Objective Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of hypsarrhythmia. Secondarily, it assesses whether response to treatment differs by etiology or developmental status. Methods The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of infantile spasms. Children were considered responders if there was clinical remission and resolution of hypsarrhythmia that was sustained at 3 months after first treatment initiation. Standard treatments of adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin were considered individually, and all other nonstandard therapies were analyzed collectively. Developmental status and etiology were assessed. We compared response rates by treatment group using chi-square tests and multivariate logistic regression models. Results Two hundred thirty infants were enrolled from 22 centers. Overall, 46% of children receiving standard therapy responded, compared to only 9% who responded to nonstandard therapy (p<0.001). Fifty-five percent of infants receiving ACTH as initial treatment responded, compared to 39% for oral corticosteroids, 36% for vigabatrin, and 9% for other (p<0.001). Neither etiology nor development significantly modified the response pattern by treatment group. Interpretation Response rate varies by treatment choice. Standard therapies should be considered as initial treatment for infantile spasms, including those with impaired development or known structural or genetic/metabolic etiology. ACTH appeared to be more effective than other standard therapies.
The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full-term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre-and post-donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.
Key Points Question Does a shared decision support intervention for patients considering destination therapy left ventricular assist device (DT LVAD) improve decision quality compared with usual care? Findings In this multicenter randomized stepped-wedgeclinical trial of 248 patients being considered for DT LVAD, compared with patients in the usual care control period, patients enrolled in the intervention period had significantly better knowledge and higher concordance between stated values and patient-reported treatment choice. Meaning An intervention supporting shared decision making for DT LVAD was associated with improved patient decision quality.
Objective To determine the cardiac effects of prolonged exposure to highly active antiretroviral therapy (HAART) on HIV-infected (HIV+) children. Design In the National Institutes of Health (NIH)-funded Pediatric HIV/AIDS Cohort Study’s Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiogram measures. Setting 14 U.S. pediatric HIV clinics. Patients/Participants Perinatally-infected HIV+ children receiving HAART with HIV-exposed but uninfected (HEU) children and HIV+ (mostly HAART-unexposed) historical pediatric controls from the NIH-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2-HIV) Study. Main Exposure Long-term HAART. Outcome Measures Echocardiographic measures of left ventricular (LV) function and structure. Results The 325 AMP HIV+ children had lower viral loads, higher CD4 counts, and longer duration of antiretroviral therapy than 70 P2C2 HIV+ children (all P’s < 0·001). Z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among P2C2 HIV+ children than among the AMP HIV+ group or the 189 AMP HEU controls (P < 0.05). For HIV+ children, lower nadir CD4 percentage and higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening Z scores; P’s = 0.001) and increased LV end-systolic dimension Z score (P’s < 0.03). In an interaction analysis by HIV+ cohort, P2C2 HIV+ children with longer ART exposure or lower nadir CD4 percentage had lower mean LV fractional shortening Z scores, while mean Z scores were relatively constant among AMP HIV+ children (P<0·05 for all interactions). Conclusions HAART appears to be cardioprotective in HIV+ children and adolescents.
Objective Infantile spasms (IS) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarhythmia and whether time to treatment was related to outcome. Methods The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or “other.” Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models. Results One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset had a higher response rate to second treatment than those initially treated later (36/82 [44%] vs. 8/34 [24%], p = 0.040). Significance Greater than one third of children with IS will respond to a second medication. Choosing a standard medication (ACTH, oral corticosteroids, or vigabatrin) that has a different mechanism of action appears to be more effective. Rapid initial treatment increases the likelihood of response to the second treatment.
Poor adherence to antiretroviral therapy (ART) contributes to disease progression and emergence of drug-resistant HIV in youth with perinatally acquired HIV infection (PHIV+), necessitating reliable measures of adherence. Although electronic monitoring devices have often been considered the gold standard assessment in HIV research, they are costly, can overestimate non-adherence and are not practical for routine care. Thus, development of valid, easily administered self-report adherence measures is crucial for adherence monitoring. PHIV+ youth aged 7–16 (n=289) and their caregivers, enrolled in a multisite cohort study, were interviewed to assess several reported indicators of adherence. HIV-1 RNA viral load (VL) was dichotomized into >/≤400 copies/ml. Lower adherence was significantly associated with VL >400 copies/ml across most indicators, including ≥ 1 missed dose in past 7 days [youth report OR=2.78 (95% CI 1.46–5.27)]. Caregiver and combined youth/caregiver reports yielded similar results. Within-rater agreement between various adherence indicators was high for both youth and caregivers. Inter-rater agreement on adherence was moderate across most indicators. Age ≥13 years and living with biological mother or relative were associated with VL > 400 copies/ml. Findings support the validity of caregiver and youth adherence reports and identify youth at risk of poor adherence.
Drug use in combination with psychiatric illness may lead to unsafe sexual risk behavior and increased risk for secondary HIV transmission among adolescents with HIV infection. We compared the prevalence of substance use for perinatally HIV-infected youth to uninfected adolescents living in families affected by HIV infection, and evaluated the association of psychiatric symptoms with risk of substance use. Among 299 adolescents (196 HIV+, 103 HIV−) aged 12–18 years enrolled in IMPAACT P1055, a multisite US cohort study, 14% reported substance use at enrollment (HIV+: 13%, HIV−: 16%). In adjusted logistic regression models, adolescents had significantly higher odds of substance use if they met symptom criteria for ADHD [adjusted odds ratio (aOR) = 2.7, Wald χ2 = 5.18, P = 0.02], major depression or dysthymia (aOR = 4.0, Wald χ2 = 7.36, P = 0.01), oppositional defiant disorder (aOR = 4.8, Wald χ2 = 12.7, P = 0.001), or conduct disorder (aOR = 15.4, Wald χ2 = 28.12, P = 0.001). Among HIV-infected youth, those with lower CD4 lymphocyte percentage (CD4% < 25%) had significantly increased risk of substance use (aOR = 2.7, Wald χ2 = 4.79, P = 0.03). However, there was no overall association of substance use with HIV infection status, and the association between psychiatric symptoms and substance use did not differ by HIV status. Programs to prevent substance use should target both HIV-infected and uninfected adolescents living in families affected by HIV infection, particularly those with psychiatric symptoms.
Objective To examine the relationship between markers of vascular dysfunction and neurodevelopmental status in pediatric HIV disease. Design Cross-sectional design within a prospective, 15-site cohort study conducted in the United States. Methods Nine vascular biomarkers were examined in 89 HIV-infected children: soluble P-selectin (sP-selectin)/sCD62P, fibrinogen, adiponectin, monocyte chemoattractant protein-1/CCL-2, interleukin-6, C-reactive protein, soluble vascular cell adhesion molecule-1/sCD106, sE-selectin/sCD62E, soluble intercellular adhesion molecule-1/sCD54. The Wechsler Intelligence Scale for Children-IV (WISC-IV) was administered yielding indices for Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed, and overall composite score Full Scale IQ (FSIQ). Linear regression models were used to evaluate neurodevelopmental status (measured by WISC-IV scores) as a function of each biomarker while adjusting for demographics, disease severity and receipt of highly active antiretroviral therapy. Biomarker levels were evaluated in quartiles to evaluate trends in WISC-IV responses. Results Among the 89 HIV-infected children (median age = 12 years), 56% were female, 71% Black, 16% Hispanic, and 43% had yearly household income <$20,000. Log(sP-selectin) was significantly correlated with all WISC-IV scores; adjusted slopes showed 6 to 11 point average decrease in scores for each one log unit increase in sP-selectin. Final linear regression models for log(fibrinogen) adjusted for sociodemographic and disease characteristics also indicated a negative correlation with all WISC-IV scores (13 to 30 points decrease for each one log unit increase in fibrinogen); these decreases were significant in the Verbal Comprehension, Perceptual Reasoning and FSIQ scores. Conclusion Pro-inflammatory microvascular and immunologic mechanisms may be involved in neurodevelopmental impairment in children with perinatally-acquired HIV disease.
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