Population pharmacokinetics of continuous-infusion ceftazidime in febrile neutropenic children undergoing HSCT: implications for target attainment for empirical treatment against Pseudomonas aeruginosa

To conduct a population pharmacokinetic analysis of continuous-infusion ceftazidime in a retrospective cohort of paediatric HSCT patients who were empirically treated for febrile neutropenia (FN) and who underwent therapeutic drug monitoring of ceftazidime steady-state plasma concentrations (Css) for optimization of drug exposure

PHARMACOGENETIC OF ESCITALOPRAM AND MENTAL ADAPTATION TO CANCER IN PALLIATIVE CARE: REPORT OF 18 CASES

Aims and background. In palliative care, few data are available on the diagnosis and treatment ofmood disorders and of difficulties ofmental adaptation to cancer for patients in the advanced phases of the disease. SSRI antidepressants are the treatment of choice; the 5-HTTLPR genetic polymorphism of the serotonin transporter (SERT) has been shown in psychiatry to significantly determine the therapeutic response and the incidence of adverse effects. The aim of the present investigation has been therefore to examine the effects of the SSRI antidepressant escitalopram, also considering 5-HTTLPR, on depression, anxiety andmental adaptation to cancer in palliative care.\u2029Methods and study design. Eighteen consecutive depressed patients with different forms of advanced cancer admitted to the Hospice Ass 6 of S. Vito al Tagliamento (Pordenone, Italy) were genotyped for the \u201cs\u201d and \u201cl\u201d variants of 5-HTTLPR and were treated with escitalopram. Their response after two weeks of treatment was psychometrically evaluated.\u2029Results. Treatment with escitalopram significantly decreased anxiety scores on the Hospital Anxiety and Depression Scale (HADS) (P = 0.006) as well as anxious preoccupation (P = 0.007) and hopelessness-helplessness (P = 0.017) scores on the Mini Mental Adjustment to Cancer (Mini-MAC) scale. When patients were stratified by SERT genotype, HADS anxiety was significantly decreased in patients carrying the \u201cs/s\u201d and \u201cs/l\u201d variants (P = 0.024), whereas those with an \u201cl/l\u201d genotype displayed a significant reduction of Mini-MAC anxious preoccupation (P = 0.018).\u2029Conclusions. The results of this study indicate that the use of SSRI antidepressants is effective in the palliative care of cancer patients, and their action affects not only depression but also the patients\u2019 mental adaptation to the disease. These results encourage further examination of these drugs in a larger cohort of patients. The significant contribution of pharmacogenetics indicates the possibility of personalized treatment with SSRIs in palliative care

Post-traumatic Stress Symptoms and Serotonin Transporter (5-HTTLPR) Polymorphism in Breast Cancer Patients

Introduction: Post-traumatic Symptoms (PTSS) and Post-traumatic Stress Disorder (PTSD) have been reported to affect a quite significant proportion of cancer patients. No study has examined the relationship between serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cancer, including Gene-Environment interactions between this polymorphism and specific causes of distress, such as cancer related problems (CRP) or life stressful events (SLE). Methods: One hundred and forty five breast cancer outpatients participated in the study and were assessed using the Impact of Event Scale (IES), the Problem List (PL) developed by the National Comprehensive Cancer Network (NCCN) Distress Management Guidelines and the Paykel's Life Events Interview to evaluate the exposure to SLE during the year before the cancer diagnosis. Each patient was genotyped for 5-HTTLPR polymorphism by analyzing genomic DNA obtained from whole blood cells. Gene-Environment interactions were tested through moderation analysis. Results: Twenty-six patients (17.7%) were classified as PTSS cases using the IES. Genotype and phenotype distributions did not differ across individuals with/without PTSS (genotype: χ2 = 1.5; df = 2; p = 0.3; phenotype χ2 = 0.9; df = 1; p = 0.2). For both the genotype and phenotype model, using CRP as a predictor showed significant gene-environment interactions with IES total score (p = 0.020 and p = 0.004, respectively), with individuals carrying the l/l allele showing a greater probability of experiencing PTSS. No interaction was found in relationship to SLE (p = 0.750). Conclusion: This study showed a significant GEI between CRP and PTSS in breast cancer patients, with carriers of the l/l allele showing indicators consistent with greater sensitivity to stress

Depression and serotonin transporter (5-HTTLPR) polymorphism in breast cancer patients

Background: Mixed evidence in the general population and medically ill patients has suggested that homozygous carriers of the short allele (s/s) of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) may increase the risk of depression in comparison with carriers of the long allele (l/l) or s/l. Given the lack of data in oncology, we examined the relationship of depression with the 5-HTTLPR and psychosocial variables among breast cancer patients. Methods: A sample of 145 breast cancer patients were studied as regards depression, psychosocial-related variables (coping, Type D-personality, life events, and social support), and the 5-HTTLPR, which was genotyped by using a standard protocol with DNA extracted from the blood. Results: No difference was found between s/s, s/l and l/l patients on depression and any other psychosocial variable. No gene-by environment (GxE) interactions were observed between the 5-HTTLPR and recent life events. Conclusions: The study did not provide support of a possible association between 5-HTTLPR polymorphism, alone or in conjunction with life events, and depression in newly diagnosed breast cancer. Further follow-up studies are however necessary to confirm these data