Gender-specific Reference Range for Serum Leptin in Omani Population.

Objectives: Leptin is a hormone that contributes to glucose homeostasis and food intake regulation via its action on the hypothalamus. Leptin level increases with obesity and overfeeding and decreases with energy deficiency. Serum leptin levels vary between different ethnic groups with no reports of its reference range in the Arabic population. We sought to determine gender-specific reference ranges for serum leptin in a cohort of the Arabic population and identify the cut-off value for different metabolic derangements. Methods: The study data were obtained from the records of 1198 subjects included in the Oman Family Study. The percentile method was used in the estimation reference range and the receiver operating characteristic to identify cut-off points for multiple metabolic derangements. Results: The reference range of serum leptin was 0.5-90.6 ng/mL, and it was not correlated with the age of the subjects. Higher leptin was observed in females compared to males (p < 0.001), and the reference range for serum leptin in females was 4.9-96.3 ng/mL compared to 0.25-48.8 ng/mL in males. The optimum cut-off value for leptin ranged between 24.1-28.9 ng/mL for metabolic syndrome, obesity, central obesity, and type 2 diabetes. Conclusions: We identified gender-specific reference ranges for serum leptin in a large cohort of Arabs. The optimum cut-off value for serum leptin to determine metabolic derangement with the highest sensitivity and specificity was 24.1-28.9 ng/mL. Future studies are needed to study the relative risk of higher serum leptin using prospective studies.

Prevalence and Risk Factors of Discordance Between Hip and Spinal Bone Mineral Density Among Saudi Subjects.

Background Discordance between hip and spine on dual-energy x-ray absorptiometry is a well-known problem in diagnosing osteoporosis. The prevalence and risk factors of this problem have not been studied in the Saudi population. The objective of this study was to document this discordance in our population and its possible risk factors. Materials and methods We analyzed data obtained from subjects who had dual x-ray absorptiometry (DXA) between January 2021 and December 2021 at King Khalid University Hospital, Riyadh, Saudi Arabia. Subjects with the following conditions were excluded: secondary osteoporosis, patients taking anti-osteoporotic agents, patients on steroids or hormonal replacement therapy, hyperparathyroidism, hypoparathyroidism, and chronic renal disease. A total of 1388 patients satisfied our inclusion criteria. World Health Organization (WHO) criteria for diagnosis were implemented. Major discordance was defined as osteoporosis in one site and normal in the other. Minor discordance was defined as a difference of no more than one World Health Organization diagnostic class between two sites. Bivariate statistical analysis was achieved using appropriate statistical tests (chi-square, student's t-test, one-way analysis of variance, and Pearson's correlation), based on the type of study and outcome variables. A p-value of < 0.05 and 95% CI were used to report the statistical significance and precision of results. Results A total of 1388 subjects were analyzed, of which, 1196 (86%) were females with a mean age of 58.8 (13.8 SD) and 192 were males with a mean age of 58 (18.0 SD). Lumbar osteoporosis was found in 312 (22.5%) participants while hip osteoporosis was reported in 73 (5.3%) of the participants. Major discordance was documented in 85 (6.1%) of all participants (6.3% of the male and 6.1% of the female patients). All of these subjects had lumbar spine osteoporosis with normal hip bone mineral density (BMD). Minor discordance was found in 591 patients (42.6%). Obesity (BMI > 30) was found to be a risk factor for both major (2.10-11.6, 95% CI) and minor (2.5-11.4, 95% CI) discordance. Conclusion Discordance between hip and spine BMD is common among Saudi subjects. Lumbar spine osteoporosis with normal hip BMD caused this discordance in our subjects. Obesity could be responsible for the occurrence of this discordance. Mechanisms may include higher rate of turnover in spine, technical artifacts in the measurements of lumbar spine BMD, or due to the effects of weight loading. Caution should be exercised when interpreting DXA results, especially in obese subjects.

Incidence of hip fracture in Saudi Arabia and the development of a FRAX model.

A prospective hospital-based survey in representative regions of Saudi Arabia determined the incidence of fractures at the hip. The hip fracture rates were used to create a FRAX® model to facilitate fracture risk assessment in Saudi Arabia. OBJECTIVE: This paper describes the incidence of hip fracture in the Kingdom of Saudi Arabia that was used to characterize the current and future burden of hip fracture, to develop a country-specific FRAX® tool for fracture prediction and to compare fracture probabilities with neighbouring countries. METHODS: During a 2-year (2017/2018) prospective survey in 15 hospitals with a defined catchment population, hip fractures in Saudi citizens were prospectively identified from hospital registers. The number of hip fractures and future burden was determined from national demography. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Saudi Arabia. Fracture probabilities were compared with those from Kuwait and Abu Dhabi. RESULTS: The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 2,949 and is predicted to increase nearly sevenfold to 20,328 in 2050. Hip fracture rates were comparable with estimates from Abu Dhabi and Kuwait. By contrast, probabilities of a major osteoporotic fracture or hip fracture from the age of 70 years were much lower than those seen in Abu Dhabi and Kuwait due to higher mortality estimates for Saudi Arabia. CONCLUSION: A country-specific FRAX tool for fracture prediction has been developed for Saudi Arabia which is expected to help guide decisions about treatment.

Heritability and genetic correlations of obesity indices with ambulatory and office beat-to-beat blood pressure in the Oman Family Study.

OBJECTIVE: To more precisely and comprehensively estimate the genetic and environmental correlations between various indices of obesity and BP. METHODS: We estimated heritability and genetic correlations of obesity indices with BP in the Oman family study (n = 1231). Ambulatory and office beat-to-beat BP was measured and mean values for SBP and DBP during daytime, sleep, 24-h and 10 min at rest were calculated. Different indices were used to quantify obesity and fat distribution: BMI, percentage of body fat (%BF), waist circumference and waist-to-height ratio (WHtR). SOLAR software was used to perform univariate and bivariate quantitative genetic analyses adjusting for age, age, sex, age-sex and age--sex interactions. RESULTS: Heritabilities of BP ranged from 30.2 to 38.2% for ambulatory daytime, 16.8--21.4% for sleeping time, 32.1--40.4% for 24-h and 22--24.4% for office beat-to-beat measurements. Heritabilities for obesity indices were 67.8% for BMI, 52.2% for %BF, 37.3% for waist circumference and 37.9% for WHtR. All obesity measures had consistently positive phenotypic correlations with ambulatory and office beat-to-beat SBP and DBP (r-range: 0.14--0.32). Genetic correlations of obesity indices with SBP and DBP were higher than environmental correlations (rG: 0.16--0.50; rE: 0.01--0.31). CONCLUSION: The considerable genetic overlap between a variety of obesity indices and both ambulatory and office beat-to-beat BP highlights the relevance of pleiotropic genes. Future GWAS analyses should discover the specific genes both influencing obesity indices and BP to help unravel their shared genetic background.

Celiac disease and severe vitamin D deficiency: the case for anti-tissue transglutaminase antibody screening.

Vitamin D-deficient Saudi adolescent girls were screened for anti-tissue transglutaminase (IgA-tTG) antibodies to determine whether the presence of severe vitamin D deficiency was associated with celiac disease. All 9 participants who were positive for IgA-tTG antibodies had severe vitamin D deficiency (25(OH)D < 12.5 nmol/l), suggesting that this population should be screened for celiac disease. PURPOSE: The current cross-sectional study aimed to see if severe vitamin D deficiency is associated with celiac disease (CD) among Saudi adolescent girls. METHODS: A total 200 adolescent females aged 13-19 years old with vitamin D deficiency (serum 25(OH)D < 50 nmol/l) were screened for IgA tTG (anti-tissue transglutaminase antibodies). RESULTS: Of the 200 girls, 9 (4.5%) were positive for IgA tTG antibodies; all of whom had serum 25(OH)D < 12.5 nmol/l. A strong significant inverse association was observed between tTG antibody levels and serum 25(OH)D (R = - 0.53; p < 0.001) among antibody negative participants. Finally, participants with positive IgA tTG antibodies was 37.2 times higher for participants with 25(OH)D < 12.5 nmol/l than those whose vitamin D status was higher [OR = 37.2 (95% CI 4.6-299.7) (p = 0.0002)]. CONCLUSION: The data suggests that CD maybe a risk factor for severe vitamin D deficiency and that patients presenting with very low levels of 25(OH)D of less than 12.5 nmol/l-in the absence of an obvious cause-may need to be screened for CD.

Heritability and genetic and environmental correlations of heart rate variability and baroreceptor reflex sensitivity with ambulatory and beat-to-beat blood pressure.

This family study from Oman (n = 1231) explored the heritability and genetic and environmental correlations of heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS) with ambulatory and beat-to-beat blood pressure (BP). Ambulatory BP was measured for 24 hours to calculate mean values for daytime and sleep separately. Time and frequency domain HRV indices, BRS, office beat-to-beat BP, and heart rate (HR) were measured for 10 minutes at rest. SOLAR software was used to perform univariate and bivariate quantitative genetic analyses adjusting for age, age2, sex, their interactions and BMI. Heritability of SBP and DBP ranged from 16.8% to 40.4% for daytime, sleeping, 24-hour and office beat-to-beat measurements. HR and BRS showed a heritability of 31.9% and 20.6%, respectively, and for HRV indices heritability ranged from 11.1% to 20.5%. All HRV measurements and BRS were found to be negatively correlated with BP, but phenotypic correlation coefficients were relatively weak; HR was positively correlated with BP. None of the genetic correlations were statistically significant while environmental factors explained most of the correlations for all HRV indices with BP. Our study found consistent but weak correlations among HRV, HR, BRS and ambulatory/office beat-to-beat BP. However, environmental rather than genetic factors contributed most to those correlations.

INTRAVITREAL DEXAMETHASONE IMPLANT IN RETINITIS PIGMENTOSA-RELATED CYSTOID MACULAR EDEMA.

PURPOSE: To report the clinical outcome after intravitreal dexamethasone implant in patients with retinitis pigmentosa and cystoid macular edema. METHODS: Multicenter retrospective case series of eyes with retinitis pigmentosa and cystoid macular edema that underwent intravitreal dexamethasone implant. Primary outcome measures were best-corrected visual acuity in LogMAR and central macular thickness. Statistical analyses used two-tailed comparison with Wilcoxon signed-rank test. RESULTS: There were a total of 45 eyes from 34 patients with a mean age of 32.7 years (range 16-57) and mean follow-up of 15.5 ± 13.0 months. At Month 3 after the first injection, mean initial best-corrected visual acuity improved from 0.61 ± 0.38 (20/81) to 0.37 ± 0.16 (20/47) (P = 0.012), whereas mean central macular thickness (µm) decreased from 506 ± 288 µm to 311.7 ± 71.6 µm (P < 0.001) and mean intraocular pressure increased from 15.7 ± 2.3 mmHg to 19.8 ± 11.0 mmHg (P = 0.01). Fourteen eyes had multiple injections (1-7 reinjections) at a mean interval of 6 months. Treatment effect was durable with multiple injections, but with seven eyes developing visually significant cataracts. CONCLUSION: Best-corrected visual acuity improved up to 4 months in around half of the eyes. Eyes that benefited the most were pseudophakic, steroid nonresponsive, with large initial central macular thickness, and profuse fluorescein dye leakage.

A weekly 35,000 IU vitamin D supplementation improves bone turnover markers in vitamin D deficient Saudi adolescent females.

This study examined the effects of weekly 35,000 IU vitamin D supplementation for 4 weeks on bone turnover markers (BTMs). There was improvement in the levels of parathyroid hormone (PTH), osteocalcin, and carboxy-terminal telopeptides of crosslinks of type 1 collagen (ßCTX) which paralleled the increase in vitamin D levels. PURPOSE: The effects of vitamin D supplementation on bone turnover markers (BTMs) have been inconsistent. This study examined the effects of weekly 35,000 IU vitamin D supplementation for 1 month on BTMs. METHODS: Sixty-eight vitamin D deficient adolescent females were given 35,000 IU of vitamin D3 for 4 weeks. Pre and post intervention blood samples were taken for 25(OH) D, PTH, osteocalcin and ßCTX. RESULTS: There was a significant increase in serum 25 (OH) D in the post intervention period which was accompanied by a significant decrease in PTH, osteocalcin and ßCTX (P < 0.001). CONCLUSIONS: We concluded that weekly 35,000 IU vitamin D supplementation for 4 weeks results in significant improvement of BTMs.

Acute disseminated encephalomyelitis complicating dengue infection with neuroimaging mimicking multiple sclerosis: A report of two cases.

Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients.

Vitamin D deficiency and biochemical variations among urban Saudi adolescent girls according to season.

OBJECTIVES: To determine seasonal variations in the vitamin D status of Saudi adolescent girls in Riyadh, Kingdom of Saudi Arabia (KSA) and its effect in biochemical and clinical characteristics.  METHODS: In this prospective study, a total of 2000 Saudi females aged 12-18 years from different schools in Riyadh, KSA participated and submitted a generalized questionnaire with clinical information. Fasting blood samples were obtained in 1618 subjects for the winter season (December to February) and only 499 subjects returned to submit fasting blood samples for the summer season (June-August). Circulating serum 25(OH)D, parathyroid hormone (PTH), and other biomarkers of bone remodeling were measured during both seasons.  RESULTS: Vitamin D deficiency (serum 25(OH)D  less than 25 nmol/L) was significantly higher during summer than winter (63.5% versus 40.8%; p less than 0.001). Mean serum PTH was also significantly higher during summer than winter (p less than 0.01). In all subjects, serum PTH showed a significant inverse association with 25(OH)D at levels below 40 nmol/L (r=-0.21; p less than 0.001). The prevalence of subjects having clinical and metabolic manifestations suggestive of osteomalacia was 2.13% (N=33 out of 1548). CONCLUSION: Seasonal variations in the vitamin D status of Saudi adolescent females significantly modifies biochemical parameters as response to vitamin D status change. In the meantime, heightened public health awareness should be given to populations at higher risk for vitamin D deficiency.

A fuzzy-ontology-oriented case-based reasoning framework for semantic diabetes diagnosis.

OBJECTIVE: Case-based reasoning (CBR) is a problem-solving paradigm that uses past knowledge to interpret or solve new problems. It is suitable for experience-based and theory-less problems. Building a semantically intelligent CBR that mimic the expert thinking can solve many problems especially medical ones. METHODS: Knowledge-intensive CBR using formal ontologies is an evolvement of this paradigm. Ontologies can be used for case representation and storage, and it can be used as a background knowledge. Using standard medical ontologies, such as SNOMED CT, enhances the interoperability and integration with the health care systems. Moreover, utilizing vague or imprecise knowledge further improves the CBR semantic effectiveness. This paper proposes a fuzzy ontology-based CBR framework. It proposes a fuzzy case-base OWL2 ontology, and a fuzzy semantic retrieval algorithm that handles many feature types. MATERIAL: This framework is implemented and tested on the diabetes diagnosis problem. The fuzzy ontology is populated with 60 real diabetic cases. The effectiveness of the proposed approach is illustrated with a set of experiments and case studies. RESULTS: The resulting system can answer complex medical queries related to semantic understanding of medical concepts and handling of vague terms. The resulting fuzzy case-base ontology has 63 concepts, 54 (fuzzy) object properties, 138 (fuzzy) datatype properties, 105 fuzzy datatypes, and 2640 instances. The system achieves an accuracy of 97.67%. We compare our framework with existing CBR systems and a set of five machine-learning classifiers; our system outperforms all of these systems. CONCLUSION: Building an integrated CBR system can improve its performance. Representing CBR knowledge using the fuzzy ontology and building a case retrieval algorithm that treats different features differently improves the accuracy of the resulting systems.

Epidemiology of Diabetes Mellitus in Oman: Results from two decades of research.

OBJECTIVES: This study aimed to describe the epidemiology of diabetes mellitus over the past two decades in Oman, particularly in terms of its prevalence and incidence. In addition, the study sought to estimate the future incidence of diabetes in Oman. METHODS: Three national and three regional surveys conducted between 1991 and 2010 were analysed to obtain the age-adjusted prevalence and undiagnosed proportion of type 2 diabetes mellitus (T2DM) among Omani subjects aged ≥20 years. Diabetes mellitus registers and published studies were used to determine incidence rates of both type 1 diabetes mellitus (T1DM) and T2DM in Oman. Linear regression was used to determine trends and projections for diabetes in 2050. RESULTS: The age-adjusted prevalence of T2DM in Oman varied from 10.4% to 21.1%, while the highest prevalence of impaired fasting glucose was found in males (35.1%). In comparison to men, higher incidence rates of T2DM were found in women (2.7 cases compared to 2.3 cases per 1,000 person-years, respectively). No significant trends were observed for the prevalence or incidence of T2DM in both genders. Undiagnosed T2DM was more common in men (range: 33-68%) than women (range: 27-53%). The results of this study show that by 2050, there will be an estimated 350,000 people with T2DM living in Oman (a 174% increase compared to estimates for 2015). CONCLUSION: Health authorities need to prioritise diabetes prevention and control in order to prevent or delay long-term complications and avert a potential epidemic of diabetes in Oman.

ECG-gated coronary angiography enables submillisievert imaging in invasive cardiology.

BACKGROUND: The median dose area products (DAP) and effective doses (ED) of patients arising from coronary angiography (CA) are considerable: According the 2013 National German Registry, they amount to 19.8 Gy × cm(2) and 4.0 mSv, respectively. METHODS: We investigated the feasibility of prospective electrocardiogram (ECG)-gated coronary angiography (CA)-a novel technique in invasive cardiology-with respect to possible reduction in irradiation effects. Instead of universally fix-rated radiographic acquisition within 7.5-15 frames/s, one single frame/heartbeat was triggered toward the diastolic moment immediately before atrial contraction (77 % of ECG-RR interval) most likely to provide motion-free and hence optimized resolution of the coronary tree. For 200 patients (body mass index 27.8 kg/m(2), age 67.5 years, male 55 %, 68 bpm) undergoing ECG-gated CA, we measured various median (interquartile range) parameters for radiation exposure. RESULTS: The total DAP was 0.64 (0.46-1.00), radiographic fraction was 0.30 (0.19-0.43), and fluoroscopic fraction was 0.35 (0.21-0.57) Gy × cm(2). Radiographic imaging occurred within 21.7 s (17.1-26.3), with 25 frames (20-30) over the course of 7 runs (6-8). Fluoroscopy time was 119 s (94-141). Radiographic DAP was 12.6 mGy × cm(2)/frame and 13.8 mGy × cm(2)/s. Fluoroscopic DAP was 0.8 mGy × cm(2)/pulse and 3.1 mGy × cm(2)/s. Patient reference point air kerma was 17.0 mGy (11.1-28.1) and contrast volume was 70 ml (60-85). CONCLUSION: In conclusion, invasive ECG-gated coronary imaging is feasible in clinical routine and enables patient EDs of approx. 3 % of typical values in invasive cardiology: 0.13 mSv (0.09-0.20).