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BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. METHODS: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio and 95% confidence interval calculated. RESULTS: GLP-1RAs were associated with a lower risk of incident HCC with hazard ratio of 0.20 [0.14-0.31], 0.39 [0.21-0.69], 0.63 [0.26-1.50] compared with insulin, sulfonylureas, and metformin, respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with 6 other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. CONCLUSIONS: GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared with other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use.
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The incidence of endocarditis in the US is increasing, driven in part by the rise in intravenous drug use, mostly opioids and stimulant drugs (cocaine and methamphetamine). Recent reports have documented that individuals with COVID-19 are at increased risk for cardiovascular diseases. However, it is unknown whether COVID-19 is associated with increased risk for endocarditis in patients with opioid or stimulant use disorders. This is a retrospective cohort study based on a nationwide database of electronic health records (EHRs) of 109 million patients in the US, including 736,502 patients with a diagnosis of opioid use disorder (OUD) and 379,623 patients with a diagnosis of cocaine use disorder (CocaineUD). Since Metamphetamine use disorder is not coded we could not analyze it. We show that the incidence rate of endocarditis among patients with OUD or CocaineUD significantly increased from 2011 to 2022 with acceleration during 2021-2022. COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 2.23, 95% CI: 1.92-2.60) and with CocaineUD (HR: 2.24, 95% CI: 1.79-2.80). Clinically diagnosed COVID-19 was associated with higher risk of endocarditis than lab-test confirmed COVID-19 without clinical diagnosis. Hospitalization within 2 weeks following COVID-19 infection was associated with increased risk of new diagnosis of endocarditis. The risk for endocarditis did not differ between patients with and without EHR-recorded vaccination. There were significant racial and ethnic differences in the risk for COVID-19 associated endocarditis, lower in blacks than in whites and lower in Hispanics than in non-Hispanics. Among patients with OUD or CocaineUD, the 180-day hospitalization risk following endocarditis was 67.5% in patients with COVID-19, compared to 58.7% in matched patients without COVID-19 (HR: 1.21, 95% CI: 1.07-1.35). The 180-day mortality risk following the new diagnosis of endocarditis was 9.2% in patients with COVID-19, compared to 8.0% in matched patients without COVID-19 (HR: 1.16, 95% CI: 0.83-1.61). This study shows that COVID-19 is associated with significantly increased risk for endocarditis in patients with opioid or cocaine use disorders. These results highlight the need for endocarditis screening and for linkage to infectious disease and addiction treatment in patients with opioid or cocaine use disorders who contracted COVID-19. Future studies are needed to understand how COVID-19 damages the heart and the vascular endothelium among people who misuse opioids or cocaine (presumably also methamphetamines).
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COVID-19 , Cocaína , Endocarditis , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides/uso terapéutico , Estudios Retrospectivos , Cocaína/efectos adversos , COVID-19/complicaciones , Trastornos Relacionados con Opioides/complicaciones , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Endocarditis/complicaciones , Endocarditis/epidemiología , Endocarditis/inducido químicamenteRESUMEN
INTRODUCTION: There is lack of data on COVID-19 breakthrough infections in vaccinated patients with dementia in the United States. METHODS: This is a retrospective cohort study of 262,847 vaccinated older adults (age 73.8 ± 6.81 years old) between December 2020 and August 2021. RESULTS: Among the fully vaccinated patients with dementia, the overall risk of COVID-19 breakthrough infections ranged from 8.6% to 12.4%. Patients with dementia were at increased risk for breakthrough infections compared with patients without dementia, with the highest odds for patients with Lewy body dementia (LBD) (adjusted odds ratio or AOR: 3.06, 95% confidence interval or CI [1.45 to 6.66]), followed by vascular dementia (VD) (AOR: 1.99, 95% CI [1.42 to 2.80]), Alzheimer's disease (AD) (1.53, 95% CI [1.22 to 1.92]), and mild cognitive impairment (MCI) (AOR: 1.78, 95% CI [1.51 to 2.11]). The incidence rate of breakthrough infections among fully vaccinated patients with dementia increased since December 2020 and accelerated after May 2021. The overall risk for hospitalization after breakthrough infections in patients with dementia was 39.5% for AD, 46.2% for VD, and 30.4% for MCI. DISCUSSION: These results highlight the need to continuously monitor breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and outcomes in vaccinated patients with dementia.
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Enfermedad de Alzheimer , COVID-19 , Demencia Vascular , Humanos , Estados Unidos/epidemiología , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Infección Irruptiva , Estudios Retrospectivos , SARS-CoV-2 , Hospitalización , Enfermedad de Alzheimer/epidemiologíaRESUMEN
IMPORTANCE: More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short-term and long-term differences in cardiac and mortality outcomes between MOUD. OBJECTIVES: To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016-2022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (n = 40,938)-who were only prescribed methadone. (2) Buprenorphine cohort (n = 80,055)-who were only prescribed buprenorphine. (3) Naltrexone cohort (n = 5,738)-who were only prescribed naltrexone. EXPOSURES: methadone, buprenorphine, or naltrexone. MAIN OUTCOMES AND MEASURES: Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow-up time frames (1-month, 3-month, 6-month, 1-year, 3-year, and 5-year) by comparing propensity-score matched cohorts using Kaplan-Meier survival analysis. RESULTS: Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity-score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1-month follow-up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04-1.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75-3.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21-1.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23-1.38), long QT syndrome (HR: 3.14, 95% CI: 2.76-3.58), death (HR: 1.50, 95% CI: 1.41-1.59). CONCLUSIONS AND RELEVANCE: Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.
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Buprenorfina , Síndrome de QT Prolongado , Trastornos Relacionados con Opioides , Humanos , Estados Unidos , Naltrexona/uso terapéutico , Buprenorfina/uso terapéutico , Metadona/uso terapéutico , Estudios Retrospectivos , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Síndrome de QT Prolongado/tratamiento farmacológico , PrescripcionesAsunto(s)
Vacuna nCoV-2019 mRNA-1273 , Vacuna BNT162 , COVID-19/epidemiología , SARS-CoV-2 , Adulto , Anciano , COVID-19/mortalidad , COVID-19/prevención & control , COVID-19/virología , Vacunas contra la COVID-19 , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
Importance: Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear. Objective: To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin. Design, Setting, and Participants: This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1â¯651â¯452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024. Exposures: Prescription of GLP-1RAs, insulins, or metformin. Main Outcomes and Measures: Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates. Results: In the study population of 1â¯651â¯452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827â¯873 [50.1%] male and 775â¯687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65â¯893 [4.0%] Asian, 281â¯242 [17.0%] Black, 13â¯707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1â¯000â¯780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87). Conclusions and Relevance: In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.
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Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Neoplasias , Obesidad , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Obesidad/complicaciones , Obesidad/epidemiología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Hipoglucemiantes/uso terapéutico , Anciano , Metformina/uso terapéutico , Insulina/uso terapéutico , Estados Unidos/epidemiología , AdultoRESUMEN
Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.
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OBJECTIVE: The long-term time trend and seasonality variations of first-time medically attended respiratory syncytial virus (RSV) infections among young children are unknown. We aim to examine the time trend of medically attended first-time RSV infections among young children in the USA from January 2010 through January 2023. DESIGN: This is a population-based cohort study using electronic health records (EHRs). Monthly incidence rate of medically attended first-time RSV infection (cases per 10 000 000 person-days). A time-series regression model was used to model and predict time trends and seasonality. SETTING: Multicenter and nationwide TriNetX Network in the USA. PARTICIPANTS: The study population comprised children aged 0-5 years who had medical visits during the period of January 2010 to January 2023. RESULTS: The data included 29 013 937 medical visits for children aged 0-5 years (46.5% girls and 53.5% boys) from January 2010 through January 2023. From 2010 through 2019, the monthly incidence rate of first-time medically attended RSV infection in children aged 0-5 years followed a consistent seasonal pattern. Seasonal patterns of medically attended RSV infections were significantly disrupted during the COVID-19 pandemic. In 2020, the seasonal variation disappeared with a peak incidence rate of 20 cases per 1 000 000 person-days, a decrease of 97.4% from the expected peak rate (rate ratio or RR: 0.026, 95% CI 0.017 to 0.040). In 2021, the seasonality returned but started 4 months earlier, lasted for 9 months, and peaked in August at a rate of 753 cases per 1 000 000 person-days, a decrease of 9.6% from the expected peak rate (RR: 0.90, 95% CI 0.82 to 0.99). In 2022, the seasonal pattern is similar to prepandemic years but reached a historically high rate of 2182 cases per 10 000 000 person-days in November, an increase of 143% from the expected peak rate (RR: 2.43, 95% CI 2.25 to 2.63). The time trend and seasonality of the EHR-based medically attended RSV infections are consistent with those of RSV-associated hospitalisations from the Centers for Disease Control and Prevention (CDC) survey-based surveillance system. CONCLUSION: The findings show the disrupted seasonality during the COVID-19 pandemic and a historically high surge of paediatric RSV cases that required medical attention in 2022. Our study demonstrates the potential of EHRs as a cost-effective alternative for real-time pathogen and syndromic surveillance of unexpected disease patterns including RSV infection.
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COVID-19 , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Masculino , Femenino , Humanos , Niño , Preescolar , Estudios de Cohortes , Pandemias , COVID-19/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/prevención & controlRESUMEN
OBJECTIVE: To investigate whether COVID-19 infection was associated with increased risk for incident respiratory syncytial virus (RSV) infections and associated diseases among young children that might have contributed to the 2022 surge of severe paediatric RSV cases in the USA. DESIGN: This is a retrospective population-based cohort study. Five outcomes were examined, including overall RSV infection, positive lab test-confirmed RSV infection, clinically diagnosed RSV diseases, RSV-associated bronchiolitis and unspecified bronchiolitis. Risk ratio (RR) and 95% CI of the outcomes that occurred during the 2022 and 2021 RSV seasons were calculated by comparing propensity-score matched cohorts. SETTING: Nationwide multicentre database of electronic health records (EHRs) of 61.4 million patients in the USA including 1.7 million children 0-5 years of age, which was accessed through TriNetX Analytics that provides web-based and secure access to patient EHR data from hospitals, primary care and specialty treatment providers. PARTICIPANTS: The study population consisted of 228 940 children of 0-5 years with no prior RSV infection who had medical encounters in October 2022. Findings were replicated in a separate study population of 370 919 children of 0-5 years with no prior RSV infection who had medical encounters in July 2021-August 2021 during a non-overlapping time period. RESULTS: For the 2022 study population (average age 2.4 years, 46.8% girls, 61% white, 16% black), the risk for incident RSV infection during October 2022-December 2022 was 6.40% for children with prior COVID-19 infection, higher than 4.30% for the matched children without COVID-19 (RR 1.40, 95% CI 1.27 to 1.55); and among children aged 0-1 year, the overall risk was 7.90% for those with prior COVID-19 infection, higher than 5.64% for matched children without (RR 1.40, 95% CI 1.21 to 1.62). For the 2021 study population (average age 2.2 years, 46% girls, 57% white, 20% black), the risk for incident RSV infection during July 2021-December 2021 was 4.85% for children with prior COVID-19 infection, higher than 3.68% for the matched children without COVID-19 (RR 1.32, 95% CI 1.12 to 1.56); and 7.30% for children aged 0-1 year with prior COVID-19 infection, higher than 4.98% for matched children without (RR 1.47, 95% CI 1.18 to 1.82). CONCLUSION: COVID-19 was associated with a significantly increased risk for RSV infections among children aged 0-5 years in 2022. Similar findings were replicated for a study population of children aged 0-5 years in 2021. Our findings suggest that COVID-19 contributed to the 2022 surge of RSV cases in young children through the large buildup of COVID-19-infected children and the potential long-term adverse effects of COVID-19 on the immune and respiratory system.
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Bronquiolitis , COVID-19 , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Femenino , Humanos , Niño , Estados Unidos/epidemiología , Preescolar , Masculino , Estudios Retrospectivos , Estudios de Cohortes , COVID-19/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/terapia , Bronquiolitis/epidemiologíaRESUMEN
Respiratory syncytial virus (RSV) infections and hospitalizations surged sharply in 2022 among young children. To assess whether COVID-19 contributed to this surge, we leveraged a real-time nation-wide US database of electronic health records (EHRs) using time series analysis from January 1, 2010 through January 31, 2023, and propensity-score matched cohort comparisons for children aged 0-5 years with or without prior COVID-19 infection. Seasonal patterns of medically attended RSV infections were significantly disrupted during the COVID-19 pandemic. The monthly incidence rate for first-time medically attended cases, most of which were severe RSV-associated diseases, reached a historical high rate of 2,182 cases per 1,0000,000 person-days in November 2022, corresponding to a related increase of 143% compared to expected peak rate (rate ratio: 2.43, 95% CI: 2.25-2.63). Among 228,940 children aged 0-5 years, the risk for first-time medically attended RSV during 10/2022-12/2022 was 6.40% for children with prior COVID-19 infection, higher than 4.30% for the matched children without COVID-19 (risk ratio or RR: 1.40, 95% CI: 1.27-1.55); and among 99,105 children aged 0-1 year, the overall risk was 7.90% for those with prior COVID-19 infection, higher than 5.64% for matched children without (RR: 1.40, 95% CI: 1.21-1.62). These data provide evidence that COVID-19 contributed to the 2022 surge of severe pediatric RSV cases.
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Obesity has been epidemiologically and empirically linked with more severe diseases upon influenza infection. To ameliorate severe disease, treatment with antivirals, such as the neuraminidase inhibitor oseltamivir, is suggested to begin within days of infection especially in high-risk hosts. However, this treatment can be poorly effective and may generate resistance variants within the treated host. Here, we hypothesized that obesity would reduce oseltamivir treatment effectiveness in the genetically obese mouse model. We demonstrated that oseltamivir treatment does not improve viral clearance in obese mice. While no traditional variants associated with oseltamivir resistance emerged, we did note that drug treatment failed to quench the viral population and did lead to phenotypic drug resistance in vitro. Together, these studies suggest that the unique pathogenesis and immune responses in obese mice could have implications for pharmaceutical interventions and the within-host dynamics of the influenza virus population. IMPORTANCE Influenza virus infections, while typically resolving within days to weeks, can turn critical, especially in high-risk populations. Prompt antiviral administration is crucial to mitigating these severe sequalae, yet concerns remain if antiviral treatment is effective in hosts with obesity. Here, we show that oseltamivir does not improve viral clearance in genetically obese or type I interferon receptor-deficient mice. This suggests a blunted immune response may impair oseltamivir efficacy and render a host more susceptible to severe disease. This study furthers our understanding of oseltamivir treatment dynamics both systemically and in the lungs of obese mice, as well as the consequences of oseltamivir treatment for the within-host emergence of drug-resistant variants.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Ratones , Animales , Humanos , Oseltamivir/uso terapéutico , Ratones Obesos , Gripe Humana/tratamiento farmacológico , Antivirales/uso terapéutico , Antivirales/farmacología , Neuraminidasa , Farmacorresistencia ViralRESUMEN
Initial reports of SARS-CoV-2 caused COVID-19 suggested that patients with malignant diseases were at increased risk for infection and its severe consequences. In order to provide early United States population-based assessments of SARS-CoV-2 primary infections in unvaccinated patients with hematologic malignancies or cancer, and SARS-CoV-2 breakthrough infections in vaccinated patients with hematologic malignancies or cancer, we conducted retrospective studies using two, unique nationwide electronic health records (EHR) databases. Using these massive databases to provide highly statistically significant data, our studies demonstrated that, compared to patients without malignancies, risk for COVID-19 was increased in patients with all cancers and with all hematologic malignancies. Risks varied with specific types of malignancy. Patients with hematologic malignancies or cancer were at greatest risk for COVID-19 during the first year after diagnosis. Risk for infection was increased for patients 65 years and older, compared to younger patients and among Black patients compared to white patients. When patients with hematologic malignancies or cancer were vaccinated against SARS-CoV-2, their risk for breakthrough infections was decreased relative to primary infections but remained elevated relative to vaccinated patients without malignancies. Compared to vaccinated patients without malignancies, vaccinated patients with hematologic malignancy or cancer showed increased risk for infection at earlier post vaccination time points. As with primary infections, risk for breakthrough infections was greatest in patients during their first year of hematologic malignancy or cancer. There were no signs of racial disparities among vaccinated patients with hematologic malignancies or cancer. These results provide the population basis to understand the significance of subsequent immunologic studies showing relative defective and delayed immunoresponsiveness to SARS-CoV-2 vaccines among patients with hematologic malignancies and cancers. These studies further provide the basis for recommendations regarding COVID-19 vaccination, vigilance and maintaining mitigation strategies in patients with hematologic malignancies and cancers.
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COVID-19 , Neoplasias Hematológicas , Neoplasias , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19/uso terapéutico , Infección Irruptiva , Estudios Retrospectivos , Atención al Paciente , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias Hematológicas/terapiaRESUMEN
Purpose: To examine time trends of incidence rates of EOCRC from 2010 to 2021 among patients with and without diverticular disease and to examine whether diverticular disease is associated with increased risk of EOCRC. Methods: This is a retrospective cohort study of 46,179,351 young adults aged 20−49, including 298,117 with diverticular disease. We examined yearly incidence rate of first diagnosis of EOCRC from 2010 through 2021 among patients with and without diverticular disease. The 5-year risk of EOCRC among patients with pre-existing diverticular disease was compared to propensity-matched patients without diverticular disease and EOCRC and odds ratio (OR) and 95% confidence interval (CI) were calculated. Results: The yearly incidence rate of new diagnosis of EOCRC (measured as new cases per 100,000 people per year) in young adults with pre-existing diverticular disease increased from 100 in 2010 to 402 in 2021, 4−6 times higher than in those without diverticular disease (24 in 2010 to 77 in 2021) (p < 0.001). Patients with diverticular disease were at higher risk for EOCRC than those without (OR: 1.76, 95% CI: 1.40−2.32). Conclusion: The incidence of EOCRC continuously increased from 2010 through 2021 in patients with and without diverticular disease and was 4−6 times higher among patients with diverticular disease. Patients with pre-existing diverticular disease were at a significantly increased risk for EOCRC.
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There has been limited data presented to characterize and quantify breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with hematologic malignancies (HM). We performed a retrospective cohort study of patient electronic health records of 514,413 fully vaccinated patients from 63 healthcare organizations in the US, including 5956 with HM and 508,457 without malignancies during the period from December 2020 to October 2021. The breakthrough SARS-CoV-2 infections in patients with HM steadily increased and reached 67.7 cases per 1000 persons in October 2021. The cumulative risk of breakthrough infections during the period in patients with HM was 13.4%, ranging from 11.0% for acute lymphocytic leukemia to 17.2% and 17.4% for multiple myeloma and chronic myeloid leukemia respectively, all higher than the risk of 4.5% in patients without malignancies (p < 0.001). No significant racial disparities in breakthrough infections were observed. The overall hospitalization risk was 37.8% for patients with HM who had breakthrough infections, significantly higher than 2.2% for those who had no breakthrough infections (hazard ratio or HR: 34.49, 95% CI: 25.93-45.87). The overall mortality risk was 5.7% for patients with HM who had breakthrough infections, significantly higher than the 0.8% for those who had no breakthrough infections (HR: 10.25, 95% CI: 5.94-17.69). In summary, this study shows that among the fully vaccinated population, patients with HM had significantly higher risk for breakthrough infections compared to patients without cancer and that breakthrough infections in patients with HM were associated with significant clinical outcomes including hospitalizations and mortality.
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COVID-19 , Neoplasias Hematológicas , COVID-19/epidemiología , Vacunas contra la COVID-19 , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , Hospitalización , Humanos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Background: The Omicron SARS-CoV-2 variant is rapidly spreading in the US since December 2021 and is more contagious than earlier variants. Currently, data on the severity of the disease caused by the Omicron variant compared with the Delta variant is limited. Here we compared 3-day risks of emergency department (ED) visit, hospitalization, intensive care unit (ICU) admission, and mechanical ventilation in patients who were first infected during a time period when the Omicron variant was emerging to those in patients who were first infected when the Delta variant was predominant. Method: This is a retrospective cohort study of electronic health record (EHR) data of 577,938 first-time SARS-CoV-2 infected patients from a multicenter, nationwide database in the US during 9/1/2021-12/24/2021, including 14,054 who had their first infection during the 12/15/2021-12/24/2021 period when the Omicron variant emerged ("Emergent Omicron cohort") and 563,884 who had their first infection during the 9/1/2021-12/15/2021 period when the Delta variant was predominant ("Delta cohort"). After propensity-score matching the cohorts, the 3-day risks of four outcomes (ED visit, hospitalization, ICU admission, and mechanical ventilation) were compared. Risk ratios, and 95% confidence intervals (CI) were calculated. Results: Of 14,054 patients in the Emergent Omicron cohort (average age, 36.4 ± 24.3 years), 27.7% were pediatric patients (<18 years old), 55.4% female, 1.8% Asian, 17.1% Black, 4.8% Hispanic, and 57.3% White. The Emergent Omicron cohort differed significantly from the Delta cohort in demographics, comorbidities, and socio-economic determinants of health. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities, medications and vaccination status, the 3-day risks in the Emergent Omicron cohort outcomes were consistently less than half those in the Delta cohort: ED visit: 4.55% vs. 15.22% (risk ratio or RR: 0.30, 95% CI: 0.28-0.33); hospitalization: 1.75% vs. 3.95% (RR: 0.44, 95% CI: 0.38-0.52]); ICU admission: 0.26% vs. 0.78% (RR: 0.33, 95% CI:0.23-0.48); mechanical ventilation: 0.07% vs. 0.43% (RR: 0.16, 95% CI: 0.08-0.32). In children under 5 years old, the overall risks of ED visits and hospitalization in the Emergent Omicron cohort were 3.89% and 0.96% respectively, significantly lower than 21.01% and 2.65% in the matched Delta cohort (RR for ED visit: 0.19, 95% CI: 0.14-0.25; RR for hospitalization: 0.36, 95% CI: 0.19-0.68). Similar trends were observed for other pediatric age groups (5-11, 12-17 years), adults (18-64 years) and older adults (≥ 65 years). Conclusions: First time SARS-CoV-2 infections occurring at a time when the Omicron variant was rapidly spreading were associated with significantly less severe outcomes than first-time infections when the Delta variant predominated.
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Importance: Pediatric SARS-CoV-2 infections and hospitalizations are rising in the US and other countries after the emergence of Omicron variant. However data on disease severity from Omicron compared with Delta in children under 5 in the US is lacking. Objectives: To compare severity of clinic outcomes in children under 5 who contracted COVID infection for the first time before and after the emergence of Omicron in the US. Design Setting and Participants: This is a retrospective cohort study of electronic health record (EHR) data of 79,592 children under 5 who contracted SARS-CoV-2 infection for the first time, including 7,201 infected between 12/26/2021-1/6/2022 when the Omicron predominated (Omicron cohort), 63,203 infected between 9/1/2021-11/15/2021 when the Delta predominated (Delta cohort), and another 9,188 infected between 11/16/2021-11/30/2021 when the Delta predominated but immediately before the Omicron variant was detected in the US (Delta-2 cohort). Exposures: First time infection of SARS-CoV-2. Main Outcomes and Measures: After propensity-score matching, severity of COVID infections including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and mechanical ventilation use in the 3-day time-window following SARS-CoV-2 infection were compared between Omicron and Delta cohorts, and between Delta-2 and Delta cohorts. Risk ratios, and 95% confidence intervals (CI) were calculated. Results: Among 7,201 infected children in the Omicron cohort (average age, 1.49 ± 1.42 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. Before propensity score matching, the Omicron cohort were younger than the Delta cohort (average age 1.49 vs 1.73 years), comprised of more Black children, and had fewer comorbidities. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67% (risk ratio or RR: 0.71 [0.66-0.75]); hospitalizations: 1.04% vs. 3.14% (RR: 0.33 [0.26-0.43]); ICU admissions: 0.14% vs. 0.43% (RR: 0.32 [0.16-0.66]); mechanical ventilation: 0.33% vs. 1.15% (RR: 0.29 [0.18-0.46]). Control studies comparing Delta-2 to Delta cohorts show no difference. Conclusions and Relevance: For children under age 5, first time SARS-CoV-2 infections occurring when the Omicron predominated (prevalence >92%) was associated with significantly less severe outcomes than first-time infections in similar children when the Delta variant predominated.
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Background: SARS-CoV-2 infections and hospitalizations are rising in the US and other countries after the emergence of the Omicron variant. Currently, data on infection rates, severity and racial/ethnic and gender disparities from Omicron in the US is limited. Method: We performed a retrospective cohort study of a large, geographically diverse database of patient electronic health records (EHRs) in the US. The study population comprised 881,473 patients who contracted SARS-CoV-2 infection for the first time between 9/1/2021-1/16/2022, including 147,964 patients infected when Omicron predominated (Omicron cohort), 633,581 when Delta predominated (Delta cohort) and another 99,928 infected when the Delta predominated but just before the Omicron variant was detected in the US (Delta-2 cohort). We examined monthly incidence rates of COVID-19 infections stratified by age groups, gender, race and ethnicity, compared severe clinical outcomes including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and mechanical ventilation use between propensity-score matched Omicron and Delta cohorts stratified by age groups (0-4, 5-17, 18-64 and ≥ 65 years), and examined racial/ethnic and gender differences in severe clinical outcomes. Findings: Among 147,964 infected patients in the Omicron cohort (average age: 39.1 years), 56.7% were female, 2.4% Asian, 21.1% Black, 6.2% Hispanic, and 51.8% White. The monthly incidence rate of COVID infections (new cases per 1000 persons per day) was 0.5-0.7 when Delta predominated, and rapidly increased to 3.8-5.2 when Omicron predominated. In January 2022, the infection rate was highest in children under 5 years (11.0) among all age groups, higher in Black than in White patients (14.0 vs. 3.8), and higher in Hispanic than in non-Hispanic patients (8.9 vs. 3.1). After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than in the Delta cohort: ED visits: 10.2% vs. 14.6% (risk ratio or RR: 0.70 [0.68-0.71]); hospitalizations: 2.6% vs. 4.4% (RR: 0.58 [0.55-0.60]); ICU admissions: 0.47% vs. 1.00% (RR: 0.47 [0.43-0.51]); mechanical ventilation: 0.08% vs. 0.3% (RR: 0.25 [0.20-0.31]). Similar reduction in disease severity was observed for all age groups. There were significant racial/ethnic and gender disparities in severe clinical outcomes in the Omicron cohort, with Black, Hispanic patients having more ED visits and ICU admissions than White and non-Hispanic patients, respectively and women had fewer hospitalization and ICU admission than men. Interpretation: The incidence rate of COVID infection during the omicron predominant period (prevalence >92%) was 6-8 times higher than during the Delta predominant period that preceded it consistent with greater infectivity. The incidence rate was highest among those less than 5 years of age, and in Black and Hispanic patients. COVID infections occurring when the Omicron predominated were associated with significantly less frequent severe outcomes than in matched patients when the Delta variant predominated. There were significant racial, ethnic and gender disparities in severe clinical outcomes, with Black and Hispanic patients and men disproportionally impacted.
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Respiratory syncytial virus (RSV) infections and hospitalization have surged sharply among young children. Here we test how the seasonal patterns of RSV infections in 2022 compared with those from other COVID-19 pandemic and pre-pandemic years. For this purpose, we analyzed a nation-wide and real-time database of electronic health records of 56 million patients across 50 states in the US. The monthly incidence rate of first-time RSV infection in young children (<5 years of age) and very young children (<1 year of age) followed a seasonal pattern from 2010 to 2019 with increases during the autumn, peaking in winter, subsiding in spring and summer. This seasonal pattern was significantly disrupted during the COVID-19 pandemic. In 2020, the incidence rate of RSV infections was remarkably low throughout the year. In 2021, the RSV season expanded to 9 months starting in the early summer and peaking in October. In 2022, RSV infections started to rise in May and were significantly higher than in previous years reaching a historically highest incidence rate in November 2022. There were significant racial and ethnic disparities in the peak RSV infection rate during 2010-2021 and the disparities further exacerbated in 2022 with peak incidence rate in black and Hispanic children 2-3 times that in white children. Among RSV-infected children in 2022, 19.2% had prior documented COVID-19 infection, significantly higher than the 9.7% among uninfected children, suggesting that prior COVID-19 could be a risk factor for RSV infection or that there are common risk factors for both viral infections. Our study calls for continuous monitoring of RSV infection in young children alongside its clinical outcomes and for future work to assess potential COVID-19 related risk factors.
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Paxlovid was authorized by FDA to treat mild-to-moderate COVID-19. In May 2022, the Centers for Disease Control and Prevention (CDC) issued a Health Alert Network Health Advisory on potential COVID-19 rebound after Paxlovid treatment. Since June 2022, Omicron BA.5 has become the dominant subvariant in the US, which is more resistant to neutralizing antibodies than the previous subvariant BA.2.12.1. Questions remain as to how COVID-19 rebound after Paxlovid treatment differs between the BA.5 and BA.2.12.1 subvariants. This is a retrospective cohort study of 15,913 patients who contracted COVID-19 between 5/8/2022-7/18/2022 and were prescribed Paxlovid within 5 days of their COVID-19 infection. The study population was divided into 2 cohorts: (1) BA.5 cohort (n=5,161) - contracted COVID-19 during 6/19/22-7/18/22 when BA.5 was the predominant subvariant2. (2) BA.2.12.1 cohort (n=10,752) - contracted COVID-19 during 5/8/22-6/18/22 when the BA.2.12.1 was the predominant subvariant. The risks of both COVID-19 rebound infections and symptoms 2-8 days after Paxlovid treatment were higher in the BA.5 cohort than in the propensity-score matched BA.2.12.1 cohort: rebound infections (Hazard Ratio or HR: 1.32, 95% CI: 1.06-1.66), rebound symptoms (HR: 1.32, 95% CI: 1.04-1.68). As SARS-CoV-2 evolves with successive subvariants more evasive to antibodies, continuous vigilant monitoring is necessary for COVID-19 rebounds after Paxlovid treatment and longer time duration of Paxlovid treatment warrants evaluation.
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An infectious etiology of Alzheimer's disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk for Alzheimer's disease. In this retrospective cohort study of 6,245,282 older adults (age ≥65 years) who had medical encounters between 2/2020-5/2021, we show that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer's disease within 360 days after the initial COVID-19 diagnosis (hazard ratio or HR:1.69, 95% CI: 1.53-1.72), especially in people age ≥85 years and in women. Our findings call for research to understand the underlying mechanisms and for continuous surveillance of long-term impacts of COVID-19 on Alzheimer's disease.