Prevalence of osteoporosis and its reproductive risk factors among Jordanian women: a cross-sectional study

Extensive differences in the osteoporosis epidemiological pattern among geographic and ethnic groups have been reported. The evidence concerning association of multiple pregnancies, lactations, and other menstrual history factors with low bone mineral density (BMD) remains inconclusive. Previous local studies addressing these issues in Jordan are very restricted. We present a cross-sectional study of Jordanian women who visited outpatient clinics between August 2000 and August 2002 at two community hospitals in Amman City. BMD measurement was performed for all subjects, while comprehensive appraisal of clinical issues related to reproductive status and past medical history was carried out using a structured questionnaire administered to 50% of the subjects. We also attempted to examine the current hypothesis of possible influence of hyperlipidemia and thyroid abnormalities on decreased BMD. According to WHO criteria, 119 (29.6%) were identified as having osteoporosis, 176 (43.8%) were osteopenic, and 107 (26.6%) had normal BMD. The multiple-linear regression analyses at different bone sites revealed that age, years of menopause, low-density lipoprotein (LDL), and follicle-stimulating hormone (FSH) have strong independent associations with decreased BMD at all lumbar and femoral neck regions. The negative effect associated with number of children (live births) and frequency of lactations was only evident at femoral neck. Although years of menstruation, age at menopause, days of menstrual cycle, number of pregnancies, and duration of hormone replacement therapy (HRT) were positively correlated with BMD, they had weaker associations than previous variables. Moreover, in the final multivariable logistic regression model, variables which rendered significantly independent risk factors after adjustment for age and BMI were: current smokers of more that 25 cigarettes/day, postmenopausal women irrespective of HRT use, menopausal years of 5 year intervals, natural early menopause, gastrointestinal disease, rheumatoid arthritis, osteoarthritis, hypertension, and thyroid replacement therapy. Ever-lactation, frequent lactation of 4 or more times, duration of lactation interval of 1–6 months and clinical hyperthyroidism were significant protective factors. Hysterectomy with or without oophorectomy, premature ovarian failure, gravidity, menstrual flow pattern, family history of osteoporosis, clinical hypothyroidism, hyperlipidemia, HRT, and corticosteroids therapy were not independent predictors of osteoporosis among our population. It was concluded that the prevalence of this worldwide public health problem among the Jordanian female population is extremely high, and is even found in younger age categories compared to previous international surveys. Though, the number of pregnancies in our multiparous female population showed a negative impact on femoral neck BMD, no evidence of increased risk of osteoporosis among ever-pregnant women was noted. Conversely, the current data analysis highlight many potential risk factors including associated medical illnesses, and other hormonal alterations experienced during menopausal period. Therefore, increased health awareness and intensive screening programs are mandatory for early detection of low bone mass.     

Possible interethnic differences in omeprazole pharmacokinetics : comparison of Jordanian Arabs with other populations

BACKGROUND AND OBJECTIVE: Considerable ethnic differences have been reported in the incidence of the poor metaboliser (PM) genotype of cytochrome P450 (CYP) 2C19. The frequency of this genotype was found to be much higher in Oriental persons (13-23%) than in American or European populations (3-5%). There are, however, no valid data published for Arabic subjects. The present study was conducted to evaluate pharmacokinetic parameters of omeprazole after a single dose in healthy Jordanian Arabic subjects and to compare the results with data published for other populations. METHODS: Seventy-four healthy male Jordanian Arabic volunteers contributed to the study, which was performed at Al Essra Hospital in Amman, Jordan. After an overnight fast, omeprazole was administered as a single Losec 20mg capsule. A total of 20 blood samples were collected over a 10-hour period after administration. Omeprazole pharmacokinetic parameters were determined from the plasma concentration-time profiles using the WinNonlin software. Kolmogorov-Smirnov's test and probit plots of omeprazole area under the plasma concentration-time curve (AUC) data were used to analyse the frequency distribution of phenotypic data. RESULTS: The mean pharmacokinetic parameters and their corresponding coefficient of variation (CV%) for peak plasma concentration (Cmax), AUC from time zero to infinity (AUCinfinity), time to reach Cmax (tmax), apparent oral clearance (CL/F) and elimination half-life (t(1/2)) were 314.96 ng/mL (56%), 923.2 ng . h/mL (108.6%), 2.1h (44%), 0.66 L/h/kg (92%) and 1.5 h (56.6%), respectively. Interindividual differences in the current study were high for all pharmacokinetic parameters, yet comparable to CVs reported in nonphenotyped subjects identified within other ethnic groups (40.3-159% for AUC and 39-48.2% for Cmax).The frequency distribution of all parameters, particularly the AUC, was shown to be trimodal. This has proposed the presence of three distinct phenotypes, designated as extensive metabolisers (EMs), slow-extensive metabolisers (SEMs), and PMs, with corresponding frequency of 36.5%, 39.2% and 24.3%, respectively. After stratification, the relative mean AUCs of omeprazole in EMs, SEMs and PMs were 1 : 2.7 : 9.3 (all p < 0.001). Accordingly, the CL/F of omeprazole showed a ratio of 9.8 : 3.6 : 1 for three phenotype groups, respectively. For other pharmacokinetic parameters including Cmax, t1/2, AUC normalised for bodyweight (AUCN), Cmax/dose and AUC/dose, there were also significant differences between the three groups. CONCLUSIONS: The current pharmacokinetic study revealed that the majority of the Jordanian Arabics seemed to be more properly classified within the EM phenotype. More specifically, the observed metabolic rates of heterozygous and homozygous Jordanian Arabic EMs were more comparable to those of Caucasian EMs than Oriental EMs. Consequently, higher dosage requirements can be expected among most of the Jordanian Arabics. Yet, the incidence of PMs is significant and they seemed to exhibit a similar pharmacokinetic pattern to Chinese PMs in terms of long-term exposure (clearance and AUC) as well as short-term exposure (Cmax) parameters, after adjustment for dose and bodyweight.Therefore, further clinical application of CYP2C19 polymorphism is anticipated in Jordanian Arabic mixed population, particularly if long-term use of omeprazole is intended.     

A Markov Chain Model to Evaluate the Effect of CYP3A5 and ABCB1 Polymorphisms on Adverse Events Associated with Tacrolimus in Pediatric Renal Transplantation

The SNP A6986G of the CYP3A5 gene (*3) results in a non-functional protein due to a splicing defect whereas the C3435T was associated with variable expression of the ABCB1 gene, due to protein instability. Part of the large interindividual variability in tacrolimus efficacy and toxicity can be accounted for by these genetic factors. Seventy-two individuals were examined for A6986G and C3435T polymorphism using a PCR-RFLP-based technique to estimate genotype and allele frequencies in the Jordanian population. The association of age, hematocrit, platelet count, CYP3A5, and ABCB1 polymorphisms with tacrolimus dose- and body-weight-normalized levels in the subset of 38 pediatric renal transplant patients was evaluated. A Markov model was used to evaluate the time-dependent probability of an adverse event occurrence by CYP3A5 phenotypes and ABCB1 genotypes. The time-dependent probability of adverse event was about double in CYP3A5 non-expressors compared to the expressors for the first 12 months of therapy. The CYP3A5 non-expressors had higher corresponding normalized tacrolimus levels compared to the expressors in the first 3 months. The correlation trend between probability of adverse events and normalized tacrolimus concentrations for the two CYP3A5 phenotypes persisted for the first 9 months of therapy. The differences among ABCB1 genotypes in terms of adverse events and normalized tacrolimus levels were only observed in the first 3 months of therapy. The information on CYP3A5 genotypes and tacrolimus dose requirement is important in designing effective programs toward management of tacrolimus side effects particularly for the initial dose when tacrolimus blood levels are not available for therapeutic drug monitoring.     

Exercise for the dialyzed: aerobic and strength training during hemodialysis

OBJECTIVE: To investigate the safety and feasibility of aerobic and strength training during hemodialysis for end-stage renal disease patients and to evaluate its impact on their cardiac fitness, muscle strength, and functional status. DESIGN: A total of 22 patients undergoing hemodialysis for end-stage renal disease had assessment of their cardiac fitness with stress tests and walk tests, assessment of their muscle strength by one repetition maximum of knee extension, and assessment of their functional status by Medical Outcomes Study Short Form-36 before and after exercise training. Training, consisting of cycle ergometer exercise and strengthening of the knee extensors two to three times a week for 3 mo, was done during dialysis. RESULTS: Eighteen of 22 patients completed 3 mo of training and four dropped out due to knee pain or medical complications unrelated to exercise. No patient developed major complications from the program. After training, there was a significant improvement in the mental and physical components of the Short Form-36 and one repetition maximum of knee extension. Among 14 of 18 patients who agreed and completed a follow-up fitness testing, five showed improvement on the stress tests and eight on the walk tests. CONCLUSIONS: A well designed exercise program during hemodialysis can be performed safely with proper supervision and patient education, improving muscle strength, mental and physical function, and possibly cardiac fitness.     

Exposure to Community Violence and the Trajectory of Internalizing and Externalizing Symptoms in a Sample of Low-Income Urban Youth

This study examined trajectories of psychopathology in a sample of low-income urban youth and tested exposure to community violence as a predictor of these trajectories. Self-report and parent-report survey measures of psychological problems and exposure to community violence were collected annually over 3 years from a sample of 364 fifth- to ninth-grade low-income urban youth (64% female; 95% youth of color). Linear growth models showed that youth experienced declines in both internalizing and externalizing symptoms across adolescence. Exposure to community violence was more strongly associated with externalizing symptoms than with internalizing symptoms but predicted declines in both types of symptoms. Results also indicated that youth reported more internalizing and externalizing symptoms than their parents reported for them. Exposure to community violence may explain unique trajectories of mental health problems among low-income urban youth. In addition, youth efforts to adopt a tough façade in the face of community violence could lead to higher rates of externalizing problems relative to internalizing problems, whereas desensitization processes may better explain reductions in both types of symptoms over time. Finally, youth report may be more valid than parent report in the context of urban poverty.     

Knowledge and Attitudes Toward Mandatory Premarital Screening Among University Students in North Jordan

A mandatory National Premarital Thalassemia Screening Program was implemented in Jordan in 2004. This cross-sectional study aimed to assess the knowledge and attitudes of university students in North Jordan toward this program. Data was collected from 542 students from four universities (two public and two private universities) located in North Jordan, using a structured questionnaire. Results of t-test and analysis of variance (ANOVA) showed that while respondents had adequate knowledge of and positive attitudes toward the premarital screening program, there was still a lack of knowledge about the disease itself. Nearly half the respondents were under the impression that β-thalassemia (β-thal) is a disease that can be treated simply. One-third of the respondents believed that if both partners were carriers of β-thal they should proceed with marriage. Negative attitude was revealed when many respondents believed that diagnosing a family member as a carrier affects other family members’ future marriage opportunities. Significant associations were detected between the knowledge scores and gender, urban/rural residence, and the university where the students were enrolled. Students in private universities showed significantly lower attitude scores. Consideration of prenatal diagnostic services as part of a β-thal prevention program is necessary. It would also be helpful to include information about β-thal as a preventable inherited illness with a severe debilitating impact on the family in the high school curriculum. There is also a need for social marketing of the program.     

Validation of knowledge and adherence assessment tools among patients on warfarin therapy in a Saudi hospital anticoagulant clinic

International Journal of Clinical Pharmacy - Background Although it can result in serious complications due to its narrow therapeutic index, warfarin is widely used in the treatment and prevention...