Revising the essential package of health services through stakeholder alignment, Somalia.

Problem: The fragmented health sector in Somalia, burdened by financial challenges and an inadequate regulatory system, struggles to provide equitable essential health services to the entire population. Approach: To revise an essential package of health services that stakeholders could support and that aligned with stakeholders' financial and technical resources, the federal health ministry invited all key stakeholders in 2020 to participate in the revision process of the essential package. The ministry distributed a concept note to invited stakeholders, describing the scope and purpose of the revision process of the essential package. The note also contained a timeline and the expected contribution of each stakeholder. Stakeholders nominated representatives based on their technical expertise and knowledge of the health sector in Somalia. Local setting: The health sector in Somalia involves multiple stakeholders, including the health ministry and many development partners. The private sector plays a substantial role in health-care provision. Public spending is an estimated 17% of the total health expenditure. Relevant changes: After an 18-month revision process, the health ministry and development partners agreed to prioritize high-impact, cost-effective services and use a progressive realization of the package to improve access and coverage. The implementation strategy considers the health system and operational capacity of service providers, particularly in security-compromised areas. Lessons learnt: The approach showed that inclusivity, collaboration and transparency were of importance for a successful revision of the package. These achievements in consensus-building and priority alignment advance the government's pursuit of equitable and comprehensive health care for all.

Aneuploidy detection in paraffin embedded tissue from products of conception by mini-STR genotyping.

Autosomal trisomy is the most common genetic abnormality observed in pregnancy loss. We designed a panel of mini-short tandem repeats (mini-STRs) for aneuploidy detection in chromosomes 13, 16, 18 and 21 from fresh and formalin fixed, paraffin embedded (FFPE) samples from products of conception (POC). FFPE POCs with trisomy 13 (n = 6), trisomy 18 (n = 6), trisomy 21 (n = 12), 6 euploid for the chromosomes of interest and two trisomy 16 samples from fresh tissue were tested. Concordance between cytogenetics and genotyping was 100% for non-mosaic samples. Mini-STR genotyping is a viable method for targeted aneuploidy detection in low quality DNA samples.

Framework for assessing governance of the health system in developing countries: gateway to good governance.

Governance is thought to be a key determinant of economic growth, social advancement and overall development, as well as for the attainment of the MDGs in low- and middle-income countries. Governance of the health system is the least well-understood aspect of health systems. A framework for assessing health system governance (HSG) at national and sub-national levels is presented, which has been applied in countries of the Eastern Mediterranean. In developing the HSG framework key issues considered included the role of the state vs. the market; role of the ministries of health vs. other state ministries; role of actors in governance; static vs. dynamic health systems; and health reform vs. human rights-based approach to health. Four existing frameworks were considered: World Health Organization's (WHO) domains of stewardship; Pan American Health Organization's (PAHO) essential public health functions; World Bank's six basic aspects of governance; and United Nations Development Programme (UNDP) principles of good governance. The proposed HSG assessment framework includes the following 10 principles-strategic vision, participation and consensus orientation, rule of law, transparency, responsiveness, equity and inclusiveness, effectiveness and efficiency, accountability, intelligence and information, and ethics. The framework permits 'diagnoses of the ills' in HSG at the policy and operational levels and points to interventions for its improvement. In the case of Pakistan, where the framework was applied, a positive aspect was the growing participation and consensus orientation among stakeholders, while weaknesses were identified in relation to strategic vision, accountability, transparency, effectiveness and efficiency and rule of law. In using the HSG framework it needs to be recognized that the principles are value driven and not normative and are to be seen in the social and political context; and the framework relies on a qualitative approach and does not follow a scoring or ranking system. It does not directly address aid effectiveness but provides insight on the ability to utilize external resources and has the ability to include the effect of global health governance on national HSG as the subject itself gets better crystallized. The improved performance of the ministries of health and state health departments is at the heart of this framework. The framework helps raise the level of awareness among policymakers of the importance of HSG. The road to good governance in health is long and uneven. Assessing HSG is only the first step; the challenge that remains is to carry out effective governance in vastly different institutional contexts.

Consensus characterization of 16 FMR1 reference materials: a consortium study.

Fragile X syndrome, which is caused by expansion of a (CGG)(n) repeat in the FMR1 gene, occurs in approximately 1:3500 males and causes mental retardation/behavioral problems. Smaller (CGG)(n) repeat expansions in FMR1, premutations, are associated with premature ovarian failure and fragile X-associated tremor/ataxia syndrome. An FMR1-sizing assay is technically challenging because of high GC content of the (CGG)(n) repeat, the size limitations of conventional PCR, and a lack of reference materials available for test development/validation and routine quality control. The Centers for Disease Control and Prevention and the Association for Molecular Pathology, together with the genetic testing community, have addressed the need for characterized fragile X mutation reference materials by developing characterized DNA samples from 16 cell lines with repeat lengths representing important phenotypic classes and diagnostic cutoffs. The alleles in these materials were characterized by consensus analysis in nine clinical laboratories. The information generated from this study is available on the Centers for Disease Control and Prevention and Coriell Cell Repositories websites. DNA purified from these cell lines is available to the genetics community through the Coriell Cell Repositories. The public availability of these reference materials should help support accurate clinical fragile X syndrome testing.

EIF2AK4 Mutations in Patients Diagnosed With Pulmonary Arterial Hypertension.

BACKGROUND: Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4 mutations in patients diagnosed clinically with IPAH or HPAH. METHODS: Sanger sequencing and deletion/duplication analysis were performed to detect mutations in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n = 9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients negative for mutations in all known PAH genes (n = 66) were then sequenced for mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations. RESULTS: Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations. CONCLUSIONS: Pathogenic biallelic EIF2AK4 mutations are rarely identified in patients diagnosed with HPAH. Identification of pathogenic biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from heritable PVOD or PCH.

Diagnostic utility of microsatellite genotyping for molar pregnancy testing.

CONTEXT: Molecular genotyping by analysis of DNA microsatellites, also known as short tandem repeats (STRs), is an established method for diagnosing and classifying hydatidiform mole. Distinction of both complete hydatidiform mole and partial hydatidiform mole from nonmolar specimens is relevant for clinical management owing to differences in risk for persistent gestational trophoblastic disease. OBJECTIVE: To determine the technical performance of microsatellite genotyping by using a commercially available multiplex assay, and to describe the application of additional methods to confirm other genetic abnormalities detected by the genotyping assay. DESIGN: Microsatellite genotyping data on 102 cases referred for molar pregnancy testing are presented. A separate panel of mini STR markers, flow cytometry, fluorescence in situ hybridization, and p57 immunohistochemistry were used to characterize cases with other incidental genetic abnormalities. RESULTS: Forty-eight cases were classified as hydatidiform mole (31, complete hydatidiform mole; 17, partial hydatidiform mole). Genotyping also revealed 11 cases of suspected trisomy and 1 case of androgenetic/biparental mosaicism. Trisomy for selected chromosomes (13, 16, 18, and 21) was confirmed in all cases by using a panel of mini STR markers. CONCLUSIONS: This series illustrates the utility of microsatellite genotyping as a stand-alone method for accurate classification of hydatidiform mole. Other genetic abnormalities may be detected by genotyping; confirmation of the suspected abnormality requires additional testing.