Extrapolation as a Default Strategy in Pediatric Drug Development.

Pediatric drug development lags adult development by about 8 years (Mulugeta et al. in Pediatr Clin 64(6):1185-1196, 2017). In such context, many incentives, regulations, and innovative techniques have been proposed to address the disparity for pediatric patients. One such strategy is extrapolation of efficacy from a reference population. Extrapolation is currently justified by providing evidence in support of the effective use of drugs in children when the course of the disease and the expected treatment response would be sufficiently similar in the pediatric and reference population. This paper's position is that, despite uncertainties, pediatric drug development programs should initially assume some degree of extrapolation. The degree to which extrapolation can be used lies along a continuum representing the uncertainties to be addressed through generation of new pediatric evidence. In addressing these uncertainties, the extrapolation strategy should reflect the level of tolerable uncertainty concerning the decision to expose a child to the risks of a new drug. This judgment about the level of tolerable uncertainty should vary with the context (e.g., disease severity, existing therapeutic options) and can be embedded into pediatric drug development archetypes to ascertain the extent of studies needed and whether simultaneous development for adults and adolescents be considered.

Herpes associated erythema multiforme: A retrospective study.

BACKGROUND: Erythema multiforme (EM), an acute dermatologic condition frequently encountered in the Emergency Department, classically presents with a targetoid rash. We reviewed all recent EM cases seen at the LAC-USC County Hospital in order to ascertain the proportion of Herpes associated EM (HAEM) cases and to inform the diagnostic workup of these patients. METHODS: ICD-9 and ICD-10 codes were used to extract a list of EM cases at our institution from 2013 to 2019. Two non-blinded abstractors screened records to confirm an EM diagnosis and entered patient data utilizing a standardized data abstraction form. Cohen's kappa statistic was used to measure inter-rater reliability on various variables. Kappa (κ) values ranged from 0.803 to 1.0. RESULTS: 70 pediatric and 56 adult EM patients were included in the study. A likely etiology was ascribed to 63% of pediatric and adult EM cases. Pediatric EM was most commonly attributed to upper respiratory infection (URI) (n = 23; 33%), Mycoplasma pneumoniae infection (n = 5; 7%), and medications (n = 4; 6%). Adult EM was most commonly attributed to HSV infection (n = 11; 20%), medications (n = 5; 9%), URIs (n = 4; 7%), and other infections (n = 4; 7%). CONCLUSION: HSV-1/2 serologic testing should be considered in most EM patients to potentially prevent repeated ED visits. In EM cases not clearly attributable to herpes or drug exposure, physicians can consider further workup: Mycoplasma serology, nasal PCR, and a respiratory viral panel in pediatric patients. Identification of an etiologic cause may suggest a different treatment approach and prevent mislabeling of medication allergies in patient charts.

Teledermatology: Meeting the Need for Specialized Care in Rural Haiti.

BACKGROUND: In Haiti, rural populations lack access to specialized care, such as dermatology, yet dermatological conditions are common causes for primary care (PC) visits. Studies on teledermatology from resource-constrained settings demonstrate promising results. We assessed the feasibility of implementing teledermatology in rural Haiti. METHODS: Patients with dermatological problems were examined by a PC provider in Haiti. Photos and intake evaluations were reviewed by U.S.-based dermatologists. RESULTS: Among 101 patients with dermatological problems, atopic disease and fungal infections were most common. Average diagnostic concordance between Haitian providers and U.S. dermatologists was 68.9%. The average time from intake to "case-closed" was 1.67 days. DISCUSSION: Diagnostic concordance and turn-around time were comparable to similar studies, demonstrating that teledermatology is well-suited for rural Haiti and could increase access to specialized care. CONCLUSION: In Haiti and similar settings, telemedicine should be considered a viable option for meeting the health care needs of underserved populations.

The aetiology of vaginal symptoms in rural Haiti.

Vaginal symptoms are a common chief complaint amongst women visiting outpatient clinics in rural Haiti. A systematic sample of 206 consecutive women over age 18 with gynaecological symptoms underwent gynaecologic examination and laboratory testing for chlamydia, gonorrhoea, syphilis, HIV infection, trichomoniasis, candidiasis, and bacterial vaginosis. Among 206 women, 174 (84%) presented with vaginal discharge, 165 (80%) with vaginal itching, 123 (60%) with vaginal pain or dysuria, and 18 (9%) with non-traumatic vaginal sores or boils. Laboratory results were positive forChlamydia trachomatisin 5.4% (11/203), syphilis in 3.5% (7/202), HIV in 1.0% (2/200), andNeisseria gonorrhoeaein 1.0% (2/203). Among those that had microscopy, hyphae suggestive of candidiasis were visualized in 2.2% (1/45) and no cases of trichomoniasis were diagnosed 0% (0/45). Bacterial vaginosis was diagnosed in 28.3% (13/46). The prevalence of chlamydia was 4.9 (95% CI: 1.3-17.7) times greater among those 25 years of age and under (10.8%) than those older (2.3%). Chlamydia and bacterial vaginosis were the most common sexually transmitted infection and vaginal condition, respectively, in this study of rural Haitian adult women. The higher risk of chlamydia in younger women suggests education and screening programmes in young women should be considered.