Eczacılık Fakültesi / Faculty of Pharmacy
Permanent URI for this collectionhttps://hdl.handle.net/11727/5700
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Item Drug-related problems and health-related quality of life among chronic disease patients in a rural region of North Cyprus(2022) Goksin, Servet; Abdi, Abdikarim; Alsaloumi, Louai; Basgut, BilgenPurpose: To evaluate the various types of drug-related problems (DRPs) and health-related quality of life (HRQoL) among chronic disease patients in a rural region of North Cyprus.Methods: A cross-sectional study of patients visiting a rural community pharmacy in North Cyprus was conducted. Patient demographic information, quality of life (QoL), laboratory data, adherence, and beliefs about medicine were assessed using standardized tools. Drug-related problems were evaluated using PCNE V.9.1.Results: Among the 200 screened participants, 97 fulfilled the enrollment criteria and were interviewed. The median age of the participants was 62 years (interquartile range = 15), with 58.8 % women. Only 54 % of hypertensive (HTN) patients reached their target blood pressure level. Over 40 % of type 2 diabetes mellitus (T2DM) patients failed to achieve their target HbA1c level. The majority (71 %) of patients with HTN, T2DM or coronary artery disease were not compliant with lifestyle recommendations and 86.6 % had >= 1 DRP. Insufficient dosing and inappropriate indication for a drug were the DRPs associated with failure to achieve target and inappropriate drugs was the DRP type mostly associated with lower quality of life scores. Other factors associated with lower QoL levels included female gender, unemployment status, and high agreement with the statement "medications do more harm than good". Conclusion: Drug related problems and non-adherence are prevalent, while therapy targets are rarely met in rural Cyprus. Community pharmacists have the potential to improve outcomes in the management of non-communicable diseases (NCDs).Item The Phytochemical Profile and Biological Activity of Malva neglecta Wallr. in Surgically Induced Endometriosis Model in Rats(2022) Akkol, Esra Kupeli; Karpuz, Busra; Turkcanoglu, Gizem; Cosguncelebi, Fatma Gul; Tastan, Hakki; Aschner, Michael; Khatkar, Anurag; Sobarzo-Sanchez, Eduardo; 000887409800001Leaves and aerial parts of Malva neglecta Wallr. have been traditionally used in Anatolia for the treatment of pain, inflammation, hemorrhoids, renal stones, constipation, and infertility. This study investigated the effects of M. neglecta leaves in a rat endometriosis model. The dried plant material was extracted with n-hexane, ethyl acetate, and methanol, successively. Experimental endometriosis was surgically induced in six-week-old female, non-pregnant, Wistar albino rats by autotransplant of endometrial tissue to the abdominal wall. After twenty-eight days, rats were evaluated for a second laparotomy. Endometrial foci areas were assessed, and intraabdominal adhesions were scored. Rats were divided into five groups as control, n-hexane, ethyl acetate, methanol, and aqueous extracts, as well as reference. At the end of the treatment, all rats were sacrificed and endometriotic foci areas and intraabdominal adhesions were re-evaluated and compared with the previous findings. Moreover, peritoneal fluid was collected to detect tumor necrosis factor- alpha (TNF-alpha), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) levels, and cDNA synthesis, and a quantitative real-time polymerase chain reaction (PCR) test was done. The phytochemical content of the most active extract was determined using High-Performance Liquid Chromatography (HPLC). Both endometrial volume and adhesion score decreased significantly in the group treated with methanol extract. In addition, significant decreases were observed in TNF-alpha, VEGF, and IL-6 levels in animals administered methanol extract. HPLC results showed that the activity caused by the methanol extract of M. neglecta was due to the polyphenols. Taken together, these novel findings indicate that M. neglecta may be a promising alternative for the treatment of endometriosis.Item Sensor-based MIP technologies for targeted metabolomics analysis(2022) Ozcelikay, G.; Kaya, S., I; Ozkan, E.; Cetinkaya, A.; Nemutlu, E.; Kir, S.; Ozkan, S.A.In recent years, metabolomics, identification and profiling of metabolites, have gained broad interest compared to other omics technologies and are progressively being utilized for biomarker discoveries. Therefore, the application of metabolomics in different fields are increasing day by day because of its high throughput results. However, the application of metabolomics requires state-of-the-art analytical approaches for the analysis. The complexity and limited availability of these instruments are restricting parameters for applying metabolomics studies in routine analysis. This problem may be overcome with molecularly imprinted polymer (MIP)-based electro sensors since they have high selectivity, sensitivity, easy applicability, portability, and low cost. This is the final step before developing end point-of-care tests (POCT), which patients can easily apply. MIP sensors will have more applications in the targeted metabolomics analysis to develop POCT systems. This review analyzes various metabolites using MIP-based electrochemical methods for their potential usage as POCT and biomarker research based on targeted metabolomics analysis requirements. The future applications for the sensitive assay of metabolites in medicine and clinical trials are also discussed. (C) 2021 Elsevier B.V. All rights reserved.Item Clinical pharmacist assessment of drug-related problems among intensive care unit patients in a Turkish university hospital(2022) Albayrak, Aslinur; Basgut, Bilgen; Bikmaz, Gulbin Aygencel; Karahalil, Bensu; 35033079Background Critically ill patients treated in the intensive care units (ICUs) often suffer from side effects and drug-related problems (DRPs) that can be life-threatening. A way to prevent DRPs and improve drug safety and efficacy is to include clinical pharmacists in the clinical team. This study aims to evaluate the classification of drug-related problems and the implementation of clinical pharmacy services by a clinical pharmacist in the ICU of a university hospital in Turkey. Methods This study was carried out prospectively between December 2020 and July 2021 in Gazi University Medical Faculty Hospital Internal Diseases ICU. All patients hospitalized in the intensive care unit for more than 24 h were included in the study. During the study, the clinical pharmacist's interventions and other clinical services for patients were recorded. DRPs were classed according to the Pharmaceutical Care Network Europe V.8.02. Results A total of 151 patients were included during the study period corresponding to 2264 patient-days. Patients with DRPs had a longer hospital stay and a higher mortality rate (p < 0.05). 108 patients had at least one DRP and the total number of DRPs was 206. There was an average of 1.36 DRPs per patient, 71.5% of patients experienced DRP and 89.22 DRPs per 1000 patient-days. A total of 35 ADEs were observed in 32 patients. ADE incidence was per 1000 patient-days 15.45. ADEs were caused by nephrotoxicity (48.57%), electrolyte disorders (17.14%), drug-induced thrombocytopenia (17.14%), liver enzyme increase (8.57%) and other causes (8.57%). Drug selection (40.29%) and dose selection (54.36%) constituted most of the causes of DRPs. Dose change was the highest percentage of planned interventions with a rate of 56.79%. Intervention was accepted at a rate of 90.8% and it was fully implemented. Conclusion In this study, the importance of the clinical pharmacist in the determination and analysis of DRPs was emphasized. Clinical pharmacy services like the one described should be implemented widely to increase patient safety.Item Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS(2022) Recber, Tuba; Ozkan, Ece; Nemutlu, Emirhan; Beksac, Mehmet Sinan; Kir, SedefDown syndrome is a common genetic disorder that results from the presence of an extra chromosome in the 21st chromosome pair of humans. Metabolomics is an alternative method in discovery of new biomarkers for the screening and diagnosis of Down syndrome. In this study, quantitative analyzes of 3-hydroxybutyric acid and 3hydroxyisovaleric acid, selected as possible markers for prenatal diagnosis of Down syndrome were performed. LCMS/MS analyzes were performed on a Phenomenex Luna NH2(100 x 4.6 mm, 3 mu m) column using a mobile phase mixture of 0.1% formic acid and acetonitrile containing 0.1% formic acid at a flow rate of 0.35 mL/minute. The MRM transitions were 103.0 -> 59.0 for 3-hydroxybutyric acid and 117.1 -> 59.0 for 3-hydroxyisovaleric acid. Under these conditions, the retention times of 3-hydroxyisovaleric acid 3-hydroxybutyric acid were 2.7 and 3.1 minute, respectively. The method was found linear from 0.1 to 10.0 mu g/mL for both metabolites. The limit of detection (LOD) was 0.017 mu g/mL for 3-hydroxybutyric acid and 0.003 mu g/mL for 3-hydroxyisovaleric acid. The lower limit quantification (LLOQ) was 0.045 mu g/mL for 3-hydroxybutyric acid and 0.008 mu g/mL for 3-hydroxyisovaleric acid. The method has been proven to be selective, precise, accurate, sensitive, and robust based on the validation studies results. Finally, the method was applied to plasma samples of the pregnant women with healthy fetus (n = 30) and with Down syndrome fetus (n = 17). As a result of the analysis, a statistically significant increase (p <0.01) was observed in the 3-hydroxybutyric acid level of the group with Down syndrome compared to the healthy group. This result strengthens the use of 3-hydroxybutyric acid as an important biomarker in the prenatal screening/diagnosis of Down syndrome.Item Electrochemical Detection of Antioxidant Activities of 4-Indolyl-5-Oxo-6,6 (Or 7,7)-Dimethyl-1,4,5,6,7,8-Hexahydroquinoline Derivatives(2021) Suslu, Incilay; Kablan, Sevilay Erdogan; Safak, Cihat; Simsek, RahimeAntioxidants used in different medical and industrial fields in order to prevent and delay oxidative stress. They play a crucial role in the protecting biological systems against many diseases. 1,4-dihydropyridines are known as calcium channel modulators. Electrochemical techniques are simple, cheap and fast detection techniques and require small amounts of sample, so they offer advantages over commonly used analytical methods. Voltammetric methods have been applied to investigated the antioxidant activity of compounds in different fields. The proposed work is aimed at examining the electrochemical behavior of the 1,4-dihydropyridines by differential pulse voltammetry and hence the assessment of its antioxidant activity from the cathodic reduction peak of oxygen values. The peak current due to oxygen reduction was found to be proportional to the 1,4-dihydropyridines concentration of 0.1 - 0.5 mg/mL. The coefficient of antioxidant activity of 1,4-dihydropyridine derivatives were calculated and compared each other. Nifedipine used as a reference drug that is known as the calcium channel modulator and it is used to compare the antioxidant activities of 1,4-dihydropyridine-derived compounds.Item In Vitro Caco-2 Cell Permeability Studies of Ziprasidone Hydrochloride Monohydrate Nanocrystals(2021) Karakucuk, Alptug; Tashan, Emine; Ozturk, Naile; Celebi, Nevin; 0000-0002-6402-5042; 33902264Objectives: The current study focused on the evaluation of the cytotoxic effect and permeability of ziprasidone hydrochloride monohydrate (ZHM) nanocrystals on Caco-2 cells. Materials and Methods: ZHM nanocrystals were prepared by the microfluidization method in the presence of polyvinylpyrrolidone as a stabilizer. Particle size (PS), particle size distribution (PDI), and zeta potential (ZP) values were measured in characterization studies. In vitro cytotoxic effects of ZHM nanocrystals were investigated using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Caco-2 transport studies were conducted with formulations of ZHM coarse powder and nanocrystals. Results: Nanocrystals were obtained with 400-600 nm PS, 0.1-0.4 PDI, and >20 mV ZP values. The cell viability remained 100% for all sample groups. The permeability value of ZHM nanocrystals through Caco-2 cells increased 2.3-fold in comparison with ZHM coarse powder. Cumulative drug transport also increased at the end of the sampling period. Conclusion: Nanocrystal technology helps to increase the permeability of drug particles by increasing the saturation solubility.Item Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients(2021) Arslan, Hande; 0000-0002-5708-7915; 34370578; ABG-7034-2021There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.Item Detection of COVID-19 by Machine Learning Using Routine Laboratory Tests(2021) Cubukcu, Hikmet Can; Topcu, Deniz Ilhan; Bayraktar, Nilufer; Gulsen, Murat; Sari, Nuran; Arslan, Ayse Hande; 0000-0002-1219-6368; 0000-0002-7886-3688; 34791032; E-3717-2019; Y-8758-2018Objectives The present study aimed to develop a clinical decision support tool to assist coronavirus disease 2019 (COVID-19) diagnoses with machine learning (ML) models using routine laboratory test results. Methods We developed ML models using laboratory data (n = 1,391) composed of six clinical chemistry (CC) results, 14 CBC parameter results, and results of a severe acute respiratory syndrome coronavirus 2 real-time reverse transcription-polymerase chain reaction as a gold standard method. Four ML algorithms, including random forest (RF), gradient boosting (XGBoost), support vector machine (SVM), and logistic regression, were used to build eight ML models using CBC and a combination of CC and CBC parameters. Performance evaluation was conducted on the test data set and external validation data set from Brazil. Results The accuracy values of all models ranged from 74% to 91%. The RF model trained from CC and CBC analytes showed the best performance on the present study's data set (accuracy, 85.3%; sensitivity, 79.6%; specificity, 91.2%). The RF model trained from only CBC parameters detected COVID-19 cases with 82.8% accuracy. The best performance on the external validation data set belonged to the SVM model trained from CC and CBC parameters (accuracy, 91.18%; sensitivity, 100%; specificity, 84.21%). Conclusions ML models presented in this study can be used as clinical decision support tools to contribute to physicians' clinical judgment for COVID-19 diagnoses.