Knowledge and Awareness of Rare Diseases Among Healthcare Professionals in the Kingdom of Bahrain.

Aim  Recent studies highlighted that lack of knowledge on rare diseases is a problem that requires attention. This study aims to assess healthcare professionals' general awareness and knowledge of rare diseases in a tertiary hospital in the Kingdom of Bahrain. Method  The study employed a cross-sectional design, utilizing a survey questionnaire derived from the most recent literature. The survey encompassed socio-demographic factors and quiz-based questions that were previously created by Domaradzi and Walkowiak to assess knowledge and awareness of rare diseases. To ensure convenience and accessibility, the survey was made available in both Arabic and English languages. Results  Of a total of 333 responses, 25.2% were physicians, 53.8% were nurses, and 21.0% were allied health personnel. The majority of participants (87.4%) were aware of and had heard the term "rare diseases" prior to this survey. Participants were able to recognize what age group is frequently affected by rare diseases (p=0.023) and what the common cause of rare diseases worldwide is (p<0.001). Overall scores showed that only four participants answered all questions correctly, testing their knowledge of rare diseases. There was a weak correlation between self-declared knowledge and the overall score achieved (r=0.190; p<0.001), which indicates that the population's self-declared knowledge did not portray their actual knowledge of rare diseases.  Conclusion  This study highlights the need for improved knowledge of rare diseases among healthcare professionals, which aligns with the global knowledge landscape. To bridge the knowledge gap, we recommend action plans to ensure that healthcare professionals have rich knowledge of rare diseases and further improve patient care. Additionally, enhancing advocacy efforts is crucial to ensure optimal local and global patient care services.

Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel.

Germline variants in BRCA1 and BRCA2 (BRCA1/2) genes are the most common cause of hereditary breast cancer. However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-generation sequencing (NGS) allowed simultaneous sequencing of multiple cancer-susceptibility genes and prompted research in this field. So far, cancer-predisposition genes other than BRCA1/2 have not been studied in the population of Bahrain. We performed a targeted NGS using a multi-panel covering 180 genes associated with cancer predisposition to investigate the spectrum and frequency of germline variants in 54 women with a positive personal and/or family history of breast cancer. Sequencing analysis revealed germline variants in 29 (53.7%) patients. Five pathogenic/likely pathogenic variants in four DNA repair pathway-related genes were identified in five unrelated patients (9.3%). Two BRCA1 variants, namely the missense variant c.287A>G (p.Asp96Gly) and the truncating variant c.1066C>T (p.Gln356Ter), were detected in two patients (3.7%). Three variants in non-BRCA1/2 genes were detected in three patients (1.85% each) with a strong family history of breast cancer. These included a monoallelic missense variant c.1187G>A (p.Gly396Asp) in MUTYH gene, and two truncating variants namely c.3343C>T (p.Arg1115Ter) in MLH3 gene and c.1826G>A (p.Trp609Ter) in PMS1 gene. Other variants of uncertain significance (VUS) were also detected, and some of them were found together with the deleterious variants. In this first application of NGS-based multigene testing in Bahraini women with breast cancer, we show that multigene testing can yield additional genomic information on low-penetrance genes, although the clinical significance of these genes has not been fully appreciated yet. Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling.

Whole Exome Sequencing Achieved a Definite Diagnosis of Kaufman Oculocerebrofacial Syndrome in a Bahraini Family: A Case Report.

A 1 year and 7 months old girl presented to the medical genetic clinic as a referral from the pediatrics clinic. Upon examining the patient and assessing past medical history, an autosomal recessive disorder was suspected. The family underwent whole exome sequencing, which resulted in the diagnosis of Kaufman oculocerebrofacial syndrome (OMIM #244450) in the patient due to the fact that both parents were heterozygous carriers of a novel pathogenic variant in the gene UBE3B that lies on 12q24. It has been recommended for the family that preimplantation genetic testing should be considered for future pregnancies. In this case report, we present a novel variant of the gene and highlight the support of whole exome sequencing in the unveiling of genetic disorders.

When Recurrent Strokes, Back Pain, and Alopecia Constitute a Hereditary Cause of Small-Vessel Disease, CARASIL in an Arabic Woman.

INTRODUCTION: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare autosomal recessive etiology of cerebral small-vessel disease. The bulk of CARASIL cases reported in the literature was from Japan and China. Herein, we report the first genetically confirmed case of CARASIL in the Arabic population. CASE PRESENTATION: We present the case of a 35-year-old Bahraini woman diagnosed with an acute ischemic stroke after experiencing right-sided weakness and slurred speech. She had complained of persistent headaches, decreased memory, hair loss, joint pain, and personality changes. CARASIL was suspected on her medical history and brain imaging results, and genetic testing confirmed the diagnosis. CONCLUSION: This case contributes to our understanding of CARASIL, which is an extremely rare disease. It adds to the growing data on disease reporting outside China and Japan. We also report the first case of CARASIL in an Arabic patient and describe magnetic resonance spectroscopy finding partially different from what has been reported before.

Generalisability theory analyses of concept mapping assessment scores in a problem-based medical curriculum.

CONTEXT: In problem-based learning (PBL), students construct concept maps that integrate different concepts related to the PBL case and are guided by the learning needs generated in small-group tutorials. Although an instrument to measure students' concept maps in PBL programmes has been developed, the psychometric properties of this instrument have not yet been assessed. OBJECTIVES: This study evaluated the generalisability of and sources of variance in medical students' concept map assessment scores in a PBL context. METHODS: Medical students (Year 4, n = 116) were asked to construct three integrated concept maps in which the content domain of each map was to be focused on a PBL clinical case. Concept maps were independently evaluated by four raters based on five criteria: valid selection of concepts; hierarchical arrangement of concepts; degree of integration; relationship to the context of the problem, and degree of student creativity. Generalisability theory was used to compute the reliability of the concept map scores. RESULTS: The dependability coefficient, which indicates the reliability of scores across the measured facets for making absolute decisions, was 0.814. Students' concept map scores (universe scores) accounted for the largest proportion of total variance (47%) across all score comparisons. Rater differences accounted for 10% of total variance, and the student × rater interaction accounted for 25% of total variance. The variance attributable to differences in the content domain of the maps was negligible (2%). The remaining 16% of the variance reflected unexplained sources of error. Results from the D study suggested that a dependability level of 0.80 can be achieved by using three raters who each score two concept map domains, or by using five raters who each score only one concept map domain. CONCLUSIONS: This study demonstrated that concept mapping assessment scores of medical students in PBL have high reliability. Results suggested that greater improvements in dependability might be made by increasing the number of raters rather than by increasing the number of concept map domains.

Do medical students' scores using different assessment instruments predict their scores in clinical reasoning using a computer-based simulation?

PURPOSE: The development of clinical problem-solving skills evolves over time and requires structured training and background knowledge. Computer-based case simulations (CCS) have been used for teaching and assessment of clinical reasoning skills. However, previous studies examining the psychometric properties of CCS as an assessment tool have been controversial. Furthermore, studies reporting the integration of CCS into problem-based medical curricula have been limited. METHODS: This study examined the psychometric properties of using CCS software (DxR Clinician) for assessment of medical students (n=130) studying in a problem-based, integrated multisystem module (Unit IX) during the academic year 2011-2012. Internal consistency reliability of CCS scores was calculated using Cronbach's alpha statistics. The relationships between students' scores in CCS components (clinical reasoning, diagnostic performance, and patient management) and their scores in other examination tools at the end of the unit including multiple-choice questions, short-answer questions, objective structured clinical examination (OSCE), and real patient encounters were analyzed using stepwise hierarchical linear regression. RESULTS: Internal consistency reliability of CCS scores was high (α=0.862). Inter-item correlations between students' scores in different CCS components and their scores in CCS and other test items were statistically significant. Regression analysis indicated that OSCE scores predicted 32.7% and 35.1% of the variance in clinical reasoning and patient management scores, respectively (P<0.01). Multiple-choice question scores, however, predicted only 15.4% of the variance in diagnostic performance scores (P<0.01), while students' scores in real patient encounters did not predict any of the CCS scores. CONCLUSION: Students' scores in OSCE are the most important predictors of their scores in clinical reasoning and patient management using CCS. However, real patient encounter assessment does not appear to test a construct similar to what is tested in CCS.