Laila Al-Shaar

25-Hydroxyvitamin D Assay Variations and Impact on Clinical Decision Making

CONTEXT Laboratories are increasingly shifting to new automated 25-hydroxyvitamin D (25-OHD) assays, with subsequent variability in results. OBJECTIVE/SETTING We describe the experience at our center with such a shift and illustrate its clinical implications. METHODS 25-OHD levels were measured in 494 patients using Immunodiagnostic Systems RIA (IDS-RIA) and DiaSorin Liaison assays. Sources of variability between the assays were investigated in a subset of 83 samples, retested in the reference laboratory in the United States, and by reviewing the performance reports issued by the International Vitamin D External Quality Assessment Scheme, DEQAS. 25-OHD cut-points for target levels were used to compare the two assays. RESULTS 25-OHD concentrations were significantly lower when measured with Liaison as compared to IDS-RIA: mean bias was -5 ng/ml, range was -38.1 to 18.7 ng/ml, P<0.001; the absolute bias was independent of 25-OHD value. Interassay variability was also detected in values obtained in the reference laboratory and in DEQAS reports. Using 20 ng/ml as the target 25-OHD level, 52% of patients required treatment when tested by Liaison, as opposed to 36% by IDS-RIA (P<0.001). Using 30 ng/ml as the desirable level, the proportions were 79 and 64%, respectively (P<0.001). The two assays agreed in only 41-68% of subjects, proportions that depended on criteria used to define agreement. CONCLUSION A change in 25-OHD assays has a significant impact on results, patient classification, and treatment recommendations. Such variability cannot be ignored when deriving and applying vitamin D guidelines. It also renders universal assay standardization a pressing call.

Late effects of radial artery vs saphenous vein grafting for multivessel coronary bypass surgery in diabetics: a propensity-matched analysis †

OBJECTIVES To determine whether the use of the radial artery (RA) vs the saphenous vein (SV) as the second grafting conduit with the internal thoracic artery (ITA) confers a late-survival advantage in diabetes mellitus (DM). METHODS We reviewed our 1996-2007 DM coronary artery bypass grafting (CABG) experience. Study patients (N = 2281) included all primary, non-salvage multigraft CABG discharged alive and receiving ≥1 ITA graft. Bilateral ITA, ITA-only grafts or concomitant valve/aortic surgery patients were excluded. A non-parsimonious, RA use propensity model (42 variables) was derived excluding five factors [gender, vessel disease, insulin, renal failure and left ventricular (LV) dysfunction] that were always strictly matched for all pairs. Greedy matching resulted in well-matched ITA/RA and ITA/SV cohorts (N = 578 each). The late follow-up was truncated at 16 years, and survival comparisons were done by Kaplan-Meier analysis. RESULTS RA grafting was used in 933 (41%) DM patients and was more frequent for non-insulin (513/1348; 49.1%) compared with insulin (271/784; 34.6%) dependent patients. Relatively fewer insulin ITA/RA (169; 62%) could be matched vs non-insulin (469; 71%). Late survival was significantly better for ITA/RA overall [hazard ratio, HR (95% confidence interval) = 0.78 (0.65-0.95); P = 0.012], but this was primarily due to the non-insulin sub-cohort [HR = 0.72 (0.56-0.91); P = 0.007] as opposed to no effect for insulin [HR = 0.92 (0.68-1.26); P = 0.61]. Sub-cohort analysis revealed a significant ITA/RA survival advantage in males, preserved LV function and three-vessel disease. No sub-cohorts were associated with superior ITA/SV survival. CONCLUSION Our analysis indicated that RA grafting confers a significant late-survival advantage and, thus, supports its liberal use in DM patients undergoing multivessel CABG.

Hypovitaminosis D in a sunny country: Time trends, predictors, and implications for practice guidelines

The aim of the current study is to investigate the prevalence of hypovitaminosis D in Lebanese subjects, its robust predictors, evaluate the relationship between 25 hydroxy vitamin D [25(OH)D] and parathyroid hormone levels, and derive desirable vitamin D levels, based on a large hospital laboratory database spanning all age groups. Data from a large representative digitized database of 9147 subjects, mostly outpatients, evaluated between 2000-2004 and 2007-2008, in whom information on age, gender, service, and time of the year, was analyzed. The PTH-25(OH)D relationship was studied in a subset of 657 adult subjects, in whom such data were available. At a 25(OH)D cut-off of<20 ng/ml, the prevalence of hypovitaminosis D ranged between 58% and 62% in pediatric subjects, 44% and 60% in adults, and 41% and 62% in elderly, in the 2 study periods. At a cut-off <30 ng/ml, the prevalence was above 78%, in most sub-groups. Regardless of cut-off used, the only significant predictors of high mean 25(OH)D levels were the male gender in the pediatric group, and female gender in adults and elderly, summer/fall seasons, out-patient status, as well as study period. Curve fitting of the PTH-25(OH)D relationship, in adults and elderly, revealed a plateau at 25(OH)D levels of 17-21 ng/ml, depending on sub-study group. Hypovitaminosis D is prevalent in our sunny country, even using a conservative population-derived cut-off of 20 ng/ml, and thus the need for a public health strategy for supplementation.

Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype

Solute carrier family 22 member 5 (SLC22A5) encodes a sodium‐dependent ion transporter responsible for shuffling carnitine across the plasma membrane. This process provides energy for the heart, among other organs allowing beta‐oxidation of fatty acids. Mutations in SLC22A5 result in primary carnitine deficiency (PCD), a disorder that manifests with cardiac, skeletal, or metabolic symptoms. We hereby describe two novel mutations in SLC22A5 in two Lebanese families associated exclusively with a cardiac phenotype. The frequency of the cardiac, metabolic and skeletal symptoms in PCD patients remains undefined. All the reported eight PCD patients belonging to five different Lebanese families have an exclusive cardiac phenotype. Carnitine levels appear to be directly linked to the type and position of the mutation and the severity of the phenotypic presentation does not seem to be associated with serum carnitine levels. A comprehensive review of 61 literature‐reported PCD cases revealed an exclusive cardiac manifestation frequency at 62.3% with a very low likelihood of simultaneous occurrence of cardiac and metabolic manifestation.

Primary carnitine deficiency: Novel mutations and insights into the cardiac phenotype

Solute carrier family 22 member 5 (SLC22A5) encodes a sodium‐dependent ion transporter responsible for shuffling carnitine across the plasma membrane. This process provides energy for the heart, among other organs allowing beta‐oxidation of fatty acids. Mutations in SLC22A5 result in primary carnitine deficiency (PCD), a disorder that manifests with cardiac, skeletal, or metabolic symptoms. We hereby describe two novel mutations in SLC22A5 in two Lebanese families associated exclusively with a cardiac phenotype. The frequency of the cardiac, metabolic and skeletal symptoms in PCD patients remains undefined. All the reported eight PCD patients belonging to five different Lebanese families have an exclusive cardiac phenotype. Carnitine levels appear to be directly linked to the type and position of the mutation and the severity of the phenotypic presentation does not seem to be associated with serum carnitine levels. A comprehensive review of 61 literature‐reported PCD cases revealed an exclusive cardiac manifestation frequency at 62.3% with a very low likelihood of simultaneous occurrence of cardiac and metabolic manifestation.

Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in adolescents: results from a randomized controlled trial.

Several organizations issued recommendations on desirable serum 25‐hydroxy vitamin D [25(OH)D] levels and doses of vitamin D needed to achieve them. Trials allowing the formulation of evidence‐based recommendations in adolescents are scarce. We investigated the ability of two doses of vitamin D3 in achieving recommended vitamin D levels in this age group. Post hoc analyses on data from a 1‐year double‐blind trial that randomized 336 Lebanese adolescents, aged 13 ± 2 years, to placebo, vitamin D3 at 200 IU/day (low dose), or 2000 IU/day (high dose). Serum 25(OH)D level and proportions of children achieving levels ≥20 ng/mL and 30 ng/mL were determined. At baseline, mean 25(OH)D was 15 ± 7 ng/mL, 16.4 ± 7 ng/mL in boys, and 14 ± 8 ng/mL in girls, p = 0.003, with a level ≥20 ng/mL in 18% and ≥30 ng/mL in 5% of subjects. At 1 year, mean levels were 18.6 ± 6.6 ng/mL in the low‐dose group, 17.1 ± 6 ng/mL in girls, and 20.2 ± 7 ng/mL in boys, p = 0.01, and 36.3 ± 22.3 ng/mL in the high‐dose group, with no sex differences. 25(OH)D increased to ≥20 ng/mL in 34% of children in the low‐dose and 96% in the high‐dose group, being higher in boys in the low‐dose arm only; it remained ≥30 ng/mL in 4% of children in the low‐dose arm but increased to 64% in the high‐dose arm. Baseline 25(OH)D level, body mass index (BMI), and vitamin D dose assigned were the most significant predictors for reaching a 25(OH)D level ≥20 ng/mL and 30 ng/mL. A daily dose of 2000 IU raised 25(OH)D level ≥20 ng/mL in 96% of adolescents (98% boys versus 93% girls). Dose‐response studies are needed to determine in a definitive manner the daily allowance of vitamin D for Middle Eastern adolescents with a similar profile.

Ages and Stages Questionnaires: Adaptation to an Arabic speaking population and cultural sensitivity

BACKGROUND Early detection of developmental delay is essential to initiate early intervention. The Ages and Stages Questionnaires (ASQ) correlate well with physicians assessment and have high predictive value. No such tool exists in Arabic. AIMS Translate and test the applicability and reliability of Arabic translated Ages and Stages Questionnaires (A-ASQ) in an Arabic speaking population. METHODS 733 healthy children were assessed. ASQ-II for 10 age groups (4-60 months) were translated to Arabic, back translations and cultural adaptation were performed. Test-retest reliability and internal consistency were evaluated using Pearson Correlation Coefficient (CC) and Cronbachs alpha (Cα). Mean scores per domain were compared to US normative scores using t-test. RESULTS A-ASQ, after culturally relevant adaptations, was easily administered for 4-36 months age groups but not for 4-5 year old due to numerous cultural differences in the later. For the 4-36 month age groups Pearson CC ranged from 0.345 to 0.833. The internal consistency coefficients Cα scores ranged from 0.111 to 0.816. Significant differences were found in the mean domain scores of all age groups between Lebanese and US normative sample (p-value <0.001) with some exceptions in gross motor, fine motor and personal social domains. CONCLUSION A-ASQ was easily translated and administered with acceptable internal consistency and reliability in the younger age groups. It proved to be culturally sensitive, which should be taken into consideration when adapting such tool to non-western populations.

Effect of vitamin D replacement on hip structural geometry in adolescents: A randomized controlled trial

BACKGROUND We have shown in a randomized controlled trial that vitamin D increases bone mass, lean mass and bone area in adolescent girls, but not boys. These increments may translate into improvements in bone geometry and therefore bone strength. This study investigated the impact of vitamin D on hip geometric dimensions from DXA-derived hip structural analyses in adolescents who participated in the trial. METHODS 167 girls (mean age 13.1 years) and 171 boys (mean age 12.7 years) were randomly assigned to receive weekly placebo oil or vitamin D3, at doses of 1400 IU or 14,000 IU, in a double blind placebo-controlled 1-year trial. DXA images were obtained at baseline and one year, and hip images were analyzed using the hip structural analysis (HSA) software to derive parameters of bone geometry. These include outer diameter (OD), cross sectional area (CSA), section modulus (Z), and buckling ratio (BR) at the narrow neck (NN), intertrochanteric (IT), and shaft (S) regions. Analysis of Covariance (ANCOVA) was used to examine group differences for changes of bone structural parameters. RESULTS In the overall group of girls, vitamin D supplementation increased aBMD (7.9% and 6.8% in low and high doses, versus 4.2% in placebo) and reduced the BR of NN (6.1% and 2.4% in low and high doses, versus 1.9% in placebo). It also improved aBMD (7.9% and 5.2% versus 3.6%) and CSA (7.5% and 5.1% versus 4.1%) of the IT and OD of the S (2.4% and 2.5% versus 0.8% respectively). Significant changes in the OD and BR of the NN, in the overall group of girls remained, after adjusting for lean mass, and were unaffected with further adjustments for lifestyle, pubertal status, and height measures. Conversely, boys did not exhibit any significant changes in any parameters of interest. A dose effect was not detected and subgroup analyses revealed no beneficial effect of vitamin D by pubertal stage. CONCLUSIONS Vitamin D supplementation improved bone mass and several DXA-derived structural bone parameters, in adolescent girls, but not boys. This occurred at a critical site, the femoral neck, and if maintained through adulthood could improve bone strength and lower the risk of hip fractures.

Consumer Knowledge, Attitudes and Salt-Related Behavior in the Middle-East: The Case of Lebanon

Sodium intake is high in Lebanon, a country of the Middle East region where rates of cardiovascular diseases are amongst the highest in the world. This study examines salt-related knowledge, attitude and self-reported behaviors amongst adult Lebanese consumers and investigates the association of socio-demographic factors, knowledge and attitudes with salt-related behaviors. Using a multicomponent questionnaire, a cross-sectional study was conducted in nine supermarkets in Beirut, based on systematic random sampling (n = 442). Factors associated with salt-related behaviors were examined by multivariate regression analysis. Specific knowledge and attitude gaps were documented with only 22.6% of participants identifying processed foods as the main source of salt, 55.6% discerning the relationship between salt and sodium, 32.4% recognizing the daily limit of salt intake and 44.7% reporting being concerned about the amount of salt in their diet. The majority of participants reported behavioral practices that increase salt intake with only 38.3% checking for salt label content, 43.7% reporting that their food purchases are influenced by salt content and 38.6% trying to buy low-salt foods. Knowledge, attitudes and older age were found to significantly predict salt-related behaviors. Findings offer valuable insight on salt-related knowledge, attitude and behaviors in a sample of Lebanese consumers and provide key information that could spur the development of evidence-based salt-reduction interventions specific to the Middle East.

Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in adolescents: Results from a randomized controlled trial

Several organizations issued recommendations on desirable serum 25‐hydroxy vitamin D [25(OH)D] levels and doses of vitamin D needed to achieve them. Trials allowing the formulation of evidence‐based recommendations in adolescents are scarce. We investigated the ability of two doses of vitamin D3 in achieving recommended vitamin D levels in this age group. Post hoc analyses on data from a 1‐year double‐blind trial that randomized 336 Lebanese adolescents, aged 13 ± 2 years, to placebo, vitamin D3 at 200 IU/day (low dose), or 2000 IU/day (high dose). Serum 25(OH)D level and proportions of children achieving levels ≥20 ng/mL and 30 ng/mL were determined. At baseline, mean 25(OH)D was 15 ± 7 ng/mL, 16.4 ± 7 ng/mL in boys, and 14 ± 8 ng/mL in girls, p = 0.003, with a level ≥20 ng/mL in 18% and ≥30 ng/mL in 5% of subjects. At 1 year, mean levels were 18.6 ± 6.6 ng/mL in the low‐dose group, 17.1 ± 6 ng/mL in girls, and 20.2 ± 7 ng/mL in boys, p = 0.01, and 36.3 ± 22.3 ng/mL in the high‐dose group, with no sex differences. 25(OH)D increased to ≥20 ng/mL in 34% of children in the low‐dose and 96% in the high‐dose group, being higher in boys in the low‐dose arm only; it remained ≥30 ng/mL in 4% of children in the low‐dose arm but increased to 64% in the high‐dose arm. Baseline 25(OH)D level, body mass index (BMI), and vitamin D dose assigned were the most significant predictors for reaching a 25(OH)D level ≥20 ng/mL and 30 ng/mL. A daily dose of 2000 IU raised 25(OH)D level ≥20 ng/mL in 96% of adolescents (98% boys versus 93% girls). Dose‐response studies are needed to determine in a definitive manner the daily allowance of vitamin D for Middle Eastern adolescents with a similar profile.