Marília Berlofa Visacri

Impact of pharmacist interventions on drug-related problems and laboratory markers in outpatients with human immunodeficiency virus infection.

Background Substantial complexity has been introduced into treatment regimens for patients with human immunodeficiency virus (HIV) infection. Many drug-related problems (DRPs) are detected in these patients, such as low adherence, therapeutic inefficacy, and safety issues. We evaluated the impact of pharmacist interventions on CD4+ T-lymphocyte count, HIV viral load, and DRPs in patients with HIV infection. Methods In this 18-month prospective controlled study, 90 outpatients were selected by convenience sampling from the Hospital Dia–University of Campinas Teaching Hospital (Brazil). Forty-five patients comprised the pharmacist intervention group and 45 the control group; all patients had HIV infection with or without acquired immunodeficiency syndrome. Pharmaceutical appointments were conducted based on the Pharmacotherapy Workup method, although DRPs and pharmacist intervention classifications were modified for applicability to institutional service limitations and research requirements. Pharmacist interventions were performed immediately after detection of DRPs. The main outcome measures were DRPs, CD4+ T-lymphocyte count, and HIV viral load. Results After pharmacist intervention, DRPs decreased from 5.2 (95% confidence interval [CI] =4.1–6.2) to 4.2 (95% CI =3.3–5.1) per patient (P=0.043). A total of 122 pharmacist interventions were proposed, with an average of 2.7 interventions per patient. All the pharmacist interventions were accepted by physicians, and among patients, the interventions were well accepted during the appointments, but compliance with the interventions was not measured. A statistically significant increase in CD4+ T-lymphocyte count in the intervention group was found (260.7 cells/mm3 [95% CI =175.8–345.6] to 312.0 cells/mm3 [95% CI =23.5–40.6], P=0.015), which was not observed in the control group. There was no statistical difference between the groups regarding HIV viral load. Conclusion This study suggests that pharmacist interventions in patients with HIV infection can cause an increase in CD4+ T-lymphocyte counts and a decrease in DRPs, demonstrating the importance of an optimal pharmaceutical care plan.

Cost analysis of pharmaceutical care provided to HIV-infected patients: an ambispective controlled study

BackgroundStudies have shown that pharmaceutical care can result in favorable clinical outcomes in human immunodeficiency virus (HIV)-infected patients, however, few studies have assessed the economic impact. The objective of this study was to evaluate the clinical and economic impact of pharmaceutical care of HIV-infected patients.MethodsA controlled ambispective study was conducted in Brazil from January 2009 to June 2012. Patients were allocated to either intervention or control group. The control group was followed according to standard care while the intervention group was also followed by a pharmacist at each physician appointment for one year. Effectiveness outcomes included CD4+ count, viral load, absence of co-infections and optimal immune response, and economic outcomes included expenses of physician and pharmaceutical appointments, laboratory tests, procedures, and hospitalizations, at six months and one year.ResultsIntervention and control groups included 51 patients each. We observed significant decreases in total pharmacotherapy problems during the study. At six months, the intervention group contained higher percentages of patients without co-infections and of patients with CD4+ >500 cells/mm3. None of the differences between intervention and control group considering clinical outcomes and costs were statistically significant. However, at one year, the intervention group showed higher percentage of better clinical outcomes and generated lower spending (not to procedures). An additional health care system daily investment of US

Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity

1.45, 1.09, 2.13, 4.35, 1.09, and 0.87 would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm3, and optimal immune response, respectively.ConclusionThis work demonstrated that pharmaceutical care of HIV-infected patients, for a one-year period, was able to decrease the number of pharmacotherapy problems. However, the clinical outcomes and the costs did not have statistical difference but showed higher percentage of better clinical outcomes and lower costs for some items.

XPD c.934G > A polymorphism of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

PurposeThe aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity.MethodsThis article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review.ResultsThe studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure.ConclusionsWe observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.

Evaluation of the quality of life of patients before treatment of squamous cell carcinoma of the head and neck by means of chemoradiotherapy

This study aimed to investigate the associations of XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C and ERCC1 c.354C>T single nucleotide polymorphisms (SNPs) of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin (CDDP) chemoradiation. Patients with XPC c.2815AC or CC and XPD c.934GA or AA genotypes had 0.20 and 0.38 less chances of presenting moderate/severe ototoxicity and nausea, respectively. Patients with XPD c.934AA and c.2251AC or CC genotypes had 8.64, 12.29 and 3.55 more chances of achieving complete response (CR), consistent ototoxicity and nephrotoxicity, respectively. AA haplotype of XPD and ACT haplotype of XPD and ERCC1 SNPs were associated with 9.30 and 3.41 more chances of achieving CR and consistent nephrotoxicity, respectively. At 24 months of follow-up, patients with XPD c.934AA genotype presented lower progression-free survival and overall survival in Kaplan-Meier estimates, and differences between groups remained the same in univariate Cox analysis. Patients with XPD c.934AA genotype had 2.13 and 2.04 more risks of presenting tumor progression and death than others in multivariate Cox analysis. Our data present preliminary evidence that XPC c.2815A>C, XPD c.934G>A and c.2251A>C, and ERCC1 c.354C>T SNPs alter outcome of HNSCC patients treated with CDDP chemoradiation.

Antioxidant capacity total in non-melanoma skin cancer and its relationship with food consumption of antioxidant nutrients

Aim of the study To identify predictors of quality of life (QOL) in head and neck cancer patients prior to cisplatin chemotherapy and radiotherapy treatment. Material and methods A cross-sectional study at a Clinical Oncology department of a teaching hospital in the state of São Paulo, Brazil, from September 2011 to October 2012 was performed. QOL was assessed using the University of Washington QOL Questionnaire. Demographic and clinical characteristics were obtained through interviews with patients and collected from medical records. Multivariate linear regression was used to determine the association between QOL scores and patient-related factors. Results We studied 48 head and neck cancer patients, who were mostly white (77.1%), males (83.3%), with pharyngeal cancers (66.7%), cancers with stage T4 (45.8%) and N1 (31.2%) tumours, and classified with a Karnofsky Performance Status (KPS) of 90% (37.5%). Patients had excellent scores for saliva (96.2 ±13.5) and shoulder (93.6 ±17.9), with pain and anxiety being the most affected domains (59.6 ±32.4 and 57.5 ±39.2, respectively). A significant relationship of KPS and T stage with overall QOL score was noted. The population with lowest overall QOL score was those who had low KPS scores and T4 tumours. Conclusions Head and neck cancer patients prior to cisplatin chemotherapy and radiotherapy treatment, with a low KPS and staged as T4 tumours, have worse overall QOL, and special attention should be given to these patients.

Adverse Drug Reactions and Quality Deviations monitored by Spontaneous Reports

The non-melanoma skin cancer is the most common cancer and accounts for more than half of the diagnoses of cancer, and basal cell carcinoma (BCC), the most frequent cutaneous neoplasm, corresponding to 70-80% of cutaneous tumors. Oxidative stress is an important trigger for skin carcinogenesis. Thus, it is important to evaluate oxidative stress, in order to discern effective therapeutic strategies able to stop it or attenuate it, thereby prevent the installation of non-melanoma skin cancer. Cross-sectional study with controls, involving 84 individuals of both sexes aged between 38-84 years, divided into two groups: control group of healthy people(n = 24) and the case group included individuals who presented non-melanoma skin and they have undergoing surgery (n = 60). The blood samples of the individuals were obtained for evaluation of biomarkers of oxidative stress (F2-isoprostane, nitrite, thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity). The usual dietary intake and nutritional status of the subjects were evaluated. The significance level for this study was 5%. Patients in the case group had higher serum concentrations of biomarkers of oxidative stress, F2-isoprostane concentrations were significantly higher compared to controls. The results showed high rates of overweight and obesity in the case and control groups. The dietary concentrations of antioxidant minerals zinc, copper and selenium in the case group were significantly lower compared to controls. The correlation between markers of oxidative stress and dietary concentrations of antioxidant nutrients showed the influence of food intake of vitamins A and E in reducing oxidative stress, since these nutrients behave as important antioxidants, acting as sweepers of RL, by removing of the body the negative effects on the redox balance of the skin. We emphasize the importance of adopting healthy eating habits that optimize the consumption of antioxidant nutrients as a strategy to prevent oxidative damage to the skin.

Do Genetic Polymorphisms Modulate Response Rate and Toxicity of Cisplatin Associated With Radiotherapy in Laryngeal Squamous Cell Carcinoma? A Case Report

Objectives The aim of this study was to determine the frequency and profile of spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a Brazilian teaching hospital and propose a consistent classification to study quality deviations. Methods This is a descriptive and retrospective study involving the analysis of spontaneous reports of ADRs and quality deviations in 2010. ADRs were classified according to the reaction mechanism, severity, and causality. The drugs were classified according to their therapeutic classes and symptoms according to the affected organ. The quality deviations were classified according to the type of deviation and type of medicine available in the Brazilian market. Results A total of 68 forms were examined; ADRs accounted for 39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was the most affected organ, while anti-infectives (40.7%) were the therapeutic class that caused the most ADRs. The most common ADRs were type B (74.0%), moderates (37.0%), and probables (55.6%). In relation to quality deviations, the most frequent notifications were breaks, splits and leaks (20.9%) and related to generic drugs (43.9%). Conclusion The classification system to study quality deviations was clear and consistent. This study demonstrated that practices and public policies related to more effective pharmacovigilance need to be implemented so that the number of spontaneous reports increases.

Nausea, vomiting and quality of life of patients with cancer undergoing antineoplastic treatment: an evaluation by pharmacists

AbstractCisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality. Case presentation: A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented GSTT1 deletion, variant MSH3 1045ThrThr, wild GSTP1 105IleIle, and wild BAX -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with GSTT1 gene, MSH3 AlaAla or AlaThr, GSTP1 IleVal or ValVal, and BAX GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.

High 15-F2t-Isoprostane Levels in Patients with a Previous History of Nonmelanoma Skin Cancer: The Effects of Supplementary Antioxidant Therapy.

This study aims to evaluate the frequency and severity of nausea and vomiting using two different instruments and relate them to quality of life (QOL) in patients with cancer receiving antineoplastic treatment.