Correlation of Plasma and Salivary Osteocalcin Levels with Nascent Metabolic Syndrome Components with and Without Pre/Diabetes Biochemical Parameters / Correlación de los niveles de osteocalcina en plasma y saliva con los componentes del síndrome metabólico naciente con y sin parámetros bioquímicos de prediabetes

Objectives: This study aimed to compare and correlate plasma and salivary levels of cardiometabolic risk biomarkers’ of pharmacotherapy (appraised using colorimetric assays), adiposity, and atherogenicity indices. Methods: 61 Nascent MetS subjects vs. 30 lean normoglycemic and healthy controls were recruited in Family Medicine outpatient clinics/Jordan University Hospital (a referral medical center). Fasting blood and saliva specimens were collected. Clinical and anthropometric variables were determined along with atherogenecity and adiposity indices. Results: Among nascent MetS (metabolic syndrome) recruits, almost half were normoglycemic, 43% were prediabetic and 8% were diabetic. Pronouncedly Glycemic (FPG and Alc) and lipid parameters (TG, HDL-C and non-HDL-C), adiposity indices (BMI, WHR, WtHR, Conicity-index, BAI, LAP, VAI) and atherogenicity indices (AIP, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C and TG/HDL-C) were higher in the nascent MetS group (P<0.05 vs. controls). Markedly among the plasma cardiometabolic risk biomarkers (P<0.05 vs. controls) in the nascent MetS group, adipolin, cathepsin S, ghrelin, irisin, LBP, leptin, and osteocalcin were higher but plasma FGF1 levels were oddly lower. Significantly (P<0.05 vs. controls) nascent MetS –linked salivary levels of adipolin and LBP were higher as opposed to the lower cathepsin S. Only osteocalcin, amongst 9 metabolic risk biomarkers studied, had remarkably significant correlation between plasma and saliva levels, in both total sample and MetS patients (P<0.05). Markedly in the nascent MetS only group, both plasma and salivary osteocalcin correlated with FPG and A1c (P<0.05); salivary osteocalcin correlated with BMI and LAP (P<0.05). Likewise, in the total sample plasma osteocalcin correlated significantly with BMI, BAI, WHt R, SBP, DBP, TG, LAP, VAI, TG/HDL-C and AIP (P<0.05), while salivary osteocalcin had substantial correlations only with FPG and A1c (P<0.05). Conclusion: Association of nascent MetS-related plasma and salivary osteocalcin levels and clinical characteristics and indices propagate salivary osteocalcin as a non-invasive marker for clinical control of MetS-/preDM.(AU)

Painful subacute thyroiditis occurring after the administration of influenza vaccine and hyaluronic acid dermal filler: A case report.

RATIONALE: The occurrence of subacute thyroiditis (SAT) after vaccines or after hyaluronic acid skin fillers is very rare and might be related to genetic susceptibility. We suggest that the co-administration of both products could potentially increase the possibility of development of SAT. PATIENT CONCERNS: A 58-year-old Caucasian healthy female initially presented with chills, myalgia, dysphagia, sore throat, dry cough, fatigue, and intermittent fever of 38.5°C orally after simultaneous injection of an influenza vaccine and a dermal filler containing hyaluronic acid. Ten days later the patient developed palpitations and neck pain radiating to the left jaw. DIAGNOSIS AND INTERVENTIONS: She was diagnosed with SAT on day 16 after her first visit and responded promptly to etoricoxib treatment. OUTCOMES: The patient progressed clinically from hyperthyroidism to euthyroid state and eventually to hypothyroidism and further testing showed she had HLA B-35 haplotype. LESSONS: Physicians should be aware that SAT might be associated with the administration an influenza vaccine and this possible association might increase if the vaccine was co-administered with a dermal filler.

Serotonin reuptake inhibitors effect on fluconazole activity against resistant Candida glabrata strains.

OBJECTIVES: The study aimed to evaluate four selective serotonin reuptake inhibitors (SSRIs) as modifiers of fluconazole activity against resistant strains of Candida glabrata. METHODS: The effect of SSRIs on fluconazole activity was studied using the checkerboard method against C. glabrata strains (CBS 138, CBS 850821, DSY 562, DSY 565, ATCC 22553 and ATCC 90030); fractional inhibitory concentration index (FIC) was calculated and time-kill curve was used for the most prominent combination for further evaluation. RESULTS: All used SSRIs have antifungal activity against the C. glabrata strains tested. A combination of fluconazole with fluoxetine or fluvoxamine showed indifferent effects (fractional inhibitory concentration index [FICI] in all strains >1 but <4), whereas a paroxetine-fluconazole combination showed an additive effect against DSY565 and CBS138, known to express efflux pumps as well as on ATCC strain (0.5 < FIC < 1) with indifferent effect on other strains used. The most promising combination was that of fluconazole with sertraline (FICI ≤0.5), where a synergistic effect was observed against all resistant and susceptible dose-dependent strains, including those known to express efflux pumps. This synergistic effect was confirmed by time-kill curve assay against all resistant C. glabrata and ATCC strains with a >2-log10 CFU/mL reduction caused by combination compared with a single active agent of fluconazole after 24 hours of incubation. A sertraline-fluconazole combination produced an additive effect on the reference ATCC strain. CONCLUSION: Our data suggest that blocking active efflux pumps by sertraline may be considered the probable mechanism of synergism with fluconazole. The combination of sertraline with fluconazole could be a promising remedy for treatment of infections caused by resistant C. glabrata.

Evaluation of four calcium channel blockers as fluconazole resistance inhibitors in Candida glabrata.

OBJECTIVES: The aim of this study was to evaluate the ability of four calcium channel blockers (CCBs), namely verapamil, diltiazem, nicardipine (NIC) and nifedipine (NIF), to enhance the susceptibility of Candida glabrata strains to fluconazole (FLC). METHODS: Synergistic antifungal effects of the CCBs with FLC were examined by the chequerboard method, and fractional inhibitory concentration indices (FICIs) were determined. The time-kill curve method was used for the most promising combination to further evaluate the synergetic effects. RESULTS: NIC showed an additive effect with FLC against FLC-resistant and FLC-susceptible-dose-dependent strains (DSY 565 and CBS 138) known to express efflux pumps, but not against FLC-susceptible strains. NIF exhibited an additive effect with FLC both by the chequerboard method (0.5

Home medication management review in outpatients with chronic diseases in Jordan: a randomized control trial.

BACKGROUND: Medication Management Review (MMR) is a patient-focused, structured and collaborative health care service provided in the community setting to optimize patient understanding and quality use of medicines. OBJECTIVE: To conduct a randomized control trial of the MMR program in Jordan, by a pharmacist identifying treatment related problems (TRPs) through home visits, assessing type and frequency of TRPs, and eventual effect of resolving TRPs identified by the pharmacist and accepted by the physician on the health status of participating patients. SETTING: Outpatient clinic at the Jordan University Hospital, Amman, Jordan. METHOD: Consecutive patients from outpatient clinics who were eligible for the study were recruited and randomly distributed into two groups (control and intervention). All patients were visited at home by the pharmacist who delivered only for intervention group counseling regarding self-reported adherence, frequency of monitoring and education regarding pharmacological and non-pharmacological therapy. After identifying TRPs, the pharmacist sent a letter to the physician with certain recommendations for patients in the intervention group only. Physician ticked the approved recommendations and returned the report to the pharmacist, allowing the pharmacist to convey the approved changes to the patients. Patients were referred back to their physicians for confirmation of any changes in treatment. Both groups were reassessed after 2-3 months during their regular follow-up visits to their physicians. MAIN OUTCOME MEASURE: To assess the impact of home medication review on the number of TRPs and self-reported adherence in outpatients with chronic diseases via hospital-based clinics in Jordan. RESULTS: A total of 158 TRPs were identified in 112 patients; mean TRP number was 1.63 per patient. As a result of the pharmacist intervention, there was a significant decrease in number of TRPs in the intervention group, the change in the mean was (1.23 (±1.19), P < 0.001) versus the control group (0.29 (±1.24), P = 0.114). After 3 months, a reduction in non-adherence was observed in the intervention (-0.81 (±1.48), P < 0.001) in contrast to no change in self-reported adherence in the control (0.22 (± 1.12), P = 0.168) group. CONCLUSION: Overall, home-based medication review for patients with chronic conditions decreased the total number of TRPs and improved patient self-reported adherence.

Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer--a Case-Control Study in Jordan.

BACKGROUND: Breast cancer is the leading cause of cancer death among women and the second in humans worldwide. Many published studies have suggested an association between MDR1 polymorphisms and breast cancer risk. Our aim was to study the association between genetic polymorphism of MDR1 at three sites (C3435T, G2677A/T, and C1236T) and their haplotype and the risk of breast cancer in Jordanian females. MATERIALS AND METHODS: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. The polymerase chain reaction/restriction fragment length polymorphism (PCR- RFLP) technique and sequencing were performed to analyse genotypes. RESULTS: The distribution of MDR1 C3435T genotypes differed between cases and controls [cases, CC 45.3%, CT 41.3%, and TT 13.3%; controls, CC 13.4%, CT 43.3%, and TT 30.2%, p < 0.001]. Similarly, the distribution of G2677A/T significantly differed [cases, GG 43.1 %, GT+GA 50.9% and AA+TT 6%; controls, GG 29.6 %, GT+GA 50.9%, and AA+TT 19.4%, p = 0.004]. On the other hand, genotype and allelotype distribution of C1236T was not statistically different between cases and controls (p=0.56 and 0.26, respectively). The CGC haplotype increased the risk to breast cancer by 2.5-fold compared to others, while TGC and TTC haplotypes carried 2.5- and 5-fold lower risk of breast cancer, respectively. CONCLUSIONS: Genetic polymorphisms of MDR1 C3435T and G2677A/T, but not C1236T, are associated with increased risk of breast cancer. In addition, CGC, TGC and TTC haplotypes have different impacts on the risk of breast cancer. Future, larger studies are needed to validate these findings.

Home medication reviews in a patient care experience for undergraduate pharmacy students.

OBJECTIVES: To evaluate the effectiveness of conducting medication management reviews (MMRs) and home medication reviews (HMRs) on improving undergraduate pharmacy students' pharmaceutical care skills and clinical knowledge. DESIGN: Fifth-year bachelor of science in pharmacy students were enrolled in a structured course in which MMR cases based on real patient scenarios were completed, findings were discussed in groups, and comprehensive feedback was provided by course instructors. Each student was then asked to recruit a real patient through a community pharmacy and conduct an HMR. ASSESSMENT: Students' pre- and post-course scores on the same MMR case improved significantly, with 84.6% of students passing the post-course assessment. Students also completed a new post-course MMR case and 74.8% received a passing score. Students' answers on a post-course self-assessment showed a significant improvement in their scores regarding knowledge and skills in conducting MMRs and HMRs. CONCLUSION: Medication management reviews and home medication reviews are excellent tools for educating pharmacy students and providing them with needed actual clinical practice experience.

Treatment related problems for outpatients with chronic diseases in Jordan: the value of home medication reviews.

BACKGROUND: Research conducted in Jordan has shown that suboptimal use of medications by outpatients along with the suboptimal role played by community pharmacists is currently a big dilemma highlighting the need for the Home Medication Review (HMR) service in the country. OBJECTIVES: To evaluate the prevalence and types of treatment related problems (TRPs) for outpatients with chronic diseases. SETTING: Patient interview was conducted at the patients' community pharmacy initially, then at their home to collect required data. METHODS: 167 patients with chronic conditions (mean age 58.9 ± 13.54, 53 % males) were recruited. Data collected by the graduate pharmacists to conduct a HMR included patient's demographics, income, laboratory data, medical history, medication record, and adherence. A HMR was conducted for each patient by the researchers (experienced clinical pharmacists) to identify the patients' TRPs based on published literature. A focus group interview was conducted to elicit information regarding the feasibility of the HMR process and acceptability of the patient to the service. MAIN OUTCOME MEASURE: Prevalence and nature of identified TRPs, associated diseases and drugs, and patients' acceptability to the HMR service. RESULTS: The mean number of disease conditions per patient was 4.1 ± 1.7, and the mean number of medications taken by each patient was 8.1 ± 2.7. HMR results showed a mean number of TRPs per patient of 7.4 ± 2.8. TRPs prevalence: 34.7 % of patients were found to have unnecessary drug therapy; 68.3 % had untreated conditions, and 74.9 % had ineffective/incomplete drug therapy; 50.3 % had inappropriate dosage regimen; 10.2 % were found to have actual adverse drug effects. A significant correlation between the number of TRPs and the number of disease states the patient had (r = 0.311, p = 0.003; Pearson correlation) and the number of drugs the patient was taking (r = 0.443, p < 0.001) was found. Patients accepted the HMR service well including the home visiting part. CONCLUSION: TRPs in Jordanian outpatients with chronic diseases visiting community pharmacies are of concern and this signifies the integral role of pharmacists to identify these TRPs and hence provide the HMR service in the country.

Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population.

Drug metabolizing enzymes participate in the neutralizing of xenobiotics and biotransformation of drugs. Human cytochrome P450, particularly CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, play an important role in drug metabolism. The genes encoding the CYP enzymes are polymorphic, and extensive data have shown that certain alleles confer reduced enzymatic function. The goal of this study was to determine the frequencies of important allelic variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 in the Jordanian population and compare them with the frequency in other ethnic groups. Genotyping of CYP1A1(m1 and m2), CYP2C9 (2 and 3), CYP2C19 (2 and 3), CYP3A4 5, CYP3A5 (3 and 6), was carried out on Jordanian subjects. Different variants allele were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CYP1A1 allele frequencies in 290 subjects were 0.764 for CYP1A1 1, 0.165 for CYP1A1 2A and 0.071 for CYP1A1 2C. CYP2C9 allele frequencies in 263 subjects were 0.797 for CYP2C9 1, 0.135 for CYP2C9 2 and 0.068 for CYP2C9 3. For CYP2C19, the frequencies of the wild type (CYP2C19 1) and the nonfunctional (2 and 3) alleles were 0.877, 0.123 and 0, respectively. Five subjects (3.16 %) were homozygous for 2/2. Regarding CYP3A4 1B, only 12 subjects out of 173 subjects (6.9 %) were heterozygote with none were mutant for this polymorphism. With respect to CYP3A5, 229 were analyzed, frequencies of CYP3A5 1, 3 and 6 were 0.071, 0.925 and 0.0022, respectively. Comparing our data with that obtained in several Caucasian, African-American and Asian populations, Jordanians are most similar to Caucasians with regard to allelic frequencies of the tested variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.

Comprehensive assessment of treatment related problems in hospitalized medicine patients in Jordan.

OBJECTIVES: The aim of this study was to identify the prevalence and characteristics of treatment related problems (TRPs) in hospitalized internal medicine patients in Jordan as well as to identify diseases and drugs associated with each specific TRP. We have also aimed at investigating physicians' acceptance of recommendations made by clinical pharmacist and to identify the outcomes of pharmacist interventions. SETTING: Internal medicine department of a general hospital in Jordan. METHODS: We have utilized a systematic, prospective, bedside, comprehensive clinical assessment approach that allowed us to effectively identify, communicate and follow up TRPs. MAIN OUTCOME MEASURES: prevalence and nature of identified TRPs, clinical significance of TRPs, associated diseases and drugs and clinical outcomes of clinical pharmacist interventions. RESULTS: 402 patients were included in the study. The average number of the identified TRPs was 9.35. Fifty-three percent of identified TRPs were classified as major and 28% were classified as moderate. Ninety-one percent of the recommendations were accepted by physicians. Efficacy related problems were the most common TRP category followed by safety related problems and indication related problems. Sixty-four percent of the TRPs were resolved or prevented through the clinical pharmacist intervention. CONCLUSIONS: We have found that prevalence of TRPs is substantially high among patients hospitalized at the internal medicine department. TRPs related to Dosage regimens, untreated conditions, patient monitoring, drug interactions, and drug choices were the most common. Most of TRPs identified by pharmacists were clinically significant. Pharmacists' interventions contributed substantially to the resolving of many of the identified TRPs. Patients suffering from higher number of medical conditions and receiving higher number of medications should be given the priority for clinical pharmacy service in hospitalized internal medicine patients.

Effect of chemosensitizers on minimum inhibitory concentrations of fluconazole in Candida albicans.

OBJECTIVE: To evaluate the effect of chemosensitizers on the in vitro activity of fluconazole against Candida albicans strains. MATERIALS AND METHODS: Using Clinical Laboratory Standard Institute method, antifungal activity of fluconazole was determined alone and in combination with 16 chemosensitizers that included verapamil, reserpine, quinine, quinidine, gemfibrozil, lansoprazole, tamoxifen, diltiazem, desipramine, nicardipine, cyclosporine, chlorpromazine, prochlorperazine, promethazine, thioridazine, and trifluoperazine. Further studies were done using double combinations of selected chemosensitizers with fluconazole (28 combinations). For testing combinations, half of the minimum inhibitory concentration (MIC) of each agent was selected in order to avoid the effect of the drug alone. One reference strain (ATCC90028) and one clinical isolate of C. albicans were used for testing the in vitro activity. Broth dilution method was used to determine the MICs of fluconazole and chemosensitizers. RESULTS: Of the 16 chemosensitizers tested, 3 exhibited in vitro activity by increasing fluconazole susceptibility to 7-fold. The MICs of the reference strain and clinical isolate for fluconazole were 5.5 and 0.55 microg/ml, respectively, and these were reduced to 0.76 microg/ml by gemfibrozil, 0.83 microg/ml by quinine, and 0.76 microg/ml by chlorpromazine in the reference strain, with MIC reduction to 0.08 microg/ml by all three chemosensitizers in the clinical isolate. Some double combinations reduced the MIC of fluconazole to 10- to 100-fold, even when the chemosensitizers were not effective alone. CONCLUSION: The most effective double combinations were those of chlorpromazine with either reserpine or nicardipine.

Antiplatelet therapy for primary and secondary prevention in Jordanian patients with diabetes mellitus.

INTRODUCTION: Guidelines for diabetes treatment recommend the routine use of aspirin in patients with diabetes mellitus (DM) who have cardiovascular disease (CVD), those with at least one CVD risk factor, and for anyone with DM who is>30 years of age or, if contraindicated, an alternative antiplatelet agent. We evaluated the adherence to these recommendations in a subset of diabetic patients in Jordan, and identified physician and patient characteristics associated with the use of antiplatelet therapy. MATERIALS AND METHODS: A cross-sectional observational study conducted in randomly selected outpatient clinics. The study included 199 adult patients with DM who were eligible for antiplatelet prophylaxis. Review of medical charts and direct interviews with patients were performed to obtain information on demographic characteristics of the patients, clinical factors and medication prescription. Bivariate analysis and multivariate logistic regression methods were used to determine what factors were related to antiplatelet drug use. RESULTS: Among diabetic patients eligible for antiplatelet prophylaxis, the prevalence of antiplatelet drug use for primary or secondary prevention was 84%. Factors associated with antiplatelet prophylaxis were male gender (odds ratio, OR 2.97), presence of angina (OR 3.00), history of myocardial infarction (OR 3.75), history of coronary revascularization (OR 3.12), five or more prescription medications (OR 4.61), and physician's specialty other than endocrinology ( OR 4.35). CONCLUSIONS: Adherence rates to the international guidelines regarding routine antiplatelet prophylaxis in adults with DM who are eligible for such prophylaxis are suboptimal. Efforts towards increasing these rates of antiplatelet prophylaxis are necessary.

Validation of a comprehensive classification tool for treatment-related problems.

OBJECTIVE: Several drug-related problem classification systems can be found in the literature. However, it is generally agreed that a comprehensive, well constructed and validated instrument is currently lacking. The aim of this study is the development and validation of a comprehensive treatment-related problems assessment and classification tool for use in teaching, practicing and researching pharmaceutical care and to improve identification, resolving and preventing of treatment-related problems. METHOD: The development and validation involved five steps starting with literature search to define a treatment related problem and also to form a database of treatment-related problems identified in the literature. In the next step, all problems that were identified in the first step and passed the evaluation of the three authors were pooled together and then divided into groups according to their common or shared construct, in the third step a suitable assessment method was developed according to the construct of the different problems, in the next step the developed instrument was validated for content, internal and external validity. Finally the tool was finalized and tested for reproducibility and inter-rater agreement. RESULTS: The final validated version included six main categories for treatment-related problems (Indication, Effectiveness, Safety, Knowledge, Adherence and Miscellaneous). These categories include a total of nine subcategories and a total of 29 treatment related problems. CONCLUSION: The treatment-related problems assessment and classification tool introduced in this paper was applied to actual patient cases and proved to be valid. This tool also has several features that are new.