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.

Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model.

The widespread recreational use of synthetic cannabinoids (SCs) has become a serious health issue. Reports of life-threatening intoxications related to SC consumption have markedly increased in recent years, including neurotoxicity, cardiotoxicity, nephrotoxicity, and hepatotoxicity. We investigated the impact of acute administration of the synthetic cannabinoid XLR-11 (3 mg/kg, i.p. for 5 consecutive days) on the liver in BALB/c mouse animal model. Using real-time quantitative RT-PCR, MDA assay, and TUNEL assay, we found consistent up-regulation of a variety of genes involved in oxidative stress (NOX2, NOX4, and iNOS), inflammation (TNF-α, IL-1ß, IL-6), and apoptosis (Bax) in the liver of XLR-11 treated mice compared to control mice. These finding were supported with an elevation of MDA levels and TUNEL positive cells in the liver of XLR-11 treated mice which further confirm increased oxidative stress and apoptosis, respectively. Histopathological analysis of the liver of XLR-11 treated mice confirmed pronounced hepatic necrosis associated with inflammatory cell infiltration. Furthermore, elevated ALT and AST serum levels were also identified in XLR-11 treated mice indicating possible liver damage. Overall, SC-induced hepatotoxicity seems to be mainly mediated by activated oxidative stress and inflammatory processes in the liver, but the specific mechanisms involved require further investigations. However, the present study shed light on the potential deleterious role of acute administration of SCs in the progression to acute hepatic injury which enhances our understanding of the adverse effect of SC consumption.

Quantification of Total Phenols and Antioxidants in Coffee Samples of Different Origins and Evaluation of the Effect of Degree of Roasting on Their Levels.

Phenolic and antioxidant compounds have received considerable attention due to their beneficial effects on human health. The aim of this study is to determine the content of total phenols and antioxidants in fifty-two coffee samples of different origins, purchased from the Jordanian local market, and investigate the effect of the degree of roasting on the levels of these compounds. The coffee samples were extracted using the hot water extraction method, while Folin−Ciocalteu (FC) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay methods were used to analyze these compounds. The results showed that the highest content of total phenol (16.55 mg/g equivalent to GAE) was found in the medium roasted coffee, and the highest content of antioxidants (1.07 mg/g equivalent to TEAC) content was found in the green coffee. Only light and medium roasted coffee showed a significant correlation (p < 0.05, R2 > 0.95) between the average of total phenolic and antioxidant content. A negative correlation between the antioxidant content and the degree of roasting (p < 0.05, R2 > 0.95) were shown, while it did not correlate with phenolic contents. Previously, a positive correlation between antioxidant and chlorogenic acids content was observed, with no correlation between the origin of coffee samples nor heavy metal content, which was previously determined for the same coffee samples. These findings suggest that the antioxidant content for coffee extracts is largely determined by its chlorogenic acid content, rather than the coffee origin or total phenolic and heavy metals content.

Systemic capillary leak syndrome following granulocyte colony-stimulating factor therapy in a T-lymphoblastic leukemia/lymphoma patient: a case report.

Introduction: Systemic capillary leak syndrome (SCLS) is a rare and often fatal clinical entity used to describe a generalized increase in vascular permeability leading to fluid extravasation toward the interstitial compartment. SCLS could be an idiopathic disease or secondary to infections, malignancies or drugs. Case: We present a case of presumably granulocyte colony-stimulating factor (G-CSF)-induced SCLS in a 21-year-old man diagnosed with T­lymphoblastic leukemia/lymphoma. He received the 6th cycle (part B) of the hyper-CVAD chemotherapeutic regimen followed by the initiation of neutropenic fever prophylaxis protocol which included antibiotics and G­CSF. In a course of hours, the patient became dyspneic, hypotensive, and edematous which required intensive care unit admission and was stabilized accordingly. In the following days the patient's anasarca progressively increased which was associated with hypoalbuminemia, hypotension and anemia with pericardial and bilateral plural effusions. As a diagnosis of exclusion augmented by the acuity of such clinical event, observed concomitantly with the administration of the prophylaxis protocol, the suspicion of G­CSF-induced SCLS was established. Consequently, G­CSF was discontinued and treatment with dexamethasone and intravenous immunoglobulins (IVIG) was started. The patient's condition improved significantly illustrated by hemodynamic stability in addition to improvement regarding the anasarca, hypoalbuminemia, and anemia. Follow-up scans suggest resolution of the pericardial and plural effusions. Conclusion: SCLS remains a serios and potentially fatal complication of G­CSF administration which should be taken into consideration, since such medication is widely utilized in oncology wards.

Quantification of Caffeine and Chlorogenic Acid in Green and Roasted Coffee Samples Using HPLC-DAD and Evaluation of the Effect of Degree of Roasting on Their Levels.

Chlorogenic acid and caffeine are among the important components in coffee beans, determining the taste and aroma. In addition, phenols and antioxidants content possess vital health values. The main aim of this study is to determine the levels of caffeine and chlorogenic acid in several coffee samples of different origins and degrees of roasting. The coffee samples were extracted using hot water. The levels of caffeine and chlorogenic acid were quantified using high-performance liquid chromatography (HPLC) equipped with a diode array detector, a reverse phase system, and an ODS column (C18). Total phenol and antioxidant contents were previously determined for the same samples. The results showed that the highest content of caffeine was found in the medium roasted coffee (203.63 mg/L), and the highest content of chlorogenic acid content was found in the green coffee (543.23 mg/L). The results demonstrated a negative correlation between the chlorogenic acid levels with the degree of roasting, while it showed a positive correlation between the caffeine levels with the degree of roasting till a certain point where the levels dropped in the dark roasted coffee. The origin of coffee samples did not show any effect on any of the measured variables. Antioxidant effects of coffee samples were largely determined by chlorogenic acid content.

Evaluating the Prognostic Role of Monocytopenia in Chemotherapy-Induced Febrile Neutropenia Patients Treated with Granulocyte Colony-Stimulating Factor.

OBJECTIVE: Chemotherapy-induced febrile neutropenia is a common and serious oncological emergency which carries a substantial mortality and morbidity. The main objective of this study is to evaluate the usage of absolute monocyte count (AMC) at presentation as a prognostic factor for patients with chemotherapy-induced febrile neutropenia who were subsequently treated with granulocyte colony-stimulating factor (G-CSF). STUDY DESIGN: The electronic medical records of our center were used retrospectively to identify patients diagnosed with unprecedented chemotherapy-induced febrile neutropenia treated with G-CSF between January 2010 to December 2020 and diagnosed with solid and hematological malignancies. Patient's demographics, disease characteristics and laboratory investigations were extracted. Disease progression measures were statistically compared between the study groups in the short-term period of follow-up (six days) including absolute neutrophil count (ANC), ANC difference compared to the baseline readings, hospitalization period, and mortality. RESULTS: A total of 80 patients were identified and categorized into two groups namely monocytopenia (n = 34) and non-monocytopenia (n = 46) with an AMC cutoff point of 0.1×109 cells/L. The monocytopenia group exhibited a worse prognosis with lower ANC values and slower improvement illustrated by the low ANC difference values at all follow up points (P-value ≤ 0.05) apart from day 5. A statistically significant lower hospitalization period was also observed in the non-monocytopenia group (P-value = 0.006). Linear regression analysis evaluated the association between AMC values at admission and ANC values at admission along with subsequent days of follow up which were found to be statistically significant (P-value ≤ 0.05). Receiver operating characteristic curves suggest a satisfactory predictability of ANC changes by AMC values at admission, days1, 2, 3, 4 and 6. CONCLUSION: Monocytopenia holds a worse prognosis in chemotherapy-induced febrile neutropenia patients treated with G-CSF. In addition, AMC values at presentation represents a potential risk factor that can predict short-term changes regarding ANC measures.

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.

The Effect of Nail Lacquer on Taxane-Induced Nail Changes in Women With Breast Cancer.

OBJECTIVE: Taxane-induced nail changes are considered as an important cosmetic manifestation with an incidence that reaches up to 44% of patients treated with taxane-included therapeutic regimens. In this article, we represent a clinical observational study to evaluate the effect of cosmetic nail lacquer on taxane-induced nail changes in female patients diagnosed with breast cancer. METHODS: Prospectively, we identified those women who were diagnosed with breast cancer, scheduled to have AC-Taxol protocol. Any female with previous dermatological or systemic disorders that affect nails was excluded from the study. Patients were categorized into 2 groups based on the utilization of nail lacquer. The first group includes women who started to use the nail lacquer after development of nail changes. The second group comprises those women who did not use the nail lacquer at any occasion. RESULTS: A total of 59 female patients were included in the study; 46 (78%) of them developed nail changes and the main change was nail discoloration. The first group which has used nail lacquer (17, 28.8%) showed an improvement among 15 (78.9%) patients, whereas 2 (7.4%) of them continued to have worsening symptoms. On the contrary, most of the second group (25, 92.9%) did not show any improvement in nail changes. A statistical significance between the tested groups was observed (P = .000). There is no statistical association between the progression of nail changes and the age of patients. CONCLUSIONS: Taxane-induced nail changes are considered as an important clinical, cosmetic, and psychological complication, especially for female patients with cancer. This article suggests that nail lacquer may have an effect in the improvement of nail changes, especially nail discoloration. Further investigations are recommended to prove the efficacy of nail lacquer.

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.

Chiral separations of cathinone and amphetamine-derivatives: Comparative study between capillary electrochromatography, supercritical fluid chromatography and three liquid chromatographic modes.

The screening part of an earlier defined chiral separation strategy in capillary electrochromatography (CEC) was used for the separation of ten cathinone- and amphetamine derivatives. They were analyzed using 4 polysaccharide-based chiral stationary phases (CSPs), containing cellulose tris(3,5-dimethylphenylcarbamate) (ODRH), amylose tris(3,5-dimethylphenylcarbamate) (ADH), amylose tris(5-chloro-2-methylphenylcarbamate) (LA2), and cellulose tris(4-chloro-3-methylphenylcarbamate) (LC4) as chiral selectors. After applying the screening to each compound, ADH and LC4 showed the highest success rate. In a second part of the study, a comparison between CEC and other analytical techniques used for chiral separations i.e., supercritical fluid chromatography (SFC), polar organic solvent chromatography (POSC), reversed-phase (RPLC) and normal-phase liquid chromatography (NPLC), was made. For this purpose, earlier defined screening approaches for each technique were applied to separate the 10 test substances. This allowed an overall comparison of the success rates of the screening steps of the 5 techniques for these compounds. The results showed that CEC had a similar enantioselectivity rate as NPLC and RPLC, producing the highest number of separations (9 out of 10 racemates). SFC resolved 7 compounds, while POSC gave only 2 separations. On the other hand, the baseline separation success rates for NPLC and RPLC was better than for CEC. For a second comparison, the same chiral stationary phases as in the CEC screening were also tested with all techniques at their specific screening conditions, which allowed a direct comparison of the performance of CEC versus the same CSPs in the other techniques. This comparison revealed that RPLC was able to separate all tested compounds, and also produced the highest number of baseline separations on the CSP that were used in the CEC screening step. CEC and NPLC showed the same success rate: nine out of ten substances were separated. When CEC and NPLC are combined, separation of the ten compounds can be achieved. SFC and POSC resolved eight and three compounds, respectively. POSC was the least attractive option as it expressed only limited enantioselectivity toward these compounds.

A chiral separation strategy for acidic drugs in capillary electrochromatography using both chlorinated and nonchlorinated polysaccharide-based selectors.

A generic chiral separation strategy for the analysis of acidic compounds in CEC is proposed in completion of an earlier defined strategy for nonacidic compounds. The screening step of this strategy uses a 45 mM ammonium formate (pH 2.9)/ACN (35/65, v/v) mobile phase, a temperature of 25°C, and an applied voltage of 15 kV. To update the screening step, eight chiral stationary phases, which all possessed chlorinated and nonchlorinated polysaccharide-based chiral selectors, were evaluated using the earlier defined screening conditions. A combination of the two types of polysaccharide-based chiral phases proved to have the highest cumulative success rate. In the updated screening step, amylose tris(3,5-dimethylphenylcarbamate) (ADH), cellulose tris(4-methylbenzoate) (OJH), cellulose tris(3,5-dichlorophenylcarbamate) (SP5), and cellulose tris(3,5-dimethylphenylcarbamate) (ODRH) were included as selectors and their preferred screening sequence was determined as ADH > OJH > SP5 > ODRH. New optimization steps were also defined for SP5 by investigating the influences of different parameters on the separation outcome using an experimental design approach. After application of the updated strategy, 15 of 17 acidic pharmaceuticals were separated under screening conditions, of which 9 were baseline resolved. When the optimization steps were applied, another three compounds were baseline separated, while the total number of separations was increased by one, which brings the total number of separations to 16 of 17 with 12 baseline separated compounds. This reflects the successful performance of the updated strategy on acidic compounds.