Knowledge, attitude, and practice of residents in medical research and barriers: A cross-sectional survey at Tikur Anbessa Specialized Hospital

Background: Research activity is an important component of postgraduate training in medical institutions. However, only a few residents of Tikur Anbessa Specialized Hospital were able to publish research papers. Lack of funding and time, poor infrastructure, belief about research, and inadequate research knowledge and methodology were reported to be among the hindering reasons.Objective: The objective of this study was to determine the level of knowledge, attitude, practice, and barriers to conduct research among clinical residents.Methods: Three hundred and forty-four residents from 13 clinical departments were enrolled in a cross-sectional descriptive study conducted during December 2015 - May 2016. Participants of this study were determined using convenient sampling technique. This means that residents who showed willingness to participate in the study were included. Data were collected using standardized field tested questionnaire. After collecting the responses they were entered into SPSS (version 20) software. Descriptive statistics, one sample-T, and Pearson’s chi-square tests were used to analyze the data and report the finding.Results: Mean Knowledge score was 34.6% for all participants. Knowledge score was significantly better among females compared to males (p-value < 0.01 (95% CI: 0.32-0.85). Attitude towards research undertaking was positive with mean score of 3.8 (95 % CI: 3.75-3.86). Research practice (presentations and previous publications) were found to be very low (27.6% and 2% respectively). Research training received during graduate training was positively correlated with publications (practice) (p < 0.01). Inadequate financial and mentor support as well as lack of access to research equipment were found to be the main barriers the study participants face to conduct clinical research.Conclusion: Participants’ attitude towards research was positive, but their knowledge of research made their practice inadequate. There is a need for filling the gap between high level of positive attitude, low research knowledge and low research practice. This can perhaps be achieved through increasing their training during their graduate studies. Improving research equipment and the resident’s access to financial and better research mentorship are recommended to raise their knowledge and research practice. [Ethiop. J. Health Dev. 2017;31(4):259-265]Keywords: Medical research, Knowledge, Attitude, Post graduate training, Ethiopi

Oral Health-Related Quality of Life of Children Born With Orofacial Clefts in Ethiopia and Their Parents

Objective: To assess the oral health–related quality of life (OH-RQoL) using a translated standardized measure in an understudied population of Ethiopian children born with orofacial clefts (OFCs) and their parents. Methods: Using a descriptive study design, we assessed the OH-RQoL of 41 patients with OFCs between the ages of 8 and 17 years and their parents. Participants received multidisciplinary cleft care from 2008 to 2016. They completed an Amharic translation of the Child Oral Health Impact Profile (COHIP). Results: There was strong internal reliability with the translated COHIP for parents and patients. Parents’ COHIP scores ranged from 67 to 186, and patients’ scores were 78 to 190. The mean for patients and parents was 155, indicating good OH-RQoL. Conclusion: The Amharic translation of the COHIP appears appropriate for use with families in Ethiopia. Both parents and patients reported OH-RQoL at similar levels as other international populations. </jats:sec

Novel <i>IRF6 </i>mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub-Saharan Africa

Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice-site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6-related VWS and PPS in sub-Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high-risk families

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.</p

A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in <i>GRHL3</i>

Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p = 4.08 × 10−9) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1–16.8; OR = 2.16, 95% CI 1.43–3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis