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Objectives: Patients with kidney disease have been prioritized for coronavirus disease 2019 (COVID-19) vaccination due to their susceptibility to COVID-19 infection. However, little evidence exists regarding these patients' vulnerability to COVID-19 post-vaccination. Thus, we evaluated the risk of COVID-19 in patients with kidney disease compared to individuals without kidney disease according to vaccination status. Methods: A retrospective cohort study was conducted using the Korean nationwide COVID-19 registry linked with NHIS claims data (2018-2021). Among individuals aged 12 years or older, 2 separate cohorts were constructed: a COVID-19-vaccinated cohort and an unvaccinated cohort. Within each cohort, the risk of COVID-19 infection and all-cause mortality, hospitalization, and emergency room visits within 30 days of COVID-19 infection were compared between patients with and without kidney disease. To adjust for potential confounding, we used propensity score matching. Hazard ratios (HRs) for each outcome were estimated using a Cox proportional hazard model. Results: We identified 785,390 and 836,490 individuals in the vaccinated and unvaccinated cohorts, respectively. Compared to patients without kidney disease, patients with kidney disease were at a higher risk of COVID-19 infection in both the vaccinated cohort (HR, 1.08; 95% CI, 1.02-1.16) and the unvaccinated cohort (HR, 1.09; 95% CI, 0.99-1.20). Likewise, patients with kidney disease generally were at higher risk for severe clinical outcomes within 30 days of COVID-19 infection. Subgroup and sensitivity analyses showed generally consistent results. Conclusion: Our study observed excess risk of COVID-19 in patients with kidney disease, highlighting the importance of ongoing attention to these patients even post-vaccination. .
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BACKGROUND: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. CONCLUSION: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.
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Resultado del Embarazo , Retinoides , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Adulto , República de Corea/epidemiología , Retinoides/efectos adversos , Retinoides/uso terapéutico , Administración Oral , Recién Nacido , Recién Nacido de Bajo Peso , Isotretinoína/efectos adversos , Isotretinoína/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Acitretina/efectos adversos , Acitretina/uso terapéutico , Bases de Datos Factuales , Modelos de Riesgos Proporcionales , Adulto Joven , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/tratamiento farmacológicoRESUMEN
We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/psicología , República de Corea/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Japón/epidemiología , Adulto , Anciano , Estudios de Cohortes , Trastornos Mentales/epidemiología , SARS-CoV-2 , Factores de RiesgoRESUMEN
BACKGROUND: Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea. METHODS: We conducted a self-controlled case series study using the K-COV-N cohort (2018-2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0-28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI). RESULTS: Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90-1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95-1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83-1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68-1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88-23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis. CONCLUSION: For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.
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Vacunas contra la COVID-19 , COVID-19 , Neoplasias , SARS-CoV-2 , Humanos , Masculino , Femenino , República de Corea/epidemiología , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , COVID-19/epidemiología , Persona de Mediana Edad , Anciano , SARS-CoV-2/aislamiento & purificación , Adulto , Infarto del Miocardio/etiología , Infarto del Miocardio/epidemiología , Enfermedades Cardiovasculares/etiología , Vacunación/efectos adversos , Miocarditis/etiología , ChAdOx1 nCoV-19 , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Adulto Joven , Adolescente , Pericarditis/etiología , Pericarditis/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the association between antibiotic use during pregnancy or early infancy and the risk of neurodevelopmental disorders in children. DESIGN: Nationwide population based cohort study and sibling analysis. SETTING: Korea's National Health Insurance Service mother-child linked database, 2008-21. PARTICIPANTS: All children live born between 2009 and 2020, followed up until 2021 to compare those with and without antibiotic exposure during pregnancy or early infancy (first six months of life). MAIN OUTCOMES MEASURES: Autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children. After 1:1 propensity score matching based on many potential confounders, hazard ratios with 95% confidence interval were estimated using Cox proportional hazard models. A sibling analysis additionally accounted for unmeasured familial factors. RESULTS: After propensity score matching, 1 961 744 children were identified for the pregnancy analysis and 1 609 774 children were identified for the early infancy analysis. Although antibiotic exposure during pregnancy was associated with increased risks of all four neurodevelopmental disorders in the overall cohort, these estimates were attenuated towards the null in the sibling analyses (hazard ratio for autism spectrum disorder 1.06, 95% confidence interval 1.01 to 1.12; intellectual disorder 1.00, 0.93 to 1.07; language disorder 1.05, 1.02 to 1.09; and epilepsy 1.03, 0.98 to 1.08). Likewise, no association was observed between antibiotic exposure during early infancy and autism spectrum disorder (hazard ratio 1.00, 0.96 to 1.03), intellectual disorder (1.07, 0.98 to 1.15), and language disorder (1.04, 1.00 to 1.08) in the sibling analyses; however, a small increased risk of epilepsy was observed (1.13, 1.09 to 1.18). The results generally remained consistent across several subgroup and sensitivity analyses, except for slightly elevated risks observed among children who used antibiotics during very early life and those who used antibiotics for more than 15 days. CONCLUSIONS: In this large cohort study, antibiotic exposure during pregnancy or early infancy was not associated with an increased risk of autism spectrum disorder, intellectual disorder, or language disorder in children. However, elevated risks were observed in several subgroups such as children using antibiotics during very early life and those with long term antibiotic use, which warrants attention and further investigation. Moreover, antibiotic use during infancy was modestly associated with epilepsy, even after control for indications and familial factors. When prescribing antibiotics to pregnant women and infants, clinicians should carefully balance the benefits of use against potential risks.
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Antibacterianos , Trastorno del Espectro Autista , Epilepsia , Discapacidad Intelectual , Trastornos del Lenguaje , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/inducido químicamente , Embarazo , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Lactante , Antibacterianos/efectos adversos , Masculino , Discapacidad Intelectual/epidemiología , Preescolar , Trastornos del Lenguaje/epidemiología , Trastornos del Lenguaje/inducido químicamente , Estudios de Cohortes , República de Corea/epidemiología , Factores de Riesgo , Recién Nacido , Modelos de Riesgos Proporcionales , Niño , Puntaje de Propensión , AdultoRESUMEN
BACKGROUND: There is limited evidence on the safety of coronavirus disease 2019 (COVID-19) vaccination during pregnancy and lactation. Thus, we aimed to evaluate the association between COVID-19 vaccination during pregnancy and lactation and reporting risk of adverse pregnancy or lactation outcomes. METHODS: Using VigiBase, we performed a disproportionality analysis with case/non case design. Cases were defined based on the Standardized MedDRA Queries (SMQs) of "pregnancy and neonatal topics" and non-cases were defined as all other adverse events. We included all reports with COVID-19 vaccines as the suspected cause. Using the full database as the comparators, reporting odds ratios (RORs) with 95% confidence intervals (CIs) were estimated by logistic regression while adjusting for maternal age. Infants' age and sex were additionally adjusted in analyzing the risk of COVID-19 vaccination during lactation. RESULTS: We identified 10,266 and 6,474 reports with the SMQ of "pregnancy and neonatal topics" associated with COVID-19 vaccines during pregnancy and lactation, respectively. No significant RORs of adverse pregnancy outcomes associated with COVID-19 vaccines during pregnancy were observed; however, "functional lactation disorders" showed significant disproportionality during lactation with adjusted ROR of 1.48 (95% CI, 1.21-1.79). Further analysis that analyzed "functional lactation disorders" at a preferred term level, showed higher ROR in mastitis (2.76 [95% CI, 1.45-5.27]). CONCLUSION: Overall, we did not observe a positive association between COVID-19 vaccination during pregnancy and risk of reporting adverse pregnancy outcomes. However, we found a significant disproportionate reporting association between COVID-19 vaccination during lactation and "functional lactation disorders", specifically mastitis. Continuous surveillance is warranted to confirm the safety of COVID-19 vaccine during pregnancy and lactation.
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Vacunas contra la COVID-19 , Lactancia , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Trastornos de la Lactancia , Mastitis , Vacunación/efectos adversos , MasculinoRESUMEN
AIM: To explore the risk of breakthrough infection among patients with type 2 diabetes (T2D) and risk of severe clinical outcomes after SARS-CoV-2 infection according to vaccination status. MATERIALS AND METHODS: We conducted a population-based cohort study using South Korea's linked database of nationwide COVID-19 registry and claims data between 2018 and 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breakthrough infections were measured in 1:1 propensity-score (PS)-matched fully vaccinated patients with versus without T2D (full-vaccination cohort), and HRs for all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) use, and hospitalizations after SARS-CoV-2 infection were measured in 1:1 PS-matched T2D patients with versus without full-vaccination (T2D cohort). RESULTS: After 1:1 PS matching, 2 109 970 patients with and without T2D were identified (age 63.5 years; 50.9% male). Patients with T2D showed an increased risk of breakthrough infections compared to those without T2D (HR 1.10, 95% CI 1.06-1.14). The increased risk of breakthrough infections was more notable among T2D patients receiving insulin treatment. However, the risk of severe COVID-19 outcomes was lower in fully vaccinated T2D patients compared with unvaccinated T2D patients (all-cause mortality: HR 0.54, 95% CI 0.43-0.67; ICU admission/MV use: HR 0.31, 95% CI 0.23-0.41; hospitalization: HR 0.73, 95% CI 0.68-0.78). CONCLUSIONS: While patients with T2D remain a vulnerable population to SARS-CoV-2 infection even after full-vaccination, full-vaccination was associated with a lower risk of adverse clinical outcomes after SARS-CoV-2 infection. These findings support the guidelines recommending patients with T2D as a priority vaccination group.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Persona de Mediana Edad , Femenino , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/prevención & control , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , SARS-CoV-2 , Infección IrruptivaRESUMEN
A retrospective cohort study was conducted to examine trends in the incidence and burden of pertussis among adults ≥50 years in South Korea, with/without pre-existing chronic obstructive pulmonary disease (COPD) or asthma. The nationwide Health Insurance Review and Assessment Service (HIRA) database was used to identify patients ≥50 years diagnosed with pertussis (2009-2018). Mean annual incidence of pertussis per 100 000 persons and overall mean incidence rate ratios (IRR) were calculated for patients with pre-existing COPD or asthma versus those with neither. Incremental healthcare costs (all-cause and pertussis-related) and healthcare utilisation (number of outpatient visits, emergency room visits, and number and length of hospitalisations) up to 12 months after, compared to 3 months before pertussis diagnosis, were also measured for each group (matched on sex, age, and Charlson Comorbidity Index). Of 1011 pertussis cases, 175 had asthma, 96 had COPD (not mutually exclusive), and 796 had neither. Overall mean pertussis incidence was 2.5, 3.4, and 0.5 for adults with pre-existing COPD, asthma, and those with neither. IRR (95% confidence interval) of pertussis for adults with pre-existing COPD and asthma was 4.9 (4.0-|6.1) and 6.7 (5.7-7.9). Both COPD-pertussis and asthma-pertussis groups had higher mean incremental all-cause costs and length of hospitalisations than the general-pertussis group 3 months following pertussis diagnosis. In conclusion, individuals ≥50 years in South Korea with pre-existing COPD or asthma were at an increased risk of being diagnosed with pertussis and had higher healthcare resource utilisation than those without these conditions.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , Tos Ferina , Humanos , Anciano , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Incidencia , Estudios Retrospectivos , Tos Ferina/epidemiología , Asma/epidemiología , Costos de la Atención en SaludRESUMEN
This cohort study examines whether the risk of low birth weight is associated with prenatal exposure to proton pump inhibitors.
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Recién Nacido de Bajo Peso , Inhibidores de la Bomba de Protones , Recién Nacido , Embarazo , Femenino , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Peso al Nacer , República de Corea/epidemiologíaRESUMEN
BACKGROUND: Existing data on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during late pregnancy is well established, providing assurance. However, the use of NSAIDs during early pregnancy remains inconclusive owing to conflicting findings on adverse neonatal outcomes as well as the limited data on adverse maternal outcomes. Therefore, we sought to investigate whether early prenatal exposure to NSAIDs was associated with neonatal and maternal adverse outcomes. METHODS AND FINDINGS: We conducted a nationwide, population-based cohort study using Korea's National Health Insurance Service (NHIS) database with a mother-offspring cohort constructed and validated by the NHIS to include all live births in women aged 18 to 44 years between 2010 and 2018. We defined exposure to NSAIDs as at least two records of NSAID prescriptions during early pregnancy (first 90 days of pregnancy for congenital malformations and first 19 weeks for nonmalformation outcomes) and compared against three distinct referent groups of (1) unexposed, no NSAID prescription during the 3 months before pregnancy start to end of early pregnancy; (2) acetaminophen-exposed, at least two acetaminophen prescriptions during early pregnancy (i.e., active comparator); and (3) past users, at least two NSAID prescriptions before the start of pregnancy but no relevant prescriptions during pregnancy. Outcomes of interest were adverse birth outcomes of major congenital malformations and low birth weight and adverse maternal outcomes of antepartum hemorrhage and oligohydramnios. We estimated relative risks (RRs) with 95% CIs using generalized linear models within a propensity score (PS) fine stratification weighted cohort that accounted for various potential confounders of maternal sociodemographic characteristics, comorbidities, co-medication use, and general markers of burden of illness. Of 1.8 million pregnancies in the PS weighted analyses, exposure to NSAIDs during early pregnancy was associated with slightly increased risks for neonatal outcomes of major congenital malformations (PS-adjusted RR, 1.14 [CI, 1.10 to 1.18]) and low birth weight (1.29 [1.25 to 1.33]), and for maternal outcome of oligohydramnios (1.09 [1.01 to 1.19]) but not antepartum hemorrhage (1.05 [0.99 to 1.12]). The risks of overall congenital malformations, low birth weight, and oligohydramnios remained significantly elevated despite comparing NSAIDs against acetaminophen or past users. Risks of adverse neonatal and maternal outcomes were higher with cyclooxygenase-2 selective inhibitors or use of NSAIDs for more than 10 days, whereas generally similar effects were observed across the three most frequently used individual NSAIDs. Point estimates were largely consistent across all sensitivity analyses, including the sibling-matched analysis. Main limitations of this study are residual confounding by indication and from unmeasured factors. CONCLUSIONS: This large-scale, nationwide cohort study found that exposure to NSAIDs during early pregnancy was associated with slightly higher risks of neonatal and maternal adverse outcomes. Clinicians should therefore carefully weigh the benefits of prescribing NSAIDs in early pregnancy against its modest, but possible, risk of neonatal and maternal outcomes, where if possible, consider prescribing nonselective NSAIDs for <10 days, along with continued careful monitoring for any safety signals.
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Complicaciones del Trabajo de Parto , Oligohidramnios , Recién Nacido , Femenino , Humanos , Embarazo , Acetaminofén/efectos adversos , Estudios de Cohortes , Antiinflamatorios no Esteroideos/efectos adversos , República de Corea/epidemiología , Nacimiento Vivo , HemorragiaRESUMEN
Importance: Proton pump inhibitors (PPIs) are increasingly used during pregnancy; however, several observational studies have raised concerns about an increased risk of specific types of congenital malformations. Objective: To examine the association between PPI exposure during early pregnancy and the risk of congenital malformations. Design, Setting, and Participants: This population-based cohort study used data from the National Health Insurance Service-National Health Information Database of South Korea (2010-2020); sibling-controlled analyses were conducted to account for familial factors. A total of 2 696 216 pregnancies in women aged 19 to 44 years between June 1, 2011, and December 31, 2019, and their live-born infants were identified. Pregnant women who were exposed to known teratogens or who delivered infants with chromosomal abnormalities or genetic syndromes were excluded. Data on participant race and ethnicity were not collected because the National Health Information Database does not report this information. Exposures: Proton pump inhibitor use during the first trimester. Main Outcomes and Measures: Primary outcomes were major congenital malformations, congenital heart defects, cleft palate, hydrocephalus, and hypospadias. The subtypes of major congenital malformations and congenital heart defects were evaluated as exploratory outcomes. Propensity score fine stratification was used to control for potential confounders, and a weighted generalized linear model was used to estimate relative risks with 95% CIs. Results: Of 2â¯696â¯216 pregnancies (mean [SD] maternal age, 32.1 [4.2] years), 40â¯540 (1.5%; mean [SD] age, 32.4 [4.6] years) were exposed to PPIs during the first trimester. The absolute risk of major congenital malformations was 396.7 per 10â¯000 infants in PPI-exposed pregnancies and 323.4 per 10â¯000 infants in unexposed pregnancies. The propensity score-adjusted relative risks were 1.07 (95% CI, 1.02-1.13) for major congenital malformations, 1.09 (95% CI, 1.01-1.17) for congenital heart defects, 1.02 (95% CI, 0.72-1.43) for cleft palate, 0.94 (95% CI, 0.54-1.63) for hydrocephalus, and 0.77 (95% CI, 0.51-1.17) for hypospadias. In the sibling-controlled analyses, no associations were observed between PPI use and primary outcomes, including major congenital malformations (odds ratio, 1.05; 95% CI, 0.91-1.22) and congenital heart defects (odds ratio, 1.07; 95% CI, 0.88-1.30). A range of sensitivity analyses revealed results that were similar to the main findings. Conclusions and Relevance: In this cohort study, the use of PPIs during early pregnancy was not associated with a substantial increase in the risk of congenital malformations, although small increased risks were observed for major congenital malformations and congenital heart defects; findings from sibling-controlled analyses revealed that PPIs were unlikely to be major teratogens. These findings may help guide clinicians and patients in decision-making about PPI use in the first trimester.
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Anomalías Inducidas por Medicamentos , Fisura del Paladar , Cardiopatías Congénitas , Hidrocefalia , Hipospadias , Embarazo , Femenino , Humanos , Masculino , Adulto , Inhibidores de la Bomba de Protones/efectos adversos , Estudios de Cohortes , Hipospadias/complicaciones , Teratógenos , Anomalías Inducidas por Medicamentos/etiología , Cardiopatías Congénitas/inducido químicamente , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/complicaciones , Hidrocefalia/complicacionesRESUMEN
Importance: Existing observational data have indicated positive associations of acid-suppressive medication (ASM) use in prenatal and early life with allergic diseases in children; however, no study to date has accounted for confounding by indication or within-familial factors. Objective: To evaluate the association of prenatal or infant exposure to ASMs with risk of allergic diseases in children. Design, Setting, and Participants: This nationwide, cohort study included data from South Korea's National Health Insurance Service mother-child-linked database from January 1, 2007, to December 31, 2020. Participants included mother-child pairs of neonates born from April 1, 2008, to December 31, 2019. Exposures: Prenatal and infant exposure to ASMs (histamine 2 receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]). Main Outcomes and Measures: Composite and individual outcomes of allergic diseases (asthma, allergic rhinitis, atopic dermatitis, and food allergy) in children (followed up to 13 years of age) were assessed. The ASM-exposed individuals were compared with unexposed individuals in propensity score (PS)-matched and sibling-matched analyses to control for various potential confounders and within-familial factors. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards regression models. Results: The study included 4 149 257 mother-child pairs. Prenatal exposure analyses included 808â¯067 PS-matched pairs (763â¯755 received H2RAs, 36â¯529 received PPIs) among women with a mean (SD) age of 31.8 (4.2) years. The PS-matched HR was 1.01 (95% CI, 1.01-1.02) for allergic diseases overall (asthma: HR, 1.02 [95% CI, 1.01-1.03]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.02]; atopic dermatitis: HR, 1.02 [95% CI, 1.01-1.02]; food allergy: HR, 1.03 [95% CI, 0.98-1.07]); in sibling-matched analyses, the HRs were similar to those of PS-matched analyses but were not significant (allergic diseases: HR, 1.01; 95% CI, 0.997-1.01). Infant exposure analyses included 84â¯263 PS-matched pairs (74â¯188 received H2RAs, 7496 received PPIs). The PS-matched HR was 1.06 (95% CI, 1.05-1.07) for allergic diseases overall (asthma: HR, 1.16 [95% CI, 1.14-1.18]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.03]; atopic dermatitis: HR, 1.05 [95% CI, 1.02-1.08]; food allergy: HR, 1.28 [95% CI, 1.10-1.49]); asthma risk (HR, 1.13; 95% CI, 1.09-1.17) remained significantly higher among children exposed to ASMs during infancy in sibling-matched analyses. The findings were similar for H2RAs and PPIs analyzed separately and were robust across all sensitivity analyses. Conclusions and Relevance: The findings of this cohort study suggest that there is no association between prenatal exposure to ASMs and allergic diseases in offspring. However, infant exposure to ASMs was associated with a higher risk of developing asthma, although the magnitude was more modest than previously reported. Clinicians should carefully weigh the benefits of prescribing ASMs to children, accompanied by subsequent close monitoring for any clinically relevant safety signals.
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Asma , Dermatitis Atópica , Hipersensibilidad a los Alimentos , Efectos Tardíos de la Exposición Prenatal , Rinitis Alérgica , Recién Nacido , Embarazo , Humanos , Lactante , Femenino , Adulto , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/epidemiología , Estudios de Cohortes , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiología , Asma/epidemiología , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
The phenotypes of atopic dermatitis (AD) are diverse, and ethnic differences have been suggested. To date, few studies have explored large-scale national data on the treatment patterns of AD in Asians. Therefore, we aimed to examine real-world treatment patterns for AD, including the probability of discontinuation of AD treatment and restart after discontinuation. A retrospective observational study was conducted using the nationwide healthcare database in South Korea between January 1, 2016 to July 31, 2020. We identified 944,559 pediatric patients and 1,066,453 adults with AD. Topical corticosteroids and antihistamines were the most commonly prescribed medications in all age groups. The frequency of topical corticosteroid prescription decreased as the age increased. Although immunosuppressive drugs were not widely used in both children and adults, cyclosporine was the most frequently prescribed immunosuppressant, particularly among those aged 12 years or more (1-2%). Pediatric patients were more likely to discontinue treatment than adult patients. Treatment restart for moderate-to-severe AD was earlier than that for overall AD. In conclusion, significant differences were observed in the treatment patterns of AD between pediatric and adult patients. These findings will improve our understanding of the latest treatment patterns for AD, which may contribute to decision-making in clinical practice.
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Dermatitis Atópica , Fármacos Dermatológicos , Ciclosporina/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/epidemiología , Fármacos Dermatológicos/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , República de Corea/epidemiologíaRESUMEN
OBJECTIVES: Korea's national health insurance authority introduced a drug utilization review modernization pilot project in which health professionals provided follow-up services to monitor adverse drug events. We aimed to evaluate the effects of the project on clinical and economic outcomes. METHODS: We conducted difference-in-differences analysis using National Health Insurance claims data from the Health Insurance Review and Assessment Service. We calculated the number of adverse drug events and allergic reactions as a clinical indicator and medical costs incurred to manage these events as an economic indicator. Absolute difference in each outcome measure was defined as the value after the project minus the value before the project. Difference-in-differences was defined as a difference in absolute differences between the intervention group and the control group. RESULTS: Overall, difference-in-differences were -43 and -826 for the number of drug-related adverse events and allergic reactions and -$198,700 and $53,318 for medical costs in the inpatient and outpatient settings, respectively. For outpatients, the monthly number of adverse drug events and allergic reactions has grown higher for the control group than for the intervention group after implementation of the pilot project. CONCLUSIONS: Implementation of the pilot project lowered the number of adverse drug events and allergic reactions in the inpatient and outpatient setting. The project also lowered medical costs incurred to manage these events in the inpatient setting only. Based on our findings, we recommend that the pilot project be expanded on a nationwide level at least in the inpatient setting.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hipersensibilidad , Revisión de la Utilización de Medicamentos , Humanos , Pacientes Internos , Pacientes Ambulatorios , Proyectos PilotoRESUMEN
BACKGROUND: Benzodiazepines are frequently prescribed during pregnancy; however, evidence about possible teratogenicity is equivocal. We aimed to evaluate the association between first-trimester benzodiazepine use and the risk of major congenital malformations. METHODS AND FINDINGS: Using Korea's nationwide healthcare database, we conducted a population-based cohort study of women who gave birth during 2011 to 2018 and their live-born infants. The exposure was defined as one or more benzodiazepine prescriptions during the first trimester. We determined the relative risks (RRs) and confidence intervals (CIs) of overall congenital malformations and 12 types of organ-specific malformations. Infants were followed from birth to death or 31 December 2019, whichever came first (up to 8 years of age). Propensity score fine stratification was employed to control for 45 potential confounders. Among a total of 3,094,227 pregnancies, 40,846 (1.3%) were exposed to benzodiazepines during the first trimester (mean [SD] age, 32.4 [4.1] years). The absolute risk of overall malformations was 65.3 per 1,000 pregnancies exposed to benzodiazepines versus 51.4 per 1,000 unexposed pregnancies. The adjusted RR was 1.09 (95% CI 1.05 to 1.13, p < 0.001) for overall malformations and 1.15 (1.10 to 1.21, p < 0.001) for heart defects. Based on mean daily lorazepam-equivalent doses, the adjusted RRs for overall malformations and heart defects were 1.05 (0.99 to 1.12, p = 0.077) and 1.12 (1.04 to 1.21, p = 0.004) for <1 mg/day and 1.26 (1.17 to 1.36, p < 0.001) and 1.31 (1.19 to 1.45, p < 0.001) for >2.5 mg/day doses, respectively, suggesting a dose-response relationship. A small but significant increase in risk for overall and heart defects was detected with several specific agents (range of adjusted RRs: 1.08 to 2.43). The findings were robust across all sensitivity analyses, and negative control analyses revealed a null association. Study limitations include possible exposure misclassification, residual confounding, and restriction to live births. CONCLUSIONS: In this large nationwide cohort study, we found that first-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest. The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT04856436.
Asunto(s)
Anomalías Inducidas por Medicamentos , Benzodiazepinas , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Adulto , Benzodiazepinas/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , RiesgoAsunto(s)
Reflujo Gastroesofágico/tratamiento farmacológico , Preeclampsia/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Inhibidores de la Bomba de Protones/efectos adversos , Adulto , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Preeclampsia/etiología , Embarazo , República de Corea/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: To detect the signals for drospirenone-containing oral contraceptives (DCOCs) and describe the reporting pattern of adverse events (AEs) caused by DCOCs compared with levonorgestrel/desogestrel/gestodene-containing (second/third generation) oral contraceptives. DESIGN: A descriptive analysis of claims data. SETTING: The Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database from 1 February 2008 to 31 December 2017. OUTCOME MEASURES: Signals for DCOCs were identified using three data mining indices. The characteristics, death cases, and the annual pattern of AE reports were compared between DCOCs and second/third generation oral contraceptives. RESULTS: Of the 242 DCOC-related AEs, 54 signals were detected and 10 were identified as new signals that were not included in Korea, US and UK label. The newly detected signals include deep vein thrombophlebitis and frequent urination. Serious AEs were more likely to be reported with DCOCs (7.85%) than with second/third generation oral contraceptives (2.92%). Five deaths after use of DCOCs were reported with vascular AEs, such as pulmonary embolism and thrombosis, whereas one death after use of second/third generation oral contraceptives was reported with the cardiac arrest. CONCLUSIONS: We identified 10 new signals related to DCOCs that were not included in the current label. Additionally, we found higher reports of the deaths and vascular AEs associated with DCOCs than with second/third generation oral contraceptives, which warrants careful monitoring to ensure the safe use of DCOCs.