Connor Iapoce

A new study suggests oral corticosteroid burst treatment increases the risk of adverse events, particularly in children with 

Investigators led by Tsung-Chieh Yao, MD, PhD, of the Department of Pediatrics at Chang Hung Memorial Hospital in Taiwan, found the treatment commonly prescribed to children for respiratory and allergy conditions had a 1.4 to 2.2-fold increased risk with a single corticosteroid burst. Burst are considered courses of corticosteroids for ≤14 days. 

Limited data on the harm of short-term oral corticosteroids led investigators to use a self-controlled case study design in Taiwan. They studied 4 adverse events including GI bleeding, sepsis, pneumonia, and glaucoma. 

The study was then compared to a recent longitudinal analysis of 15 million adults in Taiwan, compiled by Yao and colleagues. 

Investigators collected data through the National Health Insurance Research Database (NHIRD) for 23 million individuals in the National Health Insurance Program (NHIP) in Taiwan. 

The study took data containing records and prescription data from 2013 to 2017.

Each patient participant served as their own control in the study, given unmeasured time-invariant variables that were controlled in the succeeding analysis.

Severe adverse events were measured in the pretreatment period, considered 5-90 days prior to a burst.

Investigators compared pretreatment measurements to risks in 2 posttreatment periods after initiation of a burst. The first period collected data from 5-30 days and the second period from 31-90 days.

The team calculated incidence rates (IRRs) with a comparison of the incident rate of severe adverse events with the posttreatment period and the incidence rates of severe adverse events with the reference period. The analysis used a conditional fixed-effect Poisson regression.

The sensitivity analyses examined participants who had prescriptions of topical corticosteroids before the study period, as well as the different durations of observation periods, with 180 days as the maximum posttreatment time analyzed.

Study participants included 4,542,623 children younger than 18 years old. In the study, 1,064,587 (23%) of participants received a single corticosteroid burst, with 51.1% boys and a mean age of 9.7 years. 

The most common indications for corticosteroid use were acute respiratory tract infections and acute bronchitis and bronchiolitis, with all indications accounting for 65% of prescribed bursts.

Incidence rates per 1000 person-years for the 4 severe adverse events were greater for those administered a single burst versus those who were not prescribed corticosteroids.

The differences between the 2 groups were 0.60 (95% CI, 0.55 – 0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma.

Similarly, the IRRs for GI bleeding and pneumonia were significantly higher in the first posttreatment period versus the reference period, at 1.41 (95% CI, 1.27- 1.57) and 2.19 (95% CI, 2.13-2.25), respectively. 

Investigators found that in more than 4 million children, 42% were exposed to at least 1 corticosteroid burst in the study period of 5 years.

There was a significant association found between corticosteroid bursts and an increased rate of GI bleeding, sepsis and pneumonia, but not glaucoma, within the first month of corticosteroid therapy in children.

“Sepsis is a rare but potentially life-threatening event,” the team wrote. “Despite the small observed incidence rate difference in sepsis between children with and children without prescriptions of corticosteroid bursts, [the therapy] were associated with a 2-fold increased risk of sepsis during the first month after starting treatment.”

The team said that among the children in the study receiving corticosteroid bursts, 91% had no baseline comorbid condition. The majority were prescribed for non-life-threatening conditions.

Investigators called for a reevaluation of the prevalent use of corticosteroid bursts in children and the implementation of strategies with “optimal benefit to risk ratios for preventing avoidable harm.”

“Clinicians should be aware of these rare but potentially serious adverse events associated with use of corticosteroid bursts for children, particularly during the first month after corticosteroid initiation,” investigators wrote.

Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children

,” was published online in JAMA Pediatrics. 

Articles

Recent data finds children treated for allergies with ≥14 consecutive days of corticosteroids experienced greater incidence rates than those not treated with a corticosteroid.  

Oral Corticosteroid Burst Increases Adverse Event Risk in Children 

Jordan K. Schaefer, MD (University of Michigan)

Investigators found in a recent study that one-third of patients with atrial fibrillation (AF) and/or 

 who were treated with a direct oral anticoagulant (DOAC) also received acetylsalicylic acid (ASA; aspirin) without a clear prescribing indication.

The team, led by Jordan K. Schaefer, MD, of the Department of Internal Medicine at the University of Michigan, the concurrent use of DOAC and aspirin had associations with increased bleeding and hospitalizations in comparison to DOAC monotherapy. A similar observed thrombosis rate occurred in comparison as well.

The combination of aspirin and oral anticoagulation may be indicated for patients with certain heart devices, nonvalvular atrial fibrillation and/or VTE who experience acute coronary syndrome (ACS), or undergo percutaneous coronary intervention (PCI). 

The team hypothesized that compared with the dual therapy of aspirin and warfarin, a lower rate of bleeding in aspirin plus DOAC would be observed. However, they noted that other studies have shown higher rates of gastrointestinal bleeding with DOAC compared to warfarin. 

Investigators created a registry of adult patients starting a DOAC regimen—including apixaban, dabigatran, edoxaban, or rivaroxaban—as well as patients transitioning to a DOAC from warfarin. The data was collected from 4 medical centers in Michigan, including outpatient anticoagulation clinics.  

The collected data was assessed between January 2015 – December 2019. Patients included in the study either started DOAC therapy without recent anticoagulant use or were in transition from warfarin therapy.

Patients were excluded if they had less than 3 months of follow-up data available, a myocardial infarction (MI) 6 months prior to the start of DOAC, or a history of heart valve replacement. 

Information on patients was collected at enrollment, including patient demographics as well as comorbidities, thrombosis or bleeding risk factors and history, and concomitant medications.

The investigator’s primary outcome was the rate of bleeding events, including those reported by patients, regardless of severity. The secondary bleeding outcomes included major bleeding, nonmajor bleeding, emergency department (ED) visits for bleeding, and hospitalizations for bleeding. 

Major bleeding included outcomes of fatal bleeding, life-threatening bleeding, and intracranial or intraspinal bleeding. The study’s secondary thrombotic outcomes listed ischemic strokes, transient ischemic attack, VTE, ACS/MI, ED visits, and hospitalizations for thrombosis.

The study was comprised of 3280 patients without a clear indication for aspirin use, with 51% being men and a mean age of 68.2 years old. The team followed up with patients for a median of 12 months following the study.

Throughout the period of study, 1107 (33.8%) patients were treated with DOACs plus aspirin. In comparison, 2173 (66.3%) patients were treated with DOAC monotherapy. 

A ≤100 mg dose ASA was used by 997 of all patients on ASA. 

Investigators found limited outstanding differences between the 2 outcome groups after analysis of the cohorts, modeled in a Poisson regression. 

Patients taking DOAC plus aspirin experienced more total bleeding events in comparison to DOAC monotherapy. The rate was 26 bleeds versus 31.6 bleeds per 100 patient years.

Combination therapy had significantly higher rates of nonmajor bleeding compared to DOAC monotherapy: 26.1 bleeds versus 21.7 bleeds per 100 patient years. Major bleeding rates and bleeding subtypes were not statistically different. 

Minor gastrointestinal bleeds increased with the combination therapy at 4.6 bleeds versus 3.0 bleeds per 100 patient years. Thrombotic events had similarly low rates in both categories at 2.5 events versus 2.0 events.

Hospitalizations occurred more in combination therapy, with a 9.0 versus 6.5 admissions per 100 patient years in comparison. Bleeding hospitalizations were higher with combination therapy, while mortality and ER visits for bleeding were similar rates between each group.

The team concluded that treatment with combination DOAC and aspirin was associated with increased bleeding rates, particularly in nonmajor bleeding and hospitalizations for bleeding. 

The sensitivity analysis of the study, including patients without any vascular indication for aspirin while taking DOAC and patients in the treatment group assignment, supported the conclusion of the primary analysis. 

“There remains limited evidence on how to optimally combine DOACs with ASA outside the setting of an ACS and/or PCI procedure,” investigators wrote.

Investigators wrote there was not an observed decline in the number of patients on combination therapy, which may reflect the lack of data on how to manage these patient groups, especially those with higher-risk factors. 

“Further research is needed to determine if select high-risk patient subgroups derive a net benefit from combination therapy,” the team wrote. “Efforts should be made to help clinicians identify and deprescribe ASA for patients taking a DOAC without an indication for ASA.”

The study, “Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication,” was published online in JAMA Internal Medicine.

A new study finds patients with atrial fibrillation or venous thromboembolism were at higher risk of increased bleeding and hospitalization when treated with combination DOAC and aspirin. 

Aspirin and Anticoagulant Treatment Linked to Bleeding Risks in AFib, VTE Patients 

The US Food and Drug Administration (FDA) has approved short ragweed pollen allergen extract tablet (RAGWITEK) for the treatment of short ragweed pollen-induced allergic rhinitis in children and adolescents.

The approval, awarded to ALK, expands the RAGWITEK indication for the treatment of patients with ragweed pollen allergies between the age of 5 through 65 years old.

The tablet treatment is an allergen extract immunotherapy that provides treatment of patients with short ragweed pollen-induced allergic rhinitis, with or without conjunctivitis.

Patients can take the once-daily sublingual tablets at home following a visit with an allergist. The product does not claim to result in the immediate relief of pollen allergy symptoms.

The approval is based on data from a phase 3 clinical trial in children with ragweed allergic rhinitis, without or without conjunctivitis. It is the largest trial conducted to date, based on children and adolescents aged 5-17.

The randomized, double-blind, parallel group, multi-center clinical trial assessed the efficacy and safety of the patient population over a 20-28-week treatment period. Patients had both a history of ragweed-induced rhinoconjunctivitis and sensitivity to short ragweed.

The results show that treatment with RAGWITEK had a significant improvement in symptoms in the patient population. It decreased other symptom-relieving medication use.

Safety profiles were consistent with adult use. and treatment resulted in consistent results with no adverse events. Treatment was tolerated by the patient group and there were low discontinuation rates due to adverse events.

In a statement accompanying the approval, Jorge Alderete, ALK President, expressed pride in the company's "innovative solutions" to patients including the millions who suffer from chronic allergies.

"With the expanded approval of RAGWITEK in the US, we can now offer a treatment option for children, adolescent and adult patients across North America with seasonal ragweed pollen allergies and allergic rhinitis who continue to be burdened by symptoms despite available treatments," Alderete said.

The approval expands the current sublingual tablet treatment indications to include children with a ragweed pollen allergy. 

FDA Approves RAGWITEK for Children, Adolescents with Ragweed Allergies

A new study found that a diet with a high glycemic index is associated with an increased risk of 

 (CV) disease and death, particularly in large, geographically diverse populations. 

Investigators, led by David Jenkins MD, PhD, DSc of the University of Toronto, conducted the study to determine dietary intake and estimate the glycemic index in specific patient populations where prior data has not been collected.

The team uncovered outcomes showing patients who consumed a diet with a low glycemic index and glycemic load had a lower risk of CV disease compared to participants who consumed a diet with a higher glycemic index and glycemic load. 

The association between glycemic index rates and cardiovascular disease as well as all-cause mortality was collected in the International Prospective Urban Rural Epidemiology (PURE) study.

Jenkins and team hypothesized the study data would show the relationship between the glycemic index marker determining carbohydrate quality and chronic disease, focusing on cardiovascular disease.

The study included 137,851 participants from 20 countries, between the ages of 35-70 and included a median of 9.5 years of follow-up.

According to investigators, the 20 countries included 4 high-income countries, 11 middle-income countries, and 5 low-income countries.

Participants were classified into 7 regions: Europe and North America, South America, Africa, Middle East, South Asia, Southeast Asia, and China.

The team used standardized questionnaires to collect data on demographic factors, socioeconomic status, lifestyle, health history and medication use. Data on physical assessments included weight, height, waist and hip circumference, and blood pressure. 

Baseline data collection information on the food frequency of individuals with 28 questionnaires, of which 19 were specific to individual countries and 9 were specific to regions in India. 

A total of 3200 food items were included in the questionnaires and investigators used of 98 - 220 items per questionnaire. Participants were asked to clarify how often on average they had consumed the food item, ranging from “never” to “6 or more times per day”.

The team assigned a glycemic index to 7 categories of carbohydrate-containing food and were then weighted according to the net carbohydrate consumed in each food category. This data determined the participant’s mean glycemic index, and a multivariable Cox frailty model was used to calculate hazard ratios. 

Investigators’ primary outcome was a composite of a major CV event including CV death or nonfatal myocardial infarction or death from any cause. 

Follow-up data on primary outcomes of a major CV event was available for 119,575 participants and data on major cardiovascular events was available for 119,572. 

Investigators found the primary composite outcome occurred in 14,075 participants, with 8780 deaths discovered. In the same time period, 8252 participants had at least 1 major CV event. 

In comparisons of the highest to lowest glycemic index quintiles, investigators found diets with a high glycemic index had an increased risk of a major CV event or death, both in patients with and without preexisting CV disease.

The findings in glycemic load were similar to the index findings but did not affect those without preexisting CV disease.

Investigators also found individuals with a higher body mass index (BMI) had a higher risk of adverse effects. As BMI increases, a person with a high glycemic index may also experience an increase in postprandial glycemic response and cause insulin resistance. 

Diet may also lead to diabetes or CV death and increase the risk of death of other causes, possibly including COVID-19, investigators wrote.

“Our study showed that in a diverse population of participants, those who consumed a diet with a low glycemic index and a low glycemic load had a lower risk of cardiovascular disease and death than participants who consumed a diet with a higher glycemic index and glycemic load,” investigators wrote.

Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality

,” was published online in The New England Journal of Medicine.

Investigators collect study data from lengthy questionnaires relating to diet and demographics, finding that a high glycemic index correlates to more adverse effects in patients. 