RESUMO
Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.
Assuntos
Transtornos do Comportamento Infantil , Emergências , Transtornos Mentais , Humanos , Masculino , Feminino , Criança , Adolescente , Transtornos Mentais/terapia , Serviços Médicos de Emergência , Transtornos do Comportamento Infantil/terapia , Pessoal de Saúde , Serviços de Saúde MentalRESUMO
ABSTRACT: Hospital incident command systems (HICS) were implemented to expand mental and behavioral healthcare (MBHC) services during the COVID-19 pandemic. Data on patient census, nurse vacancies, staff injuries, and staff perceptions were analyzed to quantify issues and track progress toward HICS goals. Data, environment of care, staffing, staff support, staff education, and communication resources were developed. After HICS implementation, 84% of nurses reported confidence in providing care to youth with acute MBHC needs. Nurse leaders should consider HICS for addressing other crises.
Assuntos
COVID-19 , Adolescente , Humanos , Criança , Pandemias , HospitaisRESUMO
Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.
Assuntos
Serviços Médicos de Emergência , Transtornos Mentais , Humanos , Criança , Adolescente , Emergências , Transtornos Mentais/diagnóstico , Transtornos Mentais/terapia , Serviço Hospitalar de Emergência , Ideação SuicidaRESUMO
OBJECTIVE: To compare new mental health diagnoses (NMHD) in children after a firearm injury versus following a motor vehicle collision (MVC). BACKGROUND: A knowledge gap exists regarding childhood mental health diagnoses following firearm injuries, notably in comparison to other forms of traumatic injury. METHODS: We utilized Medicaid MarketScan claims (2010-2016) to conduct a matched case-control study of children ages 3 to 17 years. Children with firearm injuries were matched with up to 3 children with MVC injuries. Severity was determined by injury severity score and emergency department disposition. We used multivariable logistic regression to measure the association of acquiring a NMHD diagnosis in the year postinjury after firearm and MVC mechanisms. RESULTS: We matched 1450 children with firearm injuries to 3691 children with MVC injuries. Compared to MVC injuries, children with firearm injuries were more likely to be black, have higher injury severity score, and receive hospital admission from the emergency department ( P <0.001). The adjusted odds ratio (aOR) of NMHD diagnosis was 1.55 [95% confidence interval (95% CI): 1.33-1.80] greater after firearm injuries compared to MVC injuries. The odds of a NMHD were higher among children admitted to the hospital compared to those discharged. The increased odds of NMHD after firearm injuries was driven by increases in substance-related and addictive disorders (aOR: 2.08; 95% CI: 1.63-2.64) and trauma and stressor-related disorders (aOR: 2.07; 95% CI: 1.55-2.76). CONCLUSIONS: Children were found to have 50% increased odds of having a NMHD in the year following a firearm injury as compared to MVC. Programmatic interventions are needed to address children's mental health following firearm injuries.
Assuntos
Armas de Fogo , Ferimentos por Arma de Fogo , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Saúde Mental , Veículos Automotores , Estudos Retrospectivos , Estados Unidos/epidemiologia , Ferimentos por Arma de Fogo/epidemiologia , Ferimentos por Arma de Fogo/terapiaRESUMO
Certain comorbidities known to increase the risk of poor outcomes in COVID-19 exist at higher rates in people with HIV; people aging with HIV (PAWH) face additional risk due to the association of advanced age with COVID-19 mortality. Cognitive and functional deficits and social barriers have been identified in cohorts of people aging with HIV. It is postulated that the COVID-19 pandemic potentially threatens PAWH disproportionately to the general population, both in mortality risk due to age and comorbidities, and in potential deleterious effects of policies that seek to drastically limit in-person interaction and access to healthcare systems. A description of and preliminary data from a demonstration project to improve geriatric assessments of people with HIV over age 50 in an urban HIV clinic are presented, in support of this theory. Advice is offered on key strategies utilized to continue to provide care to PAWH during the COVID-19 pandemic, including transition to telemedicine, vaccination, revision of staff roles, repurposing of funding, and a new reliance on available local resources.
Assuntos
COVID-19 , Infecções por HIV , Humanos , Idoso , Pessoa de Meia-Idade , COVID-19/psicologia , SARS-CoV-2 , Pandemias/prevenção & controle , HIV , Infecções por HIV/epidemiologia , EnvelhecimentoRESUMO
OBJECTIVES: The Women in Pediatric Emergency Medicine (PEM) subcommittee of the American Academy of Pediatrics Section on Emergency Medicine identified 2 top priorities for 2021: career development and mentorship/sponsorship. The objective of this study was to catalog and delineate the career development domains for women physicians in PEM. METHODS: After a review of the literature to identify the key areas for gaps for women in PEM, we used Q sort methodology to elicit domains for this subcommittee to address by survey of a national sample. RESULTS: One hundred fourteen discrete potential areas of interest for career development were identified by the working group based on salient themes from the literature and personal experiences. Forty-one Women in PEM subcommittee members (27%) completed the survey. The career development topics were sorted into the domains of personal (40.4%; n = 46), administrative (28.1%; n = 32), research (10.5%; n = 12), teaching (10.5%; n = 12), service (7.0%; n = 8), and clinical (3.5%; n = 4). CONCLUSIONS: This study demonstrates that the career development needs of women in PEM include a range of personal, teaching, research, administrative, clinical, and service domains. However, more than two-thirds of the career development topics were categorized into just 2 domains, administrative and personal.
Assuntos
Medicina de Emergência , Medicina de Emergência Pediátrica , Criança , Medicina de Emergência/educação , Feminino , Humanos , Inquéritos e Questionários , Estados UnidosRESUMO
OBJECTIVES: To compare emergency department (ED) visit rates for suicidal ideation and/or self-harm among youth by urban-rural location of residence. STUDY DESIGN: This is a retrospective analysis of ED visits for suicidal ideation and/or self-harm by youths aged 5-19 years (n = 297 640) in the 2016 Nationwide Emergency Department Sample, a representative sample of all US ED visits. We used weighted Poisson generalized linear models to compare population-based visit rates by urban-rural location of patient residence, adjusted for age, sex, and US Census region. For self-harm visits, we compared injury mechanisms by urban-rural location. RESULTS: Among patients with ED visits for suicidal ideation and/or self-harm, the median age was 16 years, 65.9% were female, 15.9% had a rural location of patient residence, and 0.1% resulted in mortality. The adjusted ED visit rate for suicidal ideation/or and self-harm did not differ significantly by urban-rural location. For the subset of visits for self-harm, the adjusted visit rate was significantly higher in small metropolitan (adjusted incidence rate ratio [aIRR], 1.39; 95% CI, 1.01-1.90), micropolitan (aIRR, 1.46; 95% CI, 1.10-1.93), and noncore areas (aIRR, 1.39; 95% CI, 1.03-1.87) compared with large metropolitan areas. When stratified by injury mechanism, ED visit rates for self-inflicted firearm injuries were higher among youths living in rural areas compared with those in urban areas (aIRR, 3.03; 95% CI, 1.32-6.74). CONCLUSIONS: Compared with youths living in urban areas, youths living in rural areas had higher ED visit rates for self-harm, including self-inflicted firearm injuries. Preventive approaches for self-harm based in community and ED settings might help address these differences.
Assuntos
Serviço Hospitalar de Emergência , População Rural/estatística & dados numéricos , Comportamento Autodestrutivo/epidemiologia , Ideação Suicida , População Urbana/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
OBJECTIVES: To evaluate the trends and hospital variation in the use of pharmacologic restraint among pediatric mental health visits in the emergency department (ED). STUDY DESIGN: We examined ED visits with a mental health diagnosis in patients aged 3-21 years at children's hospital EDs from 2009 to 2019. We calculated the frequency of pharmacologic restraint use and determined visit characteristics associated with restraint use. We calculated cumulative percent change for visits with restraints and for all mental health visits. We used logistic regression to test trends over time and evaluate hospital variation in the frequency of restraint use. RESULTS: We identified 389 885 mental health ED visits (54.9% female, median age 14.3 years) and 13 643 (3.5%) visits with pharmacologic restraint use. Characteristics associated with pharmacologic restraint use were late adolescent age (18-21 years), male sex, Black race, non-Latino ethnicity, public insurance, and admission to the hospital (P < .001). During the study period, both mental health ED visits increased by 268% and mental health ED visits with pharmacologic restraint use increased by 370%. The rate of pharmacologic restraint in this patient population remained constant. Hospital use of pharmacologic restraint for mental health visits varied significantly across hospitals (1.6%-11.8%, P < .001). CONCLUSIONS: Pediatric mental health ED visits with and without pharmacologic restraint are increasing over time. In addition, the overall number of pharmacologic restraint use has increased threefold. Significant hospital variation in pharmacologic restraint use signifies an opportunity for standardization of care and restraint reduction.
Assuntos
Antipsicóticos/administração & dosagem , Serviço Hospitalar de Emergência , Hospitais Pediátricos , Serviços de Saúde Mental , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Injeções Intramusculares , Injeções Intravenosas , Masculino , Assistência Médica/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Fatores Raciais , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Conjugal cell-cell contact between strains of Mycobacterium smegmatis induces the esxUT transcript, which encodes the putative primary substrates of the ESAT-6 secretion system 4 (ESX-4) secretion system. This recipient response was required for conjugal transfer of chromosomal DNA from the donor strain. Here we show that the extracytoplasmic σ factor, SigM, is a cell contact-dependent activator of ESX-4 expression and is required for conjugal transfer of DNA in the recipient strain. The SigM regulon includes genes outside the seven-gene core esx4 locus that we show are also required for conjugation, and we show that some of these SigM-induced proteins likely function through ESX-4. A fluorescent reporter revealed that SigM is specifically activated in recipient cells in direct contact with donor cells. Coculture RNA-seq experiments indicated that SigM regulon induction occurred early and before transconjugants are detected. This work supports a model wherein donor contact with the recipient cell surface inactivates the transmembrane anti-SigM, thereby releasing SigM. Free SigM induces an extended ESX-4 secretion system, resulting in changes that facilitate chromosomal transfer. The contact-dependent inactivation of an extracytoplasmic σ-factor that tightly controls ESX-4 activity suggests a mechanism dedicated to detect, and appropriately respond to, external stimuli from mycobacteria.
Assuntos
Proteínas de Bactérias , Conjugação Genética/fisiologia , Regulação Bacteriana da Expressão Gênica/fisiologia , Mycobacterium smegmatis , Fatores de Transcrição , Sistemas de Secreção Tipo IV , Sistemas de Secreção Tipo VII , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Redes Reguladoras de Genes/fisiologia , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sistemas de Secreção Tipo IV/genética , Sistemas de Secreção Tipo IV/metabolismo , Sistemas de Secreção Tipo VII/genética , Sistemas de Secreção Tipo VII/metabolismoRESUMO
ABSTRACT: When youth in the emergency department become acutely agitated, it can be dangerous and distressing to patients, families, and clinicians. Timely, effective, and patient-centered management is key to reducing the potential for patient and staff injury while preserving patient dignity. We review the definition of agitation and pharmacologic management for youth with acute agitation, including common classes of medications, indications for use, and adverse effects. We also discuss the need to integrate the use of medications into a comprehensive strategy for agitation management that begins with proactive prevention of aggressive behavior, creation of a therapeutic treatment environment, and verbal de-escalation strategies.
Assuntos
Serviço Hospitalar de Emergência , Agitação Psicomotora , Adolescente , Humanos , Agitação Psicomotora/tratamento farmacológicoRESUMO
Isolated amnesia is an uncommon presenting complaint in the pediatric age group. We report the case of an 18-year-old woman who presented with the acute onset of memory difficulty and an otherwise normal neurologic examination. Brain magnetic resonance imaging demonstrated inflammation in the bilateral temporal lobes. Serum and cerebrospinal fluid testing ultimately revealed a diagnosis of autoimmune encephalitis. Although rare, the acute onset of isolated amnesia deserves a prompt, comprehensive evaluation.
Assuntos
Amnésia Anterógrada/etiologia , Encefalite/diagnóstico , Doença de Hashimoto/diagnóstico , Receptores de AMPA/imunologia , Lobo Temporal/patologia , Adolescente , Amnésia Anterógrada/diagnóstico , Autoanticorpos/sangue , Encéfalo/diagnóstico por imagem , Encefalite/complicações , Feminino , Doença de Hashimoto/complicações , Humanos , Imageamento por Ressonância Magnética , Lobo Temporal/diagnóstico por imagemRESUMO
BACKGROUND & AIMS: Cure rates in response to retreatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are high, but this regimen has not been studied in patients with a history of poor adherence or treatment interruption, nor in patients with HIV/HCV coinfection. Herein, we aimed to assess the safety and efficacy of this combination in patients with genotype 1 HCV infection who had relapsed following combination direct-acting antiviral (DAA) therapy, regardless of HIV infection or previous treatment course. METHODS: The RESOLVE study was a multicenter, open-label, phase IIb study investigating the safety, tolerability and efficacy of SOF/VEL/VOX in 77 patients with virologic rebound following combination DAA therapy. Efficacy was defined as HCV RNA below the lower limit of detection 12â¯weeks after the end of treatment (SVR12), while safety endpoints included the incidence of grade 3 and 4 adverse events (AEs) following treatment, and the proportion of patients who stopped treatment prematurely due to AEs. RESULTS: In an intent-to-treat analysis, 70/77 (90.9%, 95% CI 82.1-95.8%) patients achieved SVR12, including 14/17 (82.4%) HIV coinfected participants and 18/22 (81.8%) of those with previous non-completion of DAA therapy. In an analysis of all patients who completed 12â¯weeks of study medication, 70/71 patients (99%) achieved SVR12. One patient experienced a grade 3 AE, and 4 experienced a grade 4 AE, all unrelated to study participation. Reported AEs were similar in HIV-coinfected patients, and patients receiving dolutegravir-based antiretroviral treatment experienced no clinically significant increases in aminotransferases. CONCLUSION: Retreatment with 12â¯weeks of SOF/VEL/VOX was safe and effective in patients with relapsed HCV following initial combination DAA-based treatment. Treatment response was not affected by HIV coinfection or previous treatment course. LAY SUMMARY: Twelve weeks of the combination of direct-acting antivirals (SOF/VEL/VOX) was safe and effective in patients with relapsed hepatitis C virus infection who had previously received combination therapy with direct-acting antivirals. Treatment response was not diminished by HIV coinfection, or non-completion of previous direct-acting antiviral-based therapy.
Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Infecções por HIV/complicações , HIV-1/genética , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Macrocíclicos/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Idoso , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , Ciclopropanos , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Compostos Macrocíclicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prolina/análogos & derivados , Quinoxalinas , RNA Viral/genética , Recidiva , Sofosbuvir/efeitos adversos , Sulfonamidas/efeitos adversosRESUMO
OBJECTIVE: To determine demographic and clinical risk factors associated with boarding (length of stay ≥24â¯h) for pediatric mental health emergency department (ED) visits. METHODS: This is a retrospective cross-sectional analysis of mental health visits identified by diagnosis codes for children 5-18â¯years old presenting to a tertiary pediatric ED in 2016. We performed multivariate logistic regression to identify demographic and clinical factors associated with boarding. RESULTS: There were 1746 mental health visits and 386 (22%) visits had length of stay ≥24â¯h. In the multivariate logistic regression model, factors associated with boarding included: private insurance (OR 1.59, 95% CI 1.15, 2.19) and having both private and public insurance (OR 1.68, 95% CI 1.16, 2.43) relative to public insurance; presentation during a school month (OR 2.17, 95% CI 1.30, 3.63); physical or chemical restraint use (OR 4.80, 95% CI 2.61, 8.84); comorbid autism or developmental delay (OR 1.82, 95% CI 1.35, 2.46); prior psychiatric hospitalization (OR 2.55, 95% CI 1.93, 3.36); and reasons for presentation of agitation, aggression, or homicidal ideation (OR 2.76, 95% CI 1.40, 5.45), depression, self-injury, or suicidal ideation (OR 2.79, 95% CI 1.45, 5.40), and bipolar, mania, or psychosis (OR 5.78, 95% CI 2.36, 14.09) relative to anxiety. CONCLUSIONS: Insurance status, presentation month, restraint use, autism or developmental delay comorbidity, prior psychiatric hospitalization, and reason for presentation are associated with pediatric mental health ED boarding. Resources should be directed to improve the mental health care system for children with identified risk factors for boarding.
Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Transtornos Mentais/terapia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Before the wide availability of antiretroviral therapy (ART), tuberculosis and human immunodeficiency virus (HIV) disease among pregnant women resulted in poor maternal and neonatal outcomes, including high rates of mother-to-child transmission of both HIV and tuberculosis. We aimed to describe the impact of tuberculosis among HIV-infected mothers on obstetric and infant outcomes in a population with access to ART. Methods: In this prospective cohort study, we followed up HIV-infected pregnant women with or without tuberculosis disease from January 2011 through January 2014 in Soweto, South Africa. Two controls were enrolled for each case patient, matched by enrollment time, maternal age, gestational age, and planned delivery clinic and followed up for 12 months after delivery. Results: We recruited 80 case patients and 155 controls, resulting in 224 live-born infants. Infants of mothers with HIV infection and tuberculosis disease had a higher risk of low birth weight (20.8% vs 10.7%; P = .04), prolonged hospitalization at birth (51% vs 16%; P < .001), infant death (68 vs 7 deaths per 1000 births; P < .001), and tuberculosis disease (12% vs 0%; P < .001) despite appropriate maternal therapy and infant tuberculosis preventive therapy. HIV transmission was higher among these infants (4.1% vs 1.3%; P = .20), though this difference was not statistically significant. Obstetric outcomes in coinfected women were also poorer with higher risks of maternal hospitalization (25% vs 11%; P = .005) and preeclampsia (5.5% vs 0.7%; P = .03). Conclusions: Tuberculosis in HIV coinfected pregnant women remains a significant threat to the health of both mothers and infants. Improving tuberculosis prevention and early diagnosis among pregnant women is critical.
Assuntos
Infecções por HIV/complicações , Mortalidade Infantil , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Tuberculose/complicações , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Feminino , Idade Gestacional , Infecções por HIV/tratamento farmacológico , HIV-1 , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Mães , Pré-Eclâmpsia , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , África do Sul/epidemiologia , Tuberculose/tratamento farmacológico , Adulto Jovem , Zidovudina/uso terapêuticoRESUMO
Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis. Infants born to mothers with TB also received RH preventive therapy. Infant plasma nevirapine concentrations were measured at 1 and 6 weeks. The effects of RH preventive therapy on nevirapine disposition were investigated in a population pharmacokinetic model. Results: Of 164 infants undergoing pharmacokinetic sampling, 46 received RH preventive therapy. After adjusting for weight using allometric scaling, the model estimated a 33% reduction in nevirapine trough concentrations with RH preventive therapy compared with TB-unexposed infants not receiving concomitant rifampicin and a 30% decline in trough concentrations in a typical infant between day 7 and 35 post-partum. Conclusions: Rifampicin-based TB preventative treatment reduces nevirapine concentrations significantly in HIV-exposed infants. Although the nevirapine exposures required to prevent HIV acquisition in breastfeeding infants are undefined, given the potential risks associated with underdosing nevirapine in this setting, it is prudent to avoid rifampicin-based preventive therapy in HIV-exposed children receiving prophylactic nevirapine.
Assuntos
Fármacos Anti-HIV/sangue , Antituberculosos/uso terapêutico , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Isoniazida/uso terapêutico , Nevirapina/sangue , Rifampina/uso terapêutico , Tuberculose/prevenção & controle , Adulto , Fármacos Anti-HIV/administração & dosagem , Antituberculosos/sangue , Antituberculosos/farmacocinética , Aleitamento Materno , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Nevirapina/administração & dosagem , Profilaxia Pós-Exposição , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , Tuberculose/complicaçõesRESUMO
BACKGROUND: Pregnancy and tuberculosis treatment or prophylaxis can affect efavirenz pharmacokinetics, maternal human immunodeficiency virus type 1 (HIV-1) treatment outcomes, and mother-to-child transmission (MTCT) risk. METHODS: We evaluated a prospective cohort of pregnant, HIV-infected women with and without tuberculosis in Soweto, South Africa. Pharmacokinetic sampling was performed at gestation week 37 and during the postpartum period. Efavirenz trough concentrations (Cmin) were predicted using population pharmacokinetic models. HIV-viral load was measured at delivery for mothers and at 6 weeks of age for infants. RESULTS: Ninety-seven women participated; 44 had tuberculosis. Median efavirenz Cmin during pregnancy was 1.35 µg/mL (interquartile range [IQR], 0.90-2.07 µg/mL; 27% had an efavirenz Cmin of < 1 µg/mL), compared with a median postpartum value of 2.00 µg/mL (IQR, 1.40-3.59 µg/mL; 13% had an efavirenz Cmin of < 1 µg/mL). A total of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz Cmin of <1 µg/mL. Rifampin did not reduce the efavirenz Cmin. Isoniazid (for prophylaxis or treatment), though, reduced the rate of efavirenz clearance. At delivery, median durations of ART were 13 weeks (IQR, 9-18 weeks) and 21 weeks (IQR, 13-64 weeks) for women with and those without tuberculosis, respectively; 55% and 83%, respectively, had a viral load of <20 copies/mL (P = .021). There was 1 case of MTCT. CONCLUSIONS: Pregnancy increased the risk of low efavirenz concentrations, but MTCT was rare. A detectable HIV-viral load at delivery was more common among pregnant women with tuberculosis, in whom ART was generally initiated later.
Assuntos
Fármacos Anti-HIV/farmacocinética , Benzoxazinas/farmacocinética , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adolescente , Adulto , Alcinos , Fármacos Anti-HIV/administração & dosagem , Benzoxazinas/administração & dosagem , Estudos de Coortes , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Ciclopropanos , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Plasma/química , Plasma/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , África do Sul , Tuberculose/complicações , Carga Viral , Adulto JovemRESUMO
Effective treatment of tuberculosis during pregnancy is essential for preventing maternal and fetal mortality, but little is known about the effects of pregnancy on the disposition of antituberculosis drugs. We explored the effects of pregnancy on the pharmacokinetics of rifampin, the key sterilizing drug in tuberculosis treatment, in Tshepiso, a prospective cohort study involving pregnant HIV-infected women with or without tuberculosis in Soweto, South Africa. Participants receiving standard first-line tuberculosis treatment underwent sparse sampling for rifampin at 37 weeks' gestation or delivery and then postpartum. Cord blood was collected when possible. A population pharmacokinetic model was developed to investigate the effects of pregnancy on rifampin pharmacokinetics. Among the 48 participants, median age and weight were 28 years and 67 kg, respectively. A one-compartment model with first-order elimination, transit compartment absorption, and allometric scaling described the data well. Pregnancy reduced rifampin clearance by 14%. The median (interquartile range) model-estimated rifampin area under the concentration-time curve over 24 h (AUC0-24) during pregnancy or intrapartum was 40.8 h · mg/liter (27.1 to 54.2 h · mg/liter) compared to 37.4 h · mg/liter (26.8 to 50.3 h · mg/liter) postpartum. The maximum concentrations were similar during pregnancy and postpartum. Rifampin was detectable in 36% (8/22) of cord blood samples, and 88% (42/48) of the women had successful treatment outcomes. There was one case of perinatal tuberculosis. In conclusion, rifampin clearance is modestly reduced during the last trimester of pregnancy. Exposures are only slightly increased, so dose adjustment during pregnancy is not needed. Rifampin was detected in cord blood samples when delivery occurred soon after dosing. The consequences of exposure to this potent inducer of metabolizing enzymes among HIV-exposed infants are unclear.
Assuntos
Antibióticos Antituberculose/farmacocinética , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Adulto , Antibióticos Antituberculose/uso terapêutico , Área Sob a Curva , Estudos de Coortes , Coinfecção/tratamento farmacológico , Feminino , Sangue Fetal/efeitos dos fármacos , Humanos , Recém-Nascido , Período Pós-Parto , Gravidez , Estudos Prospectivos , Rifampina/uso terapêutico , África do Sul , Resultado do TratamentoRESUMO
Suicide is a leading cause of death among youth, and the emergency department (ED) serves as the primary point of healthcare contact for many with suicidal ideation. As suicide-related presentations to the ED continue to rise, the implementation of time- and cost-effective care pathways becomes ever more critical. Evidence-based tools for the identification and stratification of suicide risk can aid in clinical decision-making and care linkage. This issue reviews best practices for suicide risk assessment of youth to guide evaluation, management, and disposition planning within the ED setting.