Real-world Analysis Research Articles

Multicenter Real-World Analysis of Combined MET and EGFR Inhibition in Patients With Non-Small Cell Lung Cancer and Acquired MET Amplification or Polysomy After EGFR Inhibition

PurposeMET amplification is a common resistance mechanism to EGFR inhibition in EGFR-mutant non-small cell lung cancer (NSCLC). Several trials showed encouraging results with combined EGFR and MET inhibition (EGFRi/METi). However, MET amplification has been inconsistently defined and frequently included both polysomy and true amplification. MethodsThis is a multicenter, real-world analysis in patients with disease progression on EGFR inhibition and MET copy number gain (CNG), defined as either true amplification (MET to centromere of chromosome 7 ratio [MET-CEP7] ≥ 2) or polysomy (gene copy number ≥ 5, MET-CEP7 < 2). ResultsA total of 43 patients with MET CNG were included, 42 of whom were detected by FISH. Twenty-three, 7, and 14 received EGFRi/METi, METi, and SoC, respectively. Patients in the EGFRi/METi cohort exhibited a superior real-world clinical benefit rate, defined as stable disease or better, of 82% (95% confidence interval [CI], 60-95) compared to METi (29%, 4-71) and SoC (50%, 23-77). Median real-world progression-free survival was longer with EGFRi/METi with 9.8 vs. 4.3 months with METi (hazard ratio [HR], 0.19, 95% CI, 0.06-0.57) and 3.7 months with SoC (0.41, 0.18-0.91), respectively. Overall survival was numerically improved. Interaction analysis with treatment and type of CNG (amplification vs. polysomy) suggests that differences were exclusively driven by MET-amplified patients receiving EGFRi/METi (HR for OS, 0.09, 0.01-0.54). ConclusionIn this real-world study, EGFRi/METi showed clinical benefit over METi and SoC. Future studies should focus on the differential impact of the type of MET CNG with a focus on true MET amplification as predictor of response.

Routine cardiac biomarkers for the prediction of incident major adverse cardiac events in patients with glomerulonephritis: a real-world analysis using a global federated database

Rationale & objectiveGlomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis.Study DesignRetrospective cohort study.Setting & participantsData were obtained from TriNetX, a global federated health research network of electronic health records (EHR).Exposure or predictorBiomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL.OutcomesPrimary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome.Analytical Approach1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event.ResultsFollowing PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p < 0.0001). In the NTproBNP GN cohort, 1,686 (9%) developed composite MACE outcome HR 1.99; (95% CI, 1.86, 2.14, p < 0.0001).LimitationsThe data are derived from EHR for administrative purposes; therefore, there is the potential for data errors or missing data.ConclusionsIn GN, routinely available cardiac biomarkers can predict incident MACE. The results suggest the clinical need for cardiovascular and mortality risk profiling in glomerular disease using a combination of clinical and laboratory variables.

Exploring the Impact of Device Sourcing on Real-World Adherence and Cost Implications of Continuous Glucose Monitoring in Patients With Diabetes: Retrospective Claims Analysis.

Insurance benefit design influences whether individuals with diabetes who require a continuous glucose monitor (CGM) to provide real-time feedback on their blood glucose levels can obtain the CGM device from either a pharmacy or a durable medical equipment supplier. The impact of the acquisition channel on device adherence and health care costs has not been systematically evaluated. This study aims to compare the adherence rates for patients new to CGM therapy and the costs of care for individuals who obtained CGM devices from a pharmacy versus acquisition through a durable medical equipment supplier using retrospective claims analysis. Using the Mariner commercial claims database, individuals aged >18 years with documented diabetes and an initial CGM claim during the first quarter of 2021 (2021 Q1, index date) were identified. Patients had to maintain uninterrupted enrollment for a duration of 15 months but file no CGM claim during the 6 months preceding the index date. We used direct matching to establish comparable pharmacy and durable medical equipment cohorts. Outcomes included quarterly adherence, reinitiation, and costs for the period from 2021 Q1 to the third quarter of 2022 (2022 Q3). Between-cohort differences in adherence rates and reinitiation rates were analyzed using z tests, and cost differences were analyzed using 2-tailed t tests. Direct matching was used to establish comparable pharmacy and durable medical equipment cohorts. A total of 2356 patients were identified, with 1178 in the pharmacy cohort and 1178 in the durable medical equipment cohorts. Although adherence declined over time in both cohorts, the durable medical equipment cohort exhibited significantly superior adherence compared to the pharmacy cohort at 6 months (pharmacy n=615, 52% and durable medical equipment n=761, 65%; P<.001), 9 months (pharmacy n=579, 49% and durable medical equipment cohorts n=714, 61%; P<.001), and 12 months (pharmacy 48% and durable medical equipment n=714, 59%; P<.001). Mean annual total medical costs for adherent patients in the pharmacy cohort were 53% higher than the durable medical equipment cohort (pharmacy US $10,635 and durable medical equipment US $6967; P<.001). In nonadherent patients, the durable medical equipment cohort exhibited a significantly higher rate of therapy reinitiation during the period compared to the pharmacy cohort (pharmacy 61/613, 10% and durable medical equipment 108/485, 22%; P<.001). The results from this real-world claims analysis demonstrate that, in a matched set, individuals who received their CGM through a durable medical equipment supplier were more adherent to their device. For individuals who experienced a lapse in therapy, those whose supplies were provided through the durable medical equipment channel were more likely to resume use after an interruption than those who received their supplies from a pharmacy. In the matched cohort analysis, those who received their CGM equipment through a durable medical equipment supplier demonstrated a lower total cost of care.

Clinical burden and healthcare resource utilization associated with managing transfusion-dependent β-thalassemia in France

Objective To describe the clinical burden and healthcare resource utilization associated with managing transfusion-dependent β-thalassemia (TDT) in France. Methods We used the French National Health Data System (système national des données de santé) to identify eligible patients from January 1, 2012, to March 1, 2019. Inclusion criteria were a diagnosis of β-thalassemia, ≥8 red blood cell (RBC) transfusion episodes per year in ≥2 consecutive years following the diagnosis, and ≥1 year of follow-up data. Patients were excluded if medical records showed evidence of sickle cell disease, α-thalassemia, hereditary persistence of fetal hemoglobin, or hematopoietic stem cell transplant. Clinical complications, mortality, treatment use, and healthcare resource utilization were evaluated. Results Overall, 331 eligible patients with TDT were identified. Mean age was 26.1 (standard deviation [SD]: 18.0) years, and 50.5% were male. Common clinical complications were endocrine (26.0%), hepatobiliary (22.7%), and cardiopulmonary (18.7%). Fifteen (4.5%) patients died during follow-up, with a mortality rate of 1.16 deaths per 100 person-years (mean age of death: 52.5 years [SD: 22]). Patients had a mean of 13.5 (SD: 5.2) RBC transfusion episodes and 11.2 (SD: 5.3) iron chelation therapy treatments per year. Healthcare resource utilization was substantial, with a mean of 14.8 inpatient hospitalizations (including 13.8 mean inpatient day cases) and 16.9 outpatient prescriptions per patient per year. Conclusions Patients with TDT in France experience significant clinical complications, elevated mortality, and substantial healthcare resource utilization driven by frequent RBC transfusion episodes and inpatient hospitalizations. These results reinforce the need for disease-modifying therapies for this patient population.

Cost analysis of patiromer vs sodium zirconium cyclosilicate for the treatment of hyperkalemia in Spain and the UK

Background Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Published data have shown that potassium-binding polymer patiromer (Veltassa) is associated with reduced rates of severe edema and hospitalization for heart failure compared with sodium zirconium cyclosilicate (SZC, Lokelma) when treating hyperkalemia. The aim of this study was to evaluate the possible costs associated with these interventions in the Spanish and UK settings. Methods A cost-analysis model was developed in Microsoft Excel to compare the costs associated with patiromer and SZC for the management of hyperkalemia. Clinical event rates were taken from a published real-world comparative study, with the base case capturing the statistically significant reduction in severe edema with patiromer vs SZC and a sensitivity analysis also including the non-statistically significant reduction in hospitalization for heart failure. Country-specific costs, expressed in 2022 Euros (EUR) and British pounds sterling (GBP), were evaluated from a healthcare payer perspective and included pharmacy costs and costs of clinical events. Results Patiromer may be associated with cost savings of EUR 107 and GBP 630 per patient-year of treatment vs SZC in Spain and the UK, respectively. The majority of cost savings were due to the possible lower daily cost of patiromer compared with SZC. Including the difference in heart failure hospitalization rates in a sensitivity analysis led to greater cost savings with patiromer over SZC, increasing to EUR 460 and GBP 902 in Spain and the UK, respectively. Extrapolation of patient-level economic outcomes to a population level found that patiromer was associated with annual cost savings of EUR 30.6 million in Spain, and GBP 801.7 million in the UK vs SZC. Conclusions Patiromer has the potential to be cost saving vs SZC for the treatment of hyperkalemia in Spain and the UK based on the results of a real-world evidence analysis.

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023.

Donepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy. We retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age. Of the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18years, 16 in patients between 18 and 65years, and 113 in patients older than 65years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment. Our study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

Real-world analysis of the underdiagnosis, clinical outcomes and associated burden of hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) in the United States

BackgroundThrombotic microangiopathy (TMA) associated with hematopoietic stem cell transplantation (HSCT-TMA) is a serious post-transplant complication. Diagnosis is difficult due to overlapping symptoms with other conditions and a lack of universally adopted diagnostic criteria.MethodsThis retrospective, observational study investigated HSCT-TMA incidence between July 2009–August 2020 using the TriNetX US Electronic Medical Record database. Patients who underwent autologous or allogeneic HSCT procedures and had conditioning agents were stratified as follows: confirmed TMA (≥1 hemolytic uremic syndrome (HUS)/TMA diagnosis code), suspected TMA [no HUS/TMA code but met modified published Cho (adult) or Jodele (pediatric) diagnostic criteria (further information in main text), and non-TMA (met neither criteria). Baseline demographics, clinical characteristics and outcomes, and all-cause unadjusted healthcare resource utilization (HCRU) within 12-months of HSCT, were assessed. Statistical comparisons were against the non-TMA cohort (p&amp;lt;0.05).ResultsThe study included 16,809 adults and 901 pediatrics. Of these, 125 adults (0.7%) and 30 pediatrics (3.3%) had confirmed TMA, 3029 (18.0%) adults and 94 (10.4%) pediatrics had suspected TMA; 13,655 (81.2%) adults and 777 (86.2%) pediatrics met non-TMA criteria. Confirmed and suspected TMA incidences were higher after allogeneic HSCT in adults. In pediatrics, confirmed TMA incidence was higher following autologous transplantation, and suspected TMA higher after allogeneic transplantation. Confirmed and suspected TMA patients had significantly higher Charlson Comorbidity Indexes pre-HSCT and more post-HSCT complications. In adults with confirmed and suspected TMA, mortality estimates within 12-months of HSCT were significantly higher compared to non-TMA patients, and numerically higher in pediatrics. All confirmed and suspected TMA patients had significantly more ER visits, inpatient stays and ICU admissions. HCRU within 12-months of HSCT was higher in all confirmed TMA patients; ≤0.1% of patients with suspected TMA, and 25.6–50.0% of patients with confirmed TMA, received complement inhibitors.ConclusionsOur results demonstrate that incidence of HSCT-TMA in the real world, as per billing codes, is low compared with historical literature. However, a proportion of suspected TMA cases, based on diagnosis criteria, share similarly poor outcomes and HCRU. HSCT-TMA is likely underdiagnosed, or under-coded, in real world practice. Our study highlights the need for greater vigilance to this severe complication.

Burden of illness in patients with pulmonary hypertension due to interstitial lung disease: a real-world analysis

BackgroundPulmonary hypertension due to interstitial lung disease (PH-ILD) is associated with high rates of respiratory failure and death. Healthcare resource utilization (HCRU) and cost data are needed to characterize PH-ILD disease burden.MethodsA retrospective cohort analysis of the Truven Health MarketScan® Commercial Claims and Encounters Database and Medicare Supplemental Database between June 2015 to June 2019 was conducted. Patients with ILD were identified and indexed based on their first claim with a PH diagnosis. Patients were required to be 18 years of age on the index date and continuously enrolled for 12-months pre- and post-index. Patients were excluded for having a PH diagnosis prior to ILD diagnosis or the presence of other non-ILD, PH-associated conditions. Treatment patterns, HCRU, and healthcare costs were compared between the 12 months pre- versus 12 months post-index date.ResultsIn total, 122 patients with PH-ILD were included (mean [SD] age, 63.7 [16.6] years; female, 64.8%). The same medication classes were most frequently used both pre- and post-index (corticosteroids: pre-index 43.4%, post-index 53.5%; calcium channel blockers: 25.4%, 36.9%; oxygen: 12.3%, 25.4%). All-cause hospitalizations increased 2-fold, with 29.5% of patients hospitalized pre-index vs. 59.0% post-index (P < 0.0001). Intensive care unit (ICU) utilization increased from 6.6 to 17.2% (P = 0.0433). Mean inpatient visits increased from 0.5 (SD, 0.9) to 1.1 (1.3) (P < 0.0001); length of stay (days) increased from 5.4 (5.9) to 7.5 (11.6) (P < 0.0001); bed days from 2.5 (6.6) to 8.0 (16.3) (P < 0.0001); ICU days from 3.8 (2.3) to 7.0 (13.2) (P = 0.0362); and outpatient visits from 24.5 (16.8) to 32.9 (21.8) (P < 0.0001). Mean (SD) total all-cause healthcare costs increased from $43,201 ($98,604) pre-index to $108,387 ($190,673) post-index (P < 0.0001); this was largely driven by hospitalizations (which increased from a mean [SD] of $13,133 [$28,752] to $63,218 [$75,639] [P < 0.0001]) and outpatient costs ($16,150 [$75,639] to $25,604 [$93,964] [P < 0.0001]).ConclusionPH-ILD contributes to a high HCRU and cost burden. Timely identification, management, and treatment are needed to mitigate the clinical and economic consequences of PH-ILD development and progression.

A rapid approach with machine learning for quantifying the relative burden of antimicrobial resistance in natural aquatic environments

The massive use and discharge of antibiotics have led to increasing concerns about antimicrobial resistance (AMR) in natural aquatic environments. Since the dose-response mechanisms of pathogens with AMR have not yet been fully understood, and the antibiotic resistance genes and bacteria-related data collection via field sampling and laboratory testing is time-consuming and expensive, designing a rapid approach to quantify the burden of AMR in the natural aquatic environment has become a challenge. To cope with such a challenge, a new approach involving an integrated machine-learning framework was developed by investigating the associations between the relative burden of AMR and easily accessible variables (i.e., relevant environmental variables and adjacent land-use patterns). The results, based on a real-world case analysis, demonstrate that the quantification speed has been reduced from 3-7 days, which is typical for traditional measurement procedures with field sampling and laboratory testing, to approximately 0.5 hours using the new approach. Moreover, all five metrics for AMR relative burden quantification exceed the threshold level of 85%, with F1-score surpassing 0.92. Compared to logistic regression, decision trees, and basic random forest, the adaptive random forest model within the framework significantly improves quantification accuracy without sacrificing model interpretability. Two environmental variables, dissolved oxygen and resistivity, along with the proportion of green areas were identified as three key feature variables for the rapid quantification. This study contributes to the enrichment of burden analyses and management practices for rapid quantification of the relative burden of AMR without dose-response information.

Effectiveness and safety of finerenone in Chinese CKD patients without diabetes: a retrospective, real-world study.

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has previously demonstrated its efficacy and safety in chronic kidney disease (CKD) associated with diabetes mellitus. Given its therapeutic potential, finerenone has been preliminarily explored in clinical practice for non-diabetic CKD patients. The effectiveness and safety in this population require further investigation in a real-world setting. This retrospective, real-world analysis included non-diabetic CKD patients receiving finerenone. The main clinical outcomes assessed were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Serum potassium (sK+) levels were also monitored. Data were collected at baseline, and then at 1month and 3months following treatment initiation. Totally, 16 patients were included. There was a notable decrease in UACR from 1-month post-treatment, with a further reduction at 3months, resulting in a median reduction of 200.41mg/g (IQR, 84.04-1057.10mg/g; P = 0.028; percent change, 44.52% [IQR, 31.79-65.42%]). The average eGFR at baseline was 80.16ml/min/1.73m2, with no significant change after 1month (80.72ml/min/1.73m2, P = 0.594) and a slight numerical increase to 83.45ml/min/1.73m2 (P = 0.484) after 3months. During the 3-month follow-up, sK+ levels showed only minor fluctuations, with no significant differences compared to baseline, and remained within the normal range throughout the treatment period. No treatment discontinuation or hospitalization due to hyperkalemia was observed. In non-diabetic CKD patients, finerenone showed good effectiveness and safety within a 3-month follow-up period. This study provides valuable real-world evidence supporting the use of finerenone in non-diabetic CKD and highlights the need for future large-scale prospective research to further validate its efficacy.

Abiraterone Acetate Versus Enzalutamide Against Chemo-Naïve Castration-Resistant Prostate Cancer With Full-Dose Induction.

Purpose We recently released the multi-institutional real-world analysis about the difference in survival outcomes between abiraterone acetate and enzalutamide against chemo-naïve castration-resistant prostate cancer (CRPC) in a first-line setting. Although reduced dose induction cases were included in that analysis, induction dose reduction might correlate with reduced efficacy. In this study, we analyzed full-dose induction subgroups from our overall cohort and investigated the true difference in efficacy between these agents. Methods A total of 220 chemotherapy-naïve CRPC cases treated with full-dose induction of first-line androgen receptor signaling inhibitor (ARSI) were analyzed. Outcome measures were prostate-specific antigen (PSA) response, PSA progression-free survival (PSA-PFS), treatment failure-free survival (TFF), cancer-specific survival (CSS), and overall survival (OS). Results Abiraterone acetateand enzalutamide were administered to 58 and 162 patients, respectively. The median PSA response rate (-65.4% (A) and -81.5% (E), p = 0.0252), PSA decline ≥ 90% (22.4% (A) and 37.0% (E), p = 0.0478), PSA-PFS (median four months (A) and seven months (E), p = 0.00833), TFF (median six months (A) and 15 months (E), p<0.0001), CSS (median 45 months (A) and not reached (E), p < 0.0001), and OS (median 34 months (A) and 80 months (E), p<0.001) were significantly better in the E group. Conclusion This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes in the full-dose induction cohort.

Machine learning-based causal inference for evaluating intervention in travel behaviour research: A difference-in-differences framework

Causal inference with the difference-in-differences (DID) framework is popular in identifying causal effects with observational data and has started to be applied in recent travel behaviour studies. Most relevant transportation research adopts the conventional linear parametric DID model, which is known to be inflexible and restrictive. This study applies non-parametric DID estimators facilitated by machine learning (ML) models for causal inference in a variety of data scenarios. Semi-parametric and doubly robust estimators are established and integrated with the ML-based cross-fitting pipeline. Simulation studies and empirical case studies are conducted to showcase the ability of ML-based DID to detect causal effects from both simulated and real-world datasets. Results suggest that the proposed methods outperform conventional DID models in all data scenarios. Light working models are generally preferred over hyperparameter-dependent ones for their comparable performance, lower computational burden, and higher levels of compatibility to real-world empirical analysis. Empirical case studies also demonstrate how the proposed DID method could be applied to evaluate the impacts of various interventions on travel behaviour in different contexts. The present study adds to the existing travel behaviour literature by leveraging machine learning algorithms and non-parametric estimators to the impact evaluation of external interventions on travel characteristics and expanding the application of causal inference approaches in transportation research.

Work loss among privately insured employees with overweight and obesity in the United States.

Rising obesity rates in the workforce are accompanied by a hidden cost burden to employers due to work productivity loss. Understanding the impact of obesity on work productivity is essential for employers to provide tailored weight loss interventions in the workplace. To measure work loss and associated productivity costs among employees with overweight/obesity compared with employees with normal weight. This retrospective cohort study used the MerativeTM MarketScan® Health and Productivity Management Database to identify adult employees with ≥1 diagnosis code reporting a body mass index (BMI) between 1/1/2015-12/31/2019. Based on the earliest BMI, employees were assigned to normal weight (BMI 19-24.9), overweight (BMI 25-29.9), obesity class 1 (BMI 30-34.9), obesity class 2 (BMI 35-39.9), and obesity class 3 (BMI ≥40) cohorts. Among employees with data for each work loss category (absenteeism, short-term disability [STD], long-term disability [LTD], worker's compensation [WC]) during the 12-month follow-up, the percentage of employees with work loss, number of hours/days lost, and associated productivity costs were reported. 719,482 employees (normal weight: 106,631, overweight: 230,637, obesity class 1: 185,850, obesity class 2: 101,909, obesity class 3: 94,455) were included. Outcomes increased with each higher BMI category for the mean number of absence hours ([in order of BMI category]: 262, 273, 285, 290, 304) and percentage of employees with a claim (STD: 6.8%, 7.6%, 9.7%, 11.7%, 17.0%; LTD: 0.4%, 0.4%, 0.5%, 0.6%, 0.8%; WC: 2.7%, 2.8%, 3.4%, 3.6%, 3.5%). Estimated costs to the employer associated with absenteeism, STD, LTD, and WC were $1,036, $611, $38, and $95 higher per year (respectively) in the obesity class 3 cohort relative to the normal weight cohort. This real-world analysis demonstrated that employees with overweight/obesity had higher loss of work productivity compared with employees with normal weight. Further studies are warranted to determine the long-term impacts on work productivity loss if overweight and obesity are left untreated.

Recommendations for the selection of nucleoside analogues as antihuman herpesvirus drugs: a real-world analysis of reported cases from the FDA adverse event reporting system

ABSTRACT Objective The aim of this study is to provide guidance for refining medication protocols, developing alternative strategies, and enhancing protection against herpesvirus infections in personalized clinical settings. Methods Adverse drug events (ADEs) data for anti-herpesvirus from the first quarter of 2004 to the fourth quarter of 2022 were collected from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) methods for data mining. Results A total of 18,591, 24,206, 6,150, and 419 reports of ADEs associated with acyclovir (ACV), valacyclovir (VACV), ganciclovir (GCV), and famciclovir (FCV) were screened and extracted from the FAERS. In this study, the report summarized the high frequency and strong correlation of ADEs for the four drugs at the Preferred Term (PT) level. Additionally, the analysis also identified the relationship between ADEs and factors such as age, gender, and severity of outcome at the System Organ Class (SOC) level. Conclusion The safety reports for the four-nucleoside analogue anti-herpesvirus drugs are diverse and interconnected. Dosing for patients with herpesvirus infections should be tailored to their specific conditions and the potential risk of disease.

Differential Adherence to Free and Single-Pill Combination of Rosuvastatin/Ezetimibe: Findings from a Real-World Analysis in Italy.

Adherence to cardiovascular drug treatment can significantly benefit from a reduced pill burden, but data on this matter derived from real-life settings are currently scanty. This analysis assessed the possible changes in adherence in patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free multi-pill combination who switched to ROS/EZE as single-pill combination in the setting of real clinical practice in Italy. A retrospective analysis was conducted on the administrative databases for a catchment area of about sevenmillion health-assisted residents. Adults receiving ROS/EZE as a single-pill combination from January 2010 to June 2020 (followed up to 2021) were identified. The date of the first prescription of single-pill combination of ROS/EZE was considered as the index date. The analysis included the users of ROS/EZE as a free combination during the year before the index date. Baseline demographic and clinical characteristics were collected during the period of data availability prior to the index date. Adherence to therapy was evaluated as proportion of days covered (PDC), namely the percentage of days during which a patient had access to medication, in the 12-month interval preceding or following the index date (PDC < 25% non-adherence; PDC = 25-75% partial adherence; PDC > 75% adherence). A total of 1219 patients (61.1% male, aged 66.2 ± 10.4years) were included. Cardiovascular comorbidities were found in 83.3% of them, diabetes in 26.4%, and a combination of both in 16.2%. Single-pill combination of ROS/EZE was associated with a higher proportion of adherent patients compared to free-pill combination (75.2% vs 51.8%, p < 0.001). This real-world analysis suggested that switching from a regimen based on separate pills to one based on a single-pill combination resulted in improved adherence to ROS/EZE therapy.

Treatment modification patterns of glucose-lowering agents in Saudi Arabia: A retrospective real-world data analysis

AimThe growing number of antidiabetics has broadened therapeutic options, leading to heterogeneity in prescribing patterns. Studies identifying antidiabetics modification patterns are lacking in Saudi Arabia. Therefore, the aim of this study is to describe modification patterns in Saudi patients. MethodsPatients ≥ 18 years old with at least one antidiabetic between 2016 and 2022 were included. Follow-up started from the earliest to the last prescription.Two modification types were evaluated: “add-on,” prescribing new antidiabetics within a treatment episode, and “switching”, starting a new treatment episode after the preceding ends. Descriptive statistics were used to characterize patients and estimate events proportions. ResultsOf 122,291 patients, 47.2 % had treatment interruption or modification, totaling 303,781 events. Interruptions accounted for 54 %, add-on for 11 %, and switching for 35 %. The median time to first event was 159 days. The most add-on included dipeptidyl peptidase-4 inhibitor (DPP-4) inhibitors to biguanide and sulfonylurea (8 %), and sulfonylurea to biguanide (8 %). Among 106,405 switching events, 23 % shifted from dual to monotherapy and 17 % from monotherapy to dual therapy. ConclusionNearly half of patients experienced modifications or interruptions, with notable shifts between monotherapies and dual therapies. These findings highlight the evolving landscape of treatment patterns in Saudi Arabia and guide future research and decision-making.

Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis

BackgroundManagement of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year.MethodsA retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed.ResultsAll groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy.ConclusionsOur data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO.Trial registrationNo registration, retrospective analysis.Graphical

O-090 The paradox of choice in double (DET) versus single (SET) embryo transfer: more is less!

Abstract Study question Do couples with two blastocysts opting for DET have a better outcome than those with SET, freezing of the second and eventually subsequent second SET? Summary answer More children are born after 2x SET with the overwhelming majority (96.3%) of these children being singletons, whereas after 1x DET 49.5% are multiples What is known already According to the most recent publication of the European IVF Monitoring Consortium, in 33 European countries reporting data on these topics SET is performed in 55.4% of fresh transfers whereas in the other cycles, two, three and even 4 or more embryos are transferred, often resulting in twin or higher order multiple pregnancies, but there is no information on the duration of culture and number of embryos available in these cycles. The German IVF-Registry (D·I·R) has collected more than 2.4 million datasets from German ART clinics since 1997 and has access to these data and other relevant patient characteristics. Study design, size, duration Retrospective real-world data analysis from 140 German IVF-centers collected by the German IVF-Registry (D·I·R) between 2017 and 2021. Data were collected prospectively, controlled for plausibility, and evaluated anonymously. Treatment cycles from four years between January 1st, 2017 and December 31st, 2020 were evaluated. Pregnancy outcome was monitored until end of 2021. All couples having at least 2 blastocysts available for fresh transfer in their 1st treatment cycle were identified and included in the analysis. Participants/materials, setting, methods 19,702 women with similar characteristics (i.e. first cycle of IVF or ICSI, fresh embryo transfer, two blastocysts available on the day of fresh ET, signed consent to freeze supernumerous 2PN or embryos) were stratified into two groups. Therapy results after 1x DET (fresh) vs. 1x SET (fresh) plus 1x SET (frozen-thawed) were evaluated for clinical pregnancy rates, life birth rates, number and order of multiple pregnancies, multiple deliveries, and total number of children born. Main results and the role of chance From 19,702 women meeting the inclusion criteria, 9,643 (48.9%) had a DET and 10,059 (51.1%) had a SET. The age of patients in both groups was not significantly different (DET: 34.1y vs. SET: 33.7y). As expected, ongoing pregnancy rate (OPR) and life birth rate (LBR) after DET were higher compared to SET (OPR: 49.4% vs. 42.3%; LBR 38.5% vs. 33.1%). Those opting for SET however had the chance of a second SET with the frozen-thawed blastocyst and so far, from 7,207 women who started the frozen embryo transfer cycle (FET), 6,431 had the second blastocyst transferred with a CPR of 29.5% and LBR of 19.4% per started FET. After DET, only 67.4% of deliveries were singletons. Of the 32.6% multiples, 97.4% were twins, 2.5% triplets and 0.1% quadruplets. After fresh (or frozen) SET, 98.4% (97.6%) of deliveries were singletons, the remaining were solely twins (1.6% (2.4%)) and no higher order multiples. Per 1,000 women having a DET, 514 children were born and 49.5% of those were either twins, triplets or quadruplets. Per 1,000 women after 2x SET, more children were born (536), and only 3.7% of those were twins, no triplets or quadruplets. Limitations, reasons for caution In this retrospective analysis, the reasons of the couples for the decision of having SET or DET is not known. One potential bias caused by the additional costs for freezing/thawing (not reimbursable in Germany) can be excluded (only those having opted to freeze supernumerous 2PN or embryos were evaluated). Wider implications of the findings Couples undergoing IVF understandably want to maximize their chances of success, sometimes opting for a DET, underestimating the number of multiples and neglecting the risks. We clearly show that after DET every second child is a twin, triplet or quadruplet, and even more children are born after two successive SETs. Trial registration number not applicable

Trends in Medicare Costs of Hyperbaric Oxygen Therapy, 2013 through 2022

ABSTRACT Gelly H, Fife C, Walker D, Eckert K. Trends in Medicare Costs of Hyperbaric Oxygen Therapy, 2013 through 2022. Undersea Hyperb Med. 2024 Second Quarter; 51(2):137-144. Objective: To analyze Hyperbaric Oxygen Therapy Registry (HBOTR) data to estimate the Medicare costs of hyperbaric oxygen therapy (HBO2) based on standard treatment protocols and the annual mean number of treatments per patient reported by the registry. Methods: We performed a secondary analysis of deidentified data for all payers from 53 centers registered in the HBOTR from 2013 to 2022. We estimated the mean annual per-patient costs of HBO2 based on Medicare (outpatient facility + physician) reimbursement fees adjusted to 2022 inflation using the Medicare Economic Index. Costs were calculated for the annual average number of treatments patients received each year and for a standard 40-treatment series. We estimated the 2022 costs of standard treatment protocols for HBO2 indications treated in the outpatient setting. Results: Generally, all costs decreased from 2013 to 2022. The facility cost per patient per 40 HBO2 treatments decreased by 10.7% from $21,568.58 in 2013 to $19,488.00 in 2022. The physician cost per patient per 40 treatments substantially decreased by -37.8%, from $5,993.16 to $4,346.40. The total cost per patient per 40 treatments decreased by 15.6% from $27,561.74 to $23,834.40. In 2022, a single HBO2 session cost $595.86. For different indications, estimated costs ranged from $2,383.4-$8,342.04 for crush injuries to $17,875.80-$35,751.60 for diabetic foot ulcers and delayed radiation injuries. Conclusions: This real-world analysis of registry data demonstrates that the actual cost of HBO2 is not nearly as costly as the literature has insinuated, and the per-patient cost to Medicare is decreasing, largely due to decreased physician costs.

Multiple testing of interval composite null hypotheses using randomized p-values

Equivalence tests are statistical hypothesis testing procedures that aim to establish practical equivalence rather than the usual statistical significant difference. These testing procedures are frequent in “bioequivalence studies," where one would wish to show that, for example, an existing drug and a new one under development have comparable therapeutic effects. In this article, we propose a two-stage randomized (RAND2) p-value that depends on a uniformly most powerful (UMP) p-value and an arbitrary tuning parameter c∈[0,1]\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$c\\in [0,1]$$\\end{document} for testing an interval composite null hypothesis. We investigate the behavior of the distribution function of the two p-values under the null hypothesis and alternative hypothesis for a fixed significance level t∈(0,1)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$t\\in (0,1)$$\\end{document} and varying sample sizes. We evaluate the performance of the two p-values in estimating the proportion of true null hypotheses in multiple testing. We conduct a family-wise error rate control using an adaptive Bonferroni procedure with a plug-in estimator to account for the multiplicity that arises from our multiple hypotheses under consideration. The various claims in this research are verified using a simulation study and real-world data analysis.