Modeling the evolution of the US opioid crisis for national policy development.

The opioid crisis is a major public health challenge in the United States, killing about 70,000 people in 2020 alone. Long delays and feedbacks between policy actions and their effects on drug-use behavior create dynamic complexity, complicating policy decision-making. In 2017, the National Academies of Sciences, Engineering, and Medicine called for a quantitative systems model to help understand and address this complexity and guide policy decisions. Here, we present SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects), a dynamic simulation model developed in response to that charge. SOURCE tracks the US population aged ≥12 y through the stages of prescription and illicit opioid (e.g., heroin, illicit fentanyl) misuse and use disorder, addiction treatment, remission, and overdose death. Using data spanning from 1999 to 2020, we highlight how risks of drug use initiation and overdose have evolved in response to essential endogenous feedback mechanisms, including: 1) social influence on drug use initiation and escalation among people who use opioids; 2) risk perception and response based on overdose mortality, influencing potential new initiates; and 3) capacity limits on treatment engagement; as well as other drivers, such as 4) supply-side changes in prescription opioid and heroin availability; and 5) the competing influences of illicit fentanyl and overdose death prevention efforts. Our estimates yield a more nuanced understanding of the historical trajectory of the crisis, providing a basis for projecting future scenarios and informing policy planning.

Changes in the Appropriateness of US Outpatient Antibiotic Prescribing After the Coronavirus Disease 2019 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.

Raising AWaRe-ness of Antimicrobial Stewardship Challenges in Pediatric Emergency Care: Results from the PERFORM Study Assessing Consistency and Appropriateness of Antibiotic Prescribing Across Europe.

BACKGROUND: Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. METHODS: Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final "bacterial" or "viral" phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. RESULTS: Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/ß-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the "Watch" category. CONCLUSIONS: Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics. A significant proportion of patients with a viral phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology could significantly improve antimicrobial stewardship.

The impact of different strategies for modeling associations between medications at low doses and health outcomes: a simulation study and practical application to postpartum opioid use.

Pharmacoepidemiological studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a non-linear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose-response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose-response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).

Interventional Pharmacoepidemiology: Design and evaluation of interventions to improve prescribing.

Despite the value of modern therapeutics, many obstacles prevent their optimal use. Overuse, underuse and misuse are common, resulting in morbidity and mortality impacting billions of individuals across the world. Pharmacoepidemiology provides important insights into drug utilization, safety and effectiveness in large populations, and it is an important method to identify opportunities to improve the value of therapeutics in clinical practice. However, for these opportunities to be realized, interventions to improve prescribing must be developed, evaluated and implemented in the real world. We provide an overview of this process, focusing especially on how such interventions can be designed and deployed to maximize scalability, adoption and impact. Prescribing represents a complex behavior with barriers and enablers, and interventions to improve prescribing will be most successful when developed, piloted and refined to maximize provider and patient acceptability. Carefully developed evaluations of interventions are also critical, and varied methods are available to empirically evaluate the intended and potential unintended consequences of interventions. With illustrative examples from the peer-reviewed literature, we provide readers with an overview of approaches to the essential and growing field of interventional pharmacoepidemiology.

Oncology drug pricing: potential medicare savings on cancer-directed and supportive care medications through the Mark Cuban cost plus drug model.

Prescription drug costs within oncology remain a challenge for many patients with cancer. The Mark Cuban Cost Plus Drug Company (MCCPDC) launched in 2022, aiming to provide transparently priced medications at reduced costs. In this study, we sought to describe the potential impact of MCCPDC on Medicare Part-D oncology spending related to cancer-directed (n = 7) and supportive care (n = 26) drugs. We extracted data for drug-specific Part-D claims and spending for 2021. Using 90-count purchases from MCCPDC, we found potential Part-D savings of $857.8 million (91% savings) across the 7 cancer-directed drugs and $28.7 million (67% savings) across 21/26 (5/26 did not demonstrate savings) supportive care drugs. Collectively, our findings support that alternative purchasing models like MCCPDC may promote substantial health care savings.

Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors.

PURPOSE: To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type. METHODS: This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type. RESULTS: Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI 1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant. CONCLUSIONS: Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

Active disease-related compound identification based on capsule network.

Pneumonia, especially corona virus disease 2019 (COVID-19), can lead to serious acute lung injury, acute respiratory distress syndrome, multiple organ failure and even death. Thus it is an urgent task for developing high-efficiency, low-toxicity and targeted drugs according to pathogenesis of coronavirus. In this paper, a novel disease-related compound identification model-based capsule network (CapsNet) is proposed. According to pneumonia-related keywords, the prescriptions and active components related to the pharmacological mechanism of disease are collected and extracted in order to construct training set. The features of each component are extracted as the input layer of capsule network. CapsNet is trained and utilized to identify the pneumonia-related compounds in Qingre Jiedu injection. The experiment results show that CapsNet can identify disease-related compounds more accurately than SVM, RF, gcForest and forgeNet.

Changes in Medication Utilization and Adherence Associated with Homeless Adults' Entry into Permanent Supportive Housing.

BACKGROUND: Permanent supportive housing (PSH) programs, which have grown over the last decade, have been associated with changes in health care utilization and spending. However, little is known about the impact of such programs on use of prescription drugs critical for managing chronic diseases prevalent among those with unstable housing. OBJECTIVE: To evaluate the effects of PSH on medication utilization and adherence among Medicaid enrollees in Pennsylvania. DESIGN: Difference-in-differences study comparing medication utilization and adherence between PSH participants and a matched comparison cohort from 7 to 18 months before PSH entry to 12 months post PSH entry. SUBJECTS: Pennsylvania Medicaid enrollees (n = 1375) who entered PSH during 2011-2016, and a propensity-matched comparison cohort of 5405 enrollees experiencing housing instability who did not receive PSH but received other housing services indicative of episodic or chronic homelessness (e.g., emergency shelter stays). MAIN MEASURES: Proportion with prescription fill, mean proportion of days covered (PDC), and percent adherent (PDC ≥ 80%) for antidepressants, antipsychotics, anti-asthmatics, and diabetes medications. KEY RESULTS: The PSH cohort saw a 4.77% (95% CI 2.87% to 6.67%) relative increase in the proportion filling any prescription, compared to the comparison cohort. Percent adherent among antidepressant users in the PSH cohort rose 7.41% (95% CI 0.26% to 14.57%) compared to the comparison cohort. While utilization increased in the other medication classes among the PSH cohort, differences from the comparison cohort were not statistically significant. CONCLUSIONS: PSH participation is associated with increases in filling prescription medications overall and improved adherence to antidepressant medications. These results can inform state and federal policy to increase PSH placement among Medicaid enrollees experiencing homelessness.

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

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

Availability and Cost of Expensive and Common Generic Prescription Drugs: A Cross-sectional Analysis of Direct-to-Consumer Pharmacies.

BACKGROUND: Direct-to-consumer (DTC) pharmacies sell generic prescription drugs, often at lower prices than traditional retail pharmacies; however, not all drugs are available, and prices vary. OBJECTIVE: To determine the availability and cost of generic drugs at DTC pharmacies. DESIGN: Cross-sectional study. SETTING: Five national DTC pharmacies in April and May 2023. PARTICIPANTS: Each qualifying form of 100 generic drugs with the highest cost-per-patient (expensive) and the 50 generic drugs with the highest number of patients (common) in Medicare Part D in 2020 MAIN MEASURES: Availability of these drugs and the lowest DTC pharmacy price for a standardized drug strength and supply (e.g., 30 pills), compared to GoodRx retail pharmacy prices. KEY RESULTS: Of the 118 expensive generic dosage forms, 94 (80%) were available at 1 or more DTC pharmacies; out of 52 common generic dosage forms, 51 (98%) were available (p < 0.001). Of the 88 expensive generics available in comparable quantities and strengths across pharmacies, 42 (47%) had the lowest cost at Amazon, 23 (26%) at Mark Cuban Cost Plus Drug Company, 13 (14%) at Health Warehouse, and 12 (13%) at Costco; for 51 common generic formulations, 16 (31%) had the lowest cost at Costco, 14 (27%) at Amazon, 10 (20%) at Walmart, 6 (12%) at Health Warehouse, and 5 (10%) at Mark Cuban Cost Plus Drug Company. For the 77 expensive generics with available GoodRx retail pharmacy prices, the median cost savings at DTC pharmacies were $231 (95% CI, $129-$792) or 76% (IQR, 53-91%); for 51 common generics, savings were $19 (95% CI, $10-$34) or 75% (IQR, 67-83%). CONCLUSIONS: Many of the most expensive generic drugs are unavailable at direct-to-consumer pharmacies. Meanwhile, less expensive, commonly used generics are widely available, but drug prices vary by pharmacy and savings are modest, requiring patients to shop around for the lowest cost.

A personalized protocol for prescribing opioids after cesarean delivery: leveraging the electronic medical record to reduce outpatient opioid prescriptions.

BACKGROUND: Although cesarean delivery is the most common surgery performed in the United States, prescribing practices for analgesia vary. Strategies to manage postpartum pain have mostly focused on the immediate postpartum period when patients are still admitted to the hospital. At discharge, most providers prescribe a fixed number of opioid tablets. Most patients do not use all the opioids that they are prescribed at hospital discharge. This leads to an excess of opioids in the community, which can ultimately lead to misuse and diversion. OBJECTIVE: This study aimed to determine whether a transition from universal opioid prescribing to a personalized, patient-specific protocol decreases morphine milligram equivalents prescribed at hospital discharge after cesarean delivery while adequately controlling pain. STUDY DESIGN: This was a prospective cohort study of patients undergoing cesarean delivery before and after the implementation of a personalized opioid-prescribing practice at the time of hospital discharge. Each patient was prescribed scheduled ibuprofen and acetaminophen, with a prescription for oxycodone tablets equal to 5 times the morphine milligram equivalents used in the 24 hours before discharge, calculated via an electronic order set. The previous traditional cohorts were routinely prescribed 30 tablets of acetaminophen-codeine 300/30 mg. The primary outcome was morphine milligram equivalents prescribed at discharge. A hotline to address pain control issues after discharge was established, and calls, emergency department visits, and readmissions were examined. Statistical analyses was performed using chi-square and Wilcoxon rank-sum test, with a P value of <.05 considered statistically significant. RESULTS: Overall, 412 patients underwent cesarean delivery in the 6 weeks after initiation of the personalized prescribing protocol and were compared with 367 patients before the change. The median morphine milligram equivalents prescribed at discharge was lower with personalized prescribing (37.5 [interquartile range, 0-75] vs 135 [interquartile range, 135-135]; P<.001). Moreover, 176 patients (43%) were not prescribed opioids at discharge, which was a substantial change as all 367 patients in the traditional cohort received opioids at discharge (P<.001). Of note, 9 hotline phone calls were received; none required additional opioids after a 24-hour trial of scheduled ibuprofen, which none had taken before the call. In addition, 11 patients (2.7%) presented to the emergency department for pain evaluation, of which none required readmission or an outpatient prescription of opioids. CONCLUSION: A personalized protocol for opioid prescriptions after cesarean delivery decreased the total morphine milligram equivalents and the number of opioid tablets at discharge, without hospital readmissions or need for rescue opioid prescriptions after discharge. Opioids released into our community will be reduced by more than 90,000 tablets per year, without demonstrable adverse effect.

A qualitative study on determinants of the use of malaria rapid diagnostic test and anti-malarial drug prescription practices by primary healthcare workers in Ebonyi state, Nigeria.

BACKGROUND: The increased availability and use of malaria rapid diagnostic test (RDT) by primary healthcare (PHC) workers has made universal diagnostic testing before malaria treatment more feasible. However, to meaningfully resolve the problem of over-treatment with artemisinin-based combination therapy and the heightened risk of selection pressure and drug resistance, there should be appropriate response (non-prescription of anti-malarial drugs) following a negative RDT result by PHC workers. This study explored the determinants of the use of RDT and anti-malarial drug prescription practices by PHC workers in Ebonyi state, Nigeria. METHODS: Between March 2 and 10, 2020, three focus group discussions were conducted in English with 23 purposively-selected consenting PHC workers involved in the diagnosis and treatment of malaria. Data was analysed thematically as informed by the method by Braun and Clarke. RESULTS: The determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker's knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients' demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money. CONCLUSIONS: This evidence highlights many systemic, provider, client, and RDT/drug related determinants of PHC workers' use of RDT and anti-malarial drug prescription practices that should provide tailored guidance for relevant health policy actions in Ebonyi state, Nigeria, and similar settings.

Association of Regular Opioid Use With Incident Dementia and Neuroimaging Markers of Brain Health in Chronic Pain Patients: Analysis of UK Biobank.

OBJECTIVES: We aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients. DESIGN: The primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes. SETTING AND PARTICIPANTS: Dementia-free UK Biobank participants with chronic pain and regular analgesic use. MEASUREMENTS: Chronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively. RESULTS: Prospective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08-1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19-0.71] per 1000 person-years; Wald χ2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07-1.37, Wald χ2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08-1.50, Wald χ2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23-1.67, Wald χ2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes. CONCLUSION: Regular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.

Variability in the prevalence of inappropriate medication use among older adults: A review highlighting the importance of screening methods and database types.

AIMS: The global older population is growing rapidly, and the rise in polypharmacy has increased potentially inappropriate medication (PIM) encounters. PIMs pose health risks, but detecting them automatically in large medical databases is complex. This review aimed to uncover PIM prevalence in individuals aged 65 years or older using health databases and emphasized the risk of underestimating PIM prevalence due to underutilization of detection tools. METHODS: This study conducted a broad search on the Medline database to identify articles about the prevalence of PIMs in older adults using various databases. Articles published between January 2010 and June 2023 were included, and specific criteria were applied for study selection. Two literature reviews conducted before our study period were integrated to obtain a perspective from the 1990s to the present day. The selected papers were analysed for variables including database type, screening method, adaptations and PIM prevalence. The study categorized databases and original screening tools for clarity, examined adaptations and assessed concordance among different screening methods. RESULTS: This study encompassed 48 manuscripts, covering 58 sample evaluations. The mean prevalence of PIMs within the general population aged over 65 years was 27.8%. Relevant heterogeneity emerged in both the utilized databases and the detection methods. Adaptation of original screening tools was observed in 86.2% (50/58) of cases. Half of the original screening tools used for assessing PIMs belonged to the simple category. About a third of the studies employed less than half of the original criteria after adaptation. Only three studies used over 75% of the original criteria and more than 50 criteria. CONCLUSIONS: This extensive review highlights PIM prevalence among the older adults, emphasizing method intricacies and the potential for underestimation due to data limitations and algorithm adjustments. The findings call for enhanced methodologies, transparent algorithms and a deeper understanding of intricate rules' impact on public health implications.

Older adults' adherence to medications and willingness to deprescribe: A substudy of a randomized clinical trial.

Our study investigated the association between patients' willingness to have medications deprescribed and medication adherence. This longitudinal substudy of the 'Optimizing PharmacoTherapy In the Multimorbid Elderly in Primary CAre' (OPTICA) trial, a cluster randomized controlled trial, took place in Swiss primary care settings. Participants were aged ≥65 years and over, with ≥3 chronic conditions and ≥5 regular medications. At baseline, the 'revised Patient Attitudes Towards Deprescribing' (rPATD) questionnaire was measured. The A14-scale measured adherence (self-report) at the 12-month follow-up. Multilevel linear regression analyses adjusted for baseline variables were performed. Of the 298 participants, 45% were women, and the median age was 78. Participants reported a high level of adherence and willingness to have medications deprescribed. We did not find evidence for an association between patients' willingness to deprescribe and medication adherence. Further research is needed to explore the relationship between these concepts and to inform collaborative decisions about medicines in the context of polypharmacy.

The use of C-reactive protein testing and antibiotic prescribing in Italy: A population-based study in primary care.

Testing serum C-reactive protein (CRP) levels can help determine whether there is a need for antibiotics and can limit prescribing of antibiotics for illnesses that are likely viral or non-infectious in origin. Using Health Search, an Italian primary care database, we identified all patients, aged 15 years or older, being registered in the period between 1 January 2000 and 31 December 2019 and newly diagnosed with upper respiratory tract infections (URTIs) or COPD- or asthma-related exacerbations. From the date of these diagnoses, patients were followed up until occurrence of antibiotic prescription (for these indications) up to 31 December 2019. The association between the CRP testing and the outcome was investigated using a nested case-control analysis. In a cohort of 469 684 patients being diagnosed for URTI (83%), COPD- (11%) and asthma (7%)-related exacerbations, 28 688 (6.11%) were prescribed with antibiotics because of the aforementioned indications. Of note, 98% of cases, nominally those prescribed with antibiotics, were not tested with CRP. However, those receiving antibiotics were more likely to have been previously tested for CRP than controls who did not receive antibiotics (833/28 601 [3%] and 4128/277 968 [1.5%]; OR 2.0 [95% CI: 1.8-2.1]). Our findings indicate that most of the antibiotic prescriptions for the investigated conditions were given without any prior CRP testing. A small minority of GPs did properly use CRP to determine whether antibiotics were needed. Further guidance is needed in Italy on the use of CRP in guiding antibiotic prescribing in primary care.

Advanced prescription of injectable anticancer drugs: Safety assessment in a European Comprehensive Cancer Centre using the risk matrix approach.

AIMS: The purpose of this work was to assess failures in the advanced prescription of parenteral anticancer agents in an adult day oncology care unit with more than 100 patients per day. METHODS: An a priori descriptive analysis was carried out by using the risk matrix approach. After defining the scope in a multidisciplinary meeting, we determined at each step the failure modes (FMs), their effects (E) and their associated causes (C). A severity score (S) was assigned to all effects and a probability of occurrence (O) to all causes. These S and O indicators, were used to obtain a criticality index (CI) matrix. We assessed the risk control (RC) of each failure in order to define a residual criticality index (rCI) matrix. RESULTS: During risk analysis, 14 FMs were detected, and 61 scenarios were identified considering all possible effects and causes. Nine situations (15%) were highlighted with the maximum CI, 18 (30%) with a medium CI, and 34 (55%) with a negligible CI. Nevertheless, among all these critical situations, only three (5%) had an rCI to process (i.e., missed dose adjustment, multiple prescriptions and abnormal biology data); the others required monitoring only. Clinicians' and pharmacists' knowledge of these critical situations enables them to manage the associated risks. CONCLUSIONS: Advanced prescription of injectable anticancer drugs appears to be a safe practice for patients when combined with risk management. The major risks identified concerned missed dose adjustment, prescription duplication and lack of consideration for abnormal biology data.

Association of state-level prescription drug monitoring program implementation with opioid prescribing transitions in primary care in Australia.

AIMS: This study aimed to evaluate whether voluntary and mandatory prescription drug monitoring program (PDMP) use in Victoria, Australia, had an impact on prescribing behaviour, focusing on individual patients' prescribed opioid doses and transition to prescribing of nonmonitored medications. METHODS: This was a retrospective cross-sectional study using routinely collected primary healthcare data. A 90-day moving average prescribed opioid dose in oral morphine equivalents was used to estimate opioid dosage. A Markov transition matrix was used to describe how patients prescribed medications transitioned between opioid dose groups and other nonopioid treatment options during 3 transition periods: transition between 2 control periods prior to PDMP implementation (T1 to T2); during the voluntary PDMP implementation (T2 to T3); and during mandatory PDMP implementation (T3 to T4). RESULTS: Among patients prescribed opioids in our study, we noted an increased probability of transitioning to not being prescribed opioids during the mandatory PDMP period (T3 to T4). This increase was attributed mainly to the ceasing of low-dose opioid prescribing. Membership in an opioid dose group remained relatively stable for most patients who were prescribed high opioid doses. For those who were only prescribed nonmonitored medications initially, the probability of being prescribed opioids increased during the mandatory PDMP when compared to other transition periods. CONCLUSION: The introduction of PDMP mandates appeared to have an impact on the prescribing for patients who were prescribed low-dose opioids, while its impact on individuals prescribed higher opioid doses was comparatively limited.

Hospital-Wide Adherence to Postsurgical Opioid Prescribing Guidelines: A Retrospective Cohort Study.

INTRODUCTION: Lowering opioid prescription doses and quantity decreases the risk of chronic opioid usage. A tool was inserted into the brief operative note for the surgeon to assess the severity of pain associated with the procedure. We studied surgeon adherence to current opioid-prescribing recommendations. METHODS: Retrospective cohort study with 5486 patients were included in the study population. Each patient's prescription was scored yes or no for adherence on total morphine milligram equivalents (MMEs) and days prescribed with the selection in the brief operative note. The entire study population was tested for an increase from the null-hypothesis "benchmark" value of 75% using a one-sided exact binomial test of a single proportion with P < 0.05. This procedure was repeated for subgroups, with P < 0.01. RESULTS: Adherence to guidelines was higher than the 75% benchmark for "total MMEs prescribed" (79.5%; P < 0.001), but lower for "number of days prescribed" (63.5%; P > 0.999). Surgeries with severe predicted pain showed the highest adherence toward total MMEs prescribed at 87.1%, followed by moderate (80.5%) and mild (74.5%). Severe cases also showed the highest adherence in number of days prescribed (92.4%). Adherence to total MMEs prescribed was highest among attending physicians (88.1%) and lowest among residents/fellows (76.6%). CONCLUSIONS: Adherence to current guidelines was 79.5% for MMEs prescribed but only 63.5% for days prescribed. Compliance with guidelines was better for severe procedures than mild or moderate. Differences were seen across surgical departments. While an improvement from previous reports, further improvement is needed to reduce the number of days of opioids prescribed and increase compliance with recommended guidelines.