METHODS: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.
RESULTS: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).
CONCLUSIONS: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.
METHOD: B. frutescens leaves extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxicity of these extracts at various concentrations (20 to 160 μg/ml) were tested using cell viability assay after 24, 48 and 72 h of treatment. The IC50 value in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscope. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening was performed for alkaloids, flavonoids, tannins, triterpenoids, and phenols.
RESULTS: B. frutescens leaves extracts showed IC50 value ranging from 10 -127μg/ml in MCF-7 cells after 72 h of treatment. Hexane extract had the lowest IC50 value (10μg/ml), indicating its potent selective cytotoxic activity. Morphology of MCF-7 cells after treatment with B. frutescens extracts exhibited evidence of apoptosis that included membrane blebbing and chromatin condensation. In the glucose uptake assay, B. frutescens extracts suppressed glucose uptake in cancer cells as early as 24 h upon treatment. The inhibition was significantly lower compared to the positive control WZB117 at their respective IC50 value after 72 h incubation. It was also shown that the glucose inhibition is selective towards cancer cells compared to normal cells. The phytochemical analysis of the extract using hexane as the solvent in particular gave similar quantities of tannin, triterpenoids, flavonoid and phenols. Presumably, these metabolites have a synergistic effect in the in vitro testing, producing the potent IC50 value and subsequently cell death.
CONCLUSION: This study reports the potent selective cytotoxic effect of B. frutescens leaves hexane extract against MCF-7 cancer cells. B. frutescens extracts selectively suppressed cancer cells glucose uptake and subsequently induced cancer cell death. These findings suggest a new role of B. frutescens in cancer cell metabolism.
METHODS: Factors associated with survival and failure were analyzed using Cox proportional hazards and discrete time conditional logistic models.
RESULTS: TDR, found in 60 (4.1%) of 1471 Asian treatment-naive patients, was one of the significant predictors of failure. Patients with TDR to >1 drug in their regimen were >3 times as likely to fail compared to no TDR.
CONCLUSIONS: TDR was associated with failure in the context of non-fully sensitive regimens. Efforts are needed to incorporate resistance testing into national treatment programs.
MATERIALS AND METHODS: A data set of 91 patients with high-risk acute lymphoblastic leukemia (ALL) followed for five years from 1982 to 1987 was chosen for fitting the mixture cure model. We used the maximum likelihood estimation technique via R software 3.6.2 to obtain the estimates for parameters of the proposed model in the existence of cure rate, censored data, and covariates. For the best model choice, the Akaike information criterion (AIC) was implemented.
RESULTS: After comparing different parametric models fitted to the data, including or excluding cure fraction, without covariates, the smallest AIC values were obtained by the EW and the GMW distributions, (953.31/969.35) and (955.84/975.99), respectively. Besides, assuming a mixture cure model based on GMW with covariates, an estimated ratio between cure fractions for allogeneic and autologous bone marrow transplant groups (and its 95% confidence intervals) were 1.42972 (95% CI: 1.18614 - 1.72955).
CONCLUSION: The results of this study reveal that the EW and the GMW distributions are the best choices for the survival times of Leukemia patients.
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MATERIAL AND METHODS: A sample of 85 patients diagnosed with superficial bladder tumours was selected to be used in fitting the non-mixture cure model. In order to estimate the parameters of the suggested model, which takes into account the presence of a cure rate, censored data, and covariates, we utilized the maximum likelihood estimation technique using R software version 3.5.7.
RESULT: Upon conducting a comparison of various parametric models fitted to the data, both with and without considering the cure fraction and without incorporating any predictors, the EE distribution yields the lowest AIC, BIC, and HQIC values among all the distributions considered in this study, (1191.921/1198.502, 1201.692/1203.387, 1195.851/1200.467). Furthermore, when considering a non-mixture cure model utilizing the EE distribution along with covariates, an estimated ratio was obtained between the probabilities of being cured for placebo and thiotepa groups (and its 95% confidence intervals) were 0.76130 (0.13914, 6.81863).
CONCLUSION: The findings of this study indicate that EE distribution is the optimal selection for determining the duration of survival in individuals diagnosed with bladder cancer.