SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.

BACKGROUND AND PURPOSE: Primary hypothyroidism due to abnormality in the thyroid gland is the most common endocrine disease The recommended starting dose of levothyroxine replacement therapy is 1.6 µg/kg. This dose however is not optimal for every patient and dose adjustments are frequently done. Genetic polymorphisms in the absorption and metabolism pathway of levothyroxine are likely to influence its dose requirements. This study aimed to study the influence of genetic polymorphisms on levothyroxine replacement requirements. METHODS: This was a cross-sectional study. Participants were recruited through a private nutrition clinic and through announcements distributed in the University of Petra in Amman, Jordan between September 2020 and February 2021. Hypothyroid patients had already been on stable doses of levothyroxine for the previous 3 months. A questionnaire was distributed to collect demographic and clinical information and a blood sample was taken for DNA extraction and clinical biochemistry analysis. rs11249460, rs2235544, rs225014, rs225015, rs3806596, rs11185644, rs4588, rs602662 were analyzed using Applied Biosystems TaqMan™ SNP Genotyping Assays on Rotor-Gene® Q and rs3064744 by direct sequencing. SPSS and Excel were used to perform analysis. RESULTS: 76 patients were studied. The equation we calculated to find predicted daily dose of levothyroxine (mcg/kg) is 3.22+ (0.348 for CT genotype of rs11185644, 0 for other genotypes) + 0.027*disease duration (years) - 0.014*age (years) - 0.434*T3 (pmol/L) levels+ (0.296 for CC genotype of rs2235544, 0 for other genotypes). CONCLUSION: SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 affect dose requirement in hypothyroid patients and if confirmed in larger trials they can be used to individualize thyroxine starting doses.

The Role of Pharmacists and Community Pharmacies in the Screening, Knowledge, and Awareness of Diabetes Mellitus Type 2 in Jordanian People Visiting Community Pharmacies.

BACKGROUND: According to the International Diabetes Federation (IDF), diabetes is increasing exponentially worldwide and will become more prevalent than ever in the Middle East by 2045, with a 110% increase. This study aims to clarify the role of pharmacists and community pharmacies in the screening, knowledge, and awareness of Type 2 diabetes among Jordanian people who visit community pharmacies in Amman, Jordan. METHODS: Study design: This was a cross-sectional prospective study that was conducted from September to December 2021 in Amman, Jordan. Data were collected using a standardized questionnaire that was composed of multiple parts. The first part collected information on demographics, residence, educational level, and insurance status; the second part was composed of 14 knowledge assessing questions; the last part was composed of the American Diabetes Association (ADA) diabetes risk score card test. Additionally, after confirming that each participant had returned their completed sheets, participants who scored greater than 5 had their blood sugar levels checked using a finger-prick blood test. The questionnaire was administered in person by a trained researcher. Using Slovin's formula, a 95% confidence interval (CI), and a 0.05 margin of error, the sample size was determined to be 267 participants. The study included 305 participants. Descriptive and regression analyses were performed by using the Statistical Package for Social Science (SPSS) with a significance level of p < 0.05. RESULTS: A significant relationship was found between specialty (medical education) and the knowledge of risk factors for Type 2 diabetes mellitus (T2DM), (p < 0.012). In terms of knowledge, from a total of 13 correct knowledge points (13 marks for correct answers out of 14), some subjects scored slightly higher than others (n = 175; 57.4% of participants scored above 7, nearly over half of the correct answers, compared to n = 130; 42.6% scoring below 7). We found 132 individuals (44%) with risk scores of five or above (high risk for developing T2DM according to ADA). Smokers comprised n = 138, 45%, and nonsmokers comprised n = 148, 48%. Although 50.5% of the participants (n = 154) held a bachelor's, master's, or doctorate degree, these degrees did not improve the participants' overall general knowledge levels. The association was tested using chi-squared analysis, but no significance was found. CONCLUSIONS: Random visitors to Jordanian community pharmacies are expected to benefit from awareness and educational campaigns. These test results revealed a lack of knowledge, indicating the need for education to dispel myths and highlight the serious risks associated with T2DM. The study discovered that participants' understanding of diabetes disease prevention through lifestyle and dietary changes was inadequate. A specialist-led educational program may increase knowledge among visitors who participate. In order to prevent the spread of diabetes, more campaigns and health-promoting and prevention educational activities are required.

Population pharmacokinetics of doxorubicin: A systematic review.

Because of the high interindividual pharmacokinetic variability, several population pharmacokinetic (PopPK) models of doxorubicin (DOX) were developed to characterize factors influencing such variability. However, significant predictors for DOX pharmacokinetics identified using PopPK models varied across studies. Thus, this review aims to summarize PopPK models of DOX and its metabolites (if any) as well as significant covariates influencing DOX (and its metabolites) pharmacokinetic variability. A systematic search from PubMed, CINAHL Complete, Science Direct, and SCOPUS databases identified 503 studies. Of these, 16 studies met the inclusion criteria and were included in this review. DOX pharmacokinetics was described with two- or three-compartment models. Most studies found a significant increase in DOX clearance with an increase in body surface area from the median value of 1.8 m2 . Moreover, this review identified that while a 10-year increase in patient age resulted in a decrease in DOX clearance in adults and the elderly, younger children had lower DOX clearance compared to older children. Further, low DOX exposure was observed in pregnant women, and thus dosage adjustment is required. Concerning model applicability, predictive performance assessment of these published models should be performed before implementing such models in clinical practice.

Factors influencing methotrexate and methotrexate polyglutamate in patients with rheumatoid arthritis: a systematic review of population pharmacokinetics.

Low dose methotrexate (MTX) is commonly used in the treatment of rheumatoid arthritis. The clinical effect is mediated by its metabolite, methotrexate polyglutamate (MTX-PGn). The drug exhibits high interindividual pharmacokinetic variability and the optimal MTX dose is different among individuals. Thus, several MTX population pharmacokinetic (PopPK) models were developed to characterize factors affecting MTX pharmacokinetic variability. This review summarizes significant predictors for MTX pharmacokinetics and identifies knowledge gaps to be further examined. A total of 359 articles were identified from a systematic search of four databases: PubMed, Science Direct, and CINAHL Complete. Of these eight studies were included. Most studies investigated influential factors on MTX pharmacokinetics, but information on MTX-PGn is limited, with only one study performing a parent-metabolite (MTX-PG3) model. MTX pharmacokinetics was described using a two-compartment model with first-order elimination in most studies, with the MTX clearance ranging from 6.94 to 12.39 L/h. Significant predictors influencing MTX clearance included weight, creatinine clearance, sex, OATP1B3 polymorphism, and MTX multiple dosing. While body mass index and red blood cell counts were significant predictors for MTX-PG3 clearance. Providing that MTX-PGn plays a crucial role in clinical effect, further studies should determine other factors affecting MTX-PGn as well as its relationship with clinical response.

Changes in public knowledge and perceptions about antibiotic use and resistance in Jordan: a cross-sectional eight-year comparative study.

BACKGROUND: Resistance to antibiotics is a growing problem, worldwide and particularly in developing countries like Jordan. Raising public awareness on appropriate antibiotic use is crucial to combat this problem. The current study describes the change in public Knowledge and attitudes towards the use of antibiotics over a period of 8 years. METHODS: Two cross-sectional studies were performed 8 years apart on Jordanians of different age groups, and social settings, residing in Amman, Jordan. Convenience non-probability sampling techniques were used. In 2010, a questionnaire was distributed in paper form, whereas in 2018 snowball sampling was used to disseminate an identical electronic questionnaire. Chi-square test and post hoc analysis were done using the z-test to compare column proportions, adjustment for multiple testing using the Bonferroni method. Multiple logistic regression was used to adjust for case mix for each survey. Comparisons were made across the two studies and within each study. RESULTS: A total of 711 participants in 2010 and 436 participants in 2018 were surveyed. Over the 8-year period, there was a significant improvement in the beliefs regarding the use of antibiotics such as disagreeing to keeping left over antibiotics for later use from 57 to 70% (p < 0.05) and disagreeing to buying antibiotics without physicians' consent increased from 80 to 89% (P value < 0.001). There was no significant change in the beliefs that support self-medication such as: using antibiotics from a friend (72 to 77%) buying antibiotics without a prescription (42 to 45%), and getting information about medication use from leaflet without referring to a health care professional (60 to 63%). There were some areas of confusion regarding antibiotic range of effectiveness, and origin of resistance. Agreement about antibiotic resistance being a problem in Jordan increased significantly from 44 to 60% (p < 0.001). In addition, there was a significant increase in the percentage of participants who said that they don't request antibiotics from physicians (56 to 75% (P ≤ 0.001) and who said they would trust physicians' decisions about the necessity of antibiotics (70 to 83% P < 0.05). CONCLUSION: Findings indicate the need for better suited, and more inclusive, public educational campaigns.

Multi-walled Carbon Nanotubes Reinforced into Hollow Fiber by Chitosan Sol-gel for Solid/Liquid Phase Microextraction of NSAIDs from Urine Prior to HPLC-DAD Analysis.

BACKGROUND: The efficient analytical method for the analysis of nonsteroidal antiinflammatory drugs (NSAIDs) in a biological fluid is important for determining the toxicological aspects of such long-term used therapies. METHODS: In the present work, multi-walled carbon nanotubes reinforced into a hollow fiber by chitosan sol-gel assisted-solid/ liquid phase microextraction (MWCNTs-HF-CA-SPME) method followed by the high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed for the determination of three NSAIDs, ketoprofen, diclofenac, and ibuprofen in human urine samples. MWCNTs with various dimensions were characterized by various analytical techniques. The extraction device was prepared by immobilizing the MWCNTs in the pores of 2.5 cm microtube via chitosan sol-gel assisted technology while the lumen of the microtube was filled with few microliters of 1-octanol with two ends sealed. The extraction device was operated by direct immersion in the sample solution. RESULTS: The main factors influencing the extraction efficiency of the selected NSAIDs have been examined. The method showed good linearity R2 ≥ 0.997 with RSDs from 1.1 to 12.3%. The limits of detection (LODs) were 2.633, 2.035 and 2.386 µg L-1, for ketoprofen, diclofenac, and ibuprofen, respectively. The developed method demonstrated a satisfactory result for the determination of selected drugs in patient urine samples and comparable results against reference methods. CONCLUSION: The method is simple, sensitive and can be considered as an alternative for clinical laboratory analysis of selected drugs.

Potassium-3-beta-hydroxy-20-oxopregn-5-en-17-alpha-yl sulfate: a novel inhibitor of 78 kDa glucose-regulated protein.

BACKGROUND: Previous studies have shown the central role of 78 kDa glucose-regulated protein (GRP78) in colorectal cancer (CRC) survival and chemoresistance. In the present study, we aimed to design a GRP78 inhibitor and test its potential to inhibit CRC cells growth. MATERIALS AND METHODS: Computer-aided drug design was used to establish novel compounds as potential inhibitors of GRP78. Discovery Studio 3.5 software was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the protein. The cytotoxicity of the designed compounds was evaluated using the MTT assay and the propidium iodide method. The effect of the inhibitor on the expression of GRP78 was evaluated by immunoblotting. RESULTS: Among the designed compounds, only potassium-3-beta-hydroxy-20-oxopregn-5-en-17-alpha-yl sulfate (PHOS) has a potential to inhibit the growth of CRC cells. Inhibition of cellular growth was largely attributed to downregulation of GRP78 and induction of apoptotic cell death. CONCLUSION: These results introduce PHOS as a promising GRP78 inhibitor that could be used in future studies as a combination with chemotherapy in the treatment of CRC patients. Our ongoing studies aim to characterize PHOS safety profile as well as its mechanism of action.

An evaluation of the knowledge, opinions, expectations and concerns toward pharmacogenomics among Jordanian pharmacists.

AIM: To assess the knowledge of Jordanian pharmacists in pharmacogenomics, in addition to their attitudes, concerns, expectations and willingness to take further training. METHODS: A survey was distributed face to face to pharmacists practicing in three Jordanian cities in different practice settings. RESULTS: A total of (128) questionnaires were collected. The mean knowledge score for all participants was 2.63 ± 1.13 out of 5. The mean score for bachelor degree holders was 2.71 ± 1.06, Doctor of Pharmacy holders 2.75 ± 1.07 and graduate level education 2.63 ± 1.51. Perceptions of pharmacogenomics were positive. Concerns involved issues regarding privacy and insurance coverage. CONCLUSION: Attitudes of pharmacists in Jordan toward pharmacogenomics were highly positive, although their general knowledge was relatively low. An updated educational system is needed.