Pharmacist Competences and Impact of Pharmacist Intervention on Medication Adherence: an Observational Study.

BACKGROUND: The aim of this study is to determine the results of pharmacist interventions on patient's adherence to drugs in community settings. SUBJECTS AND METHODS: The study was designed using a standard EQ-SDQ questionnaire and a Culig questionnaire about the adherence to drug. General Level Framework (GLF) was used as a tool for competence assessment among community pharmacists. Participants were pharmacists that issued the medication on repeat prescription in the pharmacy. They interviewed the patient at the first visit to the pharmacy and the next time when the patient came to refill the prescription. The survey was conducted during a two-month period in the Atlantic Pharma pharmacy chain. A total of 152 patients were included at the first visit and 87 patients at the second visit. RESULTS: About two thirds of patients (65.5%) identified themselves as adherent during the first survey, and this number increased slightly during the second interview (by 3.5%), but not statistically significant (p=0.75). A total number of drugs prescribed during the first and second survey was 252 and 253 respectively. The percentage of the advices given to the patients increased during the second survey, but not statistically significant (p=0.62). CONCLUSION: It is definitely important to check that a patient understands current disease and what are doubts and difficulties in taking a therapy. The reasons for possible nonadherence are different: fears, worsening of the clinical state or other negative treatment outcomes. Enough time should always be left to clarify anything that is unclear and to listen. Application of GLF program for improving pharmacist competences resulted in slightly increased patient adherence to medication. For further development of competences, pharmacist intervention should include some other contents, i.e. tailoring the dosage scheme, counselling about drug-drug and drug-food interactions. The pharmacist counseling should be reimbursed by the Croatian Health Insurance Fund.

Comparison of two Different Methods (Patient Questionnaire and Medication Possession Ratio - MPR) for Measuring the Chronic Patient's Behavior.

BACKGROUND: Medication adherence is the extent to which patients take medications as prescribed by their health care providers. There are a number of approaches to study medication-taking behavior. The aim was to compare two most common methods for measuring adherence: Patient Adherence Questionnaire and Medication Possession Ratio (MPR). They belong to the indirect methods. METHODS: In this article four adherence studies were analysed and the results were compared, two wherein the patient questionnaire was applied and other two with medication possession ratio applied. RESULTS: The obtained results reveal that more than half of respondents (58.9%) experienced constant nonadherence behavior according to the prescribed therapy. The main reason of nonadherence is oblivion, suggesting that it is necessary to pay more attention to this problem. CONCLUSIONS: Nonadherence with therapy has negative consequences on the health of the individual, and an adverse impact on the community health and wealth. Patients should be informed of the importance of regularly taking prescribed therapy. The main problem of long-term therapy is significantly decreased of adherence to medication in a very short time. It is important to stress that almost all the interventions effective for improving patient adherence in long-term care are complex and should be repeated after a while.

Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma.

Apart from cytotoxicity, inhibitors of the COX-2 enzyme have demonstrated additional effects important for cancer treatment (such as radiosensitization of tumor cells and cell antimigratory effects); however, the relationship between the inhibition of other inflammation-related enzyme 5-LOX inhibitors and anticancer activity is still not well understood. In our study, the cytotoxicity of thirteen COX-2 and 5-LOX inhibitors previously presented by our group (1-13) was tested on three cancer cell lines (HCT 116, HT-29 and BxPC-3) and one healthy cell line (MRC-5). Compounds 3, 5, 6 and 7 showed moderate cytotoxicity, but good selectivity towards cancer cell lines. IC50 values were in the range of 22.99-51.66 µM (HCT 116 cell line), 8.63-41.20 µM (BxPC-3 cell line) and 24.78-81.60 µM (HT-29 cell line; compound 7 > 100 µM). In comparison to tested, commercially available COX-2 and 5-LOX inhibitors, both cytotoxicity and selectivity were increased. The addition of compounds 6 and 7 to irradiation treatment showed the most significant decrease in cell proliferation of the HT-29 cell line (p < 0.001). The antimigratory potential of the best dual COX-2 and 5-LOX inhibitors (compounds 1, 2, 3 and 5) was tested by a wound-healing assay using the SW620 cell line. Compounds 1 and 3 were singled out as compounds with the most potent effect (relative wound closure was 3.20% (24 h), 5,08% (48 h) for compound 1 and 3.86% (24 h), 7.68% (48 h) for compound 3). Considering all these results, compound 3 stood out as the compound with the most optimal biological activity, with the best dual COX-2 and 5-LOX inhibitory activity, good selectivity towards tested cancer cell lines, significant cell antimigratory potential and a lack of toxic effects at therapeutic doses.

Patient self-reported adherence for the most common chronic medication therapy.

AIMS: The aims of this study was to determine adherence to chronic disease medication measured by self-reported questionnaire. METHODS: The survey was conducted at 106 Zagreb pharmacies, and the questionnaire was filled out by the study subjects. RESULTS: A total 1,357 diagnoses were reported by survey respondents (i.e., an average of 2.1 diagnoses per respondent). The most common diagnoses were diseases of the circulatory system (n = 500; 36.8%). The great majority of study subjects reported forgetfulness ('I just forgot') as the main reason for skipping drug doses. CONCLUSIONS: Among the many reasons people give for not adhering to drug treatment, forgetfulness was the most common. Common barriers to adherence are under the patient's control, so that attention to them is a necessary and important step in improving adherence. The existence of more than one cause of risk considerably increases the non-adherence risk of a patient.

Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors.

Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1-13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and "type B hydroxamic acids" (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests. The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.

The medication adherence among glaucoma patients during the coronavirus disease 2019 pandemic in Croatia.

PURPOSE: This study aimed to evaluate the level of treatment adherence and identify predictors of adherence in glaucoma patients during the coronavirus disease 2019 (COVID-19) pandemic in Zagreb, Croatia. METHODS: The cross-sectional study was conducted among primary open-angle glaucoma (POAG) patients at the Department of Ophthalmology, University Hospital Centre Zagreb, between 1st April 2020 and 1st April 2021. The sociodemographic data, clinical, and drug information were recorded. The treatment adherence was assessed through a self-administered questionnaire, the Culig Adherence Scale (CAS). Statistical analyses were performed using TIBCO Statistica™ 14.0.0. RESULTS: 113 POAG patients (48M/65F) with a mean age of 65.89 ± 8.53 years were included in this study. According to the CAS, only 39.8% of patients adhered to topical glaucoma treatment. Educational level was positively related to adherence to treatment (p = 0.022). The main predictors for adherence were the patients' positive attitude towards the drug's effect, family support, and good relationship with the healthcare providers (p < 0.05, respectively). The majority of patients stated forgetfulness as the main reason for skipping drug dosing. CONCLUSIONS: Non-adherence to treatment was prevalent among patients with POAG during the COVID-19 pandemic in Zagreb, Croatia. Personal beliefs and attitudes towards treatment, family support, and patient-healthcare provider relationship were significant predictors of adherence. Special consideration should be given to the whole health system-level strategies targeting the adherence to treatment, especially in crises, in order to achieve positive therapeutic outcomes.The study protocol was registered in the DRKS - German Clinical Trials Register, DRKS-ID: DRKS00022081.

Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen.

The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1-5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 µM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent.

Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer.

Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a, 7d, and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a, 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a, 7d, and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c, 7e, and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.

Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen.

The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8-14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1-7 and 8-14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 µM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.

Pharmacy claims data as a tool to measure adherence.

Medication possession ratio (MPR) was introduced as a uniform methodology for estimating medication adherence from pharmacy claims data, but it does not provide accurate information on the continuity of medication usage and the measurement of medication persistency and identification of eventual gaps in medication supply. The combination of an MPR and a persistency metric could provide timely information on the dynamics of patient medication adherence.

Chemical profile, radical scavenging and cytotoxic activity of yellow gentian leaves (Genitaneae luteaefolium) grown in northern regions of Montenegro.

LC-ESI-MS and HPLC were used for the identification of the constituents from G. lutea leaves collected at different localities, as well as for quantification of the main compounds. Seven secoiridoids, five C-glucoflavones and three xanthones, were identified. Swertiamarin derivatives, namely eustomorusside (2), eustomoside (3) and septemfidoside (5), were detected in G. lutea for the first time. Concentrations of five constituents (swertiamarin, gentiopicrin, isovitexin, mangiferin and isogentisin) were determined. The relationship between concentrations of y-pyrones and altitude was observed with statistically significant correlation (r = 0.94). The extracts were also evaluated for their content of total phenolics, and antiradical and cytotoxic activities. The total phenolics content ranged from 7.7 to 12.7 mg GAE/g, and the IC50 values for DPPH radical scavenging activity varied between 0.45 to 2.02 mg/mL. The leaf extract exhibited moderate cytotoxic effects toward HeLa cells with an IC50 value of 41.1 microg/mL, while gentiopicrin, mangiferin and isogentisin exerted strong activity against HeLa cells, with IC50 values ranging from 5.7 to 8.8 microg/mL. The results confirm the traditional usage of G. lutea leaves and also suggest their possible utilization as hepatoprotective, hypoglycemic and anti-inflammatory agents.

Determining the difference in medication compliance between the general patient population and patients receiving antihypertensive therapy: a case study.

This study addressed the issue of medication compliance in general, compliance with antihypertensive therapy, and the relationship between these two groups. In addition to determining the reasons for noncompliance with therapy prescription, the aim of this study was to also establish whether it was considered feasible by the patients to comply with their physician's instructions and whether the patients believed that the prescribed therapy was beneficial to their health. Hypertensive patients were compared to the total study population according to age groups. The study was designed as a cross-sectional survey with the use of a 33-item self-administered questionnaire. The study included 635 individuals who were collecting or buying drugs for the treatment of chronic diseases, with special reference to subjects taking antihypertensive agents (n = 361). More than half (n = 361; 56.9%) of the 635 study subjects were on therapy for arterial hypertension and possibly for some other diseases. The great majority of study subjects reported forgetfulness as the main reason for skipping drug doses. Comparison between the total study population and the subjects treated for arterial hypertension according to age groups (compliant, noncompliant and all together) yielded no statistically significant difference. We concluded that there was no difference in medication compliance between the general patient population and patients receiving antihypertensive therapy and there was no correlation between medication compliance and age.