A risk stratification analysis of ASCVD events post-statin discontinuation in patients who underwent sleeve gastrectomy or Roux-en-Y gastric bypass bariatric/metabolic surgeries.

BACKGROUND: Cardiovascular disease remains a leading cause of mortality globally, and its prevalence is notably elevated in individuals with obesity. Bariatric surgery is an effective intervention to reduce obesity-related health risks. However, the implications of discontinuing statin therapy, particularly post-bariatric surgery, among those with a history of atherosclerotic cardiovascular disease have yet to be clarified. We aimed to ascertain the risk of atherosclerotic cardiovascular disease events following statin cessation after bariatric surgery and to delineate the variance in outcomes between primary and secondary prevention cohorts. METHODS: The TriNetX database, encompassing electronic medical records from 69 United States healthcare institutions, spanning 2012 to 2021. Using a retrospective cohort design, patients aged ≥18 years who underwent bariatric surgery and were concurrently on statin therapy were selected. Discontinuation was defined as a 90-day lapse after the last statin prescription. Patients were categorized as "primary" or "secondary" prevention based on their atherosclerotic cardiovascular disease history. The primary outcome was the occurrence of an atherosclerotic cardiovascular disease event post-statin cessation. Multivariable Cox proportional hazards models discerned factors influencing this outcome. RESULTS: Of the 453 statin users who underwent bariatric surgery, 332 (73.1%) were in the primary prevention group and 121 (26.7%) in the secondary prevention group. At 1-year post-surgery, atherosclerotic cardiovascular disease event-free rates were 93% for primary and 68% for secondary prevention groups. Primary prevention patients showed an 82% reduced risk of post-statin cessation atherosclerotic cardiovascular disease events than secondary prevention patients (hazard ratio, 0.181; 95% confidence interval, 0.119-0.274). Additionally, Hispanic/Latino patients had heightened post-statin cessation atherosclerotic cardiovascular disease risks compared to non-Hispanic/Latino peers. CONCLUSION: Post-bariatric surgery statin discontinuation can pose significant risks, especially for those with atherosclerotic cardiovascular disease history and certain demographic groups, such as those over age 40 with diabetes. Ethnic disparities in outcomes necessitate individualized, equitable healthcare strategies. Optimal decisions about statin cessation necessitate comprehensive evaluations of cardiovascular determinants, with future research crucial to refine therapeutic approaches based on these insights.

Reporting, handling, and interpretation of time-varying drug treatments in observational studies using routinely collected healthcare data.

BACKGROUND: Time-varying drug treatments are common in studies using routinely collected health data (RCD) for assessing treatment effects. This study aimed to examine how these studies reported, handled, and interpreted time-varying drug treatments. METHODS: A systematic search was conducted on PubMed from 2018 to 2020. Eligible studies were those used RCD to explore drug treatment effects. We summarized the reporting characteristics and methods employed for handling time-varying treatments. Logistic regressions were performed to investigate the association between study characteristics and the reporting of time-varying treatments. RESULTS: Two hundred and fifty-six studies were included, and 225 (87.9%) studies involved time-varying treatments. Of these, 24 (10.7%) reported the proportion of time-varying treatments and 105 (46.7%) reported methods used to handle time-varying treatments. Multivariable logistic regression showed that medical studies, prespecified protocol, and involvement of methodologists were associated with a higher likelihood of reporting the methods applied to handle time-varying treatments. Among the 105 studies that reported methods, as-treated analyses were the most commonly used analysis sets, which were employed in 73.9%, 75.3% and 88.2% of studies that reported approaches for treatment discontinuation, treatment switching and treatment add-on. Among the 225 studies involved time-varying treatments, 27 (12.0%) acknowledged the potential bias introduced by treatment change, of which 14 (51.9%) suggested that potential biases may impact acceptance or rejection of the null hypothesis. CONCLUSIONS: Among observational studies using RCD, the underreporting about the presence and methods for handling time-varying treatments was largely common. The potential biases due to time-varying treatments have frequently been disregarded. Collaborative endeavors are strongly needed to enhance the prevailing practices.

Metabolic and Bariatric Surgery Utilization Trends in the United States: Evidence From 2012 to 2021 National Electronic Medical Records Network.

Background: Bariatric surgery has evolved over the past 2 decades yet assessing trends of bariatric surgery utilization in the growing eligible population is lacking. Aim: This study aimed to update the trends in bariatric surgery utilization, changes in types of procedures performed, and the characteristics of patients who underwent bariatric surgery in the United States, using real-world data. Method: This retrospective descriptive observational study was conducted using the TriNetX, a federated electronic medical records network from 2012 to 2021, for adult patients 18 years old or older who had bariatric surgery. Descriptive statistical analysis was conducted to assess patients' demographics and characteristics. Annual secular trend analyses were conducted for the annual rate of bariatric surgery, and the specific procedural types and proportions of laparoscopic surgeries. Results: A steady increase in the number of procedures performed in the United States over the first 6 years of the study, a plateau for the following 2 years, and then a decline in 2020 and 2021 (during the coronavirus disease 2019 pandemic). The annual rate of bariatric surgery was lowest in 2012 at 59.2 and highest in 2018 at 79.6 surgeries per 100,000 adults. During the study period, 96.2% to 98.8% of procedures performed annually were conducted laparoscopically as opposed to the open technique. Beginning in 2012, the Roux-en-Y gastric bypass (RYGB) procedure fell to represent only 17.1% of cases in 2018, along with a sharp decline in the adjustable gastric band (AGB) procedure, replaced by a sharp increase in the sleeve gastrectomy (SG) procedure to represent over 74% of cases in 2018. Conclusions: Bariatric surgery utilization in the United States showed a moderate decline in the number of RYGB procedures, which was offset by a substantial increase in the number of SG procedures and a precipitous drop in the annual number of AGB procedures.

Effectiveness and safety of edoxaban versus warfarin in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia type. Patients with AF are often administered anticoagulants to reduce the risk of ischemic stroke due to an irregular heartbeat. We evaluated the efficacy and safety of edoxaban versus warfarin in patients with nonvalvular AF by conducting an updated meta-analysis of real-world studies. Methods: In this comprehensive meta-analysis, we searched two databases, PubMed and EMBASE, and included retrospective cohort observational studies that compared edoxaban with warfarin in patients with nonvalvular AF from 1 January 2009, to 30 September 2023. The effectiveness and safety outcomes were ischemic stroke and major bleeding, respectively. In the final analysis, six retrospective observational studies involving 87,236 patients treated with warfarin and 40,933 patients treated with edoxaban were included. To analyze the data, we used a random-effects model to calculate the hazard ratio (HR). Results: Patients treated with edoxaban had a significantly lower risk of ischemic stroke [hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.61-0.70; p < 0.0001] and major bleeding (HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001) than those treated with warfarin. The sensitivity analysis results for ischemic stroke and major bleeding were as follows: HR = 0.66; 95% CI = 0.61-0.70; p < 0.0001 and HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001, respectively. Conclusion: Our findings revealed that edoxaban performed better than warfarin against major bleeding and ischemic stroke.

Safety profile and signal detection of phosphodiesterase type 5 inhibitors for erectile dysfunction: a Food and Drug Administration Adverse Event Reporting System analysis.

Background: Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs). Aim: This study aims to investigate and compare the characteristics of AEs associated with PDE5Is used for erectile dysfunction and identify any safety signals in a postmarketing surveillance database between 2010 and 2021. Methods: A descriptive analysis was conducted for all AEs reported to the Food and Drug Administration Adverse Event Reporting System for 4 PDE5Is-avanafil, sildenafil, tadalafil, and vardenafil-indicated for erectile dysfunction between January 2010 and December 2021. The frequency of the most reported AEs and outcomes were identified. A disproportionality analysis based on proportional reporting ratio (PRR) and reporting odds ratio (ROR) was conducted for the most common and clinically important AEs to identify signals to gain insights into potential differences in safety profiles. Outcomes: The outcome measures of the study are frequency of reported AEs and outcomes following AE. Results: A total of 29 236 AEs were reported for PDE5Is during the study period. The most reported AE was "drug ineffective" with 7115 reports (24.3%). Eight safety signals were detected across the 4 drugs. Key signals were sexual disorders (PRR, 3.13 [95% CI, 2.69-3.65]; ROR, 3.24 [95% CI, 2.77-3.79]) and death (PRR, 3.17 [2.5-4.01]; ROR, 3.211 [2.52-4.06]) for sildenafil, priapism (PRR, 3.63 [2.11-6.24]; ROR, 3.64 [2.12-6.26]) for tadalafil, and drug administration error (PRR, 2.54 [1.84-3.52]; ROR, 2.6 [1.86-3.63]) for vardenafil. The most reported outcomes were other serious events with 6685 events (67.2%) and hospitalization with 1939 events (19.5%). Clinical Implications: The commonly reported AEs and detected signals may guide clinicians in treatment decision making for men with erectile dysfunction. Strengths and Limitations: This is the first comprehensive report and disproportionality analysis on all types of AEs associated with PDE5Is used for erectile dysfunction in the United States. The findings should be interpreted cautiously due to limitations in the Adverse Event Reporting System, which includes self-reports, duplicate and incomplete reports, and biases in reporting and selection. Therefore, establishing a causal relationship between the reported AEs and the use of PDE5Is is uncertain, and the data may be confounded by other medications and indications. Conclusion: PDE5Is demonstrate significantly increased risks of reporting certain clinically important AEs. While these events are not common, it is imperative to continually monitor PDE5I use at the levels of primary care to national surveillance to ensure safe utilization.

Drug Expenditure, Price, and Utilization in US Medicaid: A Trend Analysis for New Multiple Myeloma Medications from 2016 to 2022.

INTRODUCTION: Multiple myeloma (MM) is the most common plasma cell tumor type. In late 2015, the FDA approved three new medications for MM. These medications were ixazomib, daratumumab, and elotuzumab. However, their utilization, reimbursement, and price in the Medicaid program have not been analyzed before. METHODS: A retrospective drug utilization study using the national Medicaid pharmacy claims data from 2016 to 2022 in the US. The primary metrics of analysis were utilization (number of prescriptions), reimbursement (total spending), and price (reimbursement per prescription). RESULTS: The overall Medicaid utilization of MM medications increased from 1671 prescriptions in 2016 to 34,583 prescriptions in 2022 (1970% increase). Moreover, the overall Medicaid reimbursement for the new MM medications increased from USD 9,250,000 in 2016 to over USD 214,449,000 in 2022 (2218% increase). Daratumumab had much higher utilization, reimbursement, and market shares than its competitors. Ixazomib was the most expensive medication compared to daratumumab and elotuzumab. CONCLUSION: The results of this study demonstrate that CMS utilization and spending on MM medications have significantly grown since 2016. Daratumumab has by far the highest utilization, spending, and market share. The utilization of and spending on specific pharmaceuticals are clearly impacted by policy and clinical guideline recommendations.

Safety reporting of Essure medical device: a qualitative and quantitative assessment on the FDA manufacturer and user facility device experience database in 2018.

Background: There have been numerous cases of adverse events since the introduction of Essure medical devices for sterilization in 2002. This study analyzed the safety event reports of the Essure reported in the Manufacturer and User Facility Device Experience (MAUDE). Methods: A retrospective analysis examined the MAUDE reports between Jan-1, 2018, and Oct-31, 2018 and focused on safety reports related to the Essure device. Safety reports were categorized and analyzed by their event type, device problem, patients' symptoms and the level of harm. Of this study cohort, 10% of samples were randomly selected for quantitative analyses. Thematic analysis was conducted for reports included death cases. Results: A total of 4,994 eligible reports were analyzed. There were ten reports associated with individuals' deaths, and the main themes of safety reports from qualitative analysis were pains, bleeding, surgery, migraine, and infection. Quantitative analysis of 500 randomly selected samples showed that 98% of adverse event reports were associated with different injuries such as surgery, pain, bleeding, hysterectomy, and menorrhagia. Additionally, more than 90% of reports were submitted by the manufacturer. Conclusion: These findings indicated several safety issues of Essure. More meaningful pre- and post-marketing surveillance and regulation are warranted in the medical device market to ensure safety and effectiveness, including investigating complaints, promptly sharing relevant information with regulators and users, and implementing corrective actions.

Prognostic Factors of COVID-19: An Umbrella Review Endorsed by the International Society for Pharmacoepidemiology.

During the coronavirus disease 2019 (COVID-19) pandemic, the urgency for updated evidence to inform public health and clinical care placed systematic literature reviews (SLRs) at the cornerstone of research. We aimed to summarize evidence on prognostic factors for COVID-19 outcomes through published SLRs and to critically assess quality elements in the findings' interpretation. An umbrella review was conducted via electronic databases from January 2020 to April 2022. All SLRs (and meta-analyses) in English were considered. Data screening and extraction were conducted by two independent reviewers. AMSTAR 2 tool was used to assess SLR quality. The study was registered with PROSPERO (CRD4202232576). Out of 4,564 publications, 171 SLRs were included of which 3 were umbrella reviews. Our primary analysis included 35 SLRs published in 2022, which incorporated studies since the beginning of the pandemic. Consistent findings showed that, for adults, older age, obesity, heart disease, diabetes, and cancer were more strongly predictive of risk of hospitalization, intensive care unit admission, and mortality due to COVID-19. Male sex was associated with higher risk of short-term adverse outcomes, but female sex was associated with higher risk of long COVID. For children, socioeconomic determinants that may unravel COVID-19 disparities were rarely reported. This review highlights key prognostic factors of COVID-19, which can help clinicians and health officers identify high-risk groups for optimal care. Findings can also help optimize confounding adjustment and patient phenotyping in comparative effectiveness research. A living SLR approach may facilitate dissemination of new findings. This paper is endorsed by the International Society for Pharmacoepidemiology.

Spending, Utilization, and Price Trends for Immune Checkpoint Inhibitors in US Medicaid Programs: An Empirical Analysis from 2011 to 2021.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) have become a cornerstone in cancer treatment. With high treatment costs and an increasing number of young and low-income patients with cancer, there is a need to determine the current spending and utilization of ICIs in a real-world population. The objective of this study was to outline the drug spending, utilization, and price trends of ICIs for US Medicaid programs from 2011 to 2021. METHODS: A retrospective descriptive analysis was conducted using the Medicaid State Drug Utilization pharmacy summary files managed by the Centers for Medicare and Medicaid Services. Six ICIs for this study include ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, and cemiplimab. Yearly reimbursement and prescription numbers were calculated for six ICIs billed through Medicaid between 2011 and 2021. The average spending per prescription was calculated as a proxy for drug prices. RESULTS: Overall spending and utilization on ICIs have risen exponentially over the past decade. Between 2011 and 2021, expenditures increased from $2.8 million to $4.1 billion. Utilization increased from 94 prescriptions to 462,049 prescriptions in 2021 with six ICIs. The average spending per prescription, or average drug price, decreased 70%, from $29,795.88 in 2011 to $8914.69 in 2021. CONCLUSIONS: Spending on and utilization of ICIs have increased dramatically over the past decade. These findings shed new light on the impact of ICIs on state Medicaid programs and may provide insight into potential cost drivers that need to be addressed through policy.

Impact of Introducing Infliximab Biosimilars on Total Infliximab Consumption and Originator Infliximab Prices in Eight Regions: An Interrupted Time-Series Analysis.

OBJECTIVE: We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab. METHODS: An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU. RESULTS: Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: - 187.84 USD/SU (P < 0.001); long-term change - 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: - 145.58 (P < 0.001)], the UK [immediate change: - 34.95 (P = 0.010); long-term change: - 4.77 (P < 0.001)], and Hong Kong [long-term change: - 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA. CONCLUSIONS: Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed.

Trends in utilization, reimbursement, and price for DOACs and warfarin in the US Medicaid population from 2000 to 2020.

The use of direct oral anticoagulants (DOACs) is widely increasing in the United States (US). Warfarin has been the conventional anticoagulant used in the past few decades, but it has been gradually replaced by DOACs. The objective of the study was to analyze trends in utilization, reimbursement, and price for those anticoagulants in the US Medicaid population. Retrospective data analysis was conducted using the National Summary Files for the Medicaid State Drug Utilization Data. Study drugs included dabigatran, rivaroxaban, apixaban, edoxaban and warfarin. The study assessed secular trends of utilization, reimbursement, and per-prescription price. The data was collected from the first quarter of 2000 through to the second quarter of 2020 restricted for outpatient prescriptions only. During the 21-year study period, a substantial rise in total expenditures on warfarin and DOACs was observed from $144 million in 2000 to $694 million in 2020. Moreover, the utilization of DOACs has increased significantly since the first approval of Xarelto in 2010 from 1079 in 2011 to 1.5 million in 2019. The per-prescription price of DOACs increased from an average of $200 in 2011 to $407 in 2020. Conversely, the total number of prescriptions of Warfarin and branded Coumadin decreased from 2.4 million to 1.4 million and from 3.9 million to less than a million, respectively. The present study demonstrated a change in the trends of US expenditure and utilization for warfarin and DOACs with DOACs representing the majority of market share of both spending per prescription and reimbursement.

Impact of time-varying exposure on estimated effects in observational studies using routinely collected data: protocol for a cross-sectional study.

INTRODUCTION: Time-varying exposure is an important issue that should be addressed in longitudinal observational studies using routinely collected data (RCD) for drug treatment effects. How well investigators designed, analysed and reported time-varying exposure, and to what extent the divergence that can be observed between different methods used for handling time-varying exposure in these studies remains uncertain. We will conduct a cross-sectional study to comprehensively address this question. METHODS AND ANALYSIS: We have developed a comprehensive search strategy to identify all studies exploring drug treatment effects including both effectiveness and safety that used RCD and were published in core journals between 2018 and 2020. We will collect information regarding general study characteristics, data source profile, methods for handling time-varying exposure, results and the interpretation of findings from each eligibility. Paired reviewers will screen and extract data, resolving disagreements through discussion. We will describe the characteristics of included studies, and summarise the method used for handling time-varying exposure in primary analysis and sensitivity analysis. We will also compare the divergence between different approaches for handling time-varying exposure using ratio of risk ratios. ETHICS AND DISSEMINATION: No ethical approval is required because the data we will use do not include individual patient data. Findings will be disseminated through peer-reviewed publications.

Utilization, Spending, and Price of Opioid Medications in the US Medicaid Programs Between 1991 and 2019.

Background: The opioid epidemic and drug abuse are critical public health challenges in the United States. The number of deaths from exceeding the recommended opioid dose is increasing. Objective: To describe the recent trends in utilization, spending, and cost of opioid medications in the US Medicaid population between 1991 and 2019. Methods: This retrospective, descriptive study was designed to evaluate the utilization of, spending on, and cost of opioids from 1991 to 2019 in the Medicaid population. We extracted data from the Centers for Medicare & Medicaid Services national Medicaid pharmacy files. The opioids received included fentanyl, meperidine, morphine, hydromorphone, oxymorphone, hydrocodone, hydrocodone plus acetaminophen, oxycodone, oxycodone plus acetaminophen, tapentadol, and tramadol. The number of prescriptions and reimbursement spending were calculated for each medication per quarter year. The average per-prescription reimbursement as a proxy of drug price was calculated as the reimbursement amount divided by the number of prescriptions per quarter year. The market shares by spending and utilization were also calculated for each opioid medication. Results: The number of all opioid prescriptions in Medicaid increased from approximately 2.1 million in 1991 to approximately 41.6 million in 2015, and then reduced to approximately 19.1 million in 2019. During this 29-year study period, the opioid medications that were used as monotherapy were hydrocodone (246.8 million prescriptions), oxycodone (111.9 million prescriptions), and tramadol (75.2 million prescriptions). The total spending in the Medicaid population on opioids was $19.4 billion, including approximately $7.3 billion spending on oxycodone, approximately $3.7 billion on fentanyl, and approximately $3.3 billion on hydrocodone. The majority of opioid prices increased over time, and the highest average costs per opioid prescription in 2019 were $1188 for oxymorphone, $641 for tapentadol, and $198 for fentanyl. Conclusions: The utilization of and spending on opioid medications in Medicaid increased over time, peaked in 2015, and then declined with the initiation of nationwide programs to combat the opioid epidemic. Effective cost-containment strategies and programs to combat the abuse of opioids are warranted in Medicaid programs.

The effect of polypharmacy on quality of life in adult patients with nonalcoholic fatty liver disease in the United States.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a significant epidemiological problem with rising prevalence. Due to limited literature, the objective of this study is to examine the association between polypharmacy and health-related quality of life (QoL) in NAFLD adult patients. METHODS: A retrospective observational study design was conducted to analyze health data collected by Steatohepatitis Clinical Research Network (NASH CRN). Patients were classified as receiving a polypharmacy therapy with five or more medications in their first screening visit. QoL was measured using the Short Form 36 (SF-36) instrument. Each patient self-reported the SF-36 form during the screening visit was compared between polypharmacy and non-polypharmacy groups using Wilcoxon Rank Sum test. Multivariable generalized linear models and multinomial logistic regression were performed to examine each predictor and its effect on QoL. RESULTS: Data included 1067 NAFLD adult patients; 834 patients used polypharmacy. The mean age was 48.64 years, and most patients were female (62%). Comparing NAFLD patients without steatohepatitis, borderline NASH, and definite NASH, the non-polypharmacy group had a significantly higher QoL than the polypharmacy group in Physical Component Summary (PCS) (86.25 vs 66.88, 85 vs 67.5, and 79.375 vs 63.12, respectively, all p < 0.01) and Mental Component Summary (MCS) (83.5 vs 73.38, 78.75 vs 67.62, and 78.75 vs 70.65, respectively, all p < 0.01). DISCUSSION AND CONCLUSION: Adults with NAFLD and polypharmacy have lower QoL than adults with NAFLD and non-polypharmacy. Number of medications had a significant negative impact on PCS, MCS, and all SF-36 domains except mental health, role physical limitation and role emotional limitation domains. Other factors that affect QoL negatively in NAFLD adult patients are female gender, obesity, diabetes, depression, and unemployment. Higher income had favorable effect on QoL.

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020.

Background Obesity is a globally growing health problem, and its treatment has been challenging. The use of anti-obesity medications (AOMs) has been associated with severe adverse events (AEs). Several AOMs have been withdrawn from the market owing to documented AEs. Aim To describe, estimate and characterize the frequency of AEs attributable to the use of the AOMs, and investigate previously unreported potential AEs associated with AOMs. Method Using the US FDA Adverse Event Reporting System (FAERS) between January 2013 and June 2020, a retrospective, descriptive analysis was conducted to analyze all major reported AEs and outcomes including death, life-threatening, hospitalization, disability, and required intervention or congenital anomaly. The total numbers of AEs reports, cases, adverse reactions and outcomes were calculated for each medication. Results A total of 18,675 unique AEs reports associated with AOMs used for 15,143 patients. The mean age was 49.8 years [SD 1.83], while most patients were female adults (73.4%). The most frequently reported AEs were nausea and vomiting, followed by dizziness and headache, drug ineffectiveness, cardiovascular diseases, and kidney complications. There were 21,229 unique outcomes, including 1039 deaths (fatality ratio of 4.9% of all analyzed reports), 1613 (7.6%) life-threatening events, 7426 (35%) hospitalizations, and 1249 (5.9%) disability cases. Phentermine/topiramate fatal cases represent 6% of the overall medication's reported AEs. Cardiovascular AEs represented 31%, 23%, and 22% of phentermine, liraglutide, and phentermine/topiramate total AEs, respectively. Conclusion The analysis of FAERS database revealed numerous serious AEs associated with AOMs. These AEs can lead to serious cardiovascular and kidney complications. It is necessary to continue and systematically monitor safety of AOMs' to optimize patient anti-obesity therapy.

Cost-Effectiveness Analysis of Ultrasound Screening for Thyroid Cancer in Asymptomatic Adults.

Objectives: This study evaluated the long-term cost-effectiveness of ultrasound screening for thyroid cancer compared with non-screening in asymptomatic adults. Methods: Applying a Markov decision-tree model with effectiveness and cost data from literature, we compared the long-term cost-effectiveness of the two strategies: ultrasound screening and non-screening for thyroid cancer. A one-way sensitivity analysis and a probabilistic sensitivity analysis were performed to verify the stability of model results. Results: The cumulative cost of screening for thyroid cancer was $18,819.24, with 18.74 quality-adjusted life years (QALYs), whereas the cumulative cost of non-screening was $15,864.28, with 18.71 QALYs. The incremental cost-effectiveness ratio of $106,947.50/QALY greatly exceeded the threshold of $50,000. The result of the one-way sensitivity analysis showed that the utility values of benign nodules and utility of health after thyroid cancer surgery would affect the results. Conclusions: Ultrasound screening for thyroid cancer has no obvious advantage in terms of cost-effectiveness compared with non-screening. The optimized thyroid screening strategy for a specific population is essential.

Systematic Review and Quality Evaluation of Pharmacoeconomic Studies on Traditional Chinese Medicines.

Objectives: This study was aimed to find and appraise the available published pharmacoeconomic research on Traditional Chinese Medicine (TCM), to identify related issues and make suggestions for improvement in future research. Methods: After developing a search strategy and establishing inclusion and exclusion criteria, pharmacoeconomic studies on TCM were sourced from seven Chinese and English databases from inception to April 2020. Basic information about the studies and key pharmacoeconomic items of each study were extracted. The quality of each study was evaluated by using the British Medical Journal economic submissions checklist for authors and peer reviewers, focusing on factors such as study design, research time horizon, sample size, perspective, and evaluation methods. Results: A total of 431 published pharmacoeconomic articles with 434 studies on topics including cost-effectiveness, cost-benefit, cost-minimization, cost-utility, or combination analyses were identified and included in this review. Of these, 424 were published in Chinese and 7 in English. These studies conducted economic evaluations of 264 Chinese patent medicines and 70 types of TCM prescriptions for 143 diseases, including those of the central nervous, cardiovascular, respiratory, gynecologyical, and other systems. The studied TCMs included blood-activating agents (such as Xuesaitong tablet, Fufant Danshen tablet, and Danhong Injection), blood circulation promoting agents (such as Shuxuetong injection, Rupixiao tablet, and Fufang Danshen injection), and other therapeutic agents. The overall quality score of the studies was 0.62 (range 0.38 to 0.85). The mean quality score of studies in English was 0.72, which was higher than that of studies in Chinese with 0.62. Conclusions: The quality of pharmacoeconomic studies on TCM was relatively, generally low. Major concerns included study design, inappropriate pharmacoeconomic evaluation, insufficient sample size, or non-scientific assessment. Enhanced methodological training and cooperation, the development of a targeted pharmacoeconomic evaluation guideline, and proposal of a reasonable health outcome index are warranted to improve quality of future studies.

Cost-Effectiveness Analysis of Ginkgolide Injection in the Treatment of Ischemic Stroke Based on a Randomized Clinical Trial.

Objective: To evaluate the long-term cost-effectiveness of ginkgolide plus aspirin compared with placebo plus aspirin treatment of ischemic stroke. Background: Stroke is the leading cause of death and long-term disability in China, with high incidence, high mortality, and heavy disease burden. In addition to Western medicines, Chinese clinical guidelines for diagnosis and treatment of acute ischemic stroke recommend application of Chinese patent medicines. Ginkgolide injection is commonly used in the clinical treatment of stroke in China to promote blood circulation and remove blood stasis. The economy of ginkgolide injection needs to be evaluated. Methods: A Markov model was constructed consisting of four disease states: no significant disability, disability, stroke recurrence, and death. Therapeutic data were taken from the Ginkgolide in Ischemic Stroke Patients with Large Artery Atherosclerosis (GISAA) study. Utilities and transition probabilities were extracted from the literature. Cost data were obtained from the China Health Statistics Yearbook and hospital record survey. Expected costs and quality-adjusted life-years (QALYs) of 13 years of cycles (calculated by average age of subjects and Chinese life expectancy) were calculated through TreeAge Pro11 software. The willingness-to-pay (WTP) threshold was set as the Chinese per capita Gross Domestic Product (GDP) in 2019, CN¥70,892/QALY. The results were analyzed by single factor and probability sensitivity analyses. Results: Ginkgolide plus aspirin had a higher expected per-patient cost than placebo plus aspirin but a higher QALYs. Compared with placebo plus aspirin, ginkgolide plus aspirin produced an incremental cost-effectiveness ratio of CN¥14,866.06/QALY, which is below the WTP threshold. Probabilistic sensitivity analysis suggested the acceptability of ginkgolide plus aspirin was higher than that of placebo plus aspirin. Conclusions: The present cost-effectiveness analysis showed that addition of ginkgolides to conventional treatment is cost-effective at a threshold the Chinese per capita GDP.

Healthcare services expenditures among prostate cancer patients with and without mood disorders in the United States: A propensity score-matched cross-sectional study.

OBJECTIVES: To compare the averages of healthcare services utilization and of expenditures for men with prostate cancer with and without diagnoses of mood disorders applying propensity score matching (PSM), and to identify the potential predictors associated with increased healthcare expenditures. DESIGN: Cross-sectional study. SAMPLE AND METHODS: A total of 308,602 weighted patients with prostate cancer were identified after applying PSM. The datasets for men with prostate cancer were extracted from the Medical Expenditure Panel Survey (MEPS) from 2010 to 2015. For cohort formation, 1:1 PSM was applied. Healthcare utilization and expenditures analyzed included emergency room visits, length of stay for hospital inpatients, outpatient visits, office-based visits, and prescriptions. Generalized linear model with gamma distribution and log link was used to determine which covariates are associated with the increase in healthcare expenditures for each healthcare service. FINDINGS: The mean expenditures for emergency room visits between men with prostate cancer and mood disorders was $3,092.34, and it was $1,330.64 for patients without mood disorders (p = 0.038). The weighted total expenditures for emergency room visits in prostate cancer patients with mood disorders is 57% higher (p = 0.0109). Moreover, the weighted total expenditures for outpatient visits in prostate cancer patients with mood disorders is 93% higher (p = 0.0001). The potential predictor in total healthcare expenditures is perceived health status (fair/poor) (p = 0.0066). CONCLUSIONS AND IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS OR POLICY: Individuals with a diagnosis of mood disorders were found to have higher average healthcare expenditures in emergency room visits than those without mood disorders. Therefore, the implications of this study are to inform the patient care team that the assessment and management of mood disorders is a priority. Moreover, screening of mood- disorder symptoms should occur early to optimize care. Finally, policymakers should provide accessible care to minimize emergency room visits.

Expenditure, Utilization, and Cost of Specialty Drugs for Multiple Sclerosis in the US Medicaid Population, 2008-2018.

BACKGROUND: Multiple sclerosis (MS) is a rare, long-standing, and disabling disease that affects the central nervous system and causes several clinical manifestations. As a result, this disease is associated with a high societal economic burden. OBJECTIVE: To analyze the trends in drug expenditure, utilization, and cost of specialty drugs for the treatment of patients with MS in the US Medicaid program. METHODS: In this retrospective drug utilization research analysis, we obtained prescription data and reimbursement of disease-modifying therapies for MS from the Centers for Medicare & Medicaid Services Medicaid State Drug Utilization Data between January 2008 and December 2018. The specialty drugs considered in our analysis included dimethyl fumarate, fingolimod, teriflunomide, cladribine, siponimod, alemtuzumab, natalizumab, ocrelizumab, daclizumab, glatiramer acetate, peginterferon beta-1a, interferon beta-1a, and interferon beta-1b. The annual trends of the number of prescriptions, reimbursement expenditures, and costs were calculated. The average reimbursement per prescription was calculated as an estimate of the drug cost. RESULTS: The annual MS drug utilization increased from 85,209 prescriptions in 2008 to 223,604 in 2016, and then decreased to 194,877 in 2018. The annual reimbursement surged by 633% in the 10-year study period between 2008 and 2018, from almost $172 million in 2008 to more than $1.4 billion in 2017, and then to approximately $1.26 billion in 2018. The cost per prescription increased over time for most MS brand-name drugs (eg, from $2033 in 2008 to $5114 in 2018 for natalizumab, and from $19,138 in 2016 to $23,588 in 2018 for alemtuzumab). In 2008, self-injectable drugs dominated the market. In recent years, a shift has occurred in the utilization and reimbursement of MS drugs, with oral medications becoming predominant. CONCLUSION: The study findings indicate intermarket and interbrand competition among the MS specialty drugs. The growing utilization and spending trends for specialty MS medications are significant and sizable in the US Medicaid programs. Medicaid cost-containment strategy is warranted to control the economic burden of state budgets across the country.