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Importance: Endothelin receptor antagonists are first-line therapy for pulmonary arterial hypertension (PAH). The first 2 agents approved in the class, bosentan and ambrisentan, initially carried boxed warnings for hepatotoxicity and required monthly liver function tests (LFTs) as part of a risk evaluation and mitigation strategy (REMS); however, in 2011, as further safety data emerged on ambrisentan, the boxed hepatotoxicity warning and LFT requirements were removed. Objective: To analyze changes in the use of and LFT monitoring for ambrisentan and bosentan after changes to the ambrisentan labeling and REMS. Design, Setting, and Participants: This serial cross-sectional study used data from 3 longitudinal health care insurance claims databases-Medicaid, Optum's deidentified Clinformatics Data Mart, and Merative Marketscan-to perform an interrupted time series analysis of prescription fills and LFTs for patients taking ambrisentan and bosentan. Participants were patients filling prescriptions for ambrisentan and bosentan from July 1, 2007, to December 31, 2018. Data analysis was performed from April 2021 to August 2023. Exposure: Removal of the boxed warning for hepatotoxicity and the REMS LFT monitoring requirements on ambrisentan in March 2011. Main Outcomes and Measures: The primary outcomes were use of ambrisentan (ie, individuals with at least 1 dispensing per 1â¯000â¯000 individuals enrolled in the 3 datasets) vs bosentan and LFT monitoring (ie, proportion of initiators with at least 1 ordered test) before initiation and before the first refill. Results: A total of 10â¯261 patients received a prescription for ambrisentan during the study period (7442 women [72.5%]; mean [SD] age, 52.6 [17.6] years), and 11â¯159 patients received a prescription for bosentan (7931 women [71.1%]; mean [SD] age, 47.7 [23.7] years). Removal of the ambrisentan boxed hepatotoxicity warning and LFT monitoring requirement was associated with an immediate increase in the use of ambrisentan (1.50 patients per million enrollees; 95% CI, 1.08 to 1.92 patients per million enrollees) but no significant change in the use of bosentan. There were reductions in recorded LFTs before drug initiation (13.1% absolute decrease; 95% CI, -18.2% to -8.0%) and before the first refill (26.4% absolute decrease; 95% CI, -34.4% to -18.5%) of ambrisentan but not bosentan. Conclusions and Relevance: In this serial cross-sectional study of ambrisentan, labeling changes and removal of the REMS-related LFT requirement were associated with shifts in prescribing and testing behavior for ambrisentan but not bosentan. Further clinician education may be needed to maximize the benefits of REMS programs and labeling warnings designed to ensure the safe administration of high-risk medications.
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Bosentán , Enfermedad Hepática Inducida por Sustancias y Drogas , Pruebas de Función Hepática , Fenilpropionatos , Piridazinas , Humanos , Fenilpropionatos/uso terapéutico , Fenilpropionatos/efectos adversos , Piridazinas/efectos adversos , Piridazinas/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Pruebas de Función Hepática/métodos , Pruebas de Función Hepática/estadística & datos numéricos , Estados Unidos , Bosentán/uso terapéutico , Adulto , Etiquetado de Medicamentos/normas , United States Food and Drug Administration , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Anciano , Antagonistas de los Receptores de Endotelina/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológicoRESUMEN
INTRODUCTION: Lenalidomide, pomalidomide, and thalidomide are effective treatments for multiple myeloma but are teratogenic. To mitigate this risk, the US Food and Drug Administration (FDA) required risk evaluation and mitigation strategy (REMS) programs for these drugs, which include pregnancy testing among women of childbearing potential-twice before initiation, weekly in the first month on treatment, and every 2-4 weeks thereafter. OBJECTIVE: We evaluated dispensing trends of lenalidomide, pomalidomide, and thalidomide and assessed adherence to REMS pregnancy testing requirements among at-risk patients taking these drugs. METHODS: Using three US health insurance claims databases (Optum Clinformatics® [2004-2020], Merative Marketscan [2003-2019], and Medicaid [2000-2018]), we assessed monthly use of the drugs, patient characteristics and treatment persistence among drug initiators, and claims-based evidence for adherence to pregnancy testing requirements among initiators with child-bearing potential. RESULTS: Lenalidomide was the most prescribed agent following its approval in 2006 and through the end of the study period. A total of 48,311 lenalidomide (mean age = 59 years [standard deviation (SD) = 16]), 17,550 thalidomide (mean age = 65 years [SD = 12]), and 6560 pomalidomide initiators (mean age = 65 years [SD = 11]) were identified; 45% of initiators of each drug were women. Among initiators under follow-up on day 90, 70% were still on therapy. Initiators of childbearing potential comprised 3% (N = 1,920) of all initiators; among this cohort, 12% had evidence in claims data of two pregnancy tests before initiation, and 9% with at least 33 days of follow-up of four tests during the first month of treatment. By contrast, 52% who received a refill had claims-based evidence of a pregnancy test within 7 days of dispensing. CONCLUSION: Although most patients who initiated lenalidomide, pomalidomide, and thalidomide were not of child-bearing potential, further investigation into actual non-adherence to pregnancy testing is needed.
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Lenalidomida , Talidomida , Humanos , Talidomida/análogos & derivados , Talidomida/efectos adversos , Talidomida/uso terapéutico , Lenalidomida/efectos adversos , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Femenino , Estados Unidos , Embarazo , Persona de Mediana Edad , Adulto , Evaluación y Mitigación de Riesgos , Mieloma Múltiple/tratamiento farmacológico , United States Food and Drug Administration , Anciano , Bases de Datos FactualesRESUMEN
Prior studies have demonstrated that misclassification of study variables due to electronic health record (EHR)-discontinuity can be mitigated by restricting EHR-based analyses to subjects with high predicted EHR-continuity based on a simple algorithm. In this study, we compared EHR continuity in populations covered by Medicare, Medicaid, or commercial insurance. Using claims-linked EHRs from a multicenter network in Massachusetts, including Medicare (MA EHR-Medicare cohort) and Medicaid (MA EHR-Medicaid cohort) claims data; and TriNetX (TriNetX cohort) claims-linked EHR data from 11 US-based healthcare organizations, we assessed (1) EHR-continuity quantified by proportion of encounters captured by EHR (capture proportion (CP)); (2) area under receiver operating curve (AUROC) of previously validated model to identify patients with high EHR-continuity (CP ≥ 0.6); (3) misclassification of 40 patient characteristics, quantified by average standardized absolute mean difference (ASAMD). Study participants were ≥ 65 years (Medicare) or ≥ 18 years (Medicaid, TriNetX) with ≥ 365 days of continuous insurance enrollment overlapping with an EHR encounter. We found that the mean CP was 0.30, 0.18, and 0.19 and AUROC of the prediction model to identify patients with high EHR-continuity was 0.92, 0.89, and 0.77 in the MA EHR-Medicare, MA EHR-Medicaid, and TriNetX cohorts, respectively. Restricting to patients with predicted EHR-continuity percentile of top 20%, 50%, and 50% in MA EHR-Medicare, MA EHR-Medicaid, and TriNetX cohorts resulted in acceptable levels of misclassification (ASAMD < 0.1). Using a prediction model to identify cohorts with high EHR-continuity can improve validity, but cutoffs to achieve this goal vary by population.
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Medicaid , Medicare , Anciano , Humanos , Estados Unidos , Cobertura del Seguro , Registros Electrónicos de SaludRESUMEN
Importance: After the rapid expansion of telemedicine during the COVID-19 pandemic, there is debate about the role and reimbursement of telephone vs video visits. Missing is an understanding of what type of virtual visits clinicians may offer or patients may choose when given the option. Objective: To evaluate characteristics of Medicare beneficiaries associated with practices and clinicians offering telephone visits only and patients receiving telephone visits only, when both telephone and video were available. Design, Setting, and Participants: This survey study used 2019-2020 nationally representative Medicare Current Beneficiary Survey data. Participants included community-dwelling Medicare beneficiaries with a usual source of medical care who attended a practice offering telemedicine. Data were analyzed from May 3 to August 23, 2022. Main Outcomes and Measures: Multivariable regression analysis was used to identify patient sociodemographic (age, sex, race, ethnicity, educational level, income, English proficiency, housing type, and number living at home), clinical (dementia, mental illness, self-rated health, hearing impairment, and vision impairment), and technology (technology access and prior use of video visits) factors associated with respondents' report of (1) practices offering telephone virtual visits only, (2) being offered telephone visits only when both video and telephone visits were available, and (3) receiving telephone visits only when both video and telephone visits were offered. Results: Of 4691 respondents (representing 27â¯887â¯642 Medicare beneficiaries; mean [SD] age, 71.3[8.1] years; 55.0% female) reporting that their practice offered telemedicine, 1234 (23.3% weighted) reported that their practices offered telephone virtual visits only; factors associated with being in a practice offering telephone only included older age (adjusted odds ratio [aOR], 1.62 [95% CI, 1.10-2.39] for those aged ≥85 years vs 18-64 years), male sex (aOR, 1.36 [95% CI, 1.12-1.64]), Hispanic ethnicity (aOR, 1.41 [95% CI, 1.03-1.95]), lower income (aOR, 1.89 [95% CI, 1.43-2.49] for those with income ≤100% vs >200% of the federal poverty level), poor self-rated health (aOR, 1.25 [95% CI, 1.01-1.56]), and less technology access (aOR, 2.05 [95% CI, 1.61-2.60] for those with low vs high access). Of the 1593 patients in practices offering both video and telephone visits, 297 (16.7% weighted) were themselves offered telephone visits only; factors associated with being offered telephone only included Hispanic ethnicity (aOR, 1.96 [95% CI, 1.13-3.41]), limited English proficiency (aOR, 3.05 [95% CI, 1.28-7.31]), and less technology access (aOR, 1.68 [95% CI, 1.00-2.81] for those with low vs high access). Finally, of the 711 respondents who were themselves offered both video and telephone visits, 304 (43.1% weighted) had a telephone visit; factors associated with receiving telephone visits only were older age (aOR, 2.68 [95% CI, 1.21-5.92] for those aged 75-84 years vs 18-64 years) and less technology access (aOR, 2.65 [95% CI, 1.12-6.25] for those with moderate vs high access]). Among those who used video calls in other settings and were offered a choice, 122 (28.5%, weighted) chose telephone visits. Conclusions and Relevance: In this survey study of Medicare beneficiaries, respondents often reported being offered or choosing telephone visits even when video visits were available. Study findings suggest that policy makers and clinical leaders should support the use of telephone visits to the extent that telephone is appropriate, while addressing both practice-level and patient-level barriers to video visits.
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COVID-19 , Medicare , Anciano , Humanos , Masculino , Femenino , Estados Unidos , Pandemias , Encuestas y Cuestionarios , TeléfonoRESUMEN
Background: Identifying high data-continuity patients in an electronic health record (EHR) system may facilitate selecting cohorts with a lower degree of variable misclassification and promote study validity. We updated a previously developed algorithm for identifying patients with high EHR data-completeness by adding demographic and health utilization factors to improve adaptability to networks serving patients of diverse backgrounds. We also expanded the algorithm to accommodate data in the ICD-10 era. Methods: We used Medicare claims linked with EHR data to identify individuals aged ≥65 years. EHR-continuity was defined as the proportion of encounters captured in EHR data relative to claims. We compared the model with additional demographic factors and their interaction terms with other predictors with the original algorithm and assessed the performance by area under the ROC curve (AUC) and net reclassification index (NRI). Results: The study cohort consisted of 264,099 subjects. The updated prediction model had an AUC of 0.93 in the validation set. Compared to the previous model, the new model had an NRI of 37.4% (p<0.001) for EHR-continuity classification. Interaction terms between demographic variables and other predictors did not improve the performance. Patients within the top 20% of predicted EHR-continuity had four times less misclassification of key variables compared to the remaining population. Conclusion: Adding demographic and healthcare utilization variables significantly improved the model performance. Patients with high predicted EHR-continuity had less misclassification of study variables compared to the remaining population in both ICD-9 and 10 eras.
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INTRODUCTION: Electronic health record (EHR) discontinuity (missing out-of-network encounters) can lead to information bias. We sought to construct an algorithm that identifies high EHR-continuity among oncology patients. METHODS: Using a linked Medicare-EHR database and regression, we sought to 1) measure how often Medicare claims for outpatient encounters were substantiated by visits recorded in the EHR, and 2) predict continuity ratio, defined as the yearly proportion of outpatient encounters reported to Medicare that were captured by EHR data. The prediction model...s performance was evaluated with the coefficient of determination and Spearman...s correlation. We quantified variable misclassification by decile of continuity ratio using standardized difference and sensitivity. RESULTS: A total of 79,678 subjects met all eligibility criteria. Predicted and observed continuity was highly correlated (σSpearman=0.86). On average across all variables measured, MSD was reduced by a factor of 1/7th and sensitivity was improved 35-fold comparing subjects in the highest vs. lowest decile of CR. CONCLUSION: In the oncology population, restricting EHR-based study cohorts to subjects with high continuity may reduce misclassification without greatly impacting representativeness. Further work is needed to elucidate the best manner of implementing continuity prediction rules in cohort studies.
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Registros Electrónicos de Salud , Neoplasias , Anciano , Humanos , Estados Unidos , Investigación sobre la Eficacia Comparativa , Medicare , Algoritmos , Oncología Médica , Neoplasias/epidemiologíaRESUMEN
Importance: Increasing use of screening breast magnetic resonance imaging (MRI), including among women at low or average risk of breast cancer, raises concerns about resulting mammary and extramammary cascades (downstream services and new diagnoses) of uncertain value. Objective: To estimate rates of cascade events (ie, laboratory tests, imaging tests, procedures, visits, hospitalizations, and new diagnoses) and associated spending following screening breast MRI vs mammography among commercially insured US women. Design, Setting, and Participants: This cohort study used 2016 to 2018 data from the MarketScan research database (IBM Corporation), which includes claims and administrative data from large US employers and commercial payers. Participants included commercially insured women aged 40 to 64 years without prior breast cancer who received an index bilateral screening breast MRI or mammogram between January 1, 2017, and June 30, 2018. We used propensity scores based on sociodemographic, clinical, and utilization variables to match MRI recipients to mammogram recipients in each month of index service use. Data were analyzed from October 8, 2020, to October 28, 2021. Exposures: Breast MRI vs mammography. Main Outcomes and Measures: Mammary and extramammary cascade event rates and associated total and patient out-of-pocket spending in the 6 months following the index test. Results: In this study, 9208 women receiving breast MRI were matched with 9208 women receiving mammography (mean [SD] age, 51.4 [6.7] years). Compared with mammogram recipients, breast MRI recipients had 39.0 additional mammary cascade events per 100 women (95% CI, 33.7-44.2), including 5.0 additional imaging tests (95% CI, 3.8-6.2), 17.3 additional procedures (95% CI, 15.5-19.0), 13.0 additional visits (95% CI, 9.4-17.2), 0.34 additional hospitalizations (95% CI, 0.18-0.50), and 3.0 additional new diagnoses (95% CI, 2.5-3.6). For extramammary cascades, breast MRI recipients had 19.6 additional events per 100 women (95% CI, 8.6-30.7) including 15.8 additional visits (95% CI, 10.2-21.4) and no statistically significant differences in other events. Breast MRI recipients had higher total spending for mammary events ($564 more per woman; 95% CI, $532-$596), extramammary events ($42 more per woman; 95% CI, $16-$69), and overall ($1404 more per woman; 95% CI, $1172-$1636). They also had higher overall out-of-pocket spending ($31 more per woman; 95% CI, $6-$55). Conclusions and Relevance: In this cohort study of commercially insured women, breast MRI was associated with more mammary and extramammary cascade events and spending relative to mammography. These findings can inform cost-benefit assessments and coverage policies to ensure breast MRI is reserved for patients for whom benefits outweigh harms.
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Neoplasias de la Mama , Mamografía , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Mamografía/métodos , Persona de Mediana EdadRESUMEN
OBJECTIVE: To develop a claims-based model to predict persistent high-dose opioid use among patients undergoing total knee replacement (TKR). METHODS: Using Medicare claims (2010-2014), we identified patients ages ≥65 years who underwent TKR with no history of high-dose opioid use (mean >25 morphine milligram equivalents [MMEs]/day) in the year prior to TKR. We used group-based trajectory modeling to identify distinct opioid use patterns. The primary outcome was persistent high-dose opioid use in the year after TKR. We split the data into training (2010-2013) and test (2014) sets and used logistic regression with least absolute shrinkage and selection operator regularization, utilizing a total of 83 preoperative patient characteristics as candidate predictors. A reduced model with 10 prespecified variables, which included demographic characteristics, opioid use, and medication history was also considered. RESULTS: The final study cohort included 142,089 patients who underwent TKR. The group-based trajectory model identified 4 distinct trajectories of opioid use (group 1: short-term, low-dose; group 2: moderate-duration, low-dose; group 3: moderate-duration, high-dose; and group 4: persistent high-dose). The model predicting persistent high-dose opioid use achieved high discrimination (receiver operating characteristic area under the curve [AUC] 0.85 [95% confidence interval (95% CI) 0.84-0.86]) in the test set. The reduced model with 10 predictors performed equally well (AUC 0.84 [95% CI 0.84-0.85]). CONCLUSION: In this cohort of older patients, 10.6% became persistent high-dose (mean 22.4 MME/day) opioid users after TKR. Our model with 10 readily available clinical factors may help identify patients at high risk of future adverse outcomes from persistent opioid use after TKR.
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Artroplastia de Reemplazo de Rodilla , Anciano , Analgésicos Opioides/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios de Cohortes , Humanos , Medicare , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Ambulatory antibiotic prescriptions without a clinic visit or without documentation of infection could represent overuse and contribute to adverse outcomes. We aim to describe US ambulatory antibiotic prescribing, including those without an associated visit or infection diagnosis. METHODS: We conducted an observational cohort study using data of all patients receiving antibacterial, antibiotic prescriptions from 04/01/2016 to 06/30/2018 in a large US private health insurance plan. We identified outpatient antibiotic prescriptions as (1) associated with a clinician visit and an infection-related diagnosis; (2) associated with a clinician visit but no infection-related diagnosis; or (3) not associated with an in-person clinician visit in the 7 days before the prescription (non-visit-based). We then assessed whether non-visit-based antibiotic prescriptions (NVBAPs) differed from visit-based antibiotics by patient, clinician, or antibiotic characteristics using multivariable models. RESULTS: The cohort included 8.6M enrollees who filled 22.3M antibiotic prescriptions. NVBAP accounted for 31% (6.9M) of fills, and non-infection-related prescribing accounted for 22% (4.9M). NVBAP rates were lower for children than for adults (0-17 years old, 16%; 18-64 years old, 33%;â >65 years old, 34%). Among most commonly prescribed antibiotic classes, NVBAP was highest for penicillins (36%) and lowest for cephalosporins (25%) and macrolides (25%). Specialist physicians had the highest rate of NVBAP (38%), followed by internists (28%), family medicine (20%), and pediatricians (10%). In multivariable models, NVBAP was associated with increasing age, and NVBAP was less likely for patients in the South, those with more baseline clinical visits, or those with chronic lung disease. CONCLUSIONS: Over half of ambulatory antibiotic use was either non-visit-based or non-infection-related. Particularly given health care changes due to the coronavirus disease 2019 pandemic, efforts to improve antibiotic prescribing must account for non-visit-based and non-infection-related prescribing.
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BACKGROUND: Anti-nerve growth factor (NGF) has shown promise for osteoarthritis (OA) pain efficacy, but an unanticipated joint safety signal occurred in trials. To what extent this was related to OA natural history, or was a consequence of anti-NGF agents is unclear. Of the adverse joint safety events identified, osteonecrosis has specific diagnostic codes available in the medical record to enable assessment of its frequency in the general community. We therefore investigated the rates of knee osteonecrosis in three real-world cohorts using two data sources to place these trial data in context. METHODS: We used data from UK-based IQVIA Medical Research Data (IMRD) of adults diagnosed with incident knee OA between 2000-2018 to examine the incidence of knee osteonecrosis using different definitions. Additionally, we evaluated the incidence of knee osteonecrosis in the year prior to knee replacement in IMRD and among US Medicare beneficiaries who received a knee replacement in 2011-2014. RESULTS: In IMRD, among 122,343 subjects with incident knee OA (mean age 68 years, 58% female), incidence estimates for knee osteonecrosis were 0.006-0.10%, with incidence rates of 0.01-0.17 per 1000 person-years. Among the 81,807 who had a knee replacement, the incidence of knee osteonecrosis in the year prior to knee replacement was 0.004-0.06%. In Medicare, among 316,593 with knee replacement (mean age 74, 68% female), the incidence of knee osteonecrosis was 0.24-0.7%. CONCLUSION: Knee osteonecrosis is rare among people with knee OA, including in the year prior to knee replacement. These data provide context for interpreting osteonecrosis events in NGF trials.
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PURPOSE: There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. DESIGN: We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use. PARTICIPANTS: The study population included cases with nAMD and risk set matched controls. METHODS: We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). MAIN OUTCOME MEASURES: Progression to nAMD. RESULTS: Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. CONCLUSIONS: This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.
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Neovascularización Coroidal/diagnóstico , Evaluación Preclínica de Medicamentos/métodos , Medicamentos Genéricos/uso terapéutico , Degeneración Macular Húmeda/diagnóstico , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Neovascularización Coroidal/prevención & control , Minería de Datos , Progresión de la Enfermedad , Reposicionamiento de Medicamentos/métodos , Femenino , Humanos , Revisión de Utilización de Seguros , Masculino , Medicare/estadística & datos numéricos , Estados Unidos , Degeneración Macular Húmeda/prevención & controlAsunto(s)
Alopurinol/uso terapéutico , Etiquetado de Medicamentos , Febuxostat/uso terapéutico , Supresores de la Gota/uso terapéutico , Gota/tratamiento farmacológico , Pautas de la Práctica en Medicina/tendencias , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Humanos , Mortalidad , Polietilenglicoles/uso terapéutico , Probenecid/uso terapéutico , Factores de Riesgo , Tioglicolatos/uso terapéutico , Triazoles/uso terapéutico , Estados Unidos , United States Food and Drug Administration , Urato Oxidasa/uso terapéuticoRESUMEN
BACKGROUND: Treatment decisions for Coronavirus Disease 2019 (COVID-19) depend on disease severity, but the prescribing pattern by severity and drivers of therapeutic choices remain unclear. OBJECTIVES: The objectives of the study were to evaluate pharmacological treatment patterns by COVID-19 severity and identify the determinants of prescribing for COVID-19. METHODS: Using electronic health record data from a large Massachusetts-based healthcare system, we identified all patients aged ≥ 18 years hospitalized with laboratory-confirmed COVID-19 from 1 March to 24 May, 2020. We defined five levels of COVID-19 severity at hospital admission: (1) hospitalized but not requiring supplemental oxygen; (2-4) hospitalized and requiring oxygen ≤ 2, 3-4, and ≥ 5 L per minute, respectively; and (5) intubated or admitted to an intensive care unit. We assessed the medications used to treat COVID-19 or as supportive care during hospitalization. RESULTS: Among 2821 patients hospitalized for COVID-19, we found inpatient mortality increased by severity from 5% for level 1 to 23% for level 5. As compared to patients with severity level 1, those with severity level 5 were 3.53 times (95% confidence interval 2.73-4.57) more likely to receive a medication used to treat COVID-19. Other predictors of treatment were fever, low oxygen saturation, presence of co-morbidities, and elevated inflammatory biomarkers. The use of most COVID-19 relevant medications has dropped substantially while the use of remdesivir and therapeutic anticoagulants has increased over the study period. CONCLUSIONS: Careful consideration of disease severity and other determinants of COVID-19 drug use is necessary for appropriate conduct and interpretation of non-randomized studies evaluating outcomes of COVID-19 treatments.
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Tratamiento Farmacológico de COVID-19 , COVID-19/mortalidad , Hospitalización , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Antivirales/uso terapéutico , Productos Biológicos/uso terapéutico , Índice de Masa Corporal , COVID-19/epidemiología , Comorbilidad , Comoras , Quimioterapia Combinada , Utilización de Medicamentos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno/métodos , Pandemias , Grupos Raciales , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Fumar/epidemiología , Adulto JovenRESUMEN
Ambulatory antibiotic stewardship policies focus on prescribing decisions made when patients present to clinicians with possible infections. They do not capture antibiotics prescribed outside of clinician visits or without clear indications for use. Antibiotic prescribing for vulnerable patients in the US has not been comprehensively measured. We measured the frequency with which all filled antibiotic prescriptions were associated with infections and in-person visits for Medicaid patients in the period 2004-13. We found that among 298 million antibiotic fills (62 percent for children) for 53 million patients, 55 percent were for clinician visits with an infection-related diagnosis, 17 percent were for clinician visits without an infection-related diagnosis, and 28 percent were not associated with a visit. Non-visit-based antibiotic prescriptions were less common for children than for adults and more common in the West than in other US regions. Large fractions of antibiotic prescriptions are filled without evidence of infection-related diagnoses or accompanying clinician visits. Current ambulatory antibiotic stewardship policies miss about half of antibiotic prescribing.
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Antibacterianos , Medicaid , Adulto , Instituciones de Atención Ambulatoria , Antibacterianos/uso terapéutico , Niño , Humanos , Prescripción Inadecuada , Pautas de la Práctica en Medicina , Prescripciones , Estados UnidosAsunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Recall de Medicamento , Utilización de Medicamentos/estadística & datos numéricos , Medicamentos Genéricos/uso terapéutico , Humanos , Revisión de Utilización de Seguros , Seguro de Servicios Farmacéuticos , Estados UnidosAsunto(s)
Artroplastia de Reemplazo , Glucemia/metabolismo , Complicaciones de la Diabetes/metabolismo , Hemoglobina Glucada/metabolismo , Hiperglucemia/diagnóstico , Atención Perioperativa , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo/estadística & datos numéricos , Biomarcadores/metabolismo , Femenino , Humanos , Hiperglucemia/epidemiología , Masculino , Tamizaje Masivo , Medicare , Estados Unidos/epidemiologíaRESUMEN
Importance: Prescription opioid use is common among patients with moderate to severe knee osteoarthritis before undergoing total knee replacement (TKR). Preoperative opioid use may be associated with worse clinical and safety outcomes after TKR. Objective: To determine the association of preoperative opioid use among patients 65 years and older with mortality and other complications at 30 days post-TKR. Design, Setting, And Participants: This cohort study used claims data from January 1, 2010, to December 31, 2014, from a random sample of US Medicare enrollees 65 years and older who underwent TKR. Based on opioid dispensing in 360 days prior to TKR, patients were classified as continuous (≥1 opioid dispensing in each of the past 12 months) or intermittent (any dispensing of opioids in the past 12 months but not continuous use) opioid users or as opioid-naive patients (no opioids dispensed in the past 12 months). Data analyses were conducted from October 3, 2017, to November 8, 2018. Main Outcomes and Measures: Primary outcomes included in-hospital mortality and 30-day post-TKR mortality, hospital readmission, and revision operation. Secondary safety outcomes at 30 days post-TKR included opioid overdose and vertebral and nonvertebral fracture. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs. Results: Of 316â¯593 patients (mean [SD] age, 73.9 [5.8] years; 214â¯677 [67.8%] women) who underwent TKR, 22â¯895 (7.2%) were continuous opioid users, 161â¯511 (51.0%) were intermittent opioid users, and 132â¯187 (41.7%) were opioid naive. In-hospital mortality occurred in 276 patients (0.09%). At 30 days post-TKR, 828 patients (0.26%) died, 16â¯786 patients (5.30%) had hospital readmission, and 921 patients (0.29%) had a revision operation. All primary and secondary outcomes occurred more frequently among continuous opioid users compared with opioid-naive patients. Compared with opioid-naive patients and after adjusting for demographic characteristics, combined comorbidity score, number of different prescription medications, and frailty, continuous opioid users had greater risk of revision operations (HR, 1.63; 95% CI, 1.15-2.32), vertebral fractures (HR, 2.37; 95% CI, 1.37-4.09), and opioid overdose (HR, 4.82; 95% CI, 1.36-17.07) at 30 days post-TKR. However, after adjusting covariates, there were no statistically significant differences in in-hospital (HR, 1.18; 95% CI, 0.73-1.90) or 30-day (HR, 1.05; 95% CI, 0.73-1.51) mortality between continuous opioid users and opioid-naive patients. Conclusions and Relevance: After adjusting for baseline risk profiles, including comorbidities and frailty, continuous opioid users had a higher risk of revision operations, vertebral fractures, and opioid overdose at 30 days post-TKR but not of in-hospital or 30-day mortality, compared with opioid-naive patients. These results highlight the need for better understanding of patient characteristics associated with chronic opioid use to optimize preoperative assessment of overall risk after TKR.
Asunto(s)
Analgésicos Opioides/efectos adversos , Artroplastia de Reemplazo de Rodilla/mortalidad , Osteoartritis de la Rodilla/mortalidad , Complicaciones Posoperatorias/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Medicare , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/cirugía , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/inducido químicamente , Periodo Preoperatorio , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Estados UnidosRESUMEN
We sought to refine understanding about associations identified in prior studies between angiotensin-II receptor blockers, metformin, selective serotonin reuptake inhibitors, fibric-acid derivatives, or calcium channel blockers and progression to glaucoma filtration surgery for open-angle glaucoma (OAG). We used new-initiator, active-comparator cohort designs to investigate these drugs in two data sources. We adjusted for confounders using stabilized inverse-probability-of-treatment weights and evaluated results using "intention-to-treat" and "as-treated" follow-up approaches. In both data sources, Kaplan-Meier curves showed trends for more rapid progression to glaucoma filtration surgery in patients taking calcium channel blockers compared with thiazides with as-treated (MarketScan P = 0.15; Medicare P = 0.03) and intention-to-treat follow-up (MarketScan P < 0.01; Medicare P = 0.10). There was suggestion of delayed progression for selective serotonin reuptake inhibitor compared with tricyclic antidepressants in Medicare, which was not observed in MarketScan. Our study provided support for a relationship between calcium channel blockers and OAG progression but not for other investigated drugs.
Asunto(s)
Bloqueadores de los Canales de Calcio , Progresión de la Enfermedad , Glaucoma de Ángulo Abierto/fisiopatología , Anciano , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Factores de Confusión Epidemiológicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Femenino , Glaucoma de Ángulo Abierto/epidemiología , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Estimación de Kaplan-Meier , Masculino , Medicare/estadística & datos numéricos , Medición de Riesgo/métodos , Estados UnidosRESUMEN
BACKGROUND: To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications. METHODS AND FINDINGS: For commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004-2013) and (2) Truven MarketScan (years: 2003-2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88-0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84-0.99] and 0.84 [0.76-0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01-1.10] and 1.07 [1.01-1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98-1.13] and 1.11 [1.05-1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by either residual confounding or generic perception bias. Limitations of this study include potential residual confounding due to the unavailability of certain clinical parameters in administrative claims data and the inability to evaluate surrogate outcomes, such as immediate changes in blood pressure, upon switching from brand products to generics. CONCLUSIONS: In this study, we observed that use of generics was associated with comparable clinical outcomes to use of brand-name products. These results could help in promoting educational interventions aimed at increasing patient and provider confidence in the ability of generic medicines to manage chronic diseases.