Clinical observation of Otitis Media Secretory during Covid-19.

OBJECTIVE: This study aims to analyze the onset of otitis media secretory, the peak period of infection with the Omicron strain of SARS-CoV-2 virus, and the time of transmigration during a pandemic of the Omicron strain. Additionally, the study aims to investigate to study the presence of SARS-CoV-2 virus in the middle ear cavity of patients with otitis media secretory and the survival time through a new method for detecting SARS-CoV-2 virus antigen in middle ear effusion. METHODS: Retrospective comparison of the incidence of otitis media secretory during infection with SARS-CoV-2 virus Omicron strain from December 15, 2022, to January 15, 2023, versus the noninfection period from December 15, 2021, to January 15, 2022. We used a questionnaire star application to investigate the demographic and epidemiological characteristics of the 40 patients with otitis media secretory who participated in this study were investigated. A novel coronavirus (2019-nCoV) antigen detection kit (colloidal gold method) was used to detect middle ear effusion in patients with otitis media secretory. The data were statistically analyzed using SPSS 29.0 software. The measurement data are expressed as x ± s , the count data are expressed as the number of cases (%), and the data were compared using the χ 2 test. p < 0.05 indicated a statistically significant difference. RESULTS: During the SARS-CoV-2 virus Omicron strain pandemic, the incidence of otitis media secretory increased by 15% compared with the noninfection period. The peak infection period for the SARS-CoV-2 virus Omicron strain was December 25, 2022, and December 15, 2022, and the peak time of conversion was 7 to 9 days after the infection. Middle ear effusion SARS-CoV-2 virus antigen testing was performed in patients with otitis media secretory after conversion; 5 patients (12%) were positive, and 35 patients (88%) were negative. The disease duration in patients with negative results was more than 3 weeks. CONCLUSIONS: Otitis media secretory is one of the most common ear complications after infection with the Omicron strain of SARS-CoV-2 virus, and the significantly higher incidence is associated with middle ear viral infection. Middle ear effusion SARS-CoV-2 virus antigen test detected the virus, which survived longer in the middle ear effusion than in the nasal cavity. The middle ear effusion test can detect SARS-CoV-2 virus antigen and determine whether the organism contains virus residue.

Approval, Evidence, and "Off-Label" Device Utilization: The Patent Foramen Ovale Closure Story.

BACKGROUND: Following regulatory approval, medical devices may be used "off-label." Patent foramen ovale (PFO) closure is indicated to reduce recurrent stroke but has been proposed for other indications, including migraine, transient ischemic attack, and diving decompression illness. We sought to evaluate PFO closure rates and indications relative to the timing of regulatory approval and publication of key randomized trials. METHODS: We performed a retrospective cohort study using the OptumLabs Data Warehouse of US commercial insurance enrollees from 2006 to 2019. We quantified PFO closure among individuals with ≥2 years of preprocedure coverage to establish indications, classified hierarchically as stroke/systemic embolism, migraine, transient ischemia attack, or other. RESULTS: We identified 5315 patients undergoing PFO closure (51.8% female, 29.2%≥60 years old), which increased from 4.75 per 100 000 person-years in 2006 to 6.60 per 100 000 person-years in 2019. Patients aged ≥60 years accounted for 29.2% of closures. Procedure volumes corresponded weakly with supportive clinical publications and device approval. Among patients with PFO closure, 58.6% underwent closure for stroke/systemic embolism, 10.2% for transient ischemia attack, 8.8% for migraine, and 22.4% for other indications; 17.6% of patients had atrial fibrillation at baseline; and 11.9% developed atrial fibrillation postprocedure. Those aged ≥60 years and male were less likely to undergo closure for migraine than stroke/systemic embolism. CONCLUSIONS: From 2006 to 2019, PFO closure use was consistently low and corresponded weakly with clinical trial publications and regulatory status. Nearly half of patients underwent PFO closure for indications unapproved by the Food and Drug Administration. Regulators and payers should coordinate mechanisms to promote utilization for approved indications to ensure patient safety and should facilitate clinical trials for other possible indications.

Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial.

Objective: To build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving and maintaining glycaemic control in adults with type 2 diabetes. Design: Emulation of a target trial. Setting: Medical and pharmacy claims data from the OptumLabs Data Warehouse, a de-identified US national dataset of beneficiaries of commercially insured and Medicare Advantage plans, 29 March 2013 to 30 June 2021. Participants: Adults (≥18 years) with type 2 diabetes who first started taking glimepiride, sitagliptin, liraglutide, insulin glargine, or canagliflozin between 29 March 2013 and 30 June 2021. Participants were treatment naive or were receiving metformin monotherapy at the time of starting the study drug. Main outcome measures: The main outcomes were time to primary and secondary metabolic failure of the assigned treatment, calculated as days to haemoglobin A1c levels of ≥7.0% and >7.5%, respectively. Secondary metabolic, cardiovascular, and microvascular outcomes were analysed as specified in the GRADE statistical analysis plan. Propensity scores were estimated with the gradient boosting method, and inverse propensity score weighting was used to emulate randomisation to the treatment groups, which were then compared with Cox proportional hazards regression. Results: The study cohort included participants starting treatment with glimepiride (n=20 511), liraglutide (n=5569), sitagliptin (n=13 039), insulin glargine (n=7262), and canagliflozin (n=5290). The insulin glargine arm was excluded because of insufficient control of confounding. Median times to primary metabolic failure were 439 (95% confidence interval 400 to 489) days in the canagliflozin arm, 439 (426 to 453) days in the glimepiride arm, 624 (567 to 731) days in the liraglutide arm, and 461 (442 to 482) days in the sitagliptin arm. Median time to secondary metabolic failure was also longest in the liraglutide arm. Adults receiving liraglutide had the lowest one year cumulative incidence rate of primary metabolic failure (0.37, 95% confidence interval 0.35 to 0.40) followed by sitagliptin (0.44, 0.43 to 0.45), glimepiride (0.45, 0.44 to 0.45), and canagliflozin (0.46, 0.44 to 0.48). Similarly, the one year cumulative incidence rate of secondary metabolic failure was 0.27 (0.25 to 0.29) in the canagliflozin arm, 0.28 (0.27 to 0.29) in the glimepiride arm, 0.23 (0.21 to 0.26) in the liraglutide arm, and 0.28 (0.27 to 0.29) in the sitagliptin arm. No differences were observed between the study arms in the rates of microvascular and macrovascular complications. Conclusions: In this target trial emulation of an expanded GRADE study framework, liraglutide was more effective in achieving and maintaining glycaemic control as a second line glucose lowering drug than canagliflozin, sitagliptin, or glimepiride.

Assessing the use of observational methods and real-world data to emulate ongoing randomized controlled trials.

BACKGROUND/AIMS: There has been growing interest in better understanding the potential of observational research methods in medical product evaluation and regulatory decision-making. Previously, we used linked claims and electronic health record data to emulate two ongoing randomized controlled trials, characterizing the populations and results of each randomized controlled trial prior to publication of its results. Here, our objective was to compare the populations and results from the emulated trials with those of the now-published randomized controlled trials. METHODS: This study compared participants' demographic and clinical characteristics and study results between the emulated trials, which used structured data from OptumLabs Data Warehouse, and the published PRONOUNCE and GRADE trials. First, we examined the feasibility of implementing the baseline participant characteristics included in the published PRONOUNCE and GRADE trials' using real-world data and classified each variable as ascertainable, partially ascertainable, or not ascertainable. Second, we compared the emulated trials and published randomized controlled trials for baseline patient characteristics (concordance determined using standardized mean differences <0.20) and results of the primary and secondary endpoints (concordance determined by direction of effect estimates and statistical significance). RESULTS: The PRONOUNCE trial enrolled 544 participants, and the emulated trial included 2226 propensity score-matched participants. In the PRONOUNCE trial publication, one of the 32 baseline participant characteristics was listed as an exclusion criterion on ClinicalTrials.gov but was ultimately not used. Among the remaining 31 characteristics, 9 (29.0%) were ascertainable, 11 (35.5%) were partially ascertainable, and 10 (32.2%) were not ascertainable using structured data from OptumLabs. For one additional variable, the PRONOUNCE trial did not provide sufficient detail to allow its ascertainment. Of the nine variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 6 (66.7%). The primary endpoint of time from randomization to the first major adverse cardiovascular event and secondary endpoints of nonfatal myocardial infarction and stroke were concordant between the emulated trial and published randomized controlled trial. The GRADE trial enrolled 5047 participants, and the emulated trial included 7540 participants. In the GRADE trial publication, 8 of 34 (23.5%) baseline participant characteristics were ascertainable, 14 (41.2%) were partially ascertainable, and 11 (32.4%) were not ascertainable using structured data from OptumLabs. For one variable, the GRADE trial did not provide sufficient detail to allow for ascertainment. Of the eight variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 4 (50.0%). The primary endpoint of time to hemoglobin A1c ≥7.0% was mostly concordant between the emulated trial and the published randomized controlled trial. CONCLUSION: Despite challenges, observational methods and real-world data can be leveraged in certain important situations for a more timely evaluation of drug effectiveness and safety in more diverse and representative patient populations.

Comparative Effectiveness of Anticoagulants in Patients With Cancer-Associated Thrombosis.

Importance: Patterns of clinical utilization and comparative effectiveness of anticoagulants for cancer-associated thrombosis (CAT) remain largely unexplored. Objectives: To assess patterns of and factors associated with anticoagulant use and to evaluate the comparative effectiveness of contemporary anticoagulants in patients with active cancer in a clinical setting. Design, Setting, and Participants: This retrospective cohort study obtained deidentified OptumLabs electronic health record claims data from January 1, 2012, to September 30, 2019. Adult patients (≥18 years of age) with a primary cancer diagnosis (except skin cancer) during at least 1 inpatient or 2 outpatient visits within 6 months before the venous thromboembolism (VTE) date were included. Data were analyzed from April 2020 to September 2021. Exposures: The patients were grouped according to the anticoagulant prescribed: (1) direct oral anticoagulants (DOACs), (2) low-molecular-weight heparin (LMWH), and (3) warfarin. Main Outcomes and Measures: Odds ratios (ORs) were used to present the association between factors of interest and utilization of anticoagulants. Main efficacy outcomes included risk of VTE recurrence and all-cause mortality. Main safety outcomes included the risk of hospitalization due to major bleeding. Relative treatment effect estimates were expressed as hazard ratios (HRs) with 95% CIs. Results: This study included 5100 patients (mean [SD] age, 66.3 [12.3] years; 2670 [52.4%] women; 799 [15.7%] Black, 389 [7.6%] Hispanic, and 3559 [69.8%] White individuals). Overall, 2512 (49.3%), 1488 (29.2%), and 1460 (28.6%) filled prescriptions for DOACs, LMWH, and warfarin, respectively. The median (IQR) treatment duration was 3.2 (1.0-6.5) months for DOACs, 3.1 (1.0-6.8) months for warfarin, and 1.8 (0.9-3.8) months for LWMH. Patients with lung (OR, 2.07; 95% CI, 1.12-3.65), urological (OR, 1.94; 95% CI,1.08-3.49), gynecological (OR, 4.25; 95% CI, 2.31-7.82), and colorectal (OR, 2.26; 95% CI, 1.20-4.32) cancer were associated with increased prescriptions for LMWH compared with DOACs. LMWH (HR, 1.47; 95% CI, 1.14-1.90) and warfarin (HR, 1.46; 95% CI, 1.13-1.87) were associated with an increased risk of VTE recurrences compared with DOACs. LMWH was associated with an increased risk of major bleeding (HR, 2.27; 95% CI, 1.62-3.20) and higher all-cause mortality (HR, 1.61; 95% CI, 1.15-2.25) compared with DOACs. Conclusions and Relevance: In this comparative effectiveness study of claims-based data, patients with CAT received anticoagulation for a remarkably short duration in clinical settings. DOACs was associated with a lower risk of VTE recurrence, major bleeding, and mortality. Warfarin may still be considered for patients with contraindications to DOACs and those with poor persistence on LMWH.

Impact of a High-Risk, Ambulatory COVID-19 Remote Patient Monitoring Program on Utilization, Cost, and Mortality.

OBJECTIVE: To evaluate care utilization, cost, and mortality among high-risk patients enrolled in a coronavirus disease 2019 (COVID-19) remote patient monitoring (RPM) program. METHODS: This retrospective analysis included patients diagnosed with COVID-19 at risk for severe disease who enrolled in the RPM program between March 2020 and October 2021. The program included in-home technology for symptom and physiologic data monitoring with centralized care management. Propensity score matching established matched cohorts of RPM-engaged (defined as ≥1 RPM technology interactions) and non-engaged patients using a logistic regression model of 59 baseline characteristics. Billing codes and the electronic death certificate system were used for data abstraction from the electronic health record and reporting of care utilization and mortality endpoints. RESULTS: Among 5796 RPM-enrolled patients, 80.0% engaged with the technology. Following matching, 1128 pairs of RPM-engaged and non-engaged patients comprised the analysis cohorts. Mean patient age was 63.3 years, 50.9% of patients were female, and 81.9% were non-Hispanic White. Patients who were RPM-engaged experienced significantly lower rates of 30-day, all-cause hospitalization (13.7% vs 18.0%, P=.01), prolonged hospitalization (3.5% vs 6.7%, P=.001), intensive care unit admission (2.3% vs 4.2%, P=.01), and mortality (0.5% vs 1.7%; odds ratio, 0.31; 95% CI, 0.12 to 0.78; P=.01), as well as cost of care ($2306.33 USD vs $3565.97 USD, P=0.04), than those enrolled in RPM but non-engaged. CONCLUSION: High-risk COVID-19 patients enrolled and engaged in an RPM program experienced lower rates of hospitalization, intensive care unit admission, mortality, and cost than those enrolled and non-engaged. These findings translate to improved hospital bed access and patient outcomes.

The investigation of construction and clinical application of image recognition technology assisted bronchoscopy diagnostic model of lung cancer.

Background: The incidence and mortality of lung cancer ranks first in China. Bronchoscopy is one of the most common diagnostic methods for lung cancer. In recent years, image recognition technology(IRT) has been more and more widely studied and applied in the medical field. We developed a diagnostic model of lung cancer under bronchoscopy based on deep learning method and tried to classify pathological types. Methods: A total of 2238 lesion images were collected retrospectively from 666 cases of lung cancer diagnosed by pathology in the bronchoscopy center of the Third Xiangya Hospital from Oct.01 2017 to Dec.31 2020 and 152 benign cases from Jun.01 2015 to Dec.31 2020. The benign and malignant images were divided into training, verification and test set according to 7:1:2 respectively. The model was trained and tested based on deep learning method. We also tried to classify different pathological types of lung cancer using the model. Furthermore, 9 clinicians with different experience were invited to diagnose the same test images and the results were compared with the model. Results: The diagnostic model took a total of 30s to diagnose 467 test images. The overall accuracy, sensitivity, specificity and area under curve (AUC) of the model to differentiate benign and malignant lesions were 0.951, 0.978, 0.833 and 0.940, which were equivalent to the judgment results of 2 doctors in the senior group and higher than those of other doctors. In the classification of squamous cell carcinoma (SCC) and adenocarcinoma (AC), the overall accuracy was 0.745, including 0.790 for SCC, 0.667 for AC and AUC was 0.728. Conclusion: The performance of our diagnostic model to distinguish benign and malignant lesions in bronchoscopy is roughly the same as that of experienced clinicians and the efficiency is much higher than manually. Our study verifies the possibility of applying IRT in diagnosis of lung cancer during white light bronchoscopy.

Emulating the GRADE trial using real world data: retrospective comparative effectiveness study.

OBJECTIVE: To emulate the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) trial using real world data before its publication. GRADE directly compared second line glucose lowering drugs for their ability to lower glycated hemoglobin A1c (HbA1c). DESIGN: Observational study. SETTING: OptumLabs® Data Warehouse (OLDW), a nationwide claims database in the US, 25 January 2010 to 30 June 2019. PARTICIPANTS: Adults with type 2 diabetes and HbA1c 6.8-8.5% while using metformin monotherapy, identified according to the GRADE trial specifications, who also used glimepiride, liraglutide, sitagliptin, or insulin glargine. MAIN OUTCOME MEASURES: The primary outcome was time to HbA1c ≥7.0%. Secondary outcomes were time to HbA1c >7.5%, incident microvascular complications, incident macrovascular complications, adverse events, all cause hospital admissions, and all cause mortality. Propensity scores were estimated using the gradient boosting machine method, and inverse propensity score weighting was used to emulate randomization of the treatment groups, which were then compared using Cox proportional hazards regression. RESULTS: 8252 people were identified (19.7% of adults starting the study drugs in OLDW) who met eligibility criteria for the GRADE trial (glimepiride arm=4318, liraglutide arm=690, sitagliptin arm=2993, glargine arm=251). The glargine arm was excluded from analyses owing to small sample size. Median times to HbA1c ≥7.0% were 442 days (95% confidence interval 394 to 480 days) for glimepiride, 764 (741 to not calculable) days for liraglutide, and 427 (380 to 483) days for sitagliptin. Liraglutide was associated with lower risk of reaching HbA1c ≥7.0% compared with glimepiride (hazard ratio 0.57, 95% confidence interval 0.43 to 0.75) and sitagliptin (0.55, 0.41 to 0.73). Results were consistent for the secondary outcome of time to HbA1c >7.5%. No significant differences were observed among treatment groups for the remaining secondary outcomes. CONCLUSIONS: In this emulation of the GRADE trial, liraglutide was statistically significantly more effective at maintaining glycemic control than glimepiride or sitagliptin when added to metformin monotherapy. Generating timely evidence on medical treatments using real world data as a complement to prospective trials is of value.

Artificial intelligence-guided screening for atrial fibrillation using electrocardiogram during sinus rhythm: a prospective non-randomised interventional trial.

BACKGROUND: Previous atrial fibrillation screening trials have highlighted the need for more targeted approaches. We did a pragmatic study to evaluate the effectiveness of an artificial intelligence (AI) algorithm-guided targeted screening approach for identifying previously unrecognised atrial fibrillation. METHODS: For this non-randomised interventional trial, we prospectively recruited patients with stroke risk factors but with no known atrial fibrillation who had an electrocardiogram (ECG) done in routine practice. Participants wore a continuous ambulatory heart rhythm monitor for up to 30 days, with the data transmitted in near real time through a cellular connection. The AI algorithm was applied to the ECGs to divide patients into high-risk or low-risk groups. The primary outcome was newly diagnosed atrial fibrillation. In a secondary analysis, trial participants were propensity-score matched (1:1) to individuals from the eligible but unenrolled population who served as real-world controls. This study is registered with ClinicalTrials.gov, NCT04208971. FINDINGS: 1003 patients with a mean age of 74 years (SD 8·8) from 40 US states completed the study. Over a mean 22·3 days of continuous monitoring, atrial fibrillation was detected in six (1·6%) of 370 patients with low risk and 48 (7·6%) of 633 with high risk (odds ratio 4·98, 95% CI 2·11-11·75, p=0·0002). Compared with usual care, AI-guided screening was associated with increased detection of atrial fibrillation (high-risk group: 3·6% [95% CI 2·3-5·4] with usual care vs 10·6% [8·3-13·2] with AI-guided screening, p<0·0001; low-risk group: 0·9% vs 2·4%, p=0·12) over a median follow-up of 9·9 months (IQR 7·1-11·0). INTERPRETATION: An AI-guided targeted screening approach that leverages existing clinical data increased the yield for atrial fibrillation detection and could improve the effectiveness of atrial fibrillation screening. FUNDING: Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery.

Rates of, and factors associated with, switching among generic levothyroxine preparations in commercially insured American adults.

IMPORTANCE: Some practice guidelines warn against generic L-thyroxine preparation switching. OBJECTIVE: To examine the rates of generic L-thyroxine preparation switching within one year of initiating L-thyroxine, and to examine factors associated with switching. DESIGN AND SETTING: Retrospective study using national data from a large administrative claims database from January 2008 through November 2018. PATIENTS: Medicare or commercially insured adults (≥18 years) who filled a generic L-thyroxine preparation. MAIN OUTCOME MEASURES: At least one switch from one generic L-thyroxine preparation to another within 1 year of L-thyroxine initiation defined by prescription fills. RESULTS: From January 2008 to November 2018, we included 483,390 patients who initiated generic L-thyroxine: mean (SD) age was 61.4 years (15.2), 75.2% were female, 72.6% were white. Within 1 year of initiating therapy, 98,013 (20%) switched to another L-thyroxine generic preparation at least once. In a multivariate logistic regression analysis, factors associated with switching included the number of pharmacies visited to fill L-thyroxine (>2 vs 1 adjusted OR [aOR] 7.15, 95% confidence interval [CI] 6.97-7.34), age ≥75 vs. <45 years (aOR 1.29, 95% CI 1.26-1.33), history of thyroid surgery (aOR 1.22, 95% CI 1.13-1.31), and first L-thyroxine fill date in 2018 vs. 2008 (aOR 3.32, 95% CI 3.14-3.51). CONCLUSIONS AND RELEVANCE: One in five patients switched among generic L-thyroxine manufacturers within one year of treatment initiation. Generic L-thyroxine switching occurred more often when more pharmacies were used to fill L-thyroxine. Given existing guideline recommendations, additional studies should clarify the impact of generic L-thyroxine switching on thyroid hormone values.

Association Between Generic-to-Generic Levothyroxine Switching and Thyrotropin Levels Among US Adults.

IMPORTANCE: Switching among generic levothyroxine sodium products made by different manufacturers typically occurs at the pharmacy and may affect serum thyrotropin (TSH) levels. OBJECTIVE: To compare TSH levels between patients who continued taking the same sourced generic levothyroxine product and those who switched. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness research study with 1:1 propensity matching used data from OptumLabs Data Warehouse, a national administrative claims database linked to laboratory test results. Adults aged 18 years or older were included if they filled a generic levothyroxine prescription between January 1, 2008, and June 30, 2019, and had a stable drug dose, the same drug manufacturer, and a normal TSH level (0.3-4.4 mIU/L) for at least 3 months before either continuing to take the same product or switching among generic levothyroxine products (index date). Patients were excluded if they were pregnant, had diagnosed hypopituitarism or hyperthyroidism, or had a medical condition or used medications that could affect thyrotropin levels. They were also excluded if they filled a prescription for other forms of thyroid replacement therapy between 6 months before the index date and when the first TSH level was obtained 6 weeks to 12 months after the index date. Data were analyzed from December 1, 2019, to November 24, 2021. MAIN OUTCOMES AND MEASURES: Proportion of individuals with a normal (0.3-4.4 mIU/L) or markedly abnormal (<0.1 or >10.0 mIU/L) TSH level using the first available laboratory result 6 weeks to 12 months after the index date. A propensity score model was developed to minimize confounding using logistic regression with the binary outcome of continuing the same sourced levothyroxine product vs switching generic levothyroxine. Covariates were demographics, comorbidities, and baseline TSH level. The balance among the treatment groups was evaluated by comparing standardized mean differences of baseline covariates between the groups. RESULTS: A total of 15 829 patients filled generic levothyroxine (mean [SD] age, 58.9 [14.6] years; 73.4% [11 624] were women; 4.5% [705] were Asian, 10.2% [1617] were Black, 11.4% [1801] were Hispanic, and 71.4% [11 295] were White individuals); of these patients, 56.3% [8905] received a daily levothyroxine dose of 50 µg or less. A total of 13 049 patients (82.4%) continued taking the same sourced preparation, and 2780 (17.6%) switched among generic levothyroxine preparations. Among 2780 propensity-matched patient pairs, the proportion of patients with a normal TSH level after the index date was 82.7% (2298) among nonswitchers and 84.5% (2348) among switchers (risk difference, -0.018; 95% CI, -0.038 to 0.002; P = .07). The proportion of patients with a markedly abnormal TSH level after the index date was 3.1% (87) among nonswitchers and 2.5% (69) among switchers (risk difference, 0.007; 95% CI, -0.002 to 0.015; P = .14). The mean (SD) TSH levels after the index date were 2.7 (2.3) mIU/L among nonswitchers and 2.7 (3.3) mIU/L among switchers (P = .94). CONCLUSIONS AND RELEVANCE: Results of this comparative effectiveness research study suggest that switching among different generic levothyroxine products was not associated with clinically significant changes in TSH level. These findings conflict with the current guideline recommendation that warns clinicians about potential changes in TSH level associated with switching among levothyroxine products sourced from different manufacturers.

Real-world Cardiovascular Outcomes Associated With Degarelix vs Leuprolide for Prostate Cancer Treatment.

Importance: With a growing interest in the use of real-world evidence for regulatory decision-making, it is important to understand whether real-world data can be used to emulate the results of randomized clinical trials. Objective: To use electronic health record and administrative claims data to emulate the ongoing PRONOUNCE trial (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease). Design, Setting, and Participants: This retrospective, propensity-matched cohort study included adult men with a diagnosis of prostate cancer and cardiovascular disease who initiated either degarelix or leuprolide between December 24, 2008, and June 30, 2019. Participants were commercially insured individuals and Medicare Advantage beneficiaries included in a large US administrative claims database. Exposures: Degarelix or leuprolide. Main Outcomes and Measures: The primary end point was time to first occurrence of a major adverse cardiovascular event (MACE), defined as death due to any cause, myocardial infarction, or stroke, analogous to the PRONOUNCE trial. Secondary end points were time to death due to any cause, myocardial infarction, stroke, and angina. Cox proportional hazards regression was used to evaluate primary and secondary end points. Results: A total of 32 172 men initiated degarelix or leuprolide for prostate cancer; of them, 9490 (29.5%) had cardiovascular disease, and 7800 (24.2%) met the PRONOUNCE trial eligibility criteria and were included in this study. Overall, 165 participants (2.1%) were Asian, 1390 (17.8%) were Black, 663 (8.5%) were Hispanic, and 5258 (67.4%) were White. The mean (SD) age was 74.4 (7.4) years. Among 2226 propensity score-matched patients, no significant difference was observed in the risk of MACE for patients taking degarelix vs those taking leuprolide (10.18 vs 8.60 events per 100 person-years; hazard ratio [HR], 1.18; 95% CI, 0.86-1.61). Degarelix was associated with a higher risk of death from any cause (HR, 1.48; 95% CI, 1.01-2.18) but not of myocardial infarction (HR, 1.16; 95% CI, 0.60-2.25), stroke (HR, 0.92; 95% CI, 0.45-1.85), or angina (HR, 1.36; 95% CI, 0.43-4.27). Conclusions and Relevance: In this emulation of a clinical trial of men with cardiovascular disease undergoing treatment for prostate cancer, degarelix was not associated with a lower risk of cardiovascular events than leuprolide. Comparison of these data with PRONOUNCE trial results, when published, will help enhance our understanding of the appropriate role of using real-world data to emulate clinical trials.

Cardiovascular outcomes and rates of fractures and falls among patients with brand-name versus generic L-thyroxine use.

PURPOSE: To compare cardiovascular outcomes and rates of fractures and falls among patients with persistent brand-name versus generic L-thyroxine use. METHODS: Retrospective, 1:1 propensity-matched longitudinal study using a national administrative claims database to examine adults (≥18 years) who initiated either brand or generic L-thyroxine between 2008 and 2018, censored at switch or discontinuation of L-thyroxine formulation or disenrollment from the health plan. Main outcome measures included rates of hospitalization for atrial fibrillation, myocardial infarction, congestive heart failure, stroke, spine and hip fractures, and rate of falls in the outpatient or inpatient setting. Hospitalizations for pneumonia were used as a negative control. RESULTS: 195,046 adults initiated treatment with L-thyroxine between 2008 and 2017: 87% generic and 13% brand formulations. They were mostly women (76%), young (94.6% under age 65), white (66%), and 47% had baseline thyroid stimulating hormone levels between 4.5 and 9.9 mIU/L. Among 35,667 propensity-matched patients, there were no significant differences between patients treated with brand versus generic L-thyroxine in atrial fibrillation (HR 0.96, 0.58-1.60), myocardial infarction (HR 0.66, 0.39-1.14), congestive heart failure (HR 1.30, 0.78-2.16), stroke (0.72, 0.49-1.06), spine (HR 0.87, 0.38-1.99) and hip fractures (HR 0.86, 0.26-2.82), or fall outcomes (HR 1.02, 0.14-7.32). Hospitalization rates for pneumonia (used as negative control) did not differ between groups (HR 0.85, 0.61-1.19). There were no interactions between brand versus generic L-thyroxine, these outcomes, and thyroid cancer, age, or L-thyroxine dose subgroups. CONCLUSIONS: We found no significant differences in cardiovascular outcomes and rates of falls and fractures for patients who filled brand versus generic L-thyroxine.

Renal Outcomes in Patients with Systolic Heart Failure Treated With Sacubitril-Valsartan or Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker.

OBJECTIVE: To assess 4 adverse renal outcomes in a heterogeneous cohort of patients with systolic heart failure (HF) who were prescribed sacubitril-valsartan vs angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB). PATIENTS AND METHODS: The OptumLabs Database Warehouse, which contains linked administrative claims and laboratory results, was used to identify patients with systolic HF who were prescribed sacubitril-valsartan or ACEi/ARB between July 1, 2015, and September 30, 2019. One-to-one propensity score matching and inverse probability of treatment weighting was used to balance baseline variables. Cox proportional hazards modeling was performed to compare renal outcomes in both medication groups, including 30% or more decline in estimated glomerular filtration rate (eGFR), doubling of serum creatinine, acute kidney injury (AKI), and kidney failure (eGFR < 15 mL/min per 1.73 m2, kidney transplant, or dialysis initiation). RESULTS: A total of 4667 matched pairs receiving sacubitril-valsartan or ACEi/ARB were included; the mean follow-up period was 7.8±7.8 months. The mean age was 69.4±11 years; 35% were female, 19% black, and 15% Hispanic. The cumulative risk at 1 year was 6% for 30% or more decline in eGFR, 2% for doubling of serum creatinine, 3% for AKI, and 2% to 3% for kidney failure. Furthermore, no significant differences in risk were observed with sacubitril-valsartan compared with ACEi/ARB for a 30% or more decline in eGFR (hazard ratio [HR], 0.96; 95% CI, 0.79 to 1.10), doubling of serum creatinine (HR, 0.94; 95% CI, 0.69 to 1.27); AKI (HR, 0.80; 95% CI, 0.63 to 1.03), and kidney failure (HR 0.80; 95% CI, 0.59 to 1.08). CONCLUSION: Among patients with systolic HF, the risk of adverse renal outcomes was similar between patients prescribed sacubitril-valsartan and those prescribed ACEi/ARB.

Comparison of Diabetes Medications Used by Adults With Commercial Insurance vs Medicare Advantage, 2016 to 2019.

Importance: Glucagonlike peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) are associated with low rates of hypoglycemia, and postmarketing trials of GLP-1RA and SGLT2i demonstrated that these medications improved cardiovascular and kidney outcomes. Objective: To compare trends in initiation of treatment with GLP-1RA, SGLT2i, and DPP-4i by older adults with type 2 diabetes insured by Medicare Advantage vs commercial health plans. Design, Setting, and Participants: This retrospective cohort study used administrative claims data from a deidentified database of commercially insured and Medicare Advantage beneficiaries. Adults aged 58 to 66 years with type 2 diabetes who filled any medication prescription to lower glucose levels from January 1, 2016, to December 31, 2019, were compared between groups. Exposure: Enrollment in a Medicare Advantage or commercial health insurance plan. Main Outcomes and Measures: The odds of initiating GLP-1RA, SGLT2i, and DPP-4i treatment were examined for Medicare Advantage vs commercial insurance beneficiaries using 3 separate logistic regression models adjusted for year and demographic and clinical factors. These models were used to calculate adjusted annual rates of medication initiation by health plan. Results: A total of 382 574 adults with pharmacologically treated type 2 diabetes (52.9% men; mean [SD] age, 62.4 [2.7] years) were identified, including 172 180 Medicare Advantage and 210 394 commercial beneficiaries. From 2016 to 2019, adjusted rates of initiation of GLP-1RA, SGLT2i, and DPP-4i treatment increased among all beneficiaries, from 2.14% to 20.02% for GLP-1RA among commercial insurance beneficiaries and from 1.50% to 11.44% among Medicare Advantage beneficiaries; from 2.74% to 18.15% for SGLT2i among commercial insurance beneficiaries and from 1.57% to 8.51% among Medicare Advantage beneficiaries; and from 3.30% to 11.71% for DPP-4i among commercial insurance beneficiaries and from 2.44% to 7.68% among Medicare Advantage beneficiaries. Initiation rates for all 3 drug classes were consistently lower among Medicare Advantage than among commercial insurance beneficiaries. Within each calendar year, the odds of initiating GLP-1RA treatment ranged from 0.28 (95% CI, 0.26-0.29) to 0.70 (95% CI, 0.65-0.75) for Medicare Advantage and commercial insurance beneficiaries, respectively; SGLT2i, from 0.21 (95% CI, 0.20-0.22) to 0.57 (95% CI, 0.53-0.61), respectively; and DPP-4i, from 0.37 (95% CI, 0.34-0.39) to 0.73 (95% CI, 0.69-0.78), respectively (P < .001 for all). The odds of starting GLP-1RA and SGLT2i increased with income; for an income of $200 000 and higher vs less than $40 000, the odds ratio for GLP-1RA was 1.23 (95% CI, 1.15-1.32) and for SGLT2i was 1.16 (95% CI, 1.09-1.24). Conclusions and Relevance: These findings suggest that Medicare Advantage beneficiaries may be less likely than commercially insured beneficiaries to be treated with newer medications to lower glucose levels, with greater disparities among lower-income patients. Better understanding of nonclinical factors contributing to treatment decisions and efforts to promote greater equity in diabetes management appear to be needed.

Proprotein convertase subtilisin/kexin type 9 inhibitor utilization and low-density lipoprotein-cholesterol control in familial hypercholesterolemia.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved in August 2015 as an adjunct to maximally tolerated statin treatment in those with familial hypercholesterolemia (FH). OBJECTIVE: To assess PCSK9 inhibitor utilization patterns and cholesterol control in the high-risk FH population. METHODS: This study was a retrospective analysis of a large administrative database that includes privately insured and Medicare Advantage patients. Individuals with diagnosis codes for FH from October 2016-September 2019 were identified. Differences in PCSK9 inhibitor utilization between various groups were evaluated using multivariable logistic regression. RESULTS: During the study period, 1:371 people enrolled in medical/pharmacy plans had a diagnosis of FH. While 62.5% (n = 33,649) had medication fills for statins (without PCSK9 inhibitors), only 2.0% (n = 1062) had medication fills for PCSK9 inhibitors (with or without other medications). Compared to men, women were more likely to be untreated (OR 1.23, 95% confidence interval (CI):1.18-1.28, p < 0.01) but more likely to be treated with PCSK9 inhibitors (OR 2.18, 95%CI:1.90-2.49, p < 0.01). Compared to those younger than 55 years of age, older individuals were more likely to be treated (OR 1.64, 95%CI:1.56-1.72, p < 0.01) but less likely to be treated with PCSK9 inhibitors (OR 0.40, 95%CI:0.34-0.47, p < 0.01). Lastly, those with household incomes ≥$40,000 were more likely to be treated with PCSK9 inhibitors than those with lower household incomes (OR 1.69, 95%CI:1.41-2.02, p < 0.01). CONCLUSION: PCSK9 inhibitor utilization in FH remains low. Significant differences exist based on demographic factors. Female sex, higher household incomes, and younger age were associated with increased PCSK9 inhibitor utilization.

Methodological Quality of Systematic Reviews and Meta-Analysis on Asthma Treatments. A Cross-Sectional Study.

Rationale: Systematic reviews (SRs) provide the best evidence of the effectiveness of treatment strategies for asthma. Carefully conducted SRs provide high-quality evidence for supporting decision-making, but the trustworthiness of conclusions can be hampered by limitation in rigor.Objectives: To appraise the methodological quality of a representative sample of SRs on asthma treatments in a cross-sectional study.Methods: A cross-sectional study was conducted to identify SRs on asthma treatment published between 2013 and 2019 by searching the Cochrane Database of Systematic Reviews, Embase, MEDLINE, and PsycINFO. SRs including at least one meta-analysis on asthma treatments were included. Methodological quality of included SRs was assessed with the Assessing the Methodological Quality of Systematic Reviews 2 instrument. Factors associated with methodological quality were explored using multivariate regression analysis.Results: One hundred thirty-six SRs were included and appraised, with a majority being non-Cochrane reviews (71.3%). Only 12 (8.8%) were of high overall quality; 9 (6.6%), 32 (23.5%), and 83 (61.0%) were of moderate, low, and critically low overall quality, respectively. More specifically, no SRs (0.0%) conducted a comprehensive literature search; only 3 (2.2%) justified why a particular primary study design was selected; 37 (27.2%) reported sources of funding among included studies; and 54 (39.7%) provided lists of excluded studies with justification. Cochrane reviews (adjusted odds ratio, 36.56; 95% confidence interval, 10.49-127.42) and SRs published after 2017 (adjusted odds ratio, 4.52; 95% confidence interval, 1.73-11.83) were positively associated with higher methodological quality.Conclusions: Methodological quality of SRs on asthma treatments are suboptimal. Future SRs should be improved by conducting comprehensive literature searches, justifying study design selection, providing a list of excluded studies, and reporting funding sources of included studies.

The impact of using an intravenous workflow management system (IVWMS) on cost and patient safety.

PURPOSE: The aim of this study was to determine the financial costs associated with wasted and missing doses before and after the implementation of an intravenous workflow management system (IVWMS) and to quantify the number and the rate of detected intravenous (IV) preparation errors. METHOD: A retrospective analysis of the sample hospital information system database was conducted using three months of data before and after the implementation of an IVWMS System (DoseEdge®) which uses barcode scanning and photographic technologies to track and verify each step of the preparation process. The financial impact associated with wasted and missing >IV doses was determined by combining drug acquisition, labor, accessory, and disposal costs. The intercepted error reports and pharmacist detected error reports were drawn from the IVWMS to quantify the number of errors by defined error categories. RESULTS: The total number of IV doses prepared before and after the implementation of the IVWMS system were 110,963 and 101,765 doses, respectively. The adoption of the IVWMS significantly reduced the amount of wasted and missing IV doses by 14,176 and 2268 doses, respectively (p < 0.001). The overall cost savings of using the system was $144,019 over 3 months. The total number of errors detected was 1160 (1.14%) after using the IVWMS. CONCLUSION: The implementation of the IVWMS facilitated workflow changes that led to a positive impact on cost and patient safety. The implementation of the IVWMS increased patient safety by enforcing standard operating procedures and bar code verifications.