Impact Of Treatment Outcome Research Articles

ABCB1 variants (C1236T, rs1128503 and G2677T/A, rs2032582) do not show an association with recurrence and survival in patients with breast cancer undergoing anthracycline-based chemotherapy

Breast cancer (BC) is the second most prevalent type of cancer worldwide and the most common among women. Also, BC shows different subtypes and patterns of chemotherapy response. Moreover, BC recurrence pattern is not well knowledge. But, genetic variants can alter drug pharmacokinetics and pharmacodynamics with an impact in treatment outcome. In many drugs in use, drug carriers act on drug absorption, distribution and elimination. ABCB1 encodes the P-glycoprotein – membrane transport protein – responsible for the cellular efflux of drugs, xenobiotics, cellular metabolites and anticancer agents, being crucial in response to chemotherapy. Our aim was to determine whether C1236T (rs1128503) and G2677 T/A (rs2032582) variants in the ABCB1 were associated with recurrence and survival in patients with BC, with invasive ductal carcinoma, treated with anthracycline-based chemotherapy. The study enrolled 146 patients with BC and 609 healthy control subjects. Genotyping in BC cases was performed by allele-specific PCR. The disease-free survival and overall survival analysis was performed by SPSS software. The χ2, Fisher's exact, univariate and multivariate logistic regression tests were performed by SAS software. ABCB1 variants were in accordance to Hardy-Weinberg equilibrium [P-value>.05]: (C1236T) CC = 57(39.1%), CT = 64(43.8%), TT = 25(17.1%); (G2677 T/A) GG = 69(47.3%), GA = 63(43.1%), AA = 10(6.8%), GT = 2(1.4%), AT = 2(1.4%) in the group including patients with BC. However, in healthy controls concerning the G2677 T/A variant, the ABCB1 variant is not in accordance with the Hardy-Weinberg equilibrium [P-value<.05]. The association between ABCB1 variants and recurrence did not show statistical significance for univariate and multivariate models (P-value>.05). Also, the Kaplan-Meier analysis of disease-free survival and overall survival regarding ABCB1 variants did not show statistical significance (P-value>.05). In our sample of patients with BC treated with anthracycline-based chemotherapy, ABCB1 variants were not associated with recurrence, disease-free survival and overall survival.

Single-item measure for assessing quality of life in children with drug-resistant epilepsy.

SummaryObjectiveThe current study investigated the psychometric properties of a single‐item quality of life (QOL) measure, the Global Quality of Life in Childhood Epilepsy question (G‐QOLCE), in children with drug‐resistant epilepsy.MethodData came from the Impact of Pediatric Epilepsy Surgery on Health‐Related Quality of Life Study (PESQOL), a multicenter prospective cohort study (n = 118) with observations collected at baseline and at 6 months of follow‐up on children aged 4–18 years. QOL was measured with the QOLCE‐76 and KIDSCREEN‐27. The G‐QOLCE was an overall QOL question derived from the QOLCE‐76. Construct validity and reliability were assessed with Spearman's correlation and intraclass correlation coefficient (ICC). Responsiveness was examined through distribution‐based and anchor‐based methods.ResultsThe G‐QOLCE showed moderate (r ≥ 0.30) to strong (r ≥ 0.50) correlations with composite scores, and most subscales of the QOLCE‐76 and KIDSCREEN‐27 at baseline and 6‐month follow‐up. The G‐QOLCE had moderate test‐retest reliability (ICC range: 0.49–0.72) and was able to detect clinically important change in patients' QOL (standardized response mean: 0.38; probability of change: 0.65; Guyatt's responsiveness statistics: 0.62 and 0.78). Caregiver anxiety and family functioning contributed most strongly to G‐QOLCE scores over time.SignificanceResults offer promising preliminary evidence regarding the validity, reliability, and responsiveness of the proposed single‐item QOL measure. The G‐QOLCE is a potentially useful tool that can be feasibly administered in a busy clinical setting to evaluate clinical status and impact of treatment outcomes in pediatric epilepsy.

Molecular diversity and polymerase gene genotypes of HIV-1 among treatment-naïve Cameroonian subjects with advanced disease

Background The progress of antiretroviral treatment roll-out programs in developing countries requires extensive monitoring of primary drug resistance prior to initiation of therapy. This is particularly relevant for Cameroon where a high HIV diversity has been reported. Objectives To determine HIV diversity in Yaoundé, Cameroon, in a cohort of HIV-infected subjects with advanced disease. To characterize HIV-1 mutations conferring primary drug resistance and to assess primary resistance patterns in the RNase H domain of the reverse transcriptase of these viruses. Study design HIV-1 RNA was extracted from plasma of 59 HIV-1 infected, drug-naïve subjects with CD4 + T-cell counts < 200/μl. HIV-1 pol (PR, RT and RNase H) regions were sequenced for subtyping and for identifying drug resistance mutations in pol (PR, RT and RNase H). Results A complex HIV-1 diversity was seen, with multiple subtypes (A1, A2, C, D, F2, H, group O), CRFs (02_AG, 09_cpx, 11_cpx, 13_cpx, 22_01A1, 30_0206, 43_02G) and URFs. Primary drug resistance was low in PR (2%) and in RT regions (4%). RNase H mutations Q509L and Q547K were found in non-CRF02_AG strains. Conclusions A high HIV-1 diversity was already present in Cameroon in the early 90s, when the subjects were likely infected. Primary HIV-1 drug resistance was low. Occurrence of RNase H mutations with proven phenotypic effect on susceptibility to antiretrovirals encourages further assessment of their impact in treatment outcome in the context of complex HIV genetic diversity and in a subtype-specific fashion.