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Jumanah Karim,1 Becher Al-Halabi,2 Yousef Marwan,3 Hussain Sadeq,4 Ahmed Dawas,5 Dalia Al-Abdulrazzaq5 1Department of Pediatrics, Al-Amiri Hospital, Kuwait City, Kuwait; 2Department of Surgery, Mubarak Al-Kabeer Hospital, Kuwait City, Kuwait; 3Department of Orthopaedic Surgery, Al-Razi Orthopaedic Hospital, Kuwait City, Kuwait; 4Department of Pediatrics, Al-Adan Hospital, Kuwait City, Kuwait; 5Department of Pediatrics, Faculty of Medicine, Health Sciences Center, Kuwait University, Kuwait City, Kuwait Background: Educational environment of an institution affects the quality of learning. We aim to assess the educational environment of the undergraduate curriculum of Faculty of Medicine, Kuwait University (FOMKU). Methods: A cross-sectional study was carried out during April 2014. The validated Dundee Ready Education Environment Measure (DREEM) questionnaire was e-mailed to 607 students. Mean scores of the main domains of the questionnaire, and for each item, were calculated, and their association with the students’ background information was measured using Student’s t-test (P-value of ≤0.05 was considered as the cut-off level of significance). Results: Of 607 students, 117 (19.3%) completed the questionnaire. The total mean score for DREEM was 108.7/200 (54.3%). The mean score for students’ perception of teaching, perception of teachers, academic self-perception, perception of atmosphere, and social self-perception were 25.2/48 (52.5%), 24.6/44 (55.9%), 18.4/32 (57.5%), 26.2/48 (54.5%), and 14.3/28 (51.0%), respectively. The highest mean score for an item of DREEM questionnaire was for “my accommodation is pleasant” (3.48±0.75), while the lowest was for “there is a good support system for students who get stressed” (0.88±0.86). The total mean score was not significantly different between the two phases of the curriculum, or among males and females; however, few significant differences among the main domains and items were noted. Conclusion: Based on the learners’ perspectives, the educational environment of FOMKU, was suboptimal. Medical educators in Kuwait should improve this environment in order to advance the quality of the delivered curriculum. Keywords: medical education, undergraduate, medical students, environment, learning, teaching

Wafa'a Al-Qabandi,1 Eman Buhamrah,2 Dalia Al-Abdulrazzaq,1 Khaled Hamadi,2 Fawaz Al Refaee3 1Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait; 2Department of Pediatrics, Al Amiri Hospital, Kuwait; 3Department of Pediatrics, Al Adan Hospital, Kuwait All authors contributed equally to the study Background: Celiac disease (CD) is a chronic inflammatory disease of the small intestine triggered by gluten ingestion. The objective of this study is to describe our experience with CD children in Kuwait. Methods: The records of children with CD seen in the pediatric gastroenterology unit between February 1998 and December 2010 were retrospectively reviewed. Patients were referred because of symptoms or positive CD antibody screening of a high-risk group (type 1 diabetes and Down syndrome). Results: Forty-seven patients were diagnosed: 53% were symptomatic and 47% were identified by screening. The median age at diagnosis was 66 (range 7–189) months. All cases were biopsy-proven except one. The symptomatic patients were significantly younger than those identified following screening (P

Objective: Exploring early-onset diabetes in terms of describing characteristics at time of diagnosis might aid in a better understanding of etiology and may have implications on management and prevention. The aim of this study was to investigate the prevalence of early-onset type 1 diabetes (T1D) in Kuwait as well as describe their baseline clinical, biochemical, and immunological characteristics., Methods: Medical records of children newly diagnosed with T1D and registered in the Childhood-Onset Diabetes electronic Registry (CODeR) in Kuwait between 2017 and 2022 were reviewed. Early-onset T1D was defined as diagnosis at age younger than 6 years., Results: 2,051 children were registered with new-onset T1D between 2017 and 2022, of which 657 (32.0%) were diagnosed at early onset. There has been a trend of slight increase in the percentage of early-onset T1D after 2020 (15.2%) with a prevalence of 18.4% and 20.2% in 2021 and 2022, respectively (p = 0.056). Age at onset was inversely related to admission to the pediatric intensive care unit (OR = 0.90, 95% CI: 0.85, 0.95, p < 0.0001) and was directly related to positive celiac autoimmunity (p = 0.022), higher hemoglobin A1C (p < 0.0001), and C-peptide levels (p < 0.0001). However, age at onset of T1D was inversely related to the higher vitamin D levels (p < 0.0001)., Conclusion: These findings reinforce the need for increased attention to be given to study the development of T1D in children of younger age. This in turn will support special management and prevention measures targeted toward this vulnerable age group., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF., Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses., Results: A total of 998 reports from 499 children with T1D aged 8 to 18 years (study = 276, control = 223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children's care during lockdown ( P  = .019). Patients had better compliance with treatment ( P  = .002), a reversed sleep pattern ( P  = .033), increased food intake ( P  ⩽ .001), and less exercise ( P  < .001). Children and parents perceived better QoL during lockdown ( P  ⩽.001) with no differences between their reports in "Diabetes Symptoms", "Treatment Adherence," and "Communication" domains. Self and proxy reports were different in all domains during non-lockdown ( P  = <.001-.009). In gap analysis, although not statistically significant, the gap was approximated between children's and parents' perceptions in all domains during lockdown., Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: With the rapid transmission of COVID-19 globally, countries have implemented strict governmental measures and social distancing rules that aimed to minimize the spread of the virus. School closures, quarantine orders, and social isolation, coupled with a surge in family stress and lack of peer interactions, are probable causes of mental health complications and psychological symptoms faced by children. This study aims at comparing the HRQoL of children and adolescents with type 1 diabetes (T1D) and affected by COVID-19 infection (personal or familial) and those who were not affected by COVID-19., Materials and Methods: A random sample was selected from children and adolescents diagnosed with T1D at the six major governmental diabetes centers in Kuwait. To measure HRQoL, parent-proxy and self-reports from the Pediatric Quality of Life Inventory (PedsQL TM ) 3.0 Diabetes Module were used., Results: A sample of 455 children and adolescents with T1D diabetes (44.6% male participants and 41.98% affected by COVID-19 infection) was studied. The total score of the HRQoL self-reports was significantly higher compared with parent-proxy reports (79.06 ± 15.19 vs. 73.79 ± 15.17, p < 0.01). Children reported significantly higher HRQoL scores in the "treatment I" domain and "worry" domain and lower scores in the "diabetes" symptoms domain, compared with their parents' reports ( p < 0.01). In the COVID-19-affected group, a major difference was noticed between the total scores of children and parent-proxy reports (77.04 ± 15.81 vs. 72.80±14.90, p = 0.047). The affected children reported significantly lower scores in "diabetes" symptoms (59.50) ( p < 0.01) and higher scores in the "treatment I" domain (81.43) than their parent-proxy reports (72.05) ( p < 0.01)., Conclusion: This is the first report on the health-related quality of life of children with T1D in Kuwait during the COVID-19 era. Parents' or caregivers' experience of caring for their children was negative, as they worried, and reported poorer HRQoL compared with their children's perceptions. There is a need to empower healthcare professionals to support parents and caregivers of children with chronic diseases such as T1D in promoting self-management, enhancing physical and psychological wellbeing, treatment adherence, and continuous health education during pandemics of any kind., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Abdulrazzaq, Khalifa, Alqaisi, Al-Juailla, Othman, Qabazard and Al-Kandari.)

Background: Monitoring the trends in the presentation of T1D over decades cannot be underestimated as it provides a rich source of information on diabetes-related complications like DKA. DKA represents a medical emergency, with potentially fatal outcome, and thus the prevention of DKA is a priority in diabetes care. The aim of this study is to report on trends in the presentation of DKA in children newly diagnosed with T1D in Kuwait., Material and Methods: This study is based on a retrospective review of children newly diagnosed with T1D aged 14 years or less at three Governmental Hospitals representing three health sectors out of the total six health sectors in the country during the period 2011-2017., Results: A total of 799 children (376 males and 423 females) were newly diagnosed with T1D. 287 children presented with DKA (35.9%) with only 73 children (9.1%) classified as severe. During the years 2011 to 2017, we note that the percentage of children older than 6 years of age presenting with severe DKA has decreased significantly (p=0.022). Unfortunately, this has not been replicated in children younger than 6 years., Conclusion: This study highlights the importance of continued monitoring of clinical characteristics of children at diagnosis of T1D specifically presenting with DKA to enable diabetes care professionals to appreciate the multifaceted aspects of T1D, in particular the importance of raising awareness of the early signs of the onset of T1D with special attention to DKA and its severe consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Abdulrazzaq, Othman, Qabazard, Al-Tararwa, Ahmad, Al-Sanae and Al-Kandari.)

Objective: Approved treatments for type 2 diabetes in pediatric patients include metformin, liraglutide, and insulin. However, approximately one-half of the youth fail metformin monotherapy within 1 year, insulin therapy is associated with challenges, and liraglutide requires daily injections. Consequently, the efficacy and safety of once-weekly injections of exenatide for the treatment of youth with type 2 diabetes was evaluated., Research Design and Methods: Participants (aged 10 to <18 years) were randomized (5:2) to once-weekly exenatide 2 mg or placebo, respectively. The primary efficacy end point was change in glycated hemoglobin from baseline to week 24. Secondary efficacy end points were also evaluated, and the frequency of adverse events (AEs) was assessed., Results: A total of 83 participants were randomized (exenatide, 59; placebo, 24) and 72 completed 24-week treatment (exenatide, 49; placebo, 23). At 24 weeks, the least squares mean change in glycated hemoglobin was -0.36% for the exenatide and +0.49% for the placebo groups (between-group difference, -0.85%; 95% CI -1.51, -0.19; P = 0.012). Nonsignificant least squares mean differences from baseline to 24 weeks favoring exenatide were observed: fasting glucose -21.6 mg/dL (-49.0, 5.7; P = 0.119), systolic blood pressure -2.8 mmHg (-8.0, 2.4; P = 0.284), and body weight -1.22 kg (-3.59, 1.15; P = 0.307). AEs occurred in 36 (61.0%) and 17 (73.9%) participants in the exenatide and placebo groups, respectively., Conclusions: In youth with type 2 diabetes suboptimally controlled with current treatments, once-weekly exenatide reduced glycated hemoglobin at 24 weeks and was well tolerated., (© 2022 by the American Diabetes Association.)

Objective: Establishing a pediatric COVID-19 registry in Kuwait (PCR-Q8) was deemed imperative during the pandemic to study children infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) focusing on mode of presentation, therapeutic interventions, disease severity, and early outcomes. This manuscript describes the rapid establishment of the PCR-Q8 registry showcasing an infrastructure of the development process and presents the results of the pilot phase., Subject and Methods: The registry was developed and implemented using the general key steps from a resource titled "Registries for Evaluating Patient Outcomes: A User's Guide" as a guide for best practice, experience from a previously established pediatric diabetes registry in Kuwait and several other COVID-19 registries developed globally. During the pilot phase, a convenience sample of 120 children was included, of whom 66 (55%) were male., Results: Experience and expertise from other COVID-19 registries; guidance provided by the World Health Organization; and effective collaboration and cooperation between the stakeholders, study group, and data enterers during these challenging times were critical for the development and implementation of the registry. Our results were similar to international reports which showed that most children presented with mild disease (69.2%), majority (70.2%) had normal chest X-ray, and the most common symptom at presentation was fever (77%)., Conclusion: We anticipate the development of PCR-Q8 to be a stepping-stone for more in-depth investigation of SARS-CoV-2 infection in children in Kuwait and for the establishment of other registries., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Genetic variants responsible for Maturity-Onset-Diabetes of the Young (MODY) in Kuwait were investigated. A newly established a National Referral Clinic, the Dasman Diabetes Institute (DDI-NRC), assessed forty-five members from 31 suspected MODY families by whole exome sequencing. Thirty-three of the 45 samples were independently sequenced at the DDI-NRI, Exeter University, UK ( https://www.diabetesgenes.org/ ) using targeted 21-gene panel approach. Pathogenic mutations in GCK, HNF1A, HNF1B, HNF4A, and PDX1 confirmed MODY in 7 families, giving an overall positivity rate of 22.6% in this cohort. Novel variants were identified in three families in PDX1, HNF1B, and HNF1B. In this cohort, Multiplex Ligation-dependent Probe Amplification assay did not add any value to MODY variant detection rate in sequencing negative cases. In highly selected familial autoantibody negative diabetes, known MODY genes represent a minority and 77.3% of the familial cases have yet to have a causal variant described., (© 2021. The Author(s).)

Background: Type 2 Diabetes (T2D) in children and adolescents has become an important public health concern due to the increase in childhood obesity worldwide. The urgency to address T2D is evident as children and adolescents are at a higher risk of complications due to prolonged disease duration. We aimed to estimate the incidence rate (IR) of T2D in Kuwaiti children and adolescents aged 14 years and younger between 2011 and 2013 and to describe their clinical characteristics at the time of diagnosis. Material and Methods: All newly diagnosed patients were registered through the Childhood-Onset Diabetes electronic Registry implemented in Kuwait. Cases who met the 2018 ISPAD guidelines for diagnosis of T2D were included. Results: A total of 32 patients were included, equally distributed gender-wise, with a mean age 12.2 years (±1.7 SD), lower for females than males (11.5 vs. 12.2, p < 0.025). Data ascertainment was 94.1% (95%CI; 91.6-96.6%). Overall IR was 2.56 (95% CI; 1.78-3.56) per 100,000 Kuwaiti children and adolescents per year. Most of the patients ( n = 30; 93.8%) presented with T2D between the ages 10-14 years, with age-specific IR of 8.0 (95%CI; 5.5-11.3). No statistically significant difference between males and females with regards to BMI z scores or HbA1C at diagnosis. Conclusion: The true incidence of T2D in Kuwaiti children and adolescents is expected to be considerably higher as we have reported only symptomatic cases. Future research should focus on screening children and adolescents at risk to enable accurate estimates. More efforts are needed to better understand the clinical course of T2D early in life to improve management, prevent complications and improve quality of life., (Copyright © 2019 Al-Kandari, Al-Abdulrazzaq, Davidsson, Sharma, Al-Tararwa, Mandani, Al-Shawaf, Al-Hussaini, Qabazard, Haddad, Al-Mahdi, Al-Jasser, Al-Anzi, Al-Sanea, Al-Basari, Al-Adsani, Shaltout and AbdulRasoul.)

Objective: In recent decades, the Arab population has experienced an increase in the prevalence of type 2 diabetes (T2DM), particularly within the Gulf Cooperation Council. In this context, early intervention programmes rely on an ability to identify individuals at risk of T2DM. We aimed to build prognostic models for the risk of T2DM in the Arab population using machine-learning algorithms vs. conventional logistic regression (LR) and simple non-invasive clinical markers over three different time scales (3, 5, and 7 years from the baseline). Design: This retrospective cohort study used three models based on LR, k -nearest neighbours (k-NN), and support vector machines (SVM) with five-fold cross-validation. The models included the following baseline non-invasive parameters: age, sex, body mass index (BMI), pre-existing hypertension, family history of hypertension, and T2DM. Setting: This study was based on data from the Kuwait Health Network (KHN), which integrated primary health and hospital laboratory data into a single system. Participants: The study included 1,837 native Kuwaiti Arab individuals (equal proportion of men and women) with mean age as 59.5 ± 11.4 years. Among them, 647 developed T2DM within 7 years of the baseline non-invasive measurements. Analytical methods: The discriminatory power of each model for classifying people at risk of T2DM within 3, 5, or 7 years and the area under the receiver operating characteristic curve (AUC) were determined. Outcome measures: Onset of T2DM at 3, 5, and 7 years. Results: The k-NN machine-learning technique, which yielded AUC values of 0.83, 0.82, and 0.79 for 3-, 5-, and 7-year prediction horizons, respectively, outperformed the most commonly used LR method and other previously reported methods. Comparable results were achieved using the SVM and LR models with corresponding AUC values of (SVM: 0.73, LR: 0.74), (SVM: 0.68, LR: 0.72), and (SVM: 0.71, LR: 0.70) for 3-, 5-, and 7-year prediction horizons, respectively. For all models, the discriminatory power decreased as the prediction horizon increased from 3 to 7 years. Conclusions: Machine-learning techniques represent a useful addition to the commonly reported LR technique. Our prognostic models for the future risk of T2DM could be used to plan and implement early prevention programmes for at risk groups in the Arab population., (Copyright © 2019 Farran, AlWotayan, Alkandari, Al-Abdulrazzaq, Channanath and Thanaraj.)

Objective: The "accelerator hypothesis" predicts early onset of Type 1 diabetes (T1D) in heavier children. Studies testing direction of correlation between body mass index (BMI) and age at onset of T1D in different continental populations have reported differing results-inverse, direct, and neutral. Evaluating the correlation in diverse ethnic populations is required to generalize the accelerator hypothesis., Methods: The study cohort comprised 474 Kuwaiti children of Arab ethnicity diagnosed with T1D at age 6 to 18 years during 2011-2013. Age- and sex-adjusted BMI z-scores were calculated by comparing the BMI measured at diagnosis with Kuwaiti pediatric population reference data recorded during comparable time-period. Multiple linear regression and Pearson correlation analyses were performed., Results: BMI z-score was seen inversely associated with onset age (r,-0.28; p-value<0.001). Children with BMI z-score>0 (i.e. BMI >national average) showed a stronger correlation (r,-0.38; p-value<0.001) than those with BMI z-score<0 (r,-0.19; p-value<0.001); the former group showed significantly lower mean onset age than the latter group (9.6±2.4 versus 10.5±2.7; p-value<0.001). Observed inverse correlation was consistent with that seen in Anglo-saxon, central european, caucasian, and white children while inconsistent with that seen in Indian, New Zealander, and Australian children., Conclusions: The accelerator hypothesis generalizes in Arab pediatric population from Kuwait.

Background: Recombinant Growth hormone (rGH) therapy is approved in many countries for treatment of short stature in a number of childhood diagnoses. Despite the increasing body of international literature on rGH use, there is paucity of data on rGH use in Kuwait and the broader Middle-East which share unique ethnic and socio-cultural backgrounds. This study aimed to describe the pattern of use and treatment outcomes of rGH therapy in Kuwait., Methods: This is a cross-sectional retrospective review of children treated with rGH in the Department of Pediatrics, in a major hospital in Kuwait between December 2013 and December 2014. Data were extracted using standard data extraction form and the response to rGH therapy was defined as a gain of ≥ 0.3 standard deviation score (SDS) of height per year., Results: A total of 60 children were treated with rGH in the center. Their Median (Interquartile) age at rGH initiation was 9.0 (6.2, 10.7) years. The most common indications for rGH therapy were Growth Hormone Deficiency (GHD) 23 (38.3 %), Idiopathic Short Stature (ISS) 12 (20.0 %) and Small for Gestational Age (SGA) 9 (15.0 %). After excluding patients with TS, no significant differences were found in gender of those who received rGH therapy in all indications combined or in each group (p ≥ 0.40). At 1-year follow-up, children in all groups had median height SDS change of ≥ 0.3 SDS except for children with ISS. Age at rGH initiation was negatively associated with 1-year treatment response, Adjusted odds ratio (AOR) 0.56 (95 % CI: 0.04-1.49); p = 0.011)., Conclusions: GHD is the most common indication of rGH therapy. All indications except for ISS showed significant 1-year treatment response to therapy. Treatment outcomes in patients with ISS should be further investigated in Kuwait. Younger age at initiation of rGH therapy was independently associated with significant response to therapy suggesting the importance of identifying children with short stature and prompt initiation of rGH therapy.

Background: Professionalism is a core competency in the medical profession worldwide. Numerous studies investigate how this competency is taught and learned. However, there are few reports on the students' views and experiences with professionalism especially in the Arab world. Our aim was to explore the experiences and views of Kuwait final-year medical students on professionalism., Methods: This was a questionnaire study of final-year medical students at Kuwait University (n = 95). Open- and close-ended questions were used to determine the students' experiences and views on: definition, teaching, learning, and assessment of professionalism., Results: Eighty-five of the students completed the questionnaire (89.5%). A total of 252 attributes defining professionalism were listed by our respondents. The majority (98.0%) of these attributes were categorized under the CanMEDS theme describing professionalism as commitment to patients, profession, and society through ethical practice. The most helpful methods in learning about professionalism for the students were contact with positive role models, patients and families, and with their own families, relatives and peers. The students' rating of the quality and quantity of teaching professionalism in the institution was quite variable. Despite this, 68.2% of the students felt very or somewhat comfortable explaining the meaning of medical professionalism to junior medical students. Almost half of the students felt that their education had always or sometimes helped them deal with professionally-challenging situations. Majority (77.6%) of the students thought that their academic assessments should include assessment of professionalism and should be used as a selection criterion in their future academic careers (62.3%). Most of the students discussed and sought advice regarding professionally-challenging situations from their fellow medical students and colleagues. Seventy-five (88.2%) students did not know which organizational body in the institution deals with matters pertaining to medical professionalism., Conclusion: This study highlights the influence of the curriculum, the hidden curriculum, and culture on medical students' perception of professionalism. Medical educators should take in account such influences when teaching and assessing professionalism. Future research should aim at creating a framework of competencies that addresses professionalism in a context suitable for the Arabian culture.

Hyperparathyroidism Jaw-Tumour Syndrome (HPT-JT) is characterized by primary hyperparathyroidism (PHPT), maxillary/mandible ossifying fibromas and by parathyroid carcinoma in 15% of cases. Inactivating mutations of the tumour suppressor CDC73/HRPT2 gene have been found in HPT-JT patients and also as genetic determinants of sporadic parathyroid carcinoma/atypical adenomas and, rarely, typical adenomas, in familial PHPT. Here we report the genetic and molecular analysis of the CDC73/HRPT2 gene in three patients affected by PHPT due to atypical and typical parathyroid adenomas, in one case belonging to familial PHPT. Flag-tagged WT and mutant CDC73/HRPT2 proteins were transiently transfected in HEK293 cells and functional assays were performed in order to investigate the effect of the variants on the whole protein expression, nuclear localization and cell overgrowth induction. We identified four CDC73/HRPT2 gene mutations, three germline (c.679&#95;680delAG, p.Val85&#95;Val86del and p.Glu81&#95;Pro84del), one somatic (p.Arg77Pro). In three cases the mutation was located within the Nucleolar Localisation Signals (NoLS). The three NoLS variants led to instability either of the corresponding mutated protein or mRNA or both. When transfected in HEK293 cells, NoLS mutated proteins mislocalized with a predeliction for cytoplasmic or nucleo-cytoplasmic localization and, finally, they resulted in overgrowth, consistent with a dominant negative interfering effect in the presence of the endogenous protein.