Assessment of adherence to carbamazepine using plasma and saliva samples, a study from Jordan.

Background: The measurement of carbamazepine levels in a biological sample is required to guide dosing, and prevent toxicity, and can be useful to assess medication adherence. Aim: The primary aim of the presented study is to analyze carbamazepine levels in saliva and plasma samples of outpatients and to assess adherence to carbamazepine using saliva and plasma levels. Methods: Adults who used carbamazepine for at least one month were recruited from the outpatient clinic department of Princess Basma Hospital, a public hospital in Irbid. Saliva and blood samples (1 ml) were collected simultaneously from subjects, and using a microanalytical method with high-performance liquid chromatography coupled with an ultraviolet detector, the level of carbamazepine (in micrograms per milliliter) was ascertained. Analysis of adherence to carbamazepine was carried out using plasma and saliva levels. Results: A total of 69 consecutive patients attending the neurology clinic were recruited, of whom 85.5% had epilepsy. Approximately one-third (34.8%) used carbamazepine as monotherapy, whereas the remainder used a combination of antiepileptic drugs to control seizures. Overall, about two-thirds (71.9%) of the studied samples were non-adherent in either plasma or saliva samples. By referring to the plasma sample carbamazepine concentration, 75.4% of the respondents were adherents, 15.9% had under-adherence, and 8.7% had over-adherence. A total of 85.9% of the responders were adherent using the carbamazepine level in saliva samples. Plasma and saliva carbamazepine levels were linearly correlated to one another. Polypharmacy was commonly utilized with the patients, as 42% of the patients used two medications, with a range of 1-7 drugs used concomitantly. The predictor associated with higher plasma and saliva carbamazepine levels, as determined by multiple linear regression analysis, was the occurrence of seizures less than once a month, as compared to seizures with higher frequencies. Conclusion: Saliva carbamazepine levels show the potential to be used as an alternative matrix to assess medication adherence, with a considerable correlation with the plasma carbamazepine level. Healthcare professionals can address routine care non-adherence through such measures.

Neurological Effects of Combining Low Toxic Dose of Tramadol and Nicotine: An Animal Model Evidence of Endoplasmic Reticulum Stress.

Tramadol abuse is a common problem in the Middle East in conjunction with smoking. The current study applied immunohistochemistry, western blot, real-time PCR, and ELISA to test the combination toxicity. Low toxic doses of tramadol induced animal brain cortex inflammation and hippocampus injury. Adding nicotine reverted hippocampus pathological changes without triggering marked brain injury. The expression of CHOP protein with real-time PCR showed mild endoplasmic reticulum stress (ER) in rat's brain. Histological, immunohistochemical, and western blotting analysis of CHOP (CCAAT-enhancer-binding protein homologous protein) and BIP (immunoglobulin heavy chain-binding protein) chaperones demonstrated endoplasmic reticulum stress in the brains of animals. Furthermore, the levels of apoptosis and autophagy markers demonstrated a mild reaction. The blood level of serotonin was high in all study groups, with a marked increase in the combined one. The high serotonin levels in the blood can be critical and associated with a high risk of serious withdrawal and pathological consequences. Serotonin receptor blockers such as olanzapine may increase systemic serotonin levels and need further investigation to utterly pinpoint their roles in managing mood disorders. In conclusion, the combination of tramadol and nicotine is less harmful than expected. However, serious withdrawal effects can occur as a result of high systemic serotonin effects.

Characterization of ESKAPE pathogens in urinary tract infections among Jordanian patients.

INTRODUCTION: ESKAPE pathogens are a small group of pathogens of remarkable importance. The present study was carried out to determine the prevalence of ESKAPE pathogens in urinary tract infections (UTIs) and their antibiotic susceptibility patterns at the Jordan University of Science and Technology Health Center in Irbid, Jordan. METHODOLOGY: A one-year retrospective study was conducted from April 2021 to April 2022. A total of 444 samples of "clean-catch" (midstream) urine from outpatients were studied. RESULTS: Our study showed that the vast majority of urinary tract infected patients were females (92%) compared to males (8%) and were most frequent in the age group 21-30 years old. The most associated co-morbidities with UTIs were hypertension followed by diabetes mellitus and hypothyroidism. ESKAPE pathogens were responsible for about 87.4% of the UTIs in this study, and all were identified in the urine samples except Acinetobacter baumannii. In this study, isolates were most sensitive to levofloxacin, ciprofloxacin, and third-generation cephalosporin's and least sensitive to doxycycline, amoxicillin, and clindamycin. CONCLUSIONS: This research work has shown that patients with UTI-associated ESKAPE pathogens in Jordan are at high risk of antibiotic resistance. To the best of our knowledge, this is the first study in the region that studies the association between ESKAPE pathogens and UTIs.

Pharmacist-lead screening for diabetic peripheral neuropathy using Michigan Neuropathy Screening Instrument (MNSI).

BACKGROUND: Diabetic peripheral neuropathy (DPN) is highly prevalent among Jordanian patients, mostly are asymptomatic. Early recognition and appropriate management of neuropathy is important to improve symptoms, reduce sequelae, and improve quality of life. This study aims at exploring the role of pharmacists in the early recognition of DPN and providing quick screening for the presence of it among diabetic patients. MATERIAL AND METHODS: A cross-sectional study was conducted at multi-pharmacy settings, in Irbid, Jordan. Twenty trained pharmacists who had bachelor's degrees in pharmacy participated in data collection. A total of 400 patients with confirmed diagnosis of type 2 diabetes mellitus (DM) according to the World Health Organization diagnostic criteria were recruited. DPN was assessed using the translated Arabic version of Michigan Neuropathy Screening Instrument (MNSI) history version. RESULTS: The mean MNSI questionnaire score for all participants was 4.40 ± 3.00. Mean age of the patients was 62.6 ± 10.7 years old and duration of diabetes was 8.25 ± 6.9. DN was present in 23.7% of the population. Diabetic patients with neuropathy were older than patients without neuropathy (p < 0.05) and had had diabetes longer (p < 0.05). Poor glycemic control, hypertension and gender, were significantly risk factors for DN (p < 0.05). CONCLUSIONS: In addition to delivering medications, this study suggests that pharmacists can have a role in screening and counseling about diabetic peripheral neuropathy using a simple objective, and non-invasive tool and also can determine level of damage and risk.

An update of polycystic ovary syndrome: causes and therapeutics options.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by menstrual irregularities, chronic anovulation, hirsutism, androgenic alopecia, and acne. At diagnosis, patients can with different manifestations according to the disease phenotype, patient's age, and lifestyle. However, most patients pursue medical care because of the clinical symptoms of PCOS, such as hyperandrogenism, menstrual irregularities and infertility. Recent studies have shown that PCOS is associated with 80% of anovulatory infertility; however, the precise mechanism of PCOS-induced anovulation is still undetermined. The treatment strategies of PCOS are symptomatic depending mainly on the desired goals and clinical benefits. Life style intervention is still the first line treatment option for overweight females seeking pregnancy. In addition, there are many pharmacological agents that could be added to induce ovulation such as metformin, and clomiphene citrate. Nowadays, many patients preferred to use some herbal medicine that was proved to have potential therapeutic benefits in many studies in the management of PCOS. The purpose of this review was to discuss PCOS-induced infertility and the available therapeutic options as well as the impact of COVID-19 infection on the success of fertility attempts. To address this purpose, Pubmed, Scopus, EMBASE and Google databases were searched for studies discussing PCOS-induced infertility. The literature search revealed the proper therapeutic plans to treat PCOS-induced infertility, and that treatment should be modified according to patient's complaints, reproductive desires, and disease phenotypes. In conclusion, the use of specific therapeutic agents and patients' adherence to lifestyle interventions could help patients recover their reproductive and metabolic health.

Toward Interprofessional Education of Pharmacogenomics: An Interdisciplinary Assessment.

INTRODUCTION: Pharmacogenomics, which emerged from disciplines such as pharmacology and genetics, is an increasingly important interdisciplinary field of health research, as indicated by the rapid growth of related literature. The aim of this study was to evaluate knowledge among genetics and pharmacology health-care students and to evaluate their exposure to and perceptions of pharmacogenomics. METHODS: An anonymous, 28-item online survey was distributed to medical and pharmacy students enrolled at Yarmouk University, Jordan. RESULTS: The respondents (n = 300) had an overall moderate level of knowledge regarding genetics and pharmacology. Most respondents recognized the benefits of pharmacogenomics for therapy optimization, but they had insufficient exposure to the topic. Most respondents supported providing pharmacogenetic testing in Jordan. The most preferred educational format in pharmacogenomics was integration in pharmacology courses. DISCUSSION/CONCLUSION: Medical and pharmacy students are becoming increasingly aware of the importance of pharmacogenomics in therapy optimization. Challenges such as the complexity of the topic and low retention of previous knowledge should be addressed to promote pharmacogenomics education. More work is needed to increase students' exposure to pharmacogenomics information. A deeper integration of pharmacogenomics applications into pharmacology courses is proposed to emphasize applications of pharmacogenomics.

Multi-element determination of essential and toxic metals in green and roasted coffee beans: A comparative study among different origins using ICP-MS.

The aim of this study is to compare the elemental composition among different coffee varieties consumed in Jordan. Levels of different metallic elements in coffee samples; green and roasted coffee beans from five origins; Brazil, Ethiopia, Kenya, Columbia, and India, collected from the Jordanian market were investigated. Twenty-two elements, including essential and toxic elements such as potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), aluminum (Al), manganese (Mn), copper (Cu), barium (Ba), strontium (Sr), zinc (Zn), chromium (Cr), lead (Pb), nickel (Ni), vanadium (V), cobalt (Co), gallium (Ga), uranium (U), cadmium (Cd), silver (Ag), lithium (Li), indium (In), bismuth (Bi), thorium (Th), and thallium (Ti), were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The detected heavy metals and their intake per 1 cup of coffee did not largely contribute to the recommended daily intake (RDI) and tolerable upper limit of daily intake (TULD) in an adult with an average body weight of 80 kg. The ICP-MS versus flame atomic absorption spectrometry (FAAS) results were linearly fitted, and the correlation coefficients (R2 > 0.95) were better than 0.95 for the three checked elements. No significant difference between the results of the two techniques was observed (p > 0.05). The ANOVA results indicated the presence of a significant difference between the levels of Cr, Co, and Zn in green and roasted coffee beans. The results of this study indicated that the coffee consumed in Jordan did not contain toxic levels of heavy elements and is safe for consumption according to health organizations.

A Decade of Pharmacogenetic Studies in Jordan: A Systemic Review.

The aim of this study was to perform a systematic overview of the pharmacogenetic studies conducted in Jordan. A structured search of Medline was conducted for articles over the last decade (January 2010-July 2020). Studies were classified by design, sample size, drug-gene combination, and the significance of the results. Thirty-two studies met the criteria for review. Most pharmacogenomic studies had a case-only design (n = 23). Only five studies included >500 participants. The total number of genetic variants in all studies was one hundred fifteen, which were found in forty genes, including dynamic (n = 27), and kinetic (n = 9) genes. The most commonly studied drugs were within the hematology and cardiology therapeutic areas and included statins, warfarin, aspirin, and clopidogrel. Most studies (n = 18) reported results with mixed p values [<0.05 and >0.05]. Pharmacogenomic research in Jordan is still in its infancy and is limited mainly to replication attempts. The need for standardization is imperative, especially in developing countries with scarce funding resources.

No Time for Lullabies Tracing down Pharmacological Effects & Uses of H1-Antihistamines in Children Younger than 6 Years.

Objectives. To provide a qualitative and a quantitative analysis of H1-antihistamines pharmacological uses pattern among children (<6 years old) and to evaluate the parental-related awareness. Methods. A cross-sectional study was carried out at 5 retail pharmacies in Jordan over 5 months (October/2019-February/2020). Parents who requested any of H1-antihistmine agent for a child (<6 years) were invited to participate. Results. A total of 516 children, most of them were toddlers (1-3) years, received at least 1 H1-antihistamine. More than half of the cases received H1-antihistamine as self-medication (56.3%). Sedating antihistamine agents were the most frequently used among children (<6 years old) (77.9%) among which Chlorpheniramine maleate was the most commonly used agent (62.9%). About half of the children (47.0%) received H1-antihistamine to induce sleep. Whereas, 21.7% and 12.9% received them to manage flu, and allergic rhinitis (AR), respectively. Around 66.6% of the cases were classified as off-label use. Most of the parents (80.5%) were aware of the sedative adverse effects of H1-antihistamines, whereas a fewer number (31.9%) were aware of their cognitive effects. Finally, more than two thirds of parents (79.7%) were unfamiliar with off-label drug use in children. Conclusion. Despite the availability of less-sedating H1-antihistamines with a wide safety and efficacy record, the use of sedating H1-antihistamines remains popular in children.

Neuroprotective brain-derived neurotrophic factor signaling in the TAU-P301L tauopathy zebrafish model.

Brain-derived neurotrophic factor (BDNF) dysregulations contribute to the neurotoxicity in neurodegenerative pathologies and could be efficiently targeted by therapies. In Alzheimer's disease (AD), although the relationship between BDNF and amyloid load has been extensively studied, how Tau pathology affects BDNF signaling remains unclear. Using the TAU-P301L transgenic zebrafish line, we investigated how early Tau-induced neurotoxicity modifies BDNF signaling. Alterations in BDNF expression levels were observed as early as 48 h post fertilization in TAU-P301L zebrafish embryos while TrkB receptor expression was not affected. Decreasing BDNF expression, using a knockdown strategy in wild-type embryos to mimic Tau-associated decrease, did not modify TrkB expression but promoted neurotoxicity as demonstrated by axonal outgrowth shortening and neuronal cell death. Moreover, the TrkB antagonist ANA-12 reduced the length of axonal projections. Rescue experiments with exogenous BDNF partially corrected neuronal alterations in TAU-P301L by counteracting primary axonal growth impairment but without effect on apoptosis. Importantly, the axonal rescue was proved functionally effective in a behavioral test, at a similar level as obtained with the GSK3ß inhibitor LiCl, known to decrease TAU phosphorylation. Finally, treatment with a TrkB agonist, 7,8-dihydroxyflavone, led to comparable results and allowed full rescue of locomotor response. We provided here strong evidence that Tau neurotoxicity provoked alterations in BDNF system and that BDNF pathway might represent an efficient therapeutic target.

Retrospective assessment of acute poisoning incidents by nonpharmaceutical agents in Jordan: Data from Pharmacy One™ Poison Call Center, 2014 to 2018-Part I.

The Pharmacy One™ Poising Call Center (P1 PCC), located in Amman, Jordan, was created to address deficiencies identified by the pharmacy service, including in the management of poisoning cases. The aims of this study were to analyze the patterns of poisoning cases reported to the P1 PCC and to describe the role of the P1 PCC pharmacist in ensuring preparedness and managing the response to poisoning cases. In addition, the information from these interventions was used to survey human poisoning in Jordan. This is a retrospective descriptive study of acute poisoning incidents in the Jordanian population, as recorded by the P1 PCC during the period 2014-2018. Inquiries received by the P1 PCC were recorded on a predesigned form. The year, patient demographics, toxic agent involved, and circumstances of the poisoning event were all fully documented utilizing Oracle and Excel spreadsheets. A total of 1992 poisoning incidents were reported to the P1PCC, predominately (68.59%) via 911 phone calls. Reports were predominantly from males (1.67:1). Children were the second most common age group after adolescents (22.62% and 42.49%, respectively). The most frequent causative nonpharmaceutical agents were household products (17%) in preschool children and animal bites (20%) in adolescents. Most of the poisoning incidents (74.63%) occurred at home. Unintentional poisoning (54.12%), with mild medical outcomes (61.45%), accounted for most of the poisoning incidents caused by exposure to household products. These data may represent the most recent picture of poisoning incidents in Jordan. Emergency medical services were provided by experienced pharmacy practitioners at the P1 PCC, to respond to emergency needs in the community in a professional manner. Therefore, the need for unnecessary hospitalization and the cost of ambulance dispatch were minimized, which are highly valuable outcomes.

Retrospective assessment of acute poisoning incidents by pharmaceutical agents in Jordan: Data from Pharmacy One™ Poison Call Center, 2014 to 2018-Part II.

Poison control centers provide surveillance data that can be used to estimate the magnitude of poisoning cases and the level of public awareness and to evaluate control measures. The aim of this study is to describe the drug-related poisoning queries received by the Pharmacy One™ Poisoning Call Center (P1 PCC) in Jordan. This is a retrospective descriptive study of the acute drug-related poisoning incidents in the Jordanian population recorded by the P1 PCC during the 2014-2018 period. The inquiries received were recorded on a predesigned form. The demographic data, including the age and the sex of the patient, the route of and reason for exposure and the drug therapeutic groups, in addition to medical outcomes, were extracted utilizing computerized Oracle and Excel spreadsheets. During the period of evaluation, 900 drug-related poisoning incidents were reported to the P1 PCC. The majority of calls (48.5%) were received via 911, followed by the public (48.56%) and healthcare professionals (27.1%). More than half of the poisoning incidents were recorded among males (52.5%). Adults were the most affected group (40.5%), followed by children (34.0%). Unintentional exposure was the most common cause of poisoning (58.6%), followed by suicide attempts (25.3%). Nonsteroidal anti-inflammatory drugs and paracetamol caused the majority of the reported cases. Poisoning incidents were mainly classified as mild to moderate (56.1%), while only 16.6% were severe. The P1 PCC has demonstrated an important and vital role in improving patient safety and providing education on rational drug use. Reflections on these data can be used to increase public awareness in promoting the rational use of medications among Jordanian citizens.

Inhibitor and substrate binding induced stability of HIV-1 protease against sequential dissociation and unfolding revealed by high pressure spectroscopy and kinetics.

High-pressure methods have become an interesting tool of investigation of structural stability of proteins. They are used to study protein unfolding, but dissociation of oligomeric proteins can be addressed this way, too. HIV-1 protease, although an interesting object of biophysical experiments, has not been studied at high pressure yet. In this study HIV-1 protease is investigated by high pressure (up to 600 MPa) fluorescence spectroscopy of either the inherent tryptophan residues or external 8-anilino-1-naphtalenesulfonic acid at 25°C. A fast concentration-dependent structural transition is detected that corresponds to the dimer-monomer equilibrium. This transition is followed by a slow concentration independent transition that can be assigned to the monomer unfolding. In the presence of a tight-binding inhibitor none of these transitions are observed, which confirms the stabilizing effect of inhibitor. High-pressure enzyme kinetics (up to 350 MPa) also reveals the stabilizing effect of substrate. Unfolding of the protease can thus proceed only from the monomeric state after dimer dissociation and is unfavourable at atmospheric pressure. Dimer-destabilizing effect of high pressure is caused by negative volume change of dimer dissociation of -32.5 mL/mol. It helps us to determine the atmospheric pressure dimerization constant of 0.92 µM. High-pressure methods thus enable the investigation of structural phenomena that are difficult or impossible to measure at atmospheric pressure.

Cholesteryl ester transfer protein rs1532624 gene polymorphism is associated with reduced response to statin therapy.

The aim of the study was to determine the allele and genotype frequencies of rs1532624 SNP of the cholesteryl ester transfer protein gene (CETP) among 116 Jordanian patients taking statins, and to study the impact of the genotypes on response to statin therapy. The study was approved by the Institutional review Board (IRB) of The Jordan University Hospital. An informed consent was signed by every participant. A single fragment encoding a 307 bp sequence of the CETP gene, including the SNP of interest at position 14645 in intron 7, was amplified using a polymerase chain reaction (PCR) technique directly from whole blood. The PCR product was then subjected to DNA sequencing. The frequencies of the genotypes of the homozygous minor allele (AA), the homozygous major allele (CC), and the heterozygous allele (CA) were 0.121, 0.405, and 0.474, respectively. The minor allele (A) frequency was 0.358. The frequencies did not deviate from Hardy-Weinberg equilibrium. The lipid profile before the start of statin therapy was similar for all genotypes regarding total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglycerides, while high density lipoprotein cholesterol (HDL-C) was significantly higher in the AA genotype. The AA genotype was also associated with significantly lower CETP activity than the other genotypes. The response to statin therapy was less in the AA genotype than the other genotypes for TC and LDL-C. In conclusion, the homozygous minor allele subjects have higher base line HDL-C, and lower CETP activity than the other genotypes (CA and CC). They also have less reduction in TC and LDL-C after statin therapy.