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1.
Am J Hum Genet ; 111(7): 1271-1281, 2024 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-38843839

RESUMO

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.


Assuntos
Testes Genéticos , Doenças Raras , Sequenciamento Completo do Genoma , Humanos , Masculino , Doenças Raras/genética , Doenças Raras/diagnóstico , Feminino , Criança , Testes Genéticos/métodos , Pré-Escolar , Adolescente , Adulto , Lactente , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/diagnóstico
3.
J Pediatr ; 213: 222-226.e2, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31255386

RESUMO

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <280/7 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.


Assuntos
Esquema de Medicação , Permeabilidade do Canal Arterial/tratamento farmacológico , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Displasia Broncopulmonar/complicações , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Prematuro/terapia , Masculino , Idade Materna , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Risco , Resultado do Tratamento
4.
J Pediatr ; 205: 41-48.e6, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30340932

RESUMO

OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN: A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS: In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.


Assuntos
Acetaminofen/uso terapêutico , Tratamento Conservador , Inibidores de Ciclo-Oxigenase/uso terapêutico , Permeabilidade do Canal Arterial/terapia , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Pressão Positiva Contínua nas Vias Aéreas , Permeabilidade do Canal Arterial/classificação , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
5.
J Perinatol ; 39(5): 599-607, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30850756

RESUMO

OBJECTIVE: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks. METHODS: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants). RESULTS: Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)). CONCLUSION: Indomethacin was more effective than acetaminophen in producing ductus constriction.


Assuntos
Acetaminofen/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Vasoconstrição/efeitos dos fármacos , Administração Intravenosa , Administração Oral , Tratamento Conservador , Canal Arterial/efeitos dos fármacos , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , São Francisco , Resultado do Tratamento
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