Pediatrics (all articles)
Review: Chronic Hand Eczema
29 Nov, 2024 | 12:28h | UTCIntroduction: Hand eczema is a highly prevalent inflammatory skin condition and one of the most common work-related disorders, with a lifetime prevalence of approximately 15%. In up to two-thirds of affected individuals, the disease becomes chronic—persisting for more than three months or recurring multiple times within a year—leading to substantial personal and occupational disability. This review by Weidinger and Novak synthesizes current knowledge on the epidemiology, risk factors, clinical features, diagnosis, mechanisms, and management of chronic hand eczema, highlighting the need for further research to enhance prevention and treatment strategies.
Key Recommendations:
- Risk Factor Identification: Recognize major risk factors, including current or past atopic dermatitis, dry skin, and occupational exposure to irritants and allergens. Occupational history is crucial, as hand eczema is prevalent in high-risk professions such as health care, hairdressing, and cleaning.
- Diagnosis and Assessment: Diagnose chronic hand eczema based on history and clinical features, considering differential diagnoses like psoriasis and tinea manus. Patch testing is recommended to identify contact allergens, especially in cases unresponsive to initial therapy.
- Patient Education and Prevention: Implement structured education on skin care, avoidance of trigger factors, and use of protective measures. Emphasize primary to tertiary prevention strategies, including workplace interventions and rehabilitation programs.
- Topical Therapies: Initiate treatment with topical glucocorticosteroids for anti-inflammatory effect. Use calcineurin inhibitors as second-line therapy, particularly for patients refractory to steroids or requiring long-term treatment. The topical pan-Janus kinase inhibitor delgocitinib is approved for moderate to severe chronic hand eczema unresponsive to corticosteroids.
- Phototherapy: Consider short-term phototherapy (4–8 weeks) with options like PUVA or narrow-band UVB for patients inadequately controlled with topical treatments.
- Systemic Therapies: For severe cases unresponsive to topical treatments, systemic retinoids such as alitretinoin are first-line therapy. Off-label use of immunosuppressants like ciclosporine, methotrexate, and azathioprine may be considered. Systemic immunomodulatory therapies approved for atopic dermatitis, including dupilumab and Janus kinase inhibitors, show promise, especially in atopic hand eczema.
- Adjunctive Measures: Encourage the use of emollients for skin barrier repair and recommend avoidance of harmful exposures. Patient self-management is crucial, including appropriate hand hygiene and use of protective gloves.
Conclusion: By adopting these evidence-based management strategies, clinicians can improve patient care by reducing symptoms, preventing disease progression, and enhancing quality of life for individuals with chronic hand eczema. Early identification of risk factors, comprehensive patient education, and individualized treatment plans are essential to mitigate the substantial personal and socioeconomic burden of this condition.
Guideline: Management of Urinary Tract Infections in Pediatrics and Adults
5 Nov, 2024 | 18:59h | UTCIntroduction: Urinary tract infections (UTIs) are among the most common infections worldwide, significantly impacting patient quality of life and imposing substantial clinical and economic burdens. Despite advancements in diagnosis and treatment, UTIs continue to cause high morbidity and mortality, ranging from simple cystitis to life-threatening sepsis. Addressing the discrepancy between evidence quality and recommendation strength in existing guidelines, the WikiGuidelines Group has developed a consensus statement. This guideline aims to provide evidence-based recommendations for the prevention, diagnosis, and management of UTIs across diverse clinical settings.
Key Recommendations:
- Cranberry Products:
- Recommendation: Cranberry juice or supplements are recommended for preventing symptomatic, culture-verified UTIs in women with recurrent UTIs, children, and individuals susceptible after interventions.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Methenamine Hippurate:
- Recommendation: Methenamine hippurate is recommended as an alternative to prophylactic antibiotics for preventing recurrent UTIs in patients with intact bladder anatomy.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Topical Estrogen:
- Recommendation: Vaginal estrogen therapy is recommended for postmenopausal women to reduce recurrent UTIs by restoring the vaginal microbiome.
- Quality of Evidence: High
- Recommendation Strength: Strong
- Empirical Treatment Regimens:
- Recommendation: For uncomplicated cystitis, nitrofurantoin is recommended as a first-line agent. For pyelonephritis, trimethoprim/sulfamethoxazole or a first-generation cephalosporin are reasonable first-line agents, depending on local resistance rates.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Treatment Duration for Acute Cystitis in Adults:
- Recommendation:
- Nitrofurantoin: 5 days
- Trimethoprim/sulfamethoxazole: 3 days
- Oral fosfomycin: Single dose
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Treatment Duration for Acute Pyelonephritis in Adults:
- Recommendation:
- Fluoroquinolones: 5–7 days
- Dose-optimized β-lactams: 7 days
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Antimicrobial Stewardship:
- Recommendation: De-escalation of antibiotics and the use of mostly or all oral treatment regimens are recommended to optimize antimicrobial use and reduce adverse effects.
- Quality of Evidence: High
- Recommendation Strength: Strong
Conclusion: The consensus highlights a significant lack of high-quality prospective data in many areas related to UTIs, limiting the ability to provide clear recommendations. Implementing these evidence-based guidelines can enhance patient care by promoting effective prevention strategies, accurate diagnosis based on clinical symptoms, appropriate treatment durations, and robust antimicrobial stewardship. This approach is expected to improve clinical outcomes, reduce antimicrobial resistance, and preserve the effectiveness of current treatments.
Review: Chronic Low-Level Lead Poisoning
3 Nov, 2024 | 01:15h | UTCIntroduction: Lead poisoning, historically known as plumbism, remains a significant health concern despite reductions in lead use. Chronic low-level lead exposure has been identified as a critical risk factor for cardiovascular disease in adults and cognitive deficits in children, even at blood lead concentrations previously deemed safe. This review by Lanphear et al. explores the multifaceted effects of chronic, low-level lead poisoning, emphasizing its impact on neurodevelopment, kidney function, and cardiovascular health, and underscores the urgent need for effective prevention strategies.
Key Findings:
- Exposure and Absorption: Lead exposure occurs primarily through ingestion and inhalation, with children absorbing lead more readily than adults. Absorption is enhanced in the presence of iron or calcium deficiency. Once absorbed, lead is predominantly stored in the skeleton, and factors altering bone metabolism can mobilize lead back into the bloodstream.
- Neurodevelopmental Effects: Lead exposure is linked to preterm birth, cognitive deficits, attention deficit–hyperactivity disorder (ADHD), and behavioral disorders in children. Notably, cognitive deficits are proportionately larger at lower blood lead levels, with significant IQ reductions observed even at the lowest measurable concentrations.
- Kidney Disease: Chronic lead exposure is a risk factor for chronic kidney disease. Higher blood lead levels are associated with reduced glomerular filtration rates and an increased risk of developing chronic kidney conditions.
- Cardiovascular Disease: Lead induces hypertension and atherosclerosis through mechanisms such as oxidative stress and endothelial dysfunction. It is a leading risk factor for mortality from cardiovascular disease, with substantial risk increases even at low blood lead concentrations. Studies indicate that lead exposure may have contributed to historical trends in coronary heart disease mortality.
- Global Burden: In 2019, lead exposure accounted for approximately 5.5 million deaths from cardiovascular disease and the loss of 765 million IQ points in children globally. The economic cost associated with lead-related health outcomes is estimated at $6 trillion annually, representing about 7% of the global gross domestic product.
- Screening and Treatment: Screening high-risk populations is recommended, including children in older housing and workers in certain industries. While chelation therapy can reduce body lead burden, its effects on health outcomes are inconsistent, highlighting the importance of primary prevention.
- Prevention Strategies: Eliminating environmental sources of lead through government-funded population strategies is essential. This includes replacing lead-containing infrastructure like water service lines, banning leaded aviation fuel, reducing lead in consumer products, and remediating contaminated soils and older housing with lead-based paints.
Conclusion: Chronic low-level lead poisoning continues to pose a significant global health threat, contributing to cardiovascular disease and neurodevelopmental deficits. The disproportionate effects at even the lowest exposure levels underscore the necessity for robust, population-wide prevention strategies. Implementing stringent regulatory actions to eliminate sources of lead exposure is imperative to reduce the substantial morbidity, mortality, and economic burdens associated with lead poisoning.
Cohort Study: Levonorgestrel IUD Use Linked to Increased Breast Cancer Risk in Premenopausal Women
20 Oct, 2024 | 18:13h | UTCBackground: Levonorgestrel-releasing intrauterine systems (LNG-IUSs) are increasingly used, especially among Danish premenopausal women over 30 years old, as a preferred method of hormonal contraception. Previous studies have suggested an increased risk of breast cancer with LNG-IUS use but did not adequately address the duration of continuous use or account for other hormonal contraceptive exposures.
Objective: To assess the risk of breast cancer associated with continuous use of LNG-IUSs, accounting for other hormonal exposures.
Methods: In this nationwide Danish cohort study, 78,595 first-time LNG-IUS users aged 15–49 years from 2000 to 2019 were identified and matched 1:1 by birth year to nonusers of hormonal contraceptives. Exclusion criteria included prior hormonal contraceptive use within 5 years, previous cancer, postmenopausal hormone therapy, and pregnancy at baseline. Participants were followed from initiation until breast cancer diagnosis, other cancer, pregnancy, hormone therapy initiation, emigration, death, or December 31, 2022. Cox proportional hazards models adjusted for confounders estimated hazard ratios (HRs) for breast cancer associated with continuous LNG-IUS use.
Results: During a mean follow-up of 6.8 years, 1,617 breast cancer cases occurred: 720 among LNG-IUS users and 897 among nonusers. The mean age was 38 years. Continuous LNG-IUS use was associated with a higher breast cancer risk compared to nonuse (HR, 1.4; 95% CI, 1.2–1.5). HRs by duration were 1.3 (95% CI, 1.1–1.5) for 0–5 years, 1.4 (95% CI, 1.1–1.7) for >5–10 years, and 1.8 (95% CI, 1.2–2.6) for >10–15 years. Excess breast cancer cases per 10,000 users were 14 (95% CI, 6–23), 29 (95% CI, 9–50), and 71 (95% CI, 15–127), respectively. The trend test for duration was not statistically significant (P = .15).
Conclusions: Continuous use of LNG-IUSs was associated with an increased risk of breast cancer among women aged 15–49 years compared to nonuse of hormonal contraceptives. The absolute increase in risk was low.
Implications for Practice: Healthcare providers should inform women about the potential increased breast cancer risk associated with LNG-IUS use, especially considering its widespread and long-term use among premenopausal women. While the absolute risk increase is small, this information is essential for making informed contraceptive choices.
Study Strengths and Limitations: Strengths include the large, nationwide cohort and adjustment for multiple confounders. Limitations include potential underestimation of risk due to unrecorded LNG-IUS removals before the recommended duration, lack of a statistically significant trend with duration suggesting possible low statistical precision or non-causal association, and the possibility of unmeasured confounding.
Future Research: Further studies are needed to confirm these findings, clarify the causal relationship, and understand the mechanisms underlying the potential increased breast cancer risk with LNG-IUS use.
EULAR/PReS Guidelines for the Diagnosis and Management of Still’s Disease
20 Oct, 2024 | 17:41h | UTCIntroduction:
Still’s disease, encompassing systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), is a systemic inflammatory disorder characterized by spiking fevers, rash, arthralgia or arthritis, and elevated inflammatory markers. Historically treated as separate entities, sJIA and AOSD are now recognized as the same disease continuum. To unify and optimize diagnosis and management across all ages, the European Alliance of Associations for Rheumatology (EULAR) and the Paediatric Rheumatology European Society (PReS) have developed comprehensive, evidence-based recommendations.
Key Recommendations:
- Unified Terminology: sJIA and AOSD are the same disease and should be collectively termed “Still’s disease” to standardize diagnosis and treatment. (Recommendation: strong)
- Rapid Diagnosis Using Operational Definitions: Key clinical features include spiking fever ≥39°C lasting ≥7 days, transient rash coinciding with fever spikes, arthralgia or arthritis, and elevated inflammatory markers (CRP, ESR, neutrophils, ferritin). Arthritis is supportive but not essential for diagnosis. (Strong)
- Diagnostic Biomarkers: Elevated serum interleukin-18 (IL-18) and S100 proteins strongly support the diagnosis and should be measured when available. (Moderate)
- Exclude Alternative Diagnoses: Carefully consider infections, malignancies, other immune-mediated inflammatory diseases, and monogenic autoinflammatory disorders to avoid misdiagnosis. (Strong)
- Treatment Goals: The ultimate goal is drug-free remission, defined as clinically inactive disease (CID) maintained for at least 6 months. CID entails absence of disease-related symptoms and normalization of ESR and CRP. Intermediate targets at specific time points guide treatment adjustments. (Strong)
- Early Use of IL-1 and IL-6 Inhibitors: To avoid prolonged glucocorticoid use, prioritize early initiation of interleukin-1 (IL-1) or interleukin-6 (IL-6) inhibitors upon diagnosis. (Strong)
- Glucocorticoid Tapering: Aim to achieve CID without glucocorticoids within 6 months. Maintain CID for 3–6 months before initiating tapering of biologic DMARDs. (Strong)
- Monitor for Complications: Be vigilant for life-threatening complications, including macrophage activation syndrome (MAS) and lung disease (LD), which require prompt recognition and management. (Strong)
- MAS Management: Consider MAS in patients with persistent fever, splenomegaly, elevated ferritin, cytopenias, abnormal liver function tests, coagulopathy, and hypertriglyceridemia. High-dose glucocorticoids are essential; anakinra, ciclosporin, and interferon-γ inhibitors may be added. (Strong)
- LD Screening and Management: Screen patients for LD via clinical assessment and pulmonary function tests; high-resolution CT scans are indicated for symptomatic patients. The presence of LD is not a contraindication for IL-1 or IL-6 inhibitors. (Strong)
Conclusion: Implementing these unified, evidence-based recommendations is expected to improve the diagnosis and management of Still’s disease across all ages, leading to earlier intervention, optimized treatment strategies, reduced complications, and enhanced patient outcomes, including achieving drug-free remission.
RCT: Milk Elimination Diet Comparable to Four-Food Elimination in Pediatric EoE
20 Oct, 2024 | 15:04h | UTCBackground: Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition characterized by eosinophil infiltration of the esophageal mucosa, leading to symptoms such as nausea, vomiting, abdominal pain, and dysphagia in children. While elimination of six common food allergens is effective, this approach is highly restrictive and may adversely affect quality of life (QoL). Less restrictive diets could potentially balance efficacy with improved QoL.
Objective: To compare the efficacy of a one-food elimination diet excluding milk (1FED) versus a four-food elimination diet excluding milk, egg, wheat, and soy (4FED) in treating pediatric EoE.
Methods: In this multicenter, randomized, nonblinded trial conducted at ten sites in the United States, 63 children aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to either 1FED (n = 38) or 4FED (n = 25) for 12 weeks. The primary endpoint was symptom improvement measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS). Secondary endpoints included the proportion achieving histologic remission (<15 eosinophils per high-power field), changes in histologic features (histology scoring system), endoscopic severity (endoscopic reference score), transcriptome profiling (EoE diagnostic panel), QoL scores, and predictors of remission.
Results: Out of 63 participants, 51 completed the study (1FED, n = 34; 4FED, n = 17). The 4FED group showed a greater improvement in mean PEESS scores compared to the 1FED group (−25.0 vs. −14.5; P = .04). However, histologic remission rates were similar between 4FED and 1FED (41% vs. 44%; P = 1.00). Changes in the histology scoring system (−0.25 vs. −0.29; P = .77), endoscopic reference score (−1.10 vs. −0.58; P = .47), and QoL scores were comparable between groups. The withdrawal rate was higher in the 4FED group compared to the 1FED group (32% vs. 11%; P = .0496).
Conclusions: While the 4FED moderately improved symptoms more than the 1FED, both diets resulted in similar histologic, endoscopic, QoL, and transcriptomic outcomes. Given its comparable effectiveness, better tolerability, and simplicity, the 1FED is a reasonable first-choice therapy for pediatric EoE.
Implications for Practice: Eliminating cow’s milk alone may be preferable as initial dietary therapy for children with EoE due to its simplicity and similar efficacy compared to more restrictive diets. Clinicians should consider starting with a milk elimination diet before progressing to more restrictive elimination diets if necessary.
Study Strengths and Limitations: Strengths of the study include its randomized, multicenter design; standardized treatment instructions; and use of validated symptom and QoL instruments. Limitations include early termination due to low enrollment, a higher withdrawal rate in the 4FED group, nonblinded interventions, and potential bias from participant expectations.
Future Research: Further large-scale, randomized studies are needed to confirm these findings and to identify biomarkers that predict response to dietary therapy in pediatric EoE.
RCT: Twice-Yearly Depemokimab Reduced Exacerbations in Severe Eosinophilic Asthma
17 Sep, 2024 | 22:39h | UTCBackground: Severe asthma with an eosinophilic phenotype often leads to frequent exacerbations despite treatment with medium- or high-dose inhaled glucocorticoids and additional controllers. Interleukin-5 is pivotal in eosinophil growth and survival, contributing to airway inflammation. Existing biologic therapies targeting interleukin-5 require frequent dosing intervals. Depemokimab is an ultra-long-acting anti–interleukin-5 biologic with enhanced binding affinity, potentially allowing effective dosing every six months.
Objective: To evaluate the efficacy and safety of twice-yearly depemokimab in reducing exacerbations in patients with severe eosinophilic asthma.
Methods: Two multicenter, randomized, double-blind, placebo-controlled phase 3A trials (SWIFT-1 and SWIFT-2) were conducted. Patients aged ≥12 years with severe asthma and an eosinophilic phenotype (blood eosinophil count ≥300 cells/μL in the previous 12 months or ≥150 cells/μL at screening) and at least two exacerbations in the prior year despite medium- or high-dose inhaled glucocorticoids plus another controller were enrolled. Participants were randomized 2:1 to receive depemokimab 100 mg or placebo subcutaneously at weeks 0 and 26, alongside standard care. The primary endpoint was the annualized rate of exacerbations over 52 weeks. Secondary endpoints included changes from baseline in the St. George’s Respiratory Questionnaire (SGRQ) score, prebronchodilator FEV₁, and asthma symptom scores at 52 weeks.
Results: A total of 792 patients were randomized, with 762 included in the full analysis set (502 depemokimab, 260 placebo). In SWIFT-1, depemokimab significantly reduced the annualized exacerbation rate compared to placebo (0.46 vs 1.11; rate ratio 0.42; 95% CI, 0.30–0.59; P < .001). Similar results were observed in SWIFT-2 (0.56 vs 1.08; rate ratio 0.52; 95% CI, 0.36–0.73; P < .001). No significant between-group differences were found in change from baseline in SGRQ scores. The incidence of adverse events was similar between groups in both trials.
Conclusions: Twice-yearly administration of depemokimab significantly reduced the annualized rate of exacerbations in patients with severe eosinophilic asthma.
Implications for Practice: Depemokimab administered every six months may offer an effective treatment option for reducing exacerbations in severe eosinophilic asthma, potentially enhancing patient adherence and reducing treatment burden associated with more frequent dosing schedules.
Study Strengths and Limitations: Strengths include large, multicenter, randomized, placebo-controlled design and replicate trials confirming efficacy. Limitations involve the lack of significant improvement in quality-of-life measures, low exacerbation rates in the placebo group, potential impact of the COVID-19 pandemic on trial conduct and outcomes, and limited data on certain subpopulations.
Future Research: Further studies are needed to assess long-term safety and efficacy, effects on quality-of-life measures, and the role of depemokimab in broader asthma populations, including those with varying eosinophil counts and biomarker profiles.
RCT: Liraglutide for Children Aged 6 to <12 Years with Obesity
14 Sep, 2024 | 19:40h | UTCSummary:
A recent phase 3a randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine examined the efficacy and safety of liraglutide in children aged 6 to less than 12 years with obesity. Currently, no medications are approved for treating nonmonogenic, nonsyndromic obesity in this age group, making this study particularly noteworthy.
Methods:
- Participants: 82 children with obesity (BMI ≥95th percentile for age and sex).
- Design: Participants were randomized in a 2:1 ratio to receive once-daily subcutaneous liraglutide (up to 3.0 mg) or placebo, alongside lifestyle interventions, over a 56-week treatment period, followed by a 26-week follow-up.
- Primary Endpoint: Percentage change in BMI from baseline to week 56.
- Secondary Endpoints: Percentage change in body weight and the proportion achieving a ≥5% reduction in BMI.
Results:
- BMI Reduction: At week 56, the liraglutide group experienced a mean BMI reduction of –5.8%, compared to a +1.6% increase in the placebo group. The estimated difference was –7.4 percentage points (95% CI, –11.6 to –3.2; P<0.001).
- Body Weight: Mean body weight increased by 1.6% in the liraglutide group versus 10.0% in the placebo group, a difference of –8.4 percentage points (95% CI, –13.4 to –3.3; P=0.001).
- BMI Reduction ≥5%: Achieved by 46% of participants in the liraglutide group versus 9% in the placebo group (adjusted odds ratio, 6.3; 95% CI, 1.4 to 28.8; P=0.02).
- Adverse Events: Reported in 89% of the liraglutide group and 88% of the placebo group. Gastrointestinal events were more common with liraglutide (80% vs. 54%).
Discussion:
While the study suggests that liraglutide can lead to a statistically significant reduction in BMI among children aged 6 to less than 12 years with obesity, several considerations should temper our enthusiasm:
- Sample Size and Diversity: The trial included only 82 participants, with a predominantly White population (72%), which may limit the generalizability of the findings to broader, more diverse populations.
- Duration and Long-Term Effects: The study spanned 56 weeks, with a 26-week follow-up. The long-term efficacy and safety of liraglutide in this age group remain uncertain, particularly concerning growth, development, and potential rebound weight gain after discontinuation.
- Clinical Significance: Although the reduction in BMI was statistically significant, the clinical significance—especially regarding long-term health outcomes and obesity-related comorbidities—is less clear. Obesity is a chronic and relapsing condition, and a modest reduction in BMI may not translate into substantial health benefits without sustained intervention.
- Adverse Events: The high incidence of gastrointestinal adverse events raises questions about the tolerability of liraglutide in young children. Managing these side effects in a pediatric population can be challenging and may affect adherence.
- Lack of Consensus on BMI Reduction: There’s no international consensus on what constitutes a clinically meaningful BMI reduction in children, complicating the interpretation of the results.
Conclusion:
This trial provides preliminary evidence that liraglutide, combined with lifestyle interventions, may help reduce BMI in children under 12 with obesity. However, given the limitations—including small sample size, short duration, and safety concerns—it’s prudent to approach these findings with cautious optimism. More extensive studies with longer follow-up periods and more diverse populations are necessary to fully assess the long-term efficacy and safety of liraglutide in this vulnerable age group.
Takeaway:
While liraglutide shows promise as an adjunct therapy for pediatric obesity, it’s essential to weigh the benefits against the potential risks and uncertainties. Clinicians should continue to prioritize established lifestyle interventions and consider pharmacotherapy on a case-by-case basis, pending further evidence.
Cohort Study: Lower Risk of Cardiovascular Complications in Post–COVID-19 Vaccine Myocarditis Compared to Conventional Etiologies
7 Sep, 2024 | 20:36h | UTCStudy Design and Population: This French nationwide cohort study included 4,635 individuals aged 12-49 hospitalized for myocarditis between December 2020 and June 2022. The cohort was divided into three groups: 558 patients with post–COVID-19 mRNA vaccine myocarditis, 298 with post–COVID-19 infection myocarditis, and 3,779 with conventional myocarditis.
Main Findings: At 18 months of follow-up, the frequency of cardiovascular events was significantly lower in the postvaccine myocarditis group (5.7%) compared to conventional myocarditis (13.2%) with a weighted hazard ratio (wHR) of 0.55 (95% CI, 0.36-0.86). Hospital readmission for myopericarditis occurred in 3.2% of postvaccine cases, 4.0% of post–COVID-19 cases, and 5.8% of conventional cases. The all-cause mortality rate was 0.2% for postvaccine myocarditis, 1.3% for post–COVID-19 myocarditis, and 1.3% for conventional myocarditis.
Implications for Practice: Postvaccine myocarditis patients, primarily young males, experience fewer complications compared to conventional myocarditis, but long-term follow-up is still needed. These findings should guide future mRNA vaccine recommendations and clinical management for myocarditis patients.
Reference: Semenzato L. et al. (2024). Long-term Prognosis of Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2, or Conventional Etiologies. JAMA, Online. DOI: http://doi.org/10.1001/jama.2024.16380
Link: https://jamanetwork.com/journals/jama/fullarticle/2822933
Cohort Study: Prenatal Exposure to Buprenorphine with Naloxone Appears Safe and More Effective than Buprenorphine Alone for Neonates and Mothers – JAMA
18 Aug, 2024 | 18:06h | UTCStudy Design and Population: This population-based cohort study used healthcare data from Medicaid-insured pregnancies in the US between 2000 and 2018. The study included 8,695 pregnant individuals linked to their liveborn infants. Participants were exposed to either buprenorphine combined with naloxone or buprenorphine alone during the first trimester.
Main Findings: The study found that prenatal exposure to buprenorphine with naloxone was associated with a lower risk of neonatal abstinence syndrome (37.4% vs 55.8%) and modest reductions in neonatal intensive care unit admission (30.6% vs 34.9%) and small for gestational age (10.0% vs 12.4%) compared to buprenorphine alone. No significant differences were observed for congenital malformations, low birth weight, preterm birth, respiratory symptoms, or cesarean delivery.
Implications for Practice: These findings suggest that buprenorphine combined with naloxone is a safe and potentially preferable option for treating opioid use disorder during pregnancy, providing more flexibility in treatment choices for pregnant individuals.
News Release – FDA Approves First Nasal Spray for Anaphylaxis Treatment: Neffy (Epinephrine Nasal Spray) – U.S. Food and Drug Administration
17 Aug, 2024 | 15:43h | UTCThe U.S. Food and Drug Administration (FDA) has approved Neffy, the first epinephrine nasal spray for the emergency treatment of anaphylaxis and other severe allergic reactions (Type I) in both adults and pediatric patients weighing at least 30 kilograms (approximately 66 pounds). This approval introduces a non-injectable option for the rapid administration of epinephrine, which is critical in managing life-threatening allergic reactions.
Key Points for Healthcare Providers:
– Alternative to Injection: Neffy provides a new option for patients who may delay or avoid epinephrine injections due to needle phobia. This could be particularly beneficial for children and others reluctant to use injectable epinephrine.
– Efficacy and Safety: Neffy’s approval is supported by studies comparing its pharmacokinetics and pharmacodynamics to traditional epinephrine injections. These studies showed comparable blood epinephrine levels and similar physiological effects, such as increased blood pressure and heart rate.
– Administration: Neffy is a single-dose nasal spray, administered into one nostril. If symptoms do not improve or worsen, a second dose may be administered in the same nostril. Patients should still seek emergency medical care to monitor the anaphylactic reaction.
– Warnings: Certain nasal conditions, such as nasal polyps or a history of nasal surgery, may impair Neffy’s absorption. In these cases, injectable epinephrine might be a more reliable option. The product also carries typical warnings for epinephrine use, particularly in patients with coexisting conditions.
– Side Effects: Common side effects include throat irritation, nasal discomfort, headaches, and jitteriness. Healthcare professionals should discuss these with patients to ensure informed use.
Clinical Implications:
Neffy may reduce barriers to the timely treatment of anaphylaxis, potentially improving outcomes by increasing the likelihood of rapid epinephrine administration. Healthcare providers should consider Neffy as an alternative for patients who are needle-averse or have difficulty using injectable epinephrine, while also ensuring patients understand the importance of prompt medical attention following its use.
Approval Background:
Neffy was granted Fast Track designation by the FDA, emphasizing the need for an alternative to injectable epinephrine. The approval was awarded to ARS Pharmaceuticals.
Source: FDA News Release: FDA Approves First Nasal Spray for Treatment of Anaphylaxis
Meta-Analysis: Daily Sedation Interruption Shortens PICU Stay Without Impacting Mortality or Ventilation Duration in Pediatric MV Patients – JAMA Netw Open
11 Aug, 2024 | 13:19h | UTCStudy Design and Population: This systematic review and meta-analysis included six randomized clinical trials (RCTs) involving 2,810 pediatric patients receiving mechanical ventilation (MV) in the pediatric intensive care unit (PICU). The trials compared the effects of daily sedation interruption (DSI) with continuous intravenous (IV) sedation on clinical outcomes such as MV duration and PICU length of stay.
Main Findings: The analysis found that DSI was associated with a significant reduction in the length of PICU stay (mean difference of -1.45 days, p = 0.03). However, there was no significant difference in the duration of MV between DSI and continuous sedation (mean difference of -0.93 days, p = 0.06). Additionally, there were no significant differences in total sedative doses, adverse events, or mortality between the two groups.
Implications for Practice: The findings suggest that DSI may reduce the length of PICU stay without increasing the risk of adverse events, making it a potentially valuable strategy in managing sedation for pediatric patients on MV. However, further research is needed to explore the long-term neurodevelopmental outcomes associated with DSI.
Cross-Sectional Study: AI Model Accurately Detects Myopia, Strabismus, and Ptosis in Children Using Smartphone Photos – JAMA Netw Open
10 Aug, 2024 | 21:21h | UTCStudy Design and Population: This cross-sectional study was conducted at Shanghai Ninth People’s Hospital from October 2022 to September 2023, including 476 children diagnosed with myopia, strabismus, or ptosis. A total of 1,419 images were used to develop an AI model to detect these conditions based on mobile phone photographs.
Main Findings: The AI model demonstrated strong performance with a sensitivity of 0.84 for myopia, 0.73 for strabismus, and 0.85 for ptosis. The model achieved overall accuracies exceeding 0.80 for myopia and strabismus and 0.92 for ptosis, indicating its effectiveness in early detection of these pediatric eye conditions using only smartphone images.
Implications for Practice: The findings suggest that AI-based screening tools could enable early detection of common pediatric eye diseases at home, reducing the reliance on hospital-based screenings. This approach could facilitate timely intervention, improving visual outcomes and reducing the burden on healthcare systems.
Phase 3 RCT: Butantan-DV Dengue Vaccine is Safe and Shows 67.3% Efficacy Over 3.7 Years in Participants Aged 2–59 Years – Lancet Infect Dis
10 Aug, 2024 | 20:23h | UTCStudy Design and Population: This double-blind, randomized, placebo-controlled, phase 3 trial conducted in Brazil evaluated the efficacy and safety of the Butantan-dengue vaccine (Butantan-DV) in 16,235 healthy participants aged 2–59 years. Participants, who had not previously received a dengue vaccine, were randomly assigned to receive either a single dose of Butantan-DV or a placebo and were followed up for an average of 3.7 years.
Main Findings: The study found that Butantan-DV demonstrated 67.3% efficacy against virologically confirmed dengue (VCD) caused by any dengue virus serotype, with no cases of VCD caused by DENV-3 or DENV-4. The proportions of serious adverse events were similar between the vaccine and placebo groups, indicating that the vaccine was generally well tolerated.
Implications for Practice: The results support the potential of the Butantan-DV vaccine as an effective intervention for preventing symptomatic dengue, particularly from DENV-1 and DENV-2, across a broad age range regardless of dengue serostatus. Continued development and monitoring are warranted to confirm long-term efficacy and safety.
Cohort Study: Prenatal opioid exposure linked to modest increase in neuropsychiatric disorders – The BMJ
25 May, 2024 | 19:50h | UTCThis nationwide birth cohort study from South Korea investigated the impact of prenatal opioid exposure on the risk of neuropsychiatric disorders among children. The study followed 3,128,571 infants born between 2010 and 2017 until the end of 2020. Researchers found that infants exposed to opioids prenatally showed a slightly increased risk of developing neuropsychiatric disorders, including mood disorders, attention deficit hyperactivity disorder, and intellectual disability. The increased risk was more pronounced with higher opioid doses, longer duration of use, and exposure during the first trimester of pregnancy. However, this association was not significant in sibling comparison cohorts, indicating a modest overall clinical impact. The study emphasizes the need for cautious interpretation due to its observational design and the specific conditions under which risk increases.
Reference (link to free full-text):
APA workgroup update maintains skepticism on pharmacogenomic tools for depression – Am J Psychiatry
25 May, 2024 | 19:47h | UTCA recent review by the American Psychiatric Association (APA) Council of Research Workgroup on Biomarkers and Novel Treatments revisits the use of pharmacogenomic (PGx) tools for selecting depression treatments. The review assesses new clinical trials and meta-analyses conducted from 2017 to 2022. Of the studies analyzed, few demonstrated significant efficacy in treatment response using PGx tools, with many suffering from methodological flaws such as lack of full blinding and insufficient control measures. Despite some trials showing promise, the overall evidence remains insufficient to support the widespread clinical application of PGx tools in managing major depressive disorder. The Workgroup reaffirms the 2018 conclusions and aligns with the U.S. Food and Drug Administration’s stance, recommending that future research should focus on more rigorous study designs and explore other potential benefits of pharmacogenomics, such as predicting rare adverse drug reactions.
Reference (link to abstract – $ for full-text)
Meta-analysis reveals 24% prevalence of eating disorders among individuals with insulin-dependent diabetes – Eat Behav
11 May, 2024 | 13:41h | UTCThis systematic review and meta-analysis evaluated the prevalence of eating disorder symptoms (EDS) in individuals aged 16 and older with insulin-dependent diabetes, covering both type 1 and type 2 diabetes. The study involved an extensive search across several databases including PubMed, Embase, Scopus, PsycINFO, and CINAHL, culminating in the inclusion of 45 studies. The meta-analysis revealed a pooled prevalence of EDS at 24% (95% CI 0.21–0.28), with prevalence reaching 27% (95% CI 0.24–0.31) among studies using the Diabetes Eating Problem Survey-Revised (DEPS-R), the most frequently utilized screening tool. Notably, the prevalence of EDS varied based on the screening tool used and was significantly associated with sex distribution; studies with a higher percentage of female participants (over 58%) reported a higher prevalence of EDS (30% vs. 18%, prevalence ratio 1.7). The study also highlighted a concerning prevalence of insulin omission, reported at 21% (95% CI 0.13–0.33). This analysis underscores the substantial occurrence of eating disorder symptoms among this patient population, emphasizing the need for tailored screening and interventions.
Reference (link to abstract – $ for full-text):
RCT: Video laryngoscopy improves first-attempt intubation success in neonates compared to direct laryngoscopy – N Engl J Med
11 May, 2024 | 13:37h | UTCStudy Design and Population: This single-center randomized clinical trial investigated the efficacy of video laryngoscopy versus direct laryngoscopy for urgent intubation in neonates. A total of 226 neonates requiring intubation either in the delivery room or neonatal intensive care unit (NICU) were enrolled and stratified by gestational age into two groups: less than 32 weeks and 32 weeks or more. The study primarily focused on the success rate of the first intubation attempt, monitored through exhaled carbon dioxide detection.
Main Findings: The trial included 214 neonates, analyzing the success of intubation on the first attempt. Video laryngoscopy significantly outperformed direct laryngoscopy, achieving a first-attempt success rate of 74% (95% confidence interval [CI], 66 to 82) compared to 45% (95% CI, 35 to 54) in the direct laryngoscopy group. Moreover, the median number of attempts for successful intubation was lower in the video-laryngoscopy group (1 attempt, 95% CI, 1 to 1) versus the direct-laryngoscopy group (2 attempts, 95% CI, 1 to 2). Additionally, neonates in the video laryngoscopy group experienced higher median lowest oxygen saturations and heart rates during intubation.
Implications for Practice: The findings suggest that video laryngoscopy could be more effective than direct laryngoscopy for urgent neonatal intubation, particularly in increasing the likelihood of success on the first attempt. These results recommend reconsidering current intubation techniques in neonatal care settings to incorporate video laryngoscopy, potentially leading to safer and more efficient intubation processes in this vulnerable population.
Reference (link to abstract – $ for full-text):
Phase 2 RCT: Preventive subcutaneous L9LS monoclonal antibody reduces malaria incidence by 66-70% in Malian children – N Engl J Med
7 May, 2024 | 15:31h | UTCThis phase 2 randomized clinical trial investigated the safety and efficacy of the monoclonal antibody L9LS in preventing Plasmodium falciparum infection and clinical malaria in children aged 6 to 10 years in Mali. The trial was structured in two parts: initial dose assessment in adults followed by a randomized, placebo-controlled test in children over a 6-month malaria season. A total of 225 children participated, divided equally among three groups to receive either 150 mg of L9LS, 300 mg of L9LS, or a placebo. Results demonstrated a significant reduction in the rate of P. falciparum infection—66% efficacy with the 150-mg dose and 70% efficacy with the 300-mg dose. Similarly, efficacy against clinical malaria was 67% with the 150-mg dose and 77% with the 300-mg dose. Both doses were well-tolerated with no safety concerns reported, underscoring the potential of L9LS as a preventative treatment against malaria in endemic regions.
Reference (link to abstract – $ for full-text):
RCT: No significant benefit of adjuvant prednisone for patients with cystic fibrosis with exacerbations unresponsive to antibiotics – Eur Respir J
6 May, 2024 | 06:32h | UTCThis randomized, double-blind, placebo-controlled trial investigated the effectiveness of adjuvant oral prednisone in enhancing lung function recovery in patients with cystic fibrosis (CF) experiencing pulmonary exacerbations (PExs) unresponsive to initial intravenous (IV) antibiotic treatment. The study involved 173 participants, with 76 not achieving more than 90% of their baseline forced expiratory volume in one second (ppFEV1) by Day 7 of antibiotic treatment and subsequently randomized to receive either oral prednisone (1 mg·kg−1 twice daily, up to 60 mg/day) or placebo for an additional 7 days. Results showed that 50% of the prednisone group and 39% of the placebo group recovered over 90% of their baseline ppFEV1 by Day 14. However, the difference was not statistically significant (11% difference; 95% CI -11, 34%; p=0.34). Additionally, prednisone did not significantly prolong the time to the next exacerbation compared to placebo. This study concludes that adjuvant oral prednisone does not significantly improve lung function recovery or delay subsequent exacerbations in CF patients not responding to initial antibiotic therapy.
Reference (link to abstract – $ for full-text):
RCT: Azithromycin fails to prevent moderate or severe chronic lung disease in preterm infants – Lancet Respir Med
6 May, 2024 | 06:28h | UTCThis randomized, placebo-controlled trial evaluated the effectiveness of azithromycin in preventing chronic lung disease (CLD) in preterm infants born at less than 30 weeks’ gestation across 28 UK neonatal intensive care units. A total of 799 infants were randomized to receive either intravenous azithromycin or a placebo. The primary outcome measured was survival without moderate or severe CLD at 36 weeks postmenstrual age. Results showed no significant difference between the azithromycin group (42% survival without CLD) and the placebo group (45% survival without CLD), with an adjusted odds ratio of 0.84 (95% CI 0.55–1.29, p=0.43). Pulmonary Ureaplasma spp colonization did not affect the treatment outcome. Given the lack of efficacy and the presence of several serious adverse events in the azithromycin group, the study concluded that azithromycin should not be recommended for preventing CLD in this population.
Reference (link to free full-text):
Randomized Crossover Trial: Prophylactic recombinant ADAMTS13 prevents acute events in congenital thrombotic thrombocytopenic purpura – N Engl J Med
6 May, 2024 | 06:22h | UTCThis study evaluates the efficacy and safety of recombinant ADAMTS13 compared to standard plasma-derived therapy in managing congenital thrombotic thrombocytopenic purpura (TTP). In a phase 3, open-label, crossover trial involving 48 patients, each participant underwent two 6-month prophylaxis periods, receiving either recombinant ADAMTS13 or standard therapy, followed by a switch to the alternate treatment. Results indicate that recombinant ADAMTS13 prevented acute TTP events during prophylaxis, with no events recorded, versus one event under standard therapy. Furthermore, recombinant ADAMTS13 was associated with significantly lower rates of thrombocytopenia and adverse events compared to standard therapy. The treatment increased ADAMTS13 activity to approximately 100% of normal levels, with no development of neutralizing antibodies. Overall, recombinant ADAMTS13 was found to be safe and more effective than standard therapy in preventing TTP events and manifestations.
Reference (link to abstract – $ for full-text):
Prospective Validation Study: High accuracy of PECARN rules in reducing unnecessary CT scans in pediatric blunt trauma – Lancet Child Adolesc Health
5 May, 2024 | 15:08h | UTCStudy Design and Population:
This multicenter prospective validation study tested the Pediatric Emergency Care Applied Research Network (PECARN) prediction rules aimed at reducing unnecessary CT scans for children presenting with blunt abdominal or minor head trauma. Over a nearly five-year period, children and adolescents under 18 from six U.S. emergency departments in cities including Sacramento, Dallas, and Los Angeles were enrolled. Exclusion criteria included pregnancy, pre-existing neurological disorders, penetrating trauma, injuries older than 24 hours, prior CT or MRI scans, or suspicion of non-accidental trauma.
Main Findings:
A total of 7,542 children with blunt abdominal trauma and 19,999 with minor head trauma were enrolled. The intra-abdominal injury rule demonstrated a sensitivity and negative predictive value (NPV) of 100%, confirming its reliability in detecting injuries requiring acute intervention. For head traumas, the sensitivity varied slightly with age; 100% for children under 2 years and 98.8% for those aged 2 years and older, with an NPV of 100% in both groups. Only two cases in the older cohort were misclassified, neither requiring neurosurgery.
Implications for Practice:
The validation of PECARN rules with high sensitivity and NPV supports their use as a safe guideline to minimize unnecessary CT scans in pediatric trauma cases, thereby promoting efficient use of resources and reducing exposure to radiation in children. These results suggest that implementation of these rules should be considered in emergency pediatric care to improve outcomes and healthcare efficiency.
Reference (link to abstract – $ for full-text):
RCT: Early patching proves more effective than extended optical treatment in pediatric amblyopia management – The Lancet
5 May, 2024 | 15:00h | UTCStudy Design and Population:
The EuPatch study was a multicenter, randomized controlled trial conducted across 30 hospitals in multiple European countries, including the UK, Greece, Austria, Germany, and Switzerland. It targeted children aged 3–8 years diagnosed with amblyopia due to anisometropia, strabismus, or both, with an interocular difference ≥0.30 logMAR in best corrected visual acuity (BCVA). Participants were divided into two groups: one underwent 18 weeks of glasses use before patching (Extended Optical Treatment, EOT), and the other just 3 weeks (early patching), each supplemented with an intensive patching regimen.
Main Findings:
Out of the 334 initially randomized participants, 317 were analyzed for the primary outcome. The early patching group demonstrated a significantly higher success rate, achieving ≤0.20 logMAR interocular difference in BCVA in 67% of cases compared to 54% in the EOT group after 12 weeks of patching (p=0.019). The median follow-up times were 42 weeks for the EOT group and 27 weeks for the early patching group, with dropout rates of 14% and 6%, respectively.
Implications for Practice:
The findings suggest that early patching is superior to EOT in the management of amblyopia in children, presenting a viable option for enhancing treatment effectiveness. This study supports the potential personalization of amblyopia treatments based on the quicker onset of patching. These results could influence future guidelines and clinical practices in pediatric ophthalmology.
Reference (link to free full-text):
Clinical Trial Follow-up: Antenatal corticosteroids not associated with adverse neurodevelopmental outcomes in late preterm births – JAMA
2 May, 2024 | 23:25h | UTCStudy Design and Population:
This research involved a prospective follow-up study of a multicenter randomized clinical trial, specifically focusing on children aged 6 years or older whose birthing parents were enrolled in the Antenatal Late Preterm Steroids (ALPS) trial. The trial initially examined the impact of administering 12 milligrams of intramuscular betamethasone, given twice 24 hours apart, on late preterm infants (34-36 completed weeks). The follow-up study involved 949 children from 13 centers in the Maternal-Fetal Medicine Units (MFMU) Network, assessed for neurodevelopmental outcomes.
Main Findings:
The primary outcome measured was the General Conceptual Ability score less than 85 on the Differential Ability Scales, 2nd Edition (DAS-II). Results showed no statistically significant differences between the betamethasone group (17.1%) and the placebo group (18.5%) in achieving this score. Secondary outcomes related to motor function and social responsiveness also showed no significant differences between the groups. Sensitivity analyses further confirmed these findings, suggesting that the administration of betamethasone did not adversely affect neurodevelopmental outcomes at age 6 or older.
Implications for Practice:
These findings support the continued use of antenatal corticosteroids for improving short-term neonatal respiratory outcomes in late preterm deliveries without concern for long-term neurodevelopmental harm. Clinicians can consider these results reassuring, as the study effectively dispels earlier concerns about potential negative long-term effects related to neurodevelopment from antenatal steroid use in late preterm infants.
Reference (link to abstract – $ for full-text):