Identification of the Medication Regimen Complexity Index as an Associated Factor of Nonadherence to Antiretroviral Treatment in HIV Positive Patients.

BACKGROUND: Multiple studies have identified a relationship between the complexity of a medication regimen and non-adherence. However, most studies in people who live with HIV (PLWH) have focused on antiretroviral use and have failed to consider the impact of other medications. OBJECTIVE: The aim of our study is to identify the Medication Regimen Complexity Index (MRCI) as an associated factor for nonadherence to antiretroviral treatment (ART). The secondary aim is to analyze the relationship between clinical and pharmacotherapeutical variables and adherence to antiretroviral treatment and to generate an adherence model. METHODS: A transversal, observational study. Patients included were PLWH over 18 years of age on active antiretroviral therapy. Patients who participated in clinical trials or who did not meet the inclusion criteria were excluded. We had studied HIV transmission mode, viral load, treatment status, number of comorbidities and complexity index as factors associated with adherence to ART. RESULTS: We included 619 patients in the study. Number of comorbidities ( p = 0.021; OR = 1.038-1.570); viral load ( p = 0.023; OR = 1.108-4.505) and MRCI ( p < 0.001; OR = 1.138-1.262) (ART and concomitant treatment) were the independent associated factors to ART nonadherence. The value of the Hosmer and Lemeshow test confirmed the validity of this model (P = 0.333). CONCLUSION: A higher MRCI was associated with non-adherence. Therefore, the regimen complexity calculation may be appropriate in daily practice for identifying patients at a higher risk of becoming non-adherent.

Novel tool for deprescribing in chronic patients with multimorbidity: List of Evidence-Based Deprescribing for Chronic Patients criteria.

AIM: To create a tool to identify drugs and clinical situations that offers an opportunity of deprescribing in patients with multimorbidity. METHODS: A literature review completed with electronic brainstorming, and subsequently, a panel of experts using the Delphi methodology were applied. The experts assessed the criteria identified in the literature and brainstorming as possible situations for deprescribing. They were also asked to assess the influence of life prognosis in each criterion. A tool was composed of the most appropriate criteria according to the strength of their evidence, usefulness in patients with multimorbidity and applicability in clinical practice. RESULTS: Out of a total of 100, 27 criteria were selected to be included in the final list. It was named the LESS-CHRON criteria (List of Evidence-baSed depreScribing for CHRONic patients), and was organized by the anatomical group of the Anatomical, Therapeutic, Chemical (ATC) classification system of the drug to be deprescribed. Each criterion contains: drug indication for which it is prescribed, clinical situation that offers an opportunity to deprescribe, clinical variable to be monitored and the minimum time to follow up the patient after deprescribing. CONCLUSIONS: The "LESS-CHRON criteria" are the result of a comprehensive and standardized methodology to identify clinical situations for deprescribing drugs in chronic patients with multimorbidity. Geriatr Gerontol Int 2017; 17: 2200-2207.

[Interventions for improving adherence to treatment in patients with multiple pathologies: overview of systematic reviews]. / Intervenciones para la mejora de la adherencia al tratamiento en pacientes pluripatológicos: resumen de revisiones sistemáticas.

OBJECTIVE: To assess the available scientific evidence regarding the efficacy of interventions aimed to enhance medication adherence in patients with multiple chronic conditions (PMCC). DESIGN: Overview of systematic reviews. DATA SOURCES: The following databases were consulted (September 2013): Pubmed, EMBASE, the Cochrane Library, CRD and WoS to identify interventions aimed to enhance medication adherence in PMCC, or otherwise, patients with chronic diseases common in the PMCC, or polypharmacy. STUDY SELECTION: Systematic reviews of clinical trials focused on PMCC or similar were included. They should compare the efficacy of any intervention aimed to improve compliance to prescribed and self-administered medications with clinical practice or other interventions. DATA EXTRACTION: Information about the study population, nature of intervention and efficacy in terms of improved adherence was extracted. RESULTS: 566 articles were retrieved of which 9 systematic reviews were included. None was specifically focused on PMCC but considered patients with chronic diseases common in the PMCC, patients with more than one chronic disease and polypharmacy. The overall effectiveness of interventions was modest without relevant differences between behavioural, educational and combined interventions. Some components of these interventions including patient counselling and regimen simplification appear to be effective tools in improving adherence in this population group. CONCLUSION: There is a large heterogeneity of interventions aimed to improve adherence with modest efficacy, none in PMCC.

[Pharmacological treatment conciliation methodology in patients with multiple conditions]. / Metodología de conciliación del tratamiento farmacológico en pacientes pluripatológicos.

OBJECTIVE: To carry out a bibliographic review in order to identify the different methodologies used along the reconciliation process of drug therapy applicable to polypathological patients. DESIGN: We performed a literature review. Data sources The bibliographic review (February 2012) included the following databases: Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME). The different methodologies, identified on those databases, to measure the conciliation process in polypathological patients, or otherwise elderly patients or polypharmacy, were studied. Study selection Two hundred and seventy three articles were retrieved, of which 25 were selected. Data extraction Specifically: the level of care, the sources of information, the use of registration forms, the established time, the medical professional in charge and the registered variables such as errors of reconciliation. RESULTS: Most of studies selected when the patient was admitted into the hospital and after the hospital discharge of the patient. The main sources of information to be highlighted are: the interview and the medical history of the patient. An established time is not explicitly stated on most of them, nor the registration form is used. The main professional in charge is the clinical pharmacologist. Apart from the home medication, the habits of self-medication and phytotherapy are also identified. The common errors of reconciliation vary from the omission of drugs to different forms of interaction with other medicinal products (drugs interactions). CONCLUSIONS: There is a large heterogeneity of methodologies used for reconciliation. There is not any work done on the specific figure of the polypathological patient, which precisely requires a standardized methodology due to its complexity and its susceptibility to errors of reconciliation.

Use of monoclonal antibodies for metastatic colorectal cancer in the Andalusian public health system.

BACKGROUND: The place of monoclonal antibodies in metastatic colorectal cancer has not been clearly defined. OBJECTIVE: To determine the treatment pattern of monoclonal antibodies in colorectal cancer patients in the Andalusian Public Healthcare System. METHOD: Data were collected from all patients treated with these drugs from July 2009 to December 2010 from pharmacy programs and medical records. RESULTS: Three hundred patients were included, of whom 227 received the antibody at the forefront. The proportion of patients who received bevacizumab in the first line is greater than that of cetuximab (62.1 vs. 37.5 % respectively) and similar in the second line and subsequent (47.8 vs. 53.8 % and 48.5 vs. 46.2 % respectively). XELOXbevacizumab was the most frequently prescribed scheme (35.3 %) followed by FOLFOX-monoclonal antibody schemes, regardless that this was bevacizumab or cetuximab (22.5 %). The median progression free survival (PFS) was 11.7 months for patients receiving cetuximab, 9.6 months for patients receiving bevacizumab and 8.2 months for those who received no monoclonal antibody in the first line. CONCLUSION: Bevacizumab was the antibody of choice in first line, showing utilization rates similar to cetuximab in second line and subsequent. The median PFS in our study is related to the PFS of the major clinical trials.

[Suitability of pharmacological treatment in patients with multiple chronic conditions]. / Adecuación del tratamiento farmacológico en pacientes pluripatológicos.

OBJECTIVE: To identify tools for measuring the appropriateness of drug therapy useful in patients with multiple chronic conditions. DESIGN: We performed a literature review. DATA SOURCES: The following database were consulted (December 2009): Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME) to detect tools for measuring the appropriateness of treatment in patients with multiple chronic conditions, or otherwise elderly or polypharmacy. STUDY SELECTION: Studies were identified both qualitative and quantitative methodology, both theoretical and field work, both original and revised work and included work from all areas of the health system. 108 articles were retrieved, of which we selected 59. The consultation of their references include 20 jobs allowed, resulting in a total of 59 articles. DATA EXTRACTION: Of all the tools identified, the researchers performed a selection of those with possible utility for classified PP. The articles were classified into implicit and explicit methods and the characteristics of the field works were tabulated. RESULTS: We identified two implicit methods (MAI and Hamdy) and 6 explicit methods (Beers criteria, IPET, STOPP/START, ACOVE, CRIME and NORGEP). None was specific to patients with multiple chronic conditions. The questionnaire MAI, the Beers criteria and its modifications are most often used in literature. The advantages of explicit criteria means that many of them have been developed recently. CONCLUSION: There are several tools to measure the appropriateness and none of them has been designed for a population of patients with multiple chronic conditions yet, which by its nature requires a specific approach spreads.

The coffee constituent chlorogenic acid induces cellular DNA damage and formation of topoisomerase I- and II-DNA complexes in cells.

Chlorogenic acid (CGA) is a plant polyphenol with known antioxidant properties. Although some studies suggest that CGA has anticancer properties, others indicate that this dietary constituent may cause DNA damage and induce carcinogenic effects. Because CGA is widely consumed in the form of coffee, it is important to further evaluate the putative DNA-damaging activity of CGA. Here we have employed two standard techniques commonly used for DNA damage detection (the comet assay and the γ- H2AX focus assay) and observed that CGA (0.5-5 mM) induces DNA damage in normal and cancer cells. We report for the first time that CGA induces high levels of topoisomerase I- and topoisomerase II-DNA complexes in cells (TARDIS assay). Catalase pretreatment abolished the formation of these topoisomerase-DNA complexes and reduced the cytotoxic activity of CGA, therefore indicating that hydrogen peroxide plays an important role in these activities. Lung cancer cells (A549) were more sensitive than normal lung fibroblasts (MRC5) to the cytotoxic activity of CGA, supporting previous findings that CGA may induce selective killing of cancer cells. Taking into consideration our results and the pharmacokinetic profile of CGA, the possible cancer preventive, carcinogenic and therapeutic potential of this dietary agent are discussed.

Guanidine-reactive agent phenylglyoxal induces DNA damage and cancer cell death.

BACKGROUND: DNA-damaging compounds (e.g., alkylating agents, cytotoxic antibiotics and DNA topoisomerase poisons) are the most widely used anticancer drugs. The inability of tumor cells to properly repair some types of DNA damage may explain why specific DNA-damaging drugs can selectively kill tumor cells. Phenylglyoxal is a dicarbonyl compound known to react with guanidine groups such as that of the DNA base guanine, therefore suggesting that phenylglyoxal could induce DNA damage and have anticancer activity. METHODS: Cellular DNA damage was measured by the alkaline comet assay and the γH2AX focus assay. Formation of topoisomerase I- and topoisomerase II-DNA complexes was assessed by the TARDIS assay, an immunofluorescence technique that employs specific antibodies to DNA topo I or topo II to detect the protein covalently bound to the DNA in individual cells. Cell growth inhibition and cytotoxicity were determined by XTT, MTT and clonogenic assays. Apoptosis was assessed by the Annexin V flow cytometry assay. RESULTS: Phenylglyoxal induced cellular DNA damage and formation of high levels of topoisomerase I- and topoisomerase II-DNA complexes in cells. These topoisomerase-DNA complexes were abolished by catalase pretreatment and correlated well with the induction of apoptosis. Phenylglyoxal-induced cell death was partially prevented by catalase pretreatment and was higher in lung cancer cells (A549) than in normal lung fibroblasts (MRC5). Mammalian cell lines defective in nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ) were more sensitive to phenylglyoxal than parental cells; this suggests that phenylglyoxal may induce bulky distortions in the shape of the DNA double helix (which are repaired by the NER pathway) and DNA double-strand breaks (which are repaired by HR and NHEJ). CONCLUSION: This report shows that phenylglyoxal is a new DNA-damaging agent with anticancer activity, and suggests that tumor cells with defects in NER, HR and NHEJ may be hypersensitive to the cytotoxic activity of phenylglyoxal.

Argan (Argania spinosa) oil lowers blood pressure and improves endothelial dysfunction in spontaneously hypertensive rats.

Traditionally hand-pressed argan oil, obtained from Argania spinosa seeds, is eaten raw in south-west Morocco; its rich composition of tocopherols, MUFA and PUFA make a study of its actions on risk factors for CVD, such as hypertension, interesting. The effects of 7 weeks of treatment with argan oil (10 ml/kg) on the blood pressure and endothelial function of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were investigated. Systolic blood pressure and heart rate were measured every week by the tail-cuff method and endothelial function was assessed by carbachol (10(-8) to 10(-4) M)-induced relaxations of aortic rings and small mesenteric arteries pre-contracted with phenylephrine. Argan-oil administration reduced the mean blood pressure of SHR after the fifth week of treatment (P<0.05) and increased (P<0.01) the endothelial responses of arteries from SHR. The NO synthase inhibitor, L-N-omega-nitroarginine (3 x 10(-5) M) revealed a greater participation of NO in the relaxant effect after the treatment. When cyclooxygenase (COX) was blocked with indomethacin (10(-5) M), an involvement of COX products in the endothelium-dependent response was characterized. Enzyme immunoassay of thromboxane B2 showed a significant decrease (P<0.05) in the release of thromboxane A2 in both aorta and small mesenteric artery after argan-oil treatment of SHR. Experiments in the presence of the thromboxane A2-prostaglandin H2 receptor antagonist ICI 192,605 (10(-5) M) confirmed this result. Results after incubation with the antioxidants superoxide dismutase and catalase suggested that a decreased oxidative stress might contribute to explain the beneficial effects of argan-oil treatment.