Journal Articles of Note

Gao Y, Zhao Y, Liu M, et al. Antiviral medications for treatment of nonsevere influenza: a systematic review and network meta-analysis. JAMA Intern Med. Published online January 13, 2025. doi:10.1001/jamainternmed.2024.7193

Abstract

Importance: The optimal antiviral drug for treatment of nonsevere influenza remains unclear.

Objective: To compare effects of antiviral drugs for treating nonsevere influenza.

Data sources: MEDLINE, Embase, CENTRAL, CINAHL, Global Health, Epistemonikos, and ClinicalTrials.gov were searched from database inception to September 20, 2023.

Study selection: Randomized clinical trials comparing direct-acting influenza antiviral drugs to placebo, standard care, or another antiviral drug for treating people with nonsevere influenza.

Data extraction and synthesis: Paired reviewers independently performed data extraction and risk of bias assessment. A frequentist network meta-analysis was performed to summarize the evidence and the certainty of evidence was evaluated using the GRADE approach.

Main outcomes and measures: Mortality, admission to hospital, admission to the intensive care unit, duration of hospitalization, time to alleviation of symptoms, emergence of resistance, and adverse events.

Results: Overall, 73 trials with 34,332 participants proved eligible. Compared with standard care or placebo, all antiviral drugs had little or no effect on mortality for low-risk patients and high-risk patients (all high certainty). All antiviral drugs (no data for peramivir and amantadine) had little or no effect on hospital admission for low-risk patients (high certainty). For hospital admission in high-risk patients, oseltamivir (risk difference [RD], -0.4%; 95% CI, -1.0 to 0.4; high certainty) had little or no effect and baloxavir may have reduced risk (RD, -1.6%; 95% CI, -2.0 to 0.4; low certainty); all other drugs may have had little or uncertain effect. For time to alleviation of symptoms, baloxavir probably reduced symptom duration (mean difference [MD], -1.02 days; 95% CI, -1.41 to -0.63; moderate certainty); umifenovir may have reduced symptom duration (MD, -1.10 days; 95% CI, -1.57 to -0.63; low certainty); oseltamivir probably had no important effect (MD, -0.75 days; 95% CI, -0.93 to -0.57; moderate certainty). For adverse events related to treatment, baloxavir (RD, -3.2%; 95% CI, -5.2 to -0.6; high certainty) had few or no adverse events; oseltamivir (RD, 2.8%; 95% CI, 1.2 to 4.8; moderate certainty) probably increased adverse events.

Conclusions and relevance: This systematic review and meta-analysis found that baloxavir probably reduced risk of hospital admission for high-risk patients and may reduce time to alleviation of symptoms, without increasing adverse events related to treatment in patients with nonsevere influenza. All other antiviral drugs either probably have little or no effect, or uncertain effects on patient-important outcomes.

Garg S, Reinhart K, Couture A, et al. Highly pathogenic avian influenza A(H5N1) virus infections in humans. N Engl J Med. Published online December 31, 2024. doi:10.1056/NEJMoa2414610

Abstract

Background: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States.

Methods: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit.

Results: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%).

Conclusions: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk.

Schraw JM, Tark JY, Desrosiers TA, et al. Risk of carcinomas among children and adolescents with birth defects. Cancer Epidemiol. Published online January 22, 2025. doi:10.1016/j.canep.2025.102748

Abstract

Background: Birth defects are associated with childhood cancer, but little is known regarding pediatric carcinomas, a group of especially rare tumors.

Methods: We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for any carcinoma, as well as thyroid, hepatocellular, and renal carcinoma specifically, up to 18 years of age among children with major, non-syndromic anomalies or chromosomal/genetic syndromes, relative to unaffected children.

Results: Our registry-linkage study included nine states and 21,933,476 children between 1990 and 2018: 641,827 with non-syndromic anomalies, and 49,619 with syndromes. Carcinomas were diagnosed in 833 children, including 35 with non-syndromic anomalies and eight with syndromes. The hazard of carcinoma was increased both among children with non-syndromic anomalies (HR: 1.7, CI: 1.2-2.4; N = 35) and syndromes (HR: 4.7, CI: 2.3-9.5; N = 7). Hepatocellular carcinoma was associated with non-syndromic anomalies (HR: 4.6, CI: 2.2-9.7; N = 8) and syndromes (HR: 8.0, CI: 1.1-58.1; N < 5). The hazard of renal carcinoma was markedly increased in children with tuberous sclerosis (HR 59.6, CI: 23.7-149.5; N = 5), a known cause of renal cancer. Thyroid carcinoma was not associated with non-syndromic anomalies or syndromes.

Yantz C, Shumate C, Betancourt D, et al. Epidemiology of colpocephaly in the Texas Birth Defects Registry, 1999 to 2020. Am J Perinatol. Published online January 31, 2025. doi:10.1055/a-2516-1967

Abstract

Objective: Colpocephaly is a congenital brain defect characterized by enlargement of the occipital horns of the lateral ventricles. Few population-based studies have focused on this central nervous system (CNS) defect. This study aimed to evaluate the birth prevalence and survival of Texas infants with colpocephaly delivered between 1999 and 2020.

Study design: Cases from the Texas Birth Defects Registry (TBDR) with a diagnosis of colpocephaly were identified. Unadjusted birth prevalence, 1-year survival estimates, and crude hazard ratios with 95% confidence intervals (CIs) were calculated from data collected from the medical record abstraction and linked vital records. Select maternal and infant variables were assessed overall and across four medical classification groups (presence of isolated, chromosomal, syndromic, or multiple major defects).

Results: From 1999 to 2020, 1,146 cases with colpocephaly were identified. The overall birth prevalence of colpocephaly was 1.36/10,000 live births (95% CI: 1.28-1.44). Significantly higher prevalence was noted for male infants, infants with low birth weight (<2,500 g), and very preterm (<32 weeks) infants. Overall, 1-year survival was 89.5%, with statistically significant differences observed in each medical classification group (e.g., isolated) across levels of maternal education, Texas/Mexico border maternal residence at delivery, infant birth weight, and gestational age.

Conclusion: These findings have important implications for pediatric neurology and future research, such as counseling on the prevalence and prognosis of colpocephaly. Additionally, these findings highlight that the population burden of CNS defects may be higher than previously believed, supporting the expansion of research of rare brain defects.

Key points: · The overall birth prevalence of colpocephaly for Texas infants delivered between 1999 and 2020 was 1.36/10,000 live births.. · Statistically significant differences in 1-year survival were observed across select maternal and infant variables.. · Longitudinal studies are necessary to fully ascertain the prevalence of colpocephaly beyond the first year of life.