The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated ...immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5-12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 10
, 9.0 × 10
or 1.8 × 10
PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 10
dose group = -6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2
Vγ9
T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2
Vγ9
T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group.
(2011)Germany Retrospective case series 151 men and women with cryptogenic stroke/transient ischemic attack and patent foramen ovale.9 women with intake of oral contraceptives Type of oral ...contraceptive not defined Univariate association between oral contraceptives and silent pulmonary emboli (p=0.07) II-2, poor Pijuan-Domènech et al., (2013)Spain Retrospective case series 237 women with CHD: 219 biventricular CHD and 18 univentricular heart COC, POP 3 undefined neurological events with COC useNo cardiac or thrombolytic events with POP II-2 fair Pundi et al.
ABSTRACT
Objectives. To review early surgical outcomes in a contemporary series of adults with congenital heart disease (CHD) undergoing cardiac operations at the University of Michigan, and to ...investigate possible preoperative and intraoperative risk factors for morbidity and mortality.
Methods. A retrospective medical record review was performed for all patients ≥18 years of age who underwent open heart operations by a pediatric cardiothoracic surgeon at the University of Michigan Congenital Heart Center between January 1, 1998 and December 31, 2004. Records from a cohort of pediatric patients ages 1–17 years were matched to a subset of the adult patients by surgical procedure and date of operation.
Results. In total, 243 cardiac surgical operations were performed in 234 adult patients with CHD. Overall mortality was 4.7% (11/234). The incidence of major postoperative complications was 10% (23/234) with a 19% (45/23) minor complication rate. The most common postoperative complication was atrial arrhythmias in 10.8% (25/234). The presence of preoperative lung or liver disease, prolonged cardiopulmonary bypass and aortic cross clamp times, and postoperative elevated inotropic score and serum lactates were significant predictors of mortality in adults. There was no difference between the adult and pediatric cohorts in terms of mortality and morbidity.
Conclusions. The postoperative course in adults following surgery for CHD is generally uncomplicated and early survival should be expected. Certain risk factors for increased mortality in this patient population may include preoperative presence of chronic lung or liver dysfunction, prolonged cardiopulmonary bypass and aortic cross‐clamp times, and postoperative elevated inotropic score and serum lactate levels.
Objective
Women with congenital heart disease (CHD) are at increased risk of pregnancy complications and need information on safe, effective contraceptive methods to avoid unintended pregnancy. This ...systematic review examines evidence regarding safety of contraceptive use among women with CHD.
Methods
The PubMed database was searched for any peer‐reviewed articles published through April 2018 that included safety outcomes associated with reversible contraceptive methods among women with CHD.
Results
Five articles met inclusion criteria: three studies comparing contraceptive users to nonusers and two noncomparative studies. Sample sizes ranged from 65 to 505 women with CHD. Two studies found a higher percent of thromboembolic complications among women with Fontan palliation or transposition of the great arteries using oral contraceptives. One study, among women with Fontan palliation, found no increased risk of thromboembolic complications between contraceptive users (not separated by type) and nonusers. Two studies found no endocarditis among intrauterine device users.
Conclusions
There is a paucity of data regarding the safety of contraceptive methods among women with CHD. Limited evidence suggests an increased incidence of thromboembolic complications with use of oral contraceptives. Further studies are needed to evaluate contraceptive safety and quantify risk in this growing population. There is also limited data regarding the safety of contraceptive methods among women with CHD. Further information is needed to assist practitioners counseling women with CHD on safety of contraceptive methods.
Abstract
Background
The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous ...inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited.
Methods
We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5–9 years, 13–59 months, and 5–12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 × 105, 9.0 × 105, and 1.8 × 106 PfSPZ, with the 2 highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for 8 days after vaccination, unsolicited AEs for 29 days, and serious AEs throughout the study. Blood taken prevaccination and 1 week postvaccination was tested for immunoglobulin G antibodies to P. falciparum circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay.
Results
Rates of AEs were similar in vaccinees and controls for solicited (35.7% vs 41.5%) and unsolicited (83.9% vs 92.5%) AEs, respectively. No related grade 3 AEs, serious AEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0 × 105 and 1.8 × 106 PfSPZ groups, 36 of 45 (80.0%) vaccinees and 4 of 21 (19.0%) placebo controls developed antibodies to PfCSP (P < .001).
Conclusions
PfSPZ vaccine in doses as high as 1.8 × 106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic.
Clinical Trials Registration
NCT02687373.
In a double-blind, placebo-controlled dose-escalation, age de-escalation trial of Plasmodium falciparum sporozoite (PfSPZ) vaccine, doses as high as 1.8 × 106 PfSPZ were found to be safe and immunogenic in infants and children aged 5 months to 9 years.
Keywords. xxx; xxx; xxx.
Objective
It is unclear whether neonates with interrupted aortic arch (IAA) and a smaller left ventricular outflow tract may have improved outcomes with a Yasui operation (ventricular outflow bypass ...procedure) over a primary complete repair. This study sought to identify preoperative echocardiographic parameters to differentiate which neonates may have improved outcomes with a primary vs Yasui operation.
Design
Patient demographics, cardiac surgery type, complications, need for reoperation and/or interventional catheterization, and date of last follow‐up were collected on neonates who underwent a biventricular repair for IAA from 2003 to 2014. Preoperative echocardiograms were analyzed for: IAA type, valve annulus size, aortic valve morphology, ventricular size and aortic arch anatomy.
Results
Seventy‐seven neonates underwent IAA repair between 2003 and 2013. 60 neonates had a primary repair and 17 a Yasui operation. Neonates that underwent a Yasui operation had significantly smaller mitral and aortic valves with aortic arch hypoplasia. Within the primary repair group, a decreasing aortic root z‐score on univariate analysis increased the odds of reoperation by twofold OR = 1.98, 95% CI: (1.15‐3.42), P = .014. A significant interaction between repair type and aortic root z‐score was identified on multivariable analysis (P = .039), for neonates with aortic root z‐scores less than −2.5, the probability of reoperation during the follow up time period mean 4.5 years (3.3 months‐10 year) was significantly higher in the primary repair group compared to the Yasui group (64.3% vs 37.5%).
Conclusions
Neonates with IAA and an aortic root z‐score less than −2.5 have lower odds of subsequent reoperations with a Yasui operation compared to a primary repair over the follow up period. These findings suggest a Yasui operation should be considered if the preoperative aortic root z‐score is less than −2.5. Careful evaluation of these morphologic predictors on preoperative echocardiograms can be helpful in surgical planning in neonates with IAA.
Objective
To examine how cognitive and motor limitations in children with heart disease are associated with education and participation in extracurricular activities.
Design
Using 2009–2010 ...parent‐reported data from the National Survey of Children with Special Health Care Needs (NS‐CSHCN), we examined prevalence of five functional limitations (learning/concentration, communication, self‐care, gross motor skills, and fine motor skills) by diagnosed heart disease status using chi‐square tests and multivariable logistic regression. Among CSHCN with heart disease, we examined the associations between severity of each functional limitation and missing ≥11 days of school in the past year, receiving special education services, and interference with extracurricular activities.
Results
CSHCN with heart disease (n = 1,416), compared to CSHCN without (n = 28,385), more commonly had “a lot” of difficulty in the five functional areas (P < .01; adjusted odds ratios: 1.8‐3.3). Among CSHCN with heart disease, “a lot” of difficulty with learning/concentration was most common (35%), followed by communication (21%), self‐care (14%), gross motor skills (12%), and fine motor skills (10%). Among CSHCN with heart disease, compared to those without, respectively, 27% and 15% missed ≥11 days of school, 45% and 29% received special education services, and 49% and 29% experienced interference with extracurricular activities (P < .01 for all). Level of difficulty with the five functional areas was associated with receipt of special education services and participation in extracurricular activities (P < .001).
Conclusion
These results support the American Heart Association recommendations to screen children with congenital heart disease for age‐appropriate development and provide services when needed.
Few data describe exercise performance after cardiac transplantation during infancy. The aim of this study was to compare the cardiorespiratory response to exercise in healthy subjects with that of ...subjects who had undergone heart transplantation during infancy to treat hypoplastic left heart syndrome.
Subjects (24 heart transplant recipients and 25 healthy controls) exercised on a treadmill using pediatric ramp protocols. We measured heart rate (HR), blood pressure, and metabolic data. Median age at transplantation was 20 days (range, 4 to 97 days). Age of recipients at exercise testing was 9.7 ± 2.3 years and in healthy subjects was 10.5 ± 1.4 years (
p = not significant NS).
Exercise duration was similar in both groups (10.3 ± 2.0 minutes in recipients vs 11.1 ± 1.5 minutes in healthy subjects, (
p = NS). Heart rate at rest was greater in recipients (94 ± 15 beats per minute bpm vs 85 ± 11 bpm,
p = 0.02). Peak HR also was less in the recipient group (158 ± 15 bpm vs 189 ± 12 bpm,
p < 0.001). Peak oxygen consumption was 14% less in the recipients (32.3 ± 5.6 ml/kg/min vs 36.8 ± 5.5 ml/kg/min,
p < 0.01). Ventilatory anaerobic threshold was decreased in recipients, 27.6 ± 9.6 vs 32.8 ± 6.0,
p < 0.05. Respiratory exchange ratio at peak exercise was equal in both groups (1.06 ± 0.06 vs 1.06 ± 0.08). Oxygen pulse index did not differ significantly, 5.5 ± 1.1 ml/beat/m
2 in recipients and 6.1 ± 1.7 ml/beat/m
2 in healthy subjects (
p = NS).
Overall, children who undergo cardiac transplantation in infancy have exercise capacities within the normal range. These recipients have a decreased heart rate reserve that may account for the differences in peak oxygen consumption when compared with healthy subjects.
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