICD locations were estimated assuming closest reasonable placement to the treatment site. We evaluated the data to set a policy to identify, in advance of treatment, situations in which ICD dose could exceed threshold of 2Gy, and we developed a risk-based workflow. <h3>Results</h3> For pelvis HDR cases, maximal total dose prescription was 28Gy and distance from treatment site to 2Gy threshold was 7cm. For pelvic permanent implantations, maximal total dose prescription was 144Gy using I-125, and distance from treatment site to 2Gy threshold was 5cm. Closest location of ICD to treatment site was estimated to be >>7cm in all pelvic cases, therefore ICD dose for pelvic cases was considered negligible. For upper abdomen/chest wall/H&N HDR cases, maximal total dose prescription was 15Gy and distance from treatment site to 2Gy threshold was 5cm. Worst-case scenario geometries for Esophagus HDR treatments, where applicator location was simulated to be close to the chest wall, predicts a distance to the ICD >5cm, with doses to ICD of 0.5-1Gy. For upper body IORT cases, due to clinical variability, applicator placement can be <5cm from the ICD, thus requiring physical measurements to confirm safety of treatment. Therefore, we proposed a risk-based workflow, taking into account (i) negligible radiation ICD risk for all pelvic cases, (ii) geometric/dosimetric assessment at time of planning for esophagus HDR cases and (iii) intra-operative assessment for IORT cases at or above upper abdomen. For cases (ii) and (iii) the physicist 2^nd checking the plan would review the electronic medical record prior to treatment to identify presence of ICD. For image-guided cases, the ICD should be contoured to evaluate distance from implant site, and dose calculated. For IORT cases, an intraoperative distance measurement from ICD to treatment area would be performed. If distance is ≤5cm, possibility of 2Gy to ICD must be acknowledged. The dose estimate should be recorded in specified form and signed by MD. Sterile lead shielding may be used, if feasible, internally to limit ICD dose. This risk-based workflow is represented in the figure. <h3>Conclusion</h3> We developed a risk-based workflow to evaluate ICD dose for brachytherapy patients. Development of this workflow could help identify patients at clinically relevant risk to ICD perturbation and conversely, reduce unnecessary interventions for negligible risk scenarios. This policy will need to be re-evaluated if new treatment modalities or fractionations are introduced. Dose rate effects were not considered (<<8Gy/min in all situations). Differences between TG43 and physical doses were not systematically explored.

The Utilization, Expenditure, and Price of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in the US Medicaid Programs: Trends Over a 31 Year Period

BackgroundAngiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used for several indications including hypertension. Our aim is to evaluate the utilization, expenditure, and drug price of ACEIs and ARBs in the US Medicaid population. MethodsA retrospective descriptive trend analysis was conducted using Medicaid State Drug Utilization outpatient pharmacy summary files managed by the Centers for Medicare and Medicaid Services from 1991 to 2021. Study drugs included ACEIs (e.g., captopril) and ARBs (e.g., losartan). Annual reimbursement and utilization were calculated for both classes. The average reimbursement per prescription was calculated as a proxy for drug prices. Market share competition between ACEIs and ARBs was analyzed over time. ResultsACEI and ARB utilization rose by 25% from 1991 to 2021. Brand ACEIs utilization peaked in 2002 with 28 million prescriptions while brand ARBs utilization continued to increase until 2005 with over 23 million prescriptions. However, generic products took the lead and exceeded brand ACEI and ARB utilization in 2006 and 2012 respectively. Medicaid spent over $ 33.7 billion on ACEIs and ARBs over 31-year. Brand ACEIs and ARBs average prices increased sharply to $8,104 and $6,908 respectively in 2021. The total prescription market share for ACEIs was 68% compared to 32% of ARBs over the entire study. ConclusionACEIs and ARBs utilization increased over the last 31 years. Brand utilization switched over to generic resulting in less reimbursement. The average prices of brand ACEIs and ARBs continue to increase even after generics were introduced to the market.

Frameless Cobalt60-Based Hypofractionated Stereotactic Radiosurgery (HSRS) for Brain Metastases: Impact of Dose and Volume

<h3>Purpose/Objective(s)</h3> Frameless, gated, image-guided, Cobalt⁶⁰-based hypofractionated stereotactic radiosurgery (Co⁶⁰-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the Co⁶⁰ based stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control (LC) and adverse radiation effects (ARE) outcomes following 5 fraction Co⁶⁰-HSRS for intact brain metastases. <h3>Materials/Methods</h3> All patients with intact brain metastases treated with 5-fraction Co⁶⁰-HSRS between 2017-2020 were retrospectively reviewed. Patients were typically selected for HSRS as opposed to single fraction SRS if the metastases were larger (>2cm diameter), were in eloquent areas, or were in proximity to another lesion receiving HSRS. Survival estimates were determined per patient using Kaplan Meier methods, and LC as well as symptomatic ARE rates were determined per lesion using competing risk methods. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression using a backwards step-wise selection technique generated the final adjusted models. <h3>Results</h3> In total 299 metastases in 146 patients were identified. The median clinical and radiologic follow-up was 10.6 (range 0.5-49.9) and 10.7 months (range 0.5-47.6), respectively. The median maximum tumor diameter and volume were 1.7 cm (range, 0.2-3.9 cm) and 2.38 cc (range, 0.004-24.92 cc), respectively. The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5 Gy) in 5 daily fractions and 52% (range, 45%-93%), respectively. The median overall survival (OS) was 12.7 months and the 1-year LC rate was 85%. MVA identified a total dose of 27.5 Gy vs. ≤25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥4.5cc (HR 7.29, p < 0.001) and a mean intra-tumoral dose of ≥39 Gy (HR 3.17, p = 0.034) as significant predictors of symptomatic ARE. <h3>Conclusion</h3> Moderate total doses in 5 daily fractions of Co⁶⁰-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE. A prescription dose of 27.5 Gy was superior with respect to local control versus ≤25 Gy in 5 daily fractions. Target volumes of 4.5cc or larger as well as mean dose >39 Gy, were associated with higher rates of symptomatic necrosis. Further study will help refine the optimal dosimetric constraints for Co⁶⁰-HSRS.

Safety and Efficacy of MR-Guided Re-Irradiation in Patients with GI Malignancies

<h3>Purpose/Objective(s)</h3> This study aimed to assess the safety of administering re-irradiation in the abdomen or pelvis with MR-guided radiation therapy to patients with primary gastrointestinal (GI) malignancies. <h3>Materials/Methods</h3> A retrospective analysis was performed on a total of 9 patients that received MR-guided re-irradiation from March 2018 to February 2022 at a single institution. Patients were re-irradiated with 5 fractions using a dose constraint to re-irradiated mucosal structures of V 20 Gy <1cc. Treatment and clinical parameters including staging, histology, prescription radiation dose, and time interval between radiation treatments were collected. Patients were monitored for acute and late toxicity. <h3>Results</h3> Majority of the patients had pancreatic adenocarcinoma (n=6; 66%) and localized disease (n=6; 66%). The median age at the time of re-irradiation was 58 years (range 36-84 years) and median follow-up was 16 months (range 0.4- 39 months). 8 patients had surgery following the first dose of radiation. The median time between radiation treatments was 11.6 months (range 6.8 -87.9 months). The mean prescription was slightly higher at the time of re-irradiation compared to the initial prescription dose). The mean total prescription was 158.0 Gy EQD2 equivalent dose (range 99.4 Gy – 200 Gy). Majority of the patients experienced no acute toxicity or grade 1 toxicity, including fatigue and abdominal pain. One patient experienced grade 2 abdominal cramping. Dose constraints were met in all patients. No patients had recurrence in the re-irradiated field. Two patients experienced additional recurrences in their initially radiated fields after re-irradiation. No patients experienced late toxicity. <h3>Conclusion</h3> MR-guided re-irradiation in patients with GI malignancies may be a safe alternative in select patients. Further studies are needed to optimize patient selection and safe dose constraints.