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BACKGROUND: Growing evidence indicates a causal relationship between SARS-CoV-2 infection and myocarditis. Post-authorization safety data have also identified myocarditis as a rare safety event following mRNA COVID-19 vaccination, particularly among adolescent and young-adult males after dose 2. We further evaluated the potential risk by querying the Moderna global safety database for myocarditis/myopericarditis reports among mRNA-1273 recipients worldwide. METHODS: Myocarditis/myopericarditis reports from 18 December 2020 to 15 February 2022 were reviewed and classified. The reported rate after any known mRNA-1273 dose was calculated according to age and sex, then compared with a population-based incidence rate to calculate observed-to-expected rate ratios (RRs). RESULTS: During the study period, 3017 myocarditis/myopericarditis cases among 252 million mRNA-1273 recipients who received at least 1 dose were reported to the Moderna global safety database. The overall reporting rate was 9.23 per 100 000 person-years, which was similar to the expected reference rate (9.0 cases per 100 000 person-years; RR [95% confidence interval (CI)], 1.03 [.97-1.08]). When stratified by sex and age, observed rates were highest for males aged <40 years, particularly those 18-24 years (53.76 per 100 000 person-years), which was higher than expected (RR [95% CI], 3.10 [2.68-3.58]). When considering only cases occurring within 7 days of a known dose, the observed rate was highest for males aged 18-24 years after dose 2 (4.23 per 100 000 doses administered). CONCLUSIONS: Myocarditis/myopericarditis rates were not higher than expected for the overall population of mRNA-1273 recipients but were higher than expected in males aged 18-24 years, with most cases occurring 7 days after dose 2.
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COVID-19 , Miocardite , Adolescente , Adulto , Masculino , Humanos , Vacina de mRNA-1273 contra 2019-nCoV , Vacinas contra COVID-19 , Miocardite/epidemiologia , SARS-CoV-2 , VacinaçãoRESUMO
Opioids affect placental development and function in animal models, but human data on their association with ischemic placental disease are limited. Using a cohort of pregnant women in the US nationwide Medicaid Analytic eXtract (2000-2014), we compared women with ≥2 opioid dispensings in pregnancy with unexposed women. Given an uncertain etiologically relevant window, we assessed exposure occurring in early pregnancy, late and not early pregnancy, and both early and late pregnancy. For placental abruption, preterm delivery, small for gestational age (SGA), and preeclampsia, we estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) using Cox proportional hazard models adjusting for demographic factors, indications/comorbidities, and medications. Among 1,833,871 eligible pregnancies, ≥2 opioid dispensings were filled in 6.5%. We observed an early exposure aHR of 1.34 (95% CI: 1.26, 1.43) for placental abruption, 1.21 (95% CI: 1.18, 1.23) for preterm delivery, 1.13 (95% CI: 1.09, 1.17) for SGA, and 0.95 (0.91, 0.98) for preeclampsia. Estimates for late exposure were attenuated. Early and late exposure was associated with higher aHRs for placental abruption, 1.62 (95% CI: 1.47, 1.78); preterm delivery, 1.37 (95% CI: 1.33, 1.42); and SGA, 1.26 (95% CI: 1.19, 1.33); but not preeclampsia, 0.99 (95% CI: 0.93, 1.05). Prescription opioids may modestly increase risk of placental abruption, preterm birth and SGA, but they do not appear to be associated with preeclampsia.
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Descolamento Prematuro da Placenta , Doenças Placentárias , Pré-Eclâmpsia , Nascimento Prematuro , Descolamento Prematuro da Placenta/epidemiologia , Descolamento Prematuro da Placenta/etiologia , Analgésicos Opioides/efeitos adversos , Feminino , Retardo do Crescimento Fetal , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Placenta , Doenças Placentárias/induzido quimicamente , Doenças Placentárias/epidemiologia , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/epidemiologia , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Fatores de RiscoRESUMO
The goal of this study was to describe patterns of selective serotonin reuptake inhibitor (SSRI) use during pregnancy in a US cohort (2005-2014) of > 1 million commercially insured women using administrative claims. We used international classification of disease (ICD-9) diagnosis and procedure and current procedural terminology codes in the OptumLabs® Data Warehouse to identify deliveries (including losses) among US women aged 15-45 (n = 1,061,023). SSRI dispensings that overlapped with the timing of pregnancy were identified using national drug codes in linked pharmacy claims. Demographic characteristics were imputed based on residential location, census data, and consumer information. We investigated patterns by trimester, agent, and demographic subgroups. A total of 46,087 of women (4.34%) were dispensed SSRIs during the estimated pregnancy period. Sertraline was the most common overall and had the highest initial use after trimester 1, including women who switched from another SSRI, although dispensing for > 1 SSRI during pregnancy was uncommon. Use of vilazodone was rare and had the highest discontinuation after trimester 1, followed by paroxetine. SSRI use was more common among women who were older, White, college-educated, higher income (≥ $100,000), or resided in the Midwest. Paroxetine and dispensings for > 1 SSRI were more common in lower education subgroups. White women had the highest proportion of use in all trimesters of pregnancy, whereas Hispanic women had the lowest. Among commercially insured US women, SSRI use during pregnancy differed by agent and demographics. More research is needed to understand whether these differences are due to symptom reporting, cultural beliefs, and/or physician preferences.
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Paroxetina , Inibidores Seletivos de Recaptação de Serotonina , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Trimestres da Gravidez , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sertralina , Adulto JovemRESUMO
PURPOSE: Identification of hospitalizations for infection is important for post-marketing surveillance of drugs, but the validity of using diagnosis codes to identify these events is unknown. Differentiating between hospitalization for and with infection is important, as the latter is common and less likely to arise from pre-admission exposure to drugs. We determined positive predictive values (PPVs) of diagnostic coding-based algorithms to identify hospitalization for infection among patients prescribed oral anti-diabetic drugs (OADs). METHODS: We identified patients initiating OADs within 2 United States claims databases (Medicare, HealthCore Integrated Research DatabaseSM [HIRDSM ]) and 2 United Kingdom electronic medical record databases (Clinical Practice Research Datalink [CPRD], The Health Improvement Network [THIN]) from 2009 to 2014. To identify potential hospitalizations for infection, we selected patients with a hospital diagnosis of infection and, within 7 days prior to hospitalization, either an outpatient/emergency department visit with an infection diagnosis or outpatient antimicrobial treatment. Hospital records were reviewed by infectious disease specialists to adjudicate hospital admissions for infection. PPVs for confirmed outcomes were determined for each database. RESULTS: Code-based algorithms to identify hospitalization for infection had PPVs exceeding 80% within Medicare (PPV, 83% [90/109]; 95% CI, 74-89%), HIRDSM (PPV, 89% [73/82]; 95% CI, 80-95%), and THIN (PPV, 86% [12/14]; 95% CI, 57-98%) but not within CPRD (PPV, 67% [14/21]; 95% CI, 43-85%). CONCLUSIONS: Algorithms identifying hospitalization for infection utilizing hospital diagnoses along with antecedent outpatient/emergency infection diagnoses or antimicrobial therapy had sufficiently high PPVs for confirmed events within Medicare, HIRDSM , and THIN to enable their use for pharmacoepidemiologic research.
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Doenças Transmissíveis/classificação , Doenças Transmissíveis/epidemiologia , Hospitalização , Hipoglicemiantes/administração & dosagem , Classificação Internacional de Doenças/normas , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Doenças Transmissíveis/tratamento farmacológico , Estudos Transversais , Bases de Dados Factuais/normas , Bases de Dados Factuais/estatística & dados numéricos , Registros Eletrônicos de Saúde/normas , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Resultado do Tratamento , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
RATIONALE: Estimates of idiopathic pulmonary fibrosis (IPF) incidence and prevalence from electronic databases without case validation may be inaccurate. OBJECTIVES: Develop claims algorithms to identify IPF and assess their positive predictive value (PPV) to estimate incidence and prevalence in the United States. METHODS: We developed three algorithms to identify IPF cases in the HealthCore Integrated Research Database. Sensitive and specific algorithms were developed based on literature review and consultation with clinical experts. PPVs were assessed using medical records. A third algorithm used logistic regression modeling to generate an IPF score and was validated using a separate set of medical records. We estimated incidence and prevalence of IPF using the sensitive algorithm corrected for the PPV. MEASUREMENTS AND MAIN RESULTS: We identified 4,598 patients using the sensitive algorithm and 2,052 patients using the specific algorithm. After medical record review, the PPVs of these algorithms using the treating clinician's diagnosis were 44.4 and 61.7%, respectively. For the IPF score, the PPV was 76.2%. Using the clinical adjudicator's diagnosis, the PPVs were 54 and 57.6%, respectively, and for the IPF score, the PPV was 83.3%. The incidence and period prevalences of IPF, corrected for the PPV, were 14.6 per 100,000 person-years and 58.7 per 100,000 persons, respectively. CONCLUSIONS: Sensitive algorithms without correction for false positive errors overestimated incidence and prevalence of IPF. An IPF score offered the greatest PPV, but it requires further validation.
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Fibrose Pulmonar Idiopática/epidemiologia , Prontuários Médicos/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Revisão da Utilização de Seguros , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Distribuição por Sexo , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: We measured birth prevalence of major congenital malformations (MCMs) after topiramate use during pregnancy to screen for a possible signal of increased risk. METHODS: Using four healthcare databases, we identified three cohorts of pregnant women: cohort 1, used topiramate during the first trimester; cohort 2, used topiramate or another antiepileptic drug previously but not during pregnancy; and cohort 3, were pregnant and did not use topiramate but had indications for use individually matched to those of users. Cohort 1 was compared with cohorts 2 and 3. MCMs were a code for any major congenital malformation dated within 30 days of the delivery date on the mother's claims or within 365 days after infant birth date, excluding a genetic or syndromic basis, and with procedure or healthcare usage consistent with the MCM diagnosis code in the 365 days after infant birth. RESULTS: Of the 10 specific common MCMs evaluated, 1 (conotruncal heart defects) had a prevalence ratio greater than 1.5 for both primary comparisons, and 4 (ventricular septal defect, atrial septal defect, hypospadias, coarctation of the aorta) had a prevalence ratio greater than 1.5 for one of the two comparisons. Following screening of organ systems with elevated MCMs, the prevalence ratio was greater than 1.5 for patent ductus arteriosus in both comparisons and for obstructive genitourinary defects in one comparison. CONCLUSION: To evaluate a large number of MCMs across many pregnancies, we used crude methods for detecting potential signals. Therefore, these results should be seen as potential signals, not causal.
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Anormalidades Induzidas por Medicamentos/epidemiologia , Frutose/análogos & derivados , Estudos de Coortes , Feminino , Frutose/efeitos adversos , Humanos , Gravidez , Prevalência , Medição de Risco , Topiramato , Estados Unidos/epidemiologiaRESUMO
PURPOSE: First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants exposed to TPM in utero. We evaluated the association between TPM use in early pregnancy and the risk of OC. METHODS: This retrospective cohort study used 1997-2011 automated data from four sources: HealthCore and OptumInsight (commercial insurance claims), Truven Health (Medicaid claims), and Kaiser Permanente Northern California Region (electronic medical records). We compared the prevalence of OCs in infants of women exposed to TPM in the first trimester (TPM cohort) with the prevalence in infants of women formerly exposed to TPM or other antiepileptic drugs (formerly exposed [FE] cohort) and infants of women with similar medical profiles (SMPs) to the TPM cohort that were not exposed to TPM (SMP cohort). To control for confounding, we used stratification and standardization for individual variables and propensity score deciles. RESULTS: The birth prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13 512) in the FE cohort, and 0.07% (9/13 614) in the SMP cohort. Standardized by site, the prevalence ratio (PR) for TPM versus FE was 2.5 (95% CI: 1.0-6.0) and for TPM versus SMP was 5.4 (95% CI: 2.0-14.6). Adjustment for covariates one at a time or by propensity score yielded similar results. CONCLUSION: Consistent with other recent epidemiologic research, first-trimester TPM exposure was associated with an elevated birth prevalence of OC.
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Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Frutose/análogos & derivados , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , California/epidemiologia , Fenda Labial/induzido quimicamente , Fissura Palatina/induzido quimicamente , Estudos de Coortes , Bases de Dados Factuais , Registros Eletrônicos de Saúde , Feminino , Frutose/administração & dosagem , Frutose/efeitos adversos , Frutose/uso terapêutico , Humanos , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Prevalência , Estudos Retrospectivos , TopiramatoRESUMO
Background: Large-scale use of mRNA COVID-19 vaccines during the pandemic was associated with enhanced safety monitoring to ensure accurate and timely review of safety. We reviewed the mRNA-1273 (original strain) safety profile following 2 years of use (>772 million administered doses), primarily focusing on predefined safety topics (ie, adverse events of special interest [AESIs]) proposed in advance of COVID-19 vaccine use. Methods: Cumulative mRNA-1273 safety data were included from spontaneous adverse event (AE) cases reported to Moderna's global safety database between 18 December 2020 and 17 December 2022. Reporting rates of AESIs were calculated per 1 million doses of mRNA-1273 administered. Observed-to-expected (OE) ratios were computed by comparing observed rates of AESIs with the background/expected rate for these events to evaluate potential associations with mRNA-1273. Results: There were 658 759 identified case reports associated with 2 517 669 AEs. Most AEs were nonserious (83.4%; 2 098 954/2 517 669). Overall 0.7% (17 751/2 517 669) were fatal. AESIs represented 13.7% of all AEs (344 921/2 517 669), with reporting rates for most AESIs below the expected background incidence. Exceptions included anaphylaxis (OE ratio 3 days after vaccination, 2.09; 95% CI, 1.93-2.25) and, among individuals aged 12 to 40 years, myocarditis (OE ratio 7 days after any dose, 3.89 [3.50-4.32]; among men after dose 2, 8.57 [6.88-10.68]) and pericarditis (OE ratio 7 days after vaccination, 3.47; 2.89-4.16). Conclusions: This safety analysis of mRNA-1273 identified evidence of increased risk for anaphylaxis, myocarditis, and pericarditis but not for other AESIs identified for enhanced monitoring ahead of COVID-19 vaccine use.
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INTRODUCTION: To compare the real-world effectiveness of a third dose of mRNA-1273 versus a third dose of BNT162b2 against breakthrough COVID-19 hospitalizations among adults aged ≥ 65 years who completed a primary series of an mRNA-based COVID-19 vaccine (regardless of which primary series was received). MATERIALS AND METHODS: This observational comparative vaccine effectiveness (VE) study was conducted using administrative claims data from the US HealthVerity database (September 22, 2021, to August 31, 2022). A third dose of mRNA-1273 versus BNT162b2 was assessed for preventing COVID-19 hospitalizations and medically attended COVID-19 among adults aged ≥ 65 years. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) with 95 % confidence intervals (CIs) using weighted Cox proportional hazards models were calculated to estimate relative VE for each outcome. RESULTS: Overall, 94,587 and 92,377 individuals received a third dose of mRNA-1273 and BNT162b2, respectively. Among the weighted population, the median age was 69 years (interquartile range, 66-74), 53 % were female, and 46 % were commercially insured. COVID-19 hospitalization rates per 1000 person-years (PYs) were 5.61 (95 % CI, 5.13-6.09) for mRNA-1273 and 7.06 (95 % CI, 6.54-7.57) for BNT162b2 (HR, 0.82; 0.69-0.98). Medically attended COVID-19 rates per 1000 PYs (95 % CI) were 95.05 (95 % CI, 93.03-97.06) for mRNA-1273 and 106.55 (95 % CI, 104.53-108.57) for BNT162b2 (HR, 0.93; 0.89-0.98). CONCLUSIONS: Results from this observational comparative VE database study provide evidence that among older adults, a third dose of mRNA-1273 was more effective in preventing breakthrough COVID-19 hospitalization and medically attended COVID-19 infection compared with a third dose of BNT162b2.
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OBJECTIVE: To assess the impact of extended-release (ER)/long-acting (LA) opioid prescriber training on prescribing behaviors. DESIGN: Retrospective cohort study. SETTING: Prescriber training was evaluated from June 1, 2013 through December 31, 2016. The full study period was 2 years longer, from June 1, 2012 through December 31, 2017, to include data for all prescribers' 1-year pretraining and post-training periods. PARTICIPANTS: 24,428 prescribers who wrote ER/LA opioid prescriptions for eligible patients, with a record of training from the partner continuing education provider between June 1, 2013 and December 31, 2016. INTERVENTION: ER/LA opioid prescriber training. MAIN OUTCOME MEASURES: Prescribing behaviors 1-year before (pretraining) and after (post-training) prescribers completed training, specifically the proportion of opioid-nontolerant patients receiving ER/LA opioids indicated for opioid-tolerant patients and for patients receiving ≥100 morphine equivalents dose daily, and the proportion of concomitant users of central nervous system depressant drugs. RESULTS: The differences in the proportion of opioid-nontolerant patients receiving ER/LA opioids indicated for opi-oid-tolerant patients and for patients receiving ≥100 morphine equivalents dose daily were -0.69 percent (95 percent confidence interval [CI]: -1.78 percent, 0.40 percent) and -0.23 percent (95 percent CI: -1.18 percent, 0.68 percent), respectively. The differences in the proportion of concomitant users of central nervous system depressant drugs were -0.94 percent (95 percent CI: -1.39 percent; -0.48 percent) for benzodiazepines, 0.06 percent (95 percent CI: -0.13 percent; 0.25 percent) for antipsychotics, -0.41 percent (95 percent CI: -0.69 percent; -0.13 percent) for hypnotics/sedatives, and 0.08 percent (95 percent CI: -0.40 percent; 0.57 percent) for muscle relaxants. CONCLUSIONS: While prescribers showed some changes in prescribing behavior after completing training, training was not associated with clinically relevant changes in prescribing behaviors.
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Analgésicos Opioides , Avaliação de Risco e Mitigação , Humanos , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Padrões de Prática Médica , Morfina , Prescrições de MedicamentosRESUMO
The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6-16.4%) and 5.1% (95% CI: 3.2-6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5-20.8%) and 10.7% (8.2-13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults.
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The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received ≥2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%-75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable ≥3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%-58.8%) and 82.7% (63.7%-91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Estados Unidos/epidemiologia , Vacina de mRNA-1273 contra 2019-nCoV , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Eficácia de Vacinas , SARS-CoV-2/genéticaRESUMO
PURPOSE: To describe the design and rationale of a series of postmarketing studies to examine the safety of saxagliptin, an oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus, in real-world settings. METHODS: We are conducting a series of retrospective cohort studies using two UK (General Practice Research Database, and The Health Improvement Network) and two US (Medicare, HealthCore Integrated Research Database(SM) ) data sources. The primary outcomes of interest will include (i) hospitalization with acute liver failure, (ii) hospitalization for acute kidney injury, (iii) hospitalization for severe hypersensitivity reactions, (iv) hospitalization for severe infections, (v) hospitalization with infections associated with T-lymphocyte dysfunction (i.e., herpes zoster, tuberculosis, or nontuberculous mycobacteria), and (vi) major cardiovascular events. Diagnosis codes for the outcomes of interest will be validated by medical record review within each data source. Projected use and estimated incidence rates of outcomes of interest suggest there will be at least 80% statistical power to detect a minimum hazard ratio of 1.5 for major cardiovascular events, 2.0 for acute kidney injury and severe infections, 2.4 for acute liver failure, and 4.0 for severe hypersensitivity reactions. RESULTS: Forthcoming. CONCLUSIONS: This postmarketing safety assessment will provide important information regarding the safety of saxagliptin and could potentially identify important dipeptidyl peptidase-4 inhibitor class effects. The methods described may be useful to others planning similar evaluations.
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Adamantano/análogos & derivados , Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Dipeptídeos/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Projetos de Pesquisa Epidemiológica , Farmacoepidemiologia , Adamantano/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Algoritmos , Estudos de Coortes , Qualidade de Produtos para o Consumidor , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Determinação de Ponto Final , Humanos , Farmacoepidemiologia/métodos , Estudos Retrospectivos , Reino UnidoRESUMO
Importance: Prescription opioids are often used during pregnancy even though they are associated with neonatal opioid withdrawal syndrome (NOWS). Most studies of adverse outcomes of opioid use for pain have assessed only the class-wide outcome despite the pharmacodynamic and pharmacokinetic heterogeneity across opioid medications. Objective: To compare the risk of NOWS across common types of opioids when prescribed as monotherapy during the last 3 months of pregnancy. Design, Setting, and Participants: This cohort study analyzed administrative claims data of Medicaid-insured mothers and newborns in 46 states and Washington DC from January 1, 2000, through December 31, 2014. Participants were mothers with 2 or more dispensed opioid prescriptions within 90 days before delivery and their eligible live-born neonates. Data were analyzed from February 2020 to March 2021. Exposure: Different types of opioid medications were compared by agonist strength (strong vs weak) and half-life (medium vs short and long vs short) of the opioid active ingredient. Main Outcomes and Measures: The primary outcome was NOWS, which was identified using an International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code in the 30 days after delivery. Relative risks (RRs) were adjusted for an exposure propensity score, including demographic characteristics, comorbidities, other medication use, and opioid treatment characteristics (including morphine milligram equivalents), using fine stratification. Results: The cohort comprised 48â¯202 opioid-exposed pregnancies with live newborns. A total of 1069 neonates (2.2%) had NOWS and 559 (1.2%) had severe NOWS. Opioid exposure during pregnancy included 16â¯202 pregnancies exposed to codeine, 4540 to oxycodone, 1244 to tramadol, 260 to methadone (dispensed for pain), 90 to hydromorphone, and 63 to morphine compared with 25â¯710 exposed to hydrocodone. Demographic characteristics varied across opioids, with tramadol, oxycodone, methadone, hydromorphone, and morphine being more commonly dispensed at older maternal age (≥35 years). Compared with hydrocodone, codeine had a lower adjusted RR of NOWS (0.57; 95% CI, 0.46-0.70), with a similar adjusted RR for tramadol (RR, 1.06; 95% CI, 0.73-1.56), and 2- to 3-fold higher adjusted RRs for oxycodone (1.87; 95% CI, 1.66-2.11), morphine (2.84; 95% CI, 1.30-6.22), methadone (3.02; 95% CI, 2.45-3.73), and hydromorphone (2.03; 95% CI, 1.09-3.78). Strong agonists were associated with a higher risk of NOWS than weak agonists (RR, 1.97; 95% CI, 1.78-2.17), and long half-life opioids were associated with an increased risk compared with short half-life products (RR, 1.33; 95% CI, 1.12-1.56). Findings were consistent across sensitivity and subgroup analyses. Conclusions and Relevance: Results of this study show higher risk of NOWS and severe NOWS among neonates with in utero exposure to strong agonists and long half-life prescription opioids. Information on the opioid-specific risk of NOWS may help prescribers select opioids for pain management in late stages of pregnancy.
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Doenças do Recém-Nascido , Síndrome de Abstinência Neonatal , Síndrome de Abstinência a Substâncias , Tramadol , Adulto , Analgésicos Opioides/efeitos adversos , Codeína , Estudos de Coortes , Feminino , Humanos , Hidrocodona , Hidromorfona , Recém-Nascido , Doenças do Recém-Nascido/induzido quimicamente , Metadona/uso terapêutico , Morfina , Síndrome de Abstinência Neonatal/tratamento farmacológico , Síndrome de Abstinência Neonatal/epidemiologia , Síndrome de Abstinência Neonatal/etiologia , Oxicodona/efeitos adversos , Dor/tratamento farmacológico , Gravidez , Prescrições , Síndrome de Abstinência a Substâncias/complicações , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Head-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences. METHODS: This observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated. RESULTS: Overall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53 % were female, and baseline immunodeficiencies included prior blood transplant (8%-9%), prior organ transplant (7%), active cancer (12%-13%), primary immunodeficiency (5-6%), HIV (20%-21%), and immunosuppressive therapy use (60%-61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83-27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75-0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67-0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96-4.51) for mRNA-1273 and 4.68 (3.91-5.59) for BNT162b2 (HR, 0.78; 0.59-1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57-0.92) and 0.66 (0.58-0.76), respectively. CONCLUSIONS: Among immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only. STUDY REGISTRATION: NCT05366322.
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COVID-19 , Vacinas , Adulto , Estados Unidos/epidemiologia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Teste para COVID-19 , Vacinas de mRNARESUMO
BACKGROUND: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy may increase risk for neural tube defects (NTDs), including spina bifida. Folic acid intake can prevent NTDs, but it is not known whether it modifies any risks associated with NSAID use. OBJECTIVES: To assess the impact of periconceptional NSAID use on the risk of spina bifida overall and stratified by folic acid intake. STUDY DESIGN: We analyzed 1998-2015 data from the Slone Epidemiology Center Birth Defects Study, a multi-site, case-control study. Mothers were interviewed to identify sociodemographic factors, behaviors, and exposures during pregnancy. Periconceptional NSAID use was defined as use of aspirin, ibuprofen, naproxen, or COX2 inhibitors within the month before or after the last menstrual period. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for NSAID use, adjusted for study center and race/ethnicity stratified by average daily folic acid intake above ("high FA") or below ("low FA") 400 mcg/day. RESULTS: We compared mothers of 267 infants with spina bifida to mothers of 6,233 nonmalformed controls. Among control mothers, 20% used NSAIDS periconceptionally (16% ibuprofen, 4% aspirin, 3% naproxen, and <1% COX-2 inhibitors). For any NSAID use, the aORs among low FA and high FA women were 1.70 (95% CI [1.13, 2.57]) and 1.09 (95% CI [0.69, 1.71]), respectively. CONCLUSIONS: We observed a small increase in the risk for spina bifida among infants born to women who used NSAIDs periconceptionally, but this risk was limited to those who had inadequate folic acid intake.
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Preparações Farmacêuticas , Disrafismo Espinal , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Casos e Controles , Feminino , Ácido Fólico , Humanos , Lactente , Gravidez , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/etiologia , Disrafismo Espinal/prevenção & controleRESUMO
INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination. METHODS: Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Databasesm were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013-March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history. RESULTS: The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history. CONCLUSIONS: In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019).
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Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Benzoxazinas , Broncodilatadores/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Brometo de Tiotrópio/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND/RATIONALE: The US Food and Drug Administration (FDA) approved a Risk Evaluation and Mitigation Strategy (REMS) for extended release/long-acting (ER/LA) opioids in 2012. The purpose of this study was to assess patient knowledge of the safe use of these products following implementation of the REMS and to determine possible effects of the REMS, including impact on medication access. OBJECTIVE: To assess patient knowledge of safe use of ER/LA opioids and use of REMS patient education tools such as the Medication Guide (MG) and Patient Counseling Document (PCD). METHODS: This was a cross-sectional survey of commercially insured (Commercial) and Medicare Advantage-insured (Medicare) adults with ≥1 pharmacy claim for an ER/LA opioid (10/01/2015 - 02/28/2017) in the HealthCore Integrated Research Database and Medicaid-insured (Medicaid) adult members of a research panel, about their knowledge of safe use of ER/LA opioids and receipt/comprehension of the MG and PCD. RESULTS: Survey respondents consisted of 382 Commercial, 43 Medicare and 40 Medicaid adults. While ≥95% of respondents received and read the MG, fewer were aware of the PCD (Commercial: 47%, Medicare: 65%, Medicaid: 53%). Almost 75% of the knowledge questions were answered correctly by ≥80% of all respondents; fewer respondents recognized that use of opioids as directed can lead to death (Commercial: 73%, Medicare: 56%, Medicaid: 63%), the MG should be read at each dispensing (Commercial: 78%, Medicare: 53%, Medicaid: 75%), opioids should not be stored in the medicine cabinet (Commercial: 77%, Medicare: 79%, Medicaid: 58%), missed doses should not be taken as soon as possible (Commercial: 56%, Medicare: 51%, Medicaid: 50%), and pills should not be crushed (Commercial: 85%, Medicare: 67%, Medicaid: 52%). CONCLUSION: Although most respondents reported reading and understanding the MG and exhibited knowledge of safe use of ER/LA opioids, providers' use of the PCD and increased understanding of safe use core messages need reinforcement.
RESUMO
BACKGROUND: Infants aged <12 months are at high risk of hospitalization for influenza. Influenza vaccine is recommended for pregnant women and for most children; however, no vaccine is approved for infants aged <6 months. Effective approaches are needed to protect this vulnerable population. Vaccination of women during pregnancy may protect the infant through transfer of antibodies from the mother. Few studies have examined the effectiveness of this strategy, and those studies produced mixed results. METHODS: In a matched case-control study, case patients were infants aged <12 months admitted to a large urban hospital in the northeastern United States because of laboratory-confirmed influenza from 2000 to 2009. For each case, we enrolled 1 or 2 control subjects who were infants who tested negative for influenza and matched cases by date of birth and date of hospitalization (within 4 weeks). Vaccine effectiveness was calculated on the basis of matched odds ratios and was adjusted for confounding. RESULTS: The mothers of 2 (2.2%) of 91 case subjects and 31 (19.9%) of 156 control subjects aged <6 months, and 1 (4.6%) of 22 case subjects and 2 (5.6%) of 36 control subjects aged ≥6 months, had received influenza vaccine during pregnancy. The effectiveness of influenza vaccine given to mothers during pregnancy in preventing hospitalization among their infants, adjusted for potential confounders, was 91.5% (95% confidence interval [CI], 61.7%-98.1%; P = .001) for infants aged <6 months. The unadjusted effectiveness was 90.7% (95% CI, 59.9%-97.8%; P = .001). CONCLUSIONS: Influenza vaccine given to pregnant women is 91.5% effective in preventing hospitalization of their infants for influenza in the first 6 months of life.