Young people’s perception of sexual and reproductive health services in Kenya

Background Addressing the Sexual and Reproductive Health (SRH) needs of young people remains a big challenge. This study explored experiences and perceptions of young people in Kenya aged 10–24 with regard to their SRH needs and whether these are met by the available healthcare services. Methods 18 focus group discussions and 39 in-depth interviews were conducted at health care facilities and youth centres across selected urban and rural settings in Kenya. All interviews were tape recorded and transcribed. Data was analysed using the thematic framework approach. Results Young people’s perceptions are not uniform and show variation between boys and girls as well as for type of service delivery. Girls seeking antenatal care and family planning services at health facilities characterise the available services as good and staff as helpful. However, boys perceive services at health facilities as designed for women and children, and therefore feel uncomfortable seeking services. At youth centres, young people value the non-health benefits including availability of recreational facilities, prevention of idleness, building of confidence, improving interpersonal communication skills, vocational training and facilitation of career progression. Conclusion Providing young people with SRH information and services through the existing healthcare system, presents an opportunity that should be further optimised. Providing recreational activities via youth centres is reported by young people themselves to not lead to increased uptake of SRH healthcare services. There is need for more research to evaluate how perceived non-health benefits young people do gain from youth centres could lead to improved SRH of young people

Low rate of cardiac events in first-degree relatives of diagnosis-negative young sudden unexplained death syndrome victims during follow-up

BACKGROUND: Sudden unexplained death syndrome (SUDS) in young individuals often results from inherited cardiac disease. Accordingly, comprehensive examination in surviving first-degree relatives unmasks such disease in approximately 35% of the families. It is unknown whether individuals from diagnosis-negative families are at risk of developing manifest disease or cardiac events during follow-up.OBJECTIVE: This study aimed to study the prognosis of first-degree relatives of young SUDS victims, in whom the initial cardiologic and genetic examination did not lead to a diagnosis.METHODS: We retrieved vital status of surviving first-degree relatives from 83 diagnosis-negative families who presented to our cardiogenetics department between 1996 and 2009 because of SUDS in ≥1 relatives aged 1-50 years. Moreover, we contacted relatives who previously visited our center for detailed information.RESULTS: We obtained detailed information (median follow-up 6.6 years; interquartile range 4.7-9.6 years) in 340 of 417 first-degree relatives (81.5%) from 77 of 83 families (92.8%). Vital status, available in 405 relatives (97.1%), showed that 20 relatives (4.9%) died during follow-up, including 1 natural death before the age of 50. This girl belonged to a family with multiple cases of idiopathic ventricular fibrillation and SUDS, including another successfully resuscitated sibling during follow-up. Two hundred thirty-four of 340 first-degree relatives (68.8%) underwent cardiologic examination. Of these, 76 (32.5%) were reevaluated. Inherited cardiac disease was diagnosed in 3 families (3.6%).CONCLUSION: In first-degree relatives of young SUDS victims with no manifest abnormalities during the initial examination, the risk of developing manifest inherited cardiac disease or cardiac events during follow-up is low. This does not apply to families with obvious familial SUDS.</p

The Role of the Epinephrine Test in the Diagnosis and Management of Children Suspected of Having Congenital Long QT Syndrome

The epinephrine test has been shown to be a powerful tool to predict the genotype of congenital long QT syndrome (LQTS). The aim of this study was to evaluate its role in the diagnosis and management of LQTS in children. The test (using the Shimizu protocol) was conducted in patients with some evidence of LQTS but in whom clinical and management decisions were challenging (n = 41, age 9.6 ± 3.9 years, 19 female). LQT1, LQT2, and negative responses to epinephrine were obtained in 16, 5, and 20 subjects, respectively. LQTS gene positivity was obtained in two subjects. Beta-blocker therapy was started in all subjects with a positive epinephrine response (n = 21) and in some negative responders because of their strong LQTS phenotype (n = 10). No therapy was given to the subset with less convincing features of LQTS who had also responded negatively to epinephrine (n = 10). Follow-up for 3.0 ± 2 years was uneventful in both management groups. Due to the discordance with genotyping, the epinephrine test cannot be used to diagnose genotype-positive LQTS but when used in combination with phenotype assessment and genetic screening, it could enable better management decisions

A Novel Standardized Method for Aiding to Determine Left Atrial Enlargement on Lateral Thoracic Radiographs in Dogs

BACKGROUND: Left atrial enlargement indicates severe cardiac disease. Although the gold standard for determining left atrial size is echocardiography, many veterinary practices lack the necessary equipment and expertise. Therefore, thoracic radiography is often used to differentiate cardiogenic pulmonary edema from primary respiratory diseases and to facilitate distinguishing dogs with stage B1 and B2 mitral valve degeneration. METHODS: The goal was to test a new standardized method for identifying radiographic left atrial enlargement. On a lateral radiograph, a straight line was drawn from the dorsal border of the tracheal bifurcation to the crossing point of the dorsal border of the caudal vena cava and the most cranial crus of the diaphragm. If a part of the left atrium extended this line dorsally, it was considered enlarged. Echocardiographic left atrial to aortic ratio (LA:Ao) was used as a reference. Thirty-nine observers with various levels of experience evaluated 90 radiographs, first subjectively, then applying the new method. RESULTS: The new method moderately correlated with LA:Ao (r = 0.56-0.66) in all groups. The diagnostic accuracy (72-74%) of the subjective assessment and the new method showed no difference. CONCLUSIONS: Though the new method was not superior to subjective assessment, it may facilitate learning and subjective interpretation

The difficulties of conducting maternal death reviews in Malawi

<p>Abstract</p> <p>Background</p> <p>Maternal death reviews is a tool widely recommended to improve the quality of obstetric care and reduce maternal mortality. Our aim was to explore the challenges encountered in the process of facility-based maternal death review in Malawi, and to suggest sustainable and logically sound solutions to these challenges.</p> <p>Methods</p> <p>SWOT (strengths, weaknesses, opportunities and threats) analysis of the process of maternal death review during a workshop in Malawi.</p> <p>Results</p> <p><it>Strengths</it>: Availability of data from case notes, support from hospital management, and having maternal death review forms. <it>Weaknesses</it>: fear of blame, lack of knowledge and skills to properly conduct death reviews, inadequate resources and missing documentation. <it>Opportunities</it>: technical assistance from expatriates, support from the Ministry of Health, national protocols and high maternal mortality which serves as motivation factor. <it>Threats</it>: Cultural practices, potential lawsuit, demotivation due to the high maternal mortality and poor planning at the district level. <it>Solutions</it>: proper documentation, conducting maternal death review in a blame-free manner, good leadership, motivation of staff, using guidelines, proper stock inventory and community involvement.</p> <p>Conclusion</p> <p>Challenges encountered during facility-based maternal death review are provider-related, administrative, client related and community related. Countries with similar socioeconomic profiles to Malawi will have similar 'pull-and-push' factors on the process of facility-based maternal death reviews, and therefore we will expect these countries to have similar potential solutions.</p

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Heart Rate Recovery After Exercise Is Associated With Arrhythmic Events in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

BACKGROUND: Risk stratification in catecholaminergic polymorphic ventricular tachycardia remains ill defined. Heart rate recovery (HRR) immediately after exercise is regulated by autonomic reflexes, particularly vagal tone, and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. Our objective was to evaluate whether HRR after maximal exercise on the exercise stress test (EST) is associated with symptoms and ventricular arrhythmias. METHODS: In this retrospective observational study, we included patients ≤65 years of age with an EST without antiarrhythmic drugs who attained at least 80% of their age- and sex-predicted maximal HR. HRR in the recovery phase was calculated as the difference in heart rate (HR) at maximal exercise and at 1 minute in the recovery phase (ΔHRR1'). RESULTS: We included 187 patients (median age, 36 years; 68 [36%] symptomatic before diagnosis). Pre-EST HR and maximal HR were equal among symptomatic and asymptomatic patients. Patients who were symptomatic before diagnosis had a greater ΔHRR1' after maximal exercise (43 [interquartile range, 25-58] versus 25 [interquartile range, 19-34] beats/min; P<0.001). Corrected for age, sex, and relatedness, patients in the upper tertile for ΔHRR1' had an odds ratio of 3.4 (95% CI, 1.6-7.4) of being symptomatic before diagnosis (P<0.001). In addition, ΔHRR1' was higher in patients with complex ventricular arrhythmias at EST off antiarrhythmic drugs (33 [interquartile range, 22-48] versus 27 [interquartile range, 20-36] beats/min; P=0.01). After diagnosis, patients with a ΔHRR1' in the upper tertile of its distribution had significantly more arrhythmic events as compared with patients in the other tertiles (P=0.045). CONCLUSIONS: Catecholaminergic polymorphic ventricular tachycardia patients with a larger HRR following exercise are more likely to be symptomatic and have complex ventricular arrhythmias during the first EST off antiarrhythmic drug

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome

BACKGROUND: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. METHODS: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. RESULTS: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P&lt;5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P&lt;10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P&lt;10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P&lt;0.005). CONCLUSIONS: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.</p

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease