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The ability of antibodies to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important correlate of protection. For routine evaluation of protection, however, a simple and cost-efficient anti-SARS-CoV-2 serological assay predictive of serum neutralizing activity is needed. We analyzed clinical epidemiological data and blood samples from two cohorts of health care workers in Barcelona and Munich to compare several immunological readouts for evaluating antibody levels that could be surrogates of neutralizing activity. We measured IgG levels against SARS-CoV-2 spike protein (S), its S2 subunit, the S1 receptor binding domain (RBD), and the full length and C terminus of nucleocapsid (N) protein by Luminex, and against RBD by enzyme-linked immunosorbent assay (ELISA), and assessed those as predictors of plasma surrogate-neutralizing activity measured by a flow cytometry assay. In addition, we determined the clinical and demographic factors affecting plasma surrogate-neutralizing capacity. Both cohorts showed a high positive correlation between IgG levels to S antigen, especially to RBD, and the levels of plasma surrogate-neutralizing activity, suggesting RBD IgG as a good correlate of plasma neutralizing activity. Symptomatic infection, with symptoms such as loss of taste, dyspnea, rigors, fever and fatigue, was positively associated with anti-RBD IgG positivity by ELISA and Luminex, and with plasma surrogate-neutralizing activity. Our serological assays allow for the prediction of serum neutralization activity without the cost, hazards, time, and expertise needed for surrogate or conventional neutralization assays. Once a cutoff is established, these relatively simple high-throughput antibody assays will provide a fast and cost-effective method of assessing levels of protection from SARS-CoV-2 infection. IMPORTANCE Neutralizing antibody titers are the best correlate of protection against SARS-CoV-2. However, current tests to measure plasma or serum neutralizing activity do not allow high-throughput screening at the population level. Serological tests could be an alternative if they are proved to be good predictors of plasma neutralizing activity. In this study, we analyzed the SARS-CoV-2 serological profiles of two cohorts of health care workers by applying Luminex and ELISA in-house serological assays. Correlations of both serological tests were assessed between them and with a flow cytometry assay to determine plasma surrogate-neutralizing activity. Both assays showed a high positive correlation between IgG levels to S antigens, especially RBD, and the levels of plasma surrogate-neutralizing activity. This result suggests IgG to RBD as a good correlate of plasma surrogate-neutralizing activity and indicates that serology of IgG to RBD could be used to assess levels of protection from SARS-CoV-2 infection.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Neutralizantes , Personal de Salud , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
Evidence suggests an increasing number of US families are adopting internationally born children with HIV (IACH). Little is known about the experiences of adoptive parents, particularly how they help children navigate adolescence. Many adopted children may have additional needs as they mature into adolescence. Forty-four parents of 51 IACH were recruited from three pediatric infectious disease clinics and social media sites. The majority identified as white (n = 43), Christian (n = 38), and female (n = 43). Mean age of adoptees was 10.1 years (range 3-19, 33 females, 25 from African countries, and Russia, Ukraine, China, Haiti, Columbia, Estonia). Participants completed semi-structured audio-recorded interviews focused on experienced and potential challenges as their child matures. Interviews were coded for emergent themes. Findings identified universal concerns about sexuality. Some parents had not yet discussed sex with their child due to age/level of maturity. Others stated they had "the talk" and some emphasized the importance of abstinence before marriage while others highlighted the importance of comprehensive sex education and open communication. Finally, parents acknowledged that HIV was a manageable illness and hoped their children lived long healthy lives. Medical and mental health clinicians can support families as their child transitions into adolescence.
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Infecciones por VIH , Niño , Humanos , Adolescente , Femenino , Preescolar , Infecciones por VIH/psicología , VIH , Salud Reproductiva , Investigación Cualitativa , Padres/psicologíaRESUMEN
BACKGROUND: COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytomegalovirus (CMV)-specific T cells with some cross-reactivity to SARS-CoV-2 in a COVID-19 intensive care unit (ICU) patient, we decided to investigate whether CMV seropositivity is associated with severe or critical COVID-19. Herpes simplex virus (HSV) serostatus was investigated as control. METHODS: National German COVID-19 bio-sample and data banks were used to retrospectively analyze the CMV and HSV serostatus of patients who experienced mild (n = 101), moderate (n = 130) or severe to critical (n = 80) disease by IgG serology. We then investigated the relationship between disease severity and herpesvirus serostatus via statistical models. RESULTS: Non-geriatric patients (< 60 years) with severe COVID-19 were found to have a very high prevalence of CMV-seropositivity, while CMV status distribution in individuals with mild disease was similar to the prevalence in the German population; interestingly, this was not detectable in older patients. Prediction models support the hypothesis that the CMV serostatus, unlike HSV, might be a strong biomarker in identifying younger individuals with a higher risk of developing severe COVID-19, in particular in absence of other co-morbidities. CONCLUSIONS: We identified 'CMV-seropositivity' as a potential novel risk factor for severe COVID-19 in non-geriatric individuals in the studied cohorts. More mechanistic analyses as well as confirmation of similar findings in cohorts representing the currently most relevant SARS-CoV-2 variants should be performed shortly.
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COVID-19 , Infecciones por Citomegalovirus , Herpes Simple , Anciano , Anticuerpos Antivirales , COVID-19/epidemiología , Citomegalovirus , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/epidemiología , Humanos , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8+ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8+ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8+ TCRs-classic features of protective immunity-are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8+ T cell immunity.
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Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , SARS-CoV-2/inmunología , Adulto , Células Cultivadas , Reacciones Cruzadas/inmunología , Epítopos de Linfocito T/inmunología , Femenino , Humanos , Epítopos Inmunodominantes/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Masculino , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Deficiencies in smell and taste are common symptoms of COVID-19. Quantitative losses are well surveyed. This study focuses on qualitative changes such as phantosmia (hallucination of smell), parosmia (alteration of smell), and dysgeusia (alteration of taste) and possible connections with the adaptive immune system. Subjective experience of deficiency in taste and smell was assessed by two different questionnaires after a median of 100 and 244 days after first positive RT-PCR test. SARS-CoV-2-specific antibody levels were measured with the iFlash-SARS-CoV-2 assay. After 100 days a psychophysical screening test for olfactory and gustatory dysfunction was administered. 30 of 44 (68.2%) participants reported a chemosensory dysfunction (14 quantitative, 6 qualitative, 10 quantitative, and qualitative) during COVID-19, eleven (25.0%) participants (1 quantitative, 7 qualitative, 3 quantitative, and quantity) after 100 days, and 14 (31.8%) participants (1 quantitative, 10 qualitative, 3 quantitative and qualitative) after 244 days. Four (9.1%) participants, who were symptom-free after 100 days reported now recently arisen qualitative changes. Serological and T-cell analysis showed no correlation with impairment of taste and smell. In conclusion, qualitative changes can persist for several months and occur as late-onset symptoms months after full recovery from COVID-19-induced quantitative losses in taste and smell.
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OBJECTIVE: To evaluate whether there is an increased risk of neurologic diagnoses in children who are HIV-exposed but uninfected (CHEU) exposed in utero to specific antiretroviral medications. DESIGN: Prospective cohort study of CHEU enrolled from 2007 to 2017. METHODS: We evaluated children for neurologic case status, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic disorders. Adjusted relative risks (aRRs) were estimated for the association between in-utero antiretroviral exposure and neurologic case using log-binomial regression, accounting for potential confounders. Sensitivity analyses were conducted to evaluate robustness of findings. RESULTS: Among 3747 eligible CHEU, 231 (6.2%) met neurologic case criteria (95% CI 5.4--7%). Most eligible children (86%) were exposed in utero to combination antiretroviral regimens. In adjusted models, children exposed to efavirenz at any time during pregnancy had higher risk of neurologic case status (aRRâ=â1.53, 95% CI 0.94--2.51). This association was stronger when comparing efavirenz exposure at conception to no exposure during pregnancy (aRRâ=â1.92, 95% CI 1.09--3.36) and considering follow-up and case diagnosis only through age 2 (aRRâ=â2.14, 95% CI 1.11--4.12). Children exposed to didanosine at conception and during the first trimester had increased risk of neurologic case status (aRRâ=â2.28, 95% CI 1.07--4.87 and aRRâ=â2.02, 95% CI 1.01--4.04, respectively), compared with didanosine-unexposed children. Children with dolutegravir exposure had some suggestion of increased risk of neurologic case (aRRâ=â2.43, 95% CI 0.75--7.84), which was observed consistently across several sensitivity analyses. CONCLUSION: Efavirenz and didanosine exposure during pregnancy were associated with higher risk of neurologic abnormalities in CHEU, and dolutegravir exposure showed some suggestive associations, which warrant further monitoring.
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Fármacos Anti-VIH/efectos adversos , Didanosina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Microcefalia/etiología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Anomalías Inducidas por Medicamentos/epidemiología , Adulto , Fármacos Anti-VIH/uso terapéutico , Niño , Preescolar , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/transmisión , Humanos , Masculino , Microcefalia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: In newborns with gastroschisis, both primary repair and delayed fascial closure with initial silo placement are considered safe with similar outcomes although cost differences have not been explored. METHODS: A retrospective review was performed of newborns admitted with gastroschisis at a single center from 2011 to 2016. Demographic, clinical, and cost data during the initial hospitalization were collected. Differences between procedure costs and clinical endpoints were analyzed using multivariable linear regression adjusting for prematurity, complicated gastroschisis, and performance of additional operations. RESULTS: 80 patients with gastroschisis met inclusion criteria. Rates of primary fascial, primary umbilical cord closure, and delayed closure were 14%, 65%, and 21%, respectively. Delayed closure was associated with an increase in total hospital costs by 57% compared to primary repair (p < 0.001). In addition, delayed closure was associated with increased total and NICU LOS (p < 0.05), parenteral nutrition duration (p = 0.02), ventilator days (p < 0.001), time to goal enteral feeds (p = 0.01), and all cost sub-categories except ward room costs (p < 0.01). CONCLUSION: Delayed fascial closure was associated with significantly greater hospital costs during the index admission.
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Fasciotomía/economía , Gastrosquisis/economía , Gastrosquisis/cirugía , Costos de Hospital/estadística & datos numéricos , Técnicas de Cierre de Heridas/economía , Femenino , Humanos , Recién Nacido , Tiempo de Internación/economía , Masculino , Nutrición Parenteral/economía , Factores de TiempoAsunto(s)
Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Adolescente , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Niño , Femenino , Volumen Espiratorio Forzado , Infecciones por VIH/inmunología , Infecciones por VIH/fisiopatología , Infecciones por VIH/transmisión , Humanos , Kenia , Pulmón/fisiopatología , Recuento de Linfocitos , Masculino , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Perinatal HIV transmission has substantially decreased with combination antiretroviral regimens, but complications in children who are HIV-exposed but uninfected, such as microcephaly, warrant ongoing surveillance. We aimed to evaluate whether individual in utero antiretroviral exposures were associated with increased risk of microcephaly based on long-term follow-up of infants and children who are HIV-exposed but uninfected. METHODS: We evaluated children aged younger than 18 years who were HIV-exposed but uninfected with at least one head circumference measurement while enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study at 22 clinical sites in the USA, including Puerto Rico. This prospective cohort study was done by the Pediatric HIV/AIDS Cohort Study network. Microcephaly was defined as having a head circumference Z score <-2 according to the 2000 US Centers for Disease Control and Prevention growth charts for children 6-36 months old and according to Nellhaus standards (head circumference <2nd percentile) after 36 months (SMARTT criteria); an alternate definition for microcephaly was based on applying Nellhaus standards across all ages (Nellhaus criteria). Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero antiretroviral exposure and microcephaly status, adjusted for potential confounders. Neurodevelopmental functioning was compared in children who are HIV-exposed but uninfected with or without microcephaly. FINDINGS: Between March 21, 2007, and Aug 1, 2017, 3055 participants enrolled in SMARTT had at least one head circumference measurement. The cumulative incidence of microcephaly over a median of 5·1 years of follow-up (IQR 3·0-7·2) was 159 (5·2%, 95% CI 4·4-6·1) by Nellhaus criteria and 70 (2·3%, 1·8-2·9) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4·7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (adjusted RR 2·02, 95% CI 1·16-3·51) and SMARTT criteria (2·56, 1·22-5·37). These associations were more pronounced in children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine than those including tenofovir plus emtricitabine. Protective associations were observed for darunavir exposure (adjusted RR 0·50, 95% CI 0·24-1·00). Children who are HIV-exposed but uninfected with microcephaly had lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment than those without microcephaly. INTERPRETATION: These findings support consideration of alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.
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Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Microcefalia/etiología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adolescente , Adulto , Alquinos , Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/efectos adversos , Benzoxazinas/uso terapéutico , Niño , Preescolar , Ciclopropanos , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Lactante , Lamivudine/efectos adversos , Lamivudine/uso terapéutico , Masculino , Microcefalia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Puerto Rico , Tenofovir/efectos adversos , Tenofovir/uso terapéutico , Adulto Joven , Zidovudina/efectos adversos , Zidovudina/uso terapéuticoRESUMEN
BACKGROUND: Late human immunodeficiency virus (HIV) diagnosis after severe co-morbidity remains common in resource-limited settings. Neurodevelopmental recovery during antiretroviral therapy (ART) for late-diagnosed children is understudied. We determined 6-month neurodevelopmental trajectories in HIV-infected children initiating ART during hospitalization. METHODS: HIV-infected children initiated ART after HIV diagnosis during hospitalization in Kenya. The Malawi Developmental Assessment Tool was administered after clinical stabilization within 1 month and at 6 months post-ART initiation. Baseline versus 6-month Z scores for each developmental domain were compared; cofactors for change in Z scores were evaluated using linear regression. RESULTS: Among 74 children, median age was 1.7 years (interquartile range, 0.8-2.4) and median Z scores for gross motor, fine motor, social and language domains were -1.34, -1.04, -0.53 and -0.95, respectively. At baseline, children with higher plasma viremia had lower social Z scores (P = 0.008). Better nourished (weight-for-age Z score [WAZ] ≥-2) children had higher Z scores in all developmental domains (all P values ≤0.05). After 6 months on ART (n = 58), gross and fine motor Z scores improved significantly (mean change 0.39; P = 0.007 and 0.43; P = 0.001, respectively), but social and language did not. Children with better immune and growth response to ART had higher gains in gross motor (0.05 per unit-gain CD4%; P = 0.04; 0.34 per unit-gain WAZ; P = 0.006 and 0.44 per unit-gain height-for-age Z score; P = 0.005), social (0.37 per unit-gain WAZ; P = 0.002) and language (0.25 per unit-gain height-for-age Z score; P = 0.01). CONCLUSIONS: Children had significant neurodevelopmental gains during 6 months of ART, and children with better growth and immune recovery had greater improvement. Prompt commencement of ART may improve neurodevelopment in addition to immunity and growth.
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Fármacos Anti-VIH/uso terapéutico , Sistema Nervioso Central/crecimiento & desarrollo , Desarrollo Infantil , Infecciones por VIH/tratamiento farmacológico , Antropometría , Terapia Antirretroviral Altamente Activa , Estatura , Peso Corporal , Preescolar , Femenino , Infecciones por VIH/diagnóstico , Humanos , Lactante , Malaui , Masculino , Resultado del TratamientoRESUMEN
Lyme disease is a common tick-borne infection caused by Borrelia burgdorferi in the United States, where infection is most prevalent in the northeastern and mid-Atlantic states. Although classically associated with erythema migrans, Lyme disease caused by Borrelia species found in Europe may also present with other cutaneous findings. Here we report the case of a girl who was clinically diagnosed with Lyme disease based on her history of recent travel and the appearance of an areolar lymphocytoma; this was confirmed by testing. Testing for European Lyme disease does not follow the testing algorithm that the Centers for Disease Control and Prevention recommends and may be easily missed. Our case serves as an important reminder that common infections can have varying presentations depending on their region of acquisition and may require specialized testing for accurate diagnosis.
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Enfermedad de Lyme/diagnóstico , Seudolinfoma/etiología , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Borrelia/inmunología , Niño , Diagnóstico Diferencial , Eritema Crónico Migrans/etiología , Femenino , Humanos , Enfermedad de Lyme/tratamiento farmacológico , Seudolinfoma/tratamiento farmacológico , Piel , Mordeduras de Garrapatas , Enfermedad Relacionada con los ViajesRESUMEN
OBJECTIVES: Improper use of maintenance intravenous fluids (IVFs) may cause serious hospital-acquired harm. We created an evidence-based clinical pathway to guide providers on the indications for IVF, its preferred composition, and appropriate clinical monitoring. METHODS: Pathway implementation was supported by the creation of an electronic order set (PowerPlan) and hospital-wide education. Outcomes were measured among pathway-eligible patients for the years before (July 1, 2014-June 30, 2015) and after (July 1, 2015-June 30, 2016) implementation. An interrupted time series analysis was used to evaluate monthly trends related to IVF use, including the following: median duration, proportions of isotonic and hypotonic IVF, adherence to monitoring recommendations, incidence of associated severe dysnatremia, potassium-containing IVF use in the emergency department, and costs. RESULTS: There were 11 602 pathway-eligible encounters (10 287 patients) across the study. Median IVF infusion hours did not change. Isotonic maintenance IVF use increased significantly from 9.3% to 50.6%, whereas the use of any hypotonic fluid decreased from 94.2% to 56.6%. There were significant increases in daily weight measurement and recommended serum sodium testing. Cases of dysnatremia increased from 2 to 4 among pathway-eligible patients and were mostly associated with hypotonic IVF use. Patients in the emergency department had a significant increase in the number of potassium-containing IVF bags (52.9% to 75.3%). Total hospitalization and laboratory test costs did not change significantly. CONCLUSIONS: This is the first report of outcomes of a clinical pathway to standardize IVF use. Implementation was feasible in both medical and surgical units, with sustained improvements for 1 year. Future improvement work includes increasing PowerPlan use and developing clinical assessment tools.
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Vías Clínicas/normas , Fluidoterapia/normas , Niño , Femenino , Humanos , Infusiones Intravenosas , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children <10 years of age initiating ART in Mali. METHODS: Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. RESULTS: One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P < 0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. CONCLUSIONS: Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.
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Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Infecciones por VIH , VIH-1/efectos de los fármacos , Fármacos Anti-VIH/farmacología , Preescolar , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , Lactante , Masculino , Malí , Estudios Prospectivos , Insuficiencia del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Cyclophosphamide is a teratogenic medication used in the treatment of adolescents with autoimmune disorders. This adolescent population is sexually active, does not receive adequate contraceptive care, and is at risk for unintended pregnancy. We undertook a quality improvement initiative to improve rates of pregnancy screening before intravenous cyclophosphamide administration in our adolescent girl patients. METHODS: Data were collected from the electronic medical record. The primary outcome was completion of a urine pregnancy test before intravenous cyclophosphamide infusion in girls aged 12 to 21 years between July 2011 and June 2015. Data were reviewed quarterly and an iterative quality improvement approach was used. Interventions included staff education, electronic order set updates, and a Maintenance of Certification project. Interrupted time series analysis and multivariable mixed effects logistic regression were used to evaluate trends over time and to adjust for potential confounders. RESULTS: Thirty girls received 153 cyclophosphamide infusions during the study. Pregnancy testing before medication administration increased from 25% to 100% by study completion. Infusions in the last time period were significantly more likely to be accompanied by a pregnancy test versus those in the first time period (odds ratio: 17.7; 95% confidence interval [CI]: 3.1-101.6) after adjustment for patient age, managing service, infusion setting, and insurance type. CONCLUSIONS: Our institution achieved a significant increase in standard pregnancy screening in adolescent girls receiving intravenous cyclophosphamide. The interventions most valuable in increasing screening rates were updating electronic order sets, educating staff, and physician engagement in the Maintenance of Certification program.
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Anomalías Teratoides Graves/prevención & control , Enfermedades Autoinmunes/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Pruebas de Embarazo/métodos , Embarazo en Adolescencia , Anomalías Teratoides Graves/inducido químicamente , Adolescente , Enfermedades Autoinmunes/diagnóstico , Niño , Bases de Datos Factuales , Femenino , Humanos , Infusiones Intravenosas , Tamizaje Masivo/métodos , Seguridad del Paciente , Embarazo , Mejoramiento de la Calidad , Estudios Retrospectivos , Medición de Riesgo , Teratógenos , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: It is unclear whether risk factors for late-onset Group B Streptococcus disease (LOD) have changed since the introduction of universal screening and treatment in 2002. METHODS: We conducted a case-control study using linked birth certificates and hospital discharge records. All infants born in Washington State from 1992 to 2011 and hospitalized between 7 and 89 days of life with a Group B Streptococcus (GBS)-related International Classification of Diseases (ICD)-9 code were included. Controls were matched 4:1 by birth year. Multivariate logistic regression was used to evaluate the association between clinical characteristics and LOD. We compared differences in the effect of risk factors on LOD between infants born before and after 2002 using likelihood ratio tests. RESULTS: We identified 138 cases of LOD. In multivariate analyses, prematurity and young maternal age were significantly associated with risk of LOD throughout the study period; positive GBS screen was associated with LOD from 2003 to 2011. Each week of decreasing gestation was associated with a 1.24 (95% confidence interval: 1.15-1.35) times greater likelihood of LOD. We did not detect differences in the association between prematurity or young maternal age and LOD comparing infants born before and after 2002. Compared with infants of non-Hispanic white mothers, risk of LOD among infants of non-Hispanic black mothers decreased after 2002 (adjusted odds ratio [aOR] = 2.74 vs 0.64; pinteraction = 0.02), whereas risk of LOD among infants of Hispanic mothers increased (aOR = 0.80 vs 2.23; pinteraction ≤ 0.001). CONCLUSIONS: Our results confirm studies conducted before 2002, which found that prematurity and young maternal age were associated with increased risk of LOD. Ethnicity-associated LOD risk differed before and after 2002, which may be related to healthcare access.
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Profilaxis Antibiótica , Tamizaje Masivo , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/prevención & control , Estudios de Casos y Controles , Niño Hospitalizado , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Edad Materna , Embarazo , Nacimiento Prematuro , Factores de Riesgo , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/etnología , Streptococcus agalactiae , Washingtón/epidemiologíaRESUMEN
OBJECTIVE: To estimate the association of age of viral suppression and central nervous system penetration effectiveness (CPE) score with neurocognitive functioning among school-age children with perinatally acquired HIV infection (PHIV+). DESIGN: We analyzed data from two US-based multisite prospective cohort studies. METHODS: Multivariable general linear regression models were used to evaluate associations of age at viral suppression and CPE scores (of initial antiretroviral therapy regimen and weighted average) with the Wechsler Intelligence Scale for Children, Third or Fourth Edition neurocognitive assessments [Full-Scale Intelligence Quotient (FSIQ); Performance IQ/Perceptual Reasoning Index (PIQ/PRI); and Verbal IQ/Verbal Comprehension Index (VIQ/VCI)], adjusted for demographic and clinical covariates. Sensitivity analyses were stratified by birth cohort (before versus after 1996). RESULTS: A total of 396 PHIV+ children were included. Estimated differences in mean FSIQ (comparing virally suppressed versus unsuppressed children) by each age cutoff were 3.7, 2.2, 3.2, 4.4, and 3.9 points at ages 1, 2, 3, 4, and 5, respectively. For PIQ/PRI, estimated mean differences were 3.7, 2.4, 2.2, 4.6, and 4.5 at ages 1 through 5, respectively. In both cases, these differences were significant only at the age 4 and 5 thresholds. After stratifying by birth cohort, the association between age at suppression and cognitive function persisted only among those born after 1996. Age at viral suppression was not associated with VIQ/VCI; CPE score was not associated with FSIQ, verbal comprehension, or perceptual reasoning indices. CONCLUSION: Virologic suppression during infancy or early childhood is associated with improved neurocognitive outcomes in school-aged PHIV+ children. In contrast, CPE scores showed no association with neurocognitive outcomes.
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Síndromes Neurocutáneos/prevención & control , Prevención Secundaria/métodos , Carga Viral , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Infecciones por VIH/virología , Humanos , Lactante , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
The prevalence of HIV-associated neurocognitive impairment in perinatally HIV-infected children has declined since the introduction of combination antiretroviral therapy (cART). Early initiation of cART in infancy has been shown to positively impact neurodevelopment; however, children continue to be diagnosed with HIV outside of the early infancy period and can experience subtle to severe neurocognitive deficits despite cART. The causes of these neurocognitive deficits despite effective cART are multifactorial and likely include continued viral replication in the CNS, ongoing neuroinflammation, irreversible CNS injury prior to cART initiation, neurotoxic effects of cART, and socioeconomic and psychosocial effects. Many aspects of our understanding of HIV-associated neurocognitive disorders have emerged from research in adult patients, but perinatally HIV-infected children represent a very different population. These children were exposed to HIV during a period of rapid brain development and have lifelong infection and potential lifelong cART exposure. HIV is no longer a rapidly fatal disease, and most HIV-infected children in resource-rich countries are living into adulthood. It is therefore critical to optimize neurocognitive outcomes of these youth. This review summarizes current understanding of the pathogenesis of HIV-associated CNS infection and the impact of cART on neurocognitive function in children and adolescents and discusses important areas for future research.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Adolescente , Niño , Preescolar , Quimioterapia Combinada , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/virologíaRESUMEN
Schistosomiasis is rarely encountered in the United States, but immigration and travel to endemic areas make it important to know its various presentations to improve diagnosis and treatment. We present our experience with a child with Schistosoma haematobium pseudotumor, initially diagnosed as a cord neoplasm.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Neuroesquistosomiasis/diagnóstico , Neuroesquistosomiasis/parasitología , Schistosoma haematobium/fisiología , Médula Espinal/parasitología , Animales , Niño , Diagnóstico Diferencial , Humanos , Kenia , Masculino , Neuroesquistosomiasis/tratamiento farmacológico , Neuroesquistosomiasis/patología , Praziquantel/administración & dosificación , Praziquantel/uso terapéutico , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Schistosoma haematobium/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Neoplasias de la Médula Espinal/diagnóstico , Neoplasias de la Médula Espinal/patologíaAsunto(s)
Enfermedades Transmisibles/complicaciones , Enfermedades Transmisibles/diagnóstico , Fiebre/diagnóstico , Fiebre/etiología , Viaje , Niño , Dengue/complicaciones , Dengue/diagnóstico , Diagnóstico Diferencial , Humanos , Leptospirosis/complicaciones , Leptospirosis/diagnóstico , Malaria/complicaciones , Malaria/diagnóstico , Anamnesis/métodos , Planificación de Atención al Paciente , Educación del Paciente como Asunto/métodos , Examen Físico/métodos , Factores de Riesgo , Esquistosomiasis/complicaciones , Esquistosomiasis/diagnóstico , Fiebre Tifoidea/complicaciones , Fiebre Tifoidea/diagnósticoRESUMEN
OBJECTIVE: We evaluated the feasibility of the oligonucleotide ligation assay (OLA), a specific, sensitive, and economical ligase-based point mutation assay designed to detect HIV-1 drug-resistance mutations at 12 codons of HIV-1 subtype B pol, for potential use in resource-poor settings. METHODS: Specimens from HIV-1-infected individuals collected by 7 international laboratories, including subtypes A, B, C, D, F, G, J, and recombinants AE and AG, were tested by the OLA developed for HIV-1 subtype B. Common polymorphisms that interfered with reactivity of the OLA were identified and modified probes designed and evaluated. RESULTS: 92.5% (2,410) of 2,604 codons in specimens from 217 individuals were successfully genotyped by the subtype B OLA. A high rate (range 8.3%-31.2%) of indeterminate results (negative OLA reaction for both mutant and wild type) was observed for 5 codons. Modified probes at reverse transcriptase codons 151 and 184 and protease codon 90 increased the rate of valid OLA to 96.1%. CONCLUSIONS: The OLA designed for HIV-1 subtype B genotyped most pol codons in non-B subtypes from Asia and Africa but was improved by addition of several modified probes. International laboratories experienced in molecular techniques were able to perform the OLA.