Bellshaw2801

PURPOSE Cross-sectional studies suggest that falls are prevalent among older breast cancer survivors. However, fall risk in this population has not been comprehensively examined. Therefore, we compared fall risk in older women post-breast cancer diagnosis to fall risk before cancer diagnosis and to risk in cancer-free matched controls. METHODS Among 2019 women in the Women's Health Initiative with localized breast cancer diagnosed at age ≥ 60 years with fall assessment data for 3 years pre-diagnosis and 3 years post-diagnosis, recurrent fall risk post-diagnosis was compared to risk in 2019 cancer-free controls matched by age, year of WHI entry, and baseline fall frequency. Generalized estimating equations under a logistic regression model were used to compare fall recurrence in breast cancer survivors and controls. Multi-variable models were adjusted for the matching factors, race/ethnicity, body mass index, and multiple chronic conditions. RESULTS In breast cancer survivors aged 70.8 years (mean) at diagnosis, over the 3-year pre-diagnosis interval, recurrent falls were reported by 18.5%. Over the 3-year post-diagnosis interval, recurrent falls were reported by 21.8% of breast cancer survivors and 20.0% of controls over the same time period (P = 0.27). Recurrent fall risk did not differ between breast cancer survivors and control women (OR 1.07, 95% CI 0.92-1.25), even after multi-variable adjustment. CONCLUSIONS In contrast to prior reports, older breast cancer survivors were not more likely to experience recurrent falls than age-matched counterparts. These findings underscore the need for incorporation of cancer-free control populations in survivorship studies to distinguish cancer sequelae from processes related to aging.The present study was intended to enhance the permeation of artemether and lumefantrine by encapsulating in dissolvable microneedle arrays for extended action. Lumefantrine-nanoparticles were synthesized using chitosan mediated gelation and optimized by 22 factorial designs. The particle size, zeta potential and % entrapment efficiency of the optimized nanoparticles F5 were 105 ± 3.64 nm, 24.4 ± 0.54 mV and 83.94 ± 1.71%, respectively. The nanoparticles showed a controlled-release of 79.15 ± 2.45% for lumefantrine after 24 h and stability for 6 months. A combination of biocompatible polymers (PVA and PVP K - 12) was used to develop dissolvable microneedle of artemether co-loaded lumefantrine nanoparticles. The SEM and TEM analysis confirmed the needle-shaped morphology with a size of 672 ± 0.99 μm. The in-vitro release of microneedle showed biphasic release pattern for both artemether and lumefantrine, with an initial burst followed by controlled-release profile. The ex-vivo study of optimized formulation showed 70.94 ± 2.45% and 65.87 ± 1.94% permeation for artemether and lumefantrine, respectively, after 24 h. Thus, microneedle-based delivery provides an alternative to painful intravenous administration and a promising approach to increase the penetration of drugs across the skin barrier. Graphical abstract Fabrication of microneedle arrays of artemether co-loaded with lumefantrine nanoparticles.BACKGROUND Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug-drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with oxaprozin. METHODS This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. RESULTS This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with oxaprozin compared to administration of dotinurad alone was 0.657 (0.624-0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) were 0.982 (0.945-1.021) and 1.165 (1.114-1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of oxaprozin alone. CONCLUSIONS In comparison with administration of dotinurad alone, co-administration with oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC0-inf of dotinurad. However, no clinically meaningful drug-drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with oxaprozin. CDK inhibitor CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT03350386.BACKGROUND Albuminuria and estimated glomerular filtration rate (eGFR) are clinically measured to evaluate the severity of chronic kidney disease (CKD). The aim of our study was to clarify the association between clinical parameters, including albuminuria and eGFR, and the risk of incident CKD in a nondiabetic population with normal range of albuminuria and eGFR. METHODS A 10-year follow-up, retrospective cohort study involving 317 Japanese men (mean age, 42 years) with eGFR ≥ 90 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR)  less then  30 mg/gCr was performed. Participants were free of diabetes mellitus. Multivariate logistic regression approaches were used to assess independent predictors of the incidence of CKD. RESULTS Twenty-nine (9%) participants developed CKD (eGFR  less then  60 mL/min/1.73 m2 and/or UACR ≥ 30 mg/gCr) through 10 years of follow-up. At the baseline examination, age, blood pressure, UACR, and eGFR were higher in participants who developed CKD than in those without CKD. After adjustment for confounders, high-normal albuminuria (P  less then  0.001) and hypertension (P = 0.045) were associated with an increased incidence of CKD. From receiver-operating characteristic curves, UACR ≥ 7.0 mg/gCr was defined as high-normal albuminuria. Logistic regression analysis also showed that, in addition to presence of hypertension, UACR ≥ 7.0 mg/gCr was identified as an independent risk of incident CKD within 10 years after adjustment for age, body mass index, smoking status, and dyslipidemia [UACR odds ratio (OR) 17.36 (95% CI 6.16-48.93, P  less then  0.001)]. CONCLUSION High-normal albuminuria and hypertension are associated with incident CKD in a nondiabetic population with normal-range UACR and eGFR.