Background and purposeAccess to evidence-based mental health care for children is an international priority. However, there are significant challenges to advancing this public health priority in an efficient and equitable manner. The purpose of this international colloquium was to convene a multidisciplinary group of health researchers to build an agenda for addressing disparities in mental health care access and treatment for children and families through collaboration among scholars from the United States and Europe engaged in innovative implementation science and mental health services research.Key highlightsGuided by the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework, presentations related to inner, outer, and bridging context factors that impact the accessibility and quality of mental health evidence-based practices (EBPs) for children and families. Three common topics emerged from the presentations and discussions from colloquium participants, which included: 1) the impact of inner and outer context factors that limit accessibility to EBPs across countries, 2) strategies to adapt EBPs to improve their fit in different settings, 3) the potential for implementation science to address emerging clinical and public health concerns.ImplicationsThe common topics discussed underscored that disparities in access to evidence-based mental health care are prevalent across countries. Opportunities for cross-country and cross-discipline learnings and collaborations can help drive solutions to address these inequities, which relate to the availability of a trained and culturally appropriate workforce, insurance reimbursement policies, and designing interventions and implementation strategies to support sustained use of evidence-based practices.

BackgroundDuchenne Muscular Dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease, characterized by progressive loss of muscle strength. Respiratory failure is the main cause of morbidity and mortality in DMD patients. Respiratory devices have been reported to increase the effectiveness of cough and pulmonary function, thus prolong the survival rate. However, there is scarcity of studies about DMD patients’ respiratory profiles and usage of respiratory devices in Indonesia.MethodsWe recruited 8 Indonesian DMD patients in Dr. Sardjito Hospital and UGM Academic Hospital, Yogyakarta. Baseline pulmonary function was measured using spirometry. Peak Cough Flow was measured at baseline, with chest compression, after air stacking with manual ventilation bag, and with the combined techniques. Data recorded was presented as mean ± SD and analysed using ANOVA.ResultsHere we show the respiratory profiles from 8 non-ambulatory DMD patients (mean age: 13.25 ± 3.96 years old) confirmed by genetic testing. None of them had access to respiratory devices. Spirometry measurements showed 7 of 8 patients had severe restrictive pulmonary function with mean FEV1/FVC 22.40 ± 10.30% of predictive values (normal ratio > 70%). In addition, all patients showed poor cough performances measured by peak cough flowmeter (160 ± 44.58 L/min (normal value > 270 L/min)) that were improved by air stacking using a manual ventilation bag (167.4 ± 46.72 L/min). Three patients who had nocturnal hypoventilation did not have daytime hypercapnia. Manual ventilation bag or mechanical in−/ex-sufflation was indicated in 75% of patients while nocturnal assisted ventilation was indicated in 50% of patients. Neither daytime assisted ventilation nor tracheostomy was indicated in these patients.ConclusionUse of manual exsufflation in combination with the manual ventilation bag for air stacking to improve cough performance is recommended as the first step of respiratory management in DMD patients. Provision of manual ventilation bag serve as an affordable and effective device for respiratory support in the early stage of respiratory involvement in those non-ambulatory patients with DMD.

BackgroundInadequate access to quality health care services due to weak health systems and recurrent public health emergencies are impediments to the attainment of Universal Health Coverage and health security in Africa. To discuss these challenges and deliberate on plausible solutions, the World Health Organization Regional Office for Africa, in collaboration with the Government of Cabo Verde, convened the second Africa Health Forum in Praia, Cabo Verde on 26–28 March 2019, under the theme Achieving Universal Health Coverage and Health Security: The Africa We Want to See.MethodsThe Forum was conducted through technical sessions consisting of high-level, moderated panel discussions on specific themes, some of them preceded by keynote addresses. There were booth exhibitions by Member States, World Health Organization and other organizations to facilitate information exchanges. A Communiqué highlighting the recommendations of the Forum was issued during the closing ceremony. More than 750 participants attended. Relevant information from the report of the Forum and notes by the authors were extracted and synthesized into these proceedings.ConclusionsThe Forum participants agreed that the role of community engagement and participation in the attainment of Universal Health Coverage, health security and ultimately the Sustainable Development Goals cannot be overemphasized. The public sector of Africa alone cannot achieve these three interrelated goals; other partners, such as the private sector, must be engaged. Technological innovations will be a key driver of the attainment of these goals; hence, there is need to harness the comparative advantages that they offer. Attainment of the three goals is also intertwined – achieving one paves the way for achieving the others. Thus, there is need for integrated public health approaches in the planning and implementation of interventions aimed at achieving them.RecommendationsTo ensure that the recommendations of this Forum are translated into concrete actions in a sustainable manner, we call on African Ministers of Health to ensure their integration into national health sector policies and strategic documents and to provide the necessary leadership required for their implementation. We also call on partners to mainstream these recommendations into their ongoing support to World Health Organization African Member States.

An increasing number of studies are focused on the epigenetic regulation of DNA to affect gene expression without modifications to the DNA sequence. Methylation plays an important role in shaping disease traits; however, previous studies were mainly experiment, based, resulting in few reports that measured gene–methylation interaction effects via statistical means. In this study, we applied the data set adaptive W-test to measure gene–methylation interactions. Performance was evaluated by the ability to detect a given set of causal markers in the data set obtained from the GAW20. Results from simulation data analyses showed that the W-test was able to detect most markers. The method was also applied to chromosome 11 of the experimental data set and identified clusters of genes with neuronal and retinal functions, including MPPED2I, GUCY2E, NAV2, and ZBTB16. Genes from the TRIM family were also identified; these genes are potentially related to the regulation of triglyceride levels. Our results suggest that the W-test could be an efficient and effective method to detect gene–methylation interactions. Furthermore, the identified genes suggest an interesting relationship between lipid levels and the etiology of neurological disorders.

Genome-wide association studies often collect multiple phenotypes for complex diseases. Multivariate joint analyses have higher power to detect genetic variants compared with the marginal analysis of each phenotype and are also able to identify loci with pleiotropic effects. We extend the unified score-based association test to incorporate family structure, apply different approaches to analyze multiple traits in GAW20 real samples, and compare the results. Through simulation studies, we confirm that the Type I error rate of the pedigree-based unified score association test is appropriately controlled. In marginalanalysis of triglyceride levels, we found 1 subgenome-wide significant variant on chromosome 6. Joint analyses identified several suggestive genome-wide significant signals, with the pedigree-based unified score association test yielding the greatest number of significant results.

The heritability of a phenotype is an estimation of the percent of variance in that phenotype that is attributable to additive genetic factors. Heritability is optimally estimated in family-based sample populations. Traditionally, this involves use of a pedigree-based kinship coefficient generated from the collected genealogical relationships between family members. An alternative, when dense genotype data are available, is to directly measure the empirical kinship between samples. This study compares the use of pedigree and empirical kinships in the GAW20 data set. Two phenotypes were assessed: triglyceride levels and high-density lipoprotein cholesterol (HDL-C) levels pre- and postintervention with the cholesterol-reducing drug fenofibrate. Using SOLAR (Sequential Oligogenic Linkage Analysis Routines), pedigree-based kinships and empirically calculated kinships (using IBDLD and LDAK) were used to calculate phenotype heritability. In addition, a genome-wide association study was conducted using each kinship model for each phenotype to identify genetic variants significantly associated with phenotypic variation. The variant rs247617 was significantly associated with HDL-C levels both pre- and post-fenofibrate intervention. Overall, the phenotype heritabilities calculated using pedigree based kinships or either of the empirical kinships generated using IBDLD or LDAK were comparable. Phenotype heritabilities estimated from empirical kinships generated using IBDLD were closest to the pedigree-based estimations. Given that there was not an appreciable amount of unknown relatedness between the pedigrees in this data set, a large increase in heritability in using empirical kinship was not expected, and our calculations support this. Importantly, these results demonstrate that when sufficient genotypic data are available, empirical kinship estimation is a practical alternative to using pedigree-based kinships.

Complex genetic traits are often characterized by multiple quantitative phenotypes. Because values of such phenotypes vary over time, it is thought that analyses of longitudinal data on the phenotypes may lead to increased power in detecting genetic association. In this paper, we extend a transmission-based association test applying quasi-likelihood that has been developed by us to the longitudinal framework and to carry out a genome-wide association analysis of triglyceride levels based on the data provided in GAW20. We consider different phenotype definitions based on administration of fenofibrate and obtain significant association findings within genes involved in heart diseases.