Type 1 diabetes incidence in children increased during Covid-19 pandemic

3rd July 2023

The incidence of type 1 diabetes in children and adolescents significantly increased during the Covid-19 pandemic compared to pre-pandemic levels, according to a recent meta-analysis.

Suggestions of an association between infection with Covid-19 and a new diagnosis of of type 1 and type 2 diabetes emerged early in the pandemic. However, the causal mechanisms responsible are unclear. Moreover, understanding the nature of any relationship between diabetes and infection with Covid-19 is complicated by several factors including the seasonality of diagnoses and evidence of an estimated 3.4% annual increase in the incidence of the condition.

In trying to untangle the potential association between the rise in cases of type 1 diabetes and infection with Covid-19, a team of Canadian researchers, writing in JAMA Network Open, compared the incidence rates of paediatric diabetes during and before the Covid-19 pandemic.

The team undertook a systematic review and meta-analysis of all medical databases, using subject headings and text terms related to Covid-19, diabetes and diabetic ketoacidosis (DKA). Studies were included in the analysis if these reported differences in incident diabetes cases during compared to before the pandemic, among individuals under 19 years of age.

Researchers set the primary outcome as the change in the incidence rate of paediatric diabetes from before and during the pandemic. The secondary outcome was the change in the incidence rate of DKA among youths with new-onset diabetes during the pandemic.

Type 1 diabetes incidence and Covid-19

In total, 42 studies with 102,984 incident diabetes cases were included in the analysis.

The type 1 diabetes incidence rate was 14% higher during the first year of the pandemic compared with the pre-pandemic period (incidence rate ratio, IRR = 1.14 95% CI 1.08 – 1.21). Nevertheless, this rate increased further during months 13 to 24 of the pandemic compared to the pre-pandemic level (IRR = 1.27, 95% CI 1.18 – 1.37). There was also a higher incidence of DKA compared to before the pandemic (IRR = 1.26, 95% CI 1.17 – 1.36).

The underlying mechanisms responsible for this observed increase are unclear and require further investigation.

RCT finds tralokinumab effective in adolescents with atopic eczema

25th April 2023

Tralokinumab targets interleukin-13 (IL-13) and appears to be both effective and tolerable in adolescents aged 12-17 with moderate-to-severe atopic eczema.

Adolescent atopic eczema gives rise to a negative impact on patient’s quality of life. There is already good evidence to suggest that IL-13 creates inflammation in atopic eczema.

Tralokinumab specifically neutralises IL-13 and therefore reduces inflammation. Previous work has demonstrated efficacy for the drug adults with moderate-to-severe atopic eczema. However, it remains uncertain whether tralokinumab is effective for adolescents with moderate-to-severe disease.

The current randomised, double-blinded, placebo-controlled enrolled adolescents aged 12-17 years with moderate-to-severe atopic eczema. Individuals received monotherapy with tralokinumab either 150 mg or 300 mg, or matching placebo, every two weeks for 16 weeks.

The primary endpoint was an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear/almost clear) at week 16.

An alternative primary endpoint was a 75% or higher improvement in EASI (i.e. an EASI 75). Those meeting the primary outcome at week 16 continued in a maintenance phase until week 52.

Tralokinumab and atopic eczema outcomes

There were 289 participants with a median age of 15 years (51.6% male). Some 97 participants were given 150 mg of tralokinumab, and 98 were assigned to 300 mg of tralokinumab.

At week 16, significantly more patients receiving tralokinumab had an IGA of 0 or 1 than placebo: 21.4% (150 mg) and 17.5% (300 mg) vs 4.3% for placebo (p < 0.01 and p = 0.002 respectively).

In addition, 28.6% of tralokinumab 150 mg patients had an EASI75, as did 27.8% of the tralokinumab 300 mg group. Only 6.4% of those in the placebo arm achieved EASI75.

Larger improvements were seen for both doses of the drug compared to placebo for itch and quality of life scores.

At week 52, 62.9% of all tralokinumab participants maintained their IGA score of 0 or 1 with doses administered either every two or four weeks. The drug was tolerable with a similar proportion of adverse events in all three arms.

The researchers concluded that tralokinumab therefore appears effective for adolescents with moderate-to-severe atopic eczema.

Citation
Paller AS et al. Efficacy and Safety of Tralokinumab in Adolescents With Moderate to Severe Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial. JAMA Dermatol 2023.

Half of paediatric opioid prescriptions deemed high risk

27th August 2021

A US analysis of over 4 million paediatric opioid prescriptions found nearly half were considered high-risk based on more than one metric.

The prescription of opioid drugs to paediatric patients, defined as those aged 0 to 17 years, can lead to not only adverse effects in the short-term, but problems in the longer-term. For example, a study in children without severe pain, found that one of every 2611 acute opioid prescriptions were followed by an opioid-related adverse event. Moreover, persistent use of opioids has been observed in nearly 5% of adolescents after surgery and which could ultimately lead to dependence. There is currently limited data on the prescription of such drugs to paediatric patients but some information derived from insurance claims suggests that 1 in 10 adolescents filled at least one opioid prescription per year. In contrast, other insurance-based studies have revealed how opioid prescribing to children and adolescents has been steadily reducing since 2012.

In trying to gain further insight of opioid prescribing, a team from the Division of General Pediatrics, University of Michigan, US, set out to assess the prevalence and safety of opioid prescriptions given to children and young adults. The team used a comprehensive prescription database that contained records for every prescription dispensed from 92% of US retail pharmacies, 70% of mail-order pharmacies and 70% of pharmacies in long-term care facilities. The team looked specifically at opioid and benzodiazepine prescriptions, excluding opioid cough and cold remedies and buprenorphine, used for substance misuse. In an effort to determine whether such prescriptions could be deemed at high-risk, the team used 6 different metrics; the proportion of prescriptions for opioid naïve patients exceeding 3 and 7-day supplies; the proportion of prescriptions dispensed for children aged 0 to 11; the proportion of opioid prescriptions given to those aged 12 to 21 years with daily dosages of > 50 morphine milligram equivalents (MME) and finally, the proportion of opioid prescriptions for adolescents, which overlapped with a benzodiazepine prescription for > 1 day and each of these metrics was derived from best-practice guidance.

Findings
The database included 4,027,701 opioid prescriptions, of which 86.6% were for patients aged 0 to 21 years, of whom 80.7% were opioid naïve. The majority of prescriptions were issued by a dentist (38.2%), followed by a surgery (23.3%), physician assistant (7.2%) and emergency department (7.1%). Overall, 3.5% of children and young adults had >1 dispensed opioid prescription. The most commonly prescribed opioid was hydrocodone (52.7%), followed by oxycodone (21.3%), codeine (13.8%) and tramadol (9.8%).

Among 3,250,443 prescriptions written for opioid naïve patients, 41.8% and 3.8% exceeded the recommended 3- and 7-day course respectively. Similarly, among 3,487,263 prescriptions for adolescents and young adults, 11.5% had a daily MME > 50 and 4.6% were co-prescribed with a benzodiazepine. In fact, 45.6% of all prescriptions were classed as being high-risk by more than one metric.
Commenting on their findings, the authors noted that the majority of prescriptions were issued by dentists and likely to have been for dental extractions although alternatives to opioid prescriptions such as non-steroidal anti-inflammatory drugs provide a similar level of pain relief. They concluded that broad-based initiatives are needed to address high-risk prescribing.

Citation
Chua KP et al. Prescribing to US children and young adults in 2019. Pediatrics. 2021