Usage Patterns and Incidence of Thyroid-related Adverse Events in Patients Treated with PD-1 Inhibitors

Objective@#PD-1 inhibitors have demonstrated improved health outcomes in cancer patients. PD-1 inhibitors are well-tolerated and associated with immune-related adverse events. The objectives of this study are to analyze use patterns of PD-1 inhibitors in patients with cancer and to investigate the incidence of thyroid-related adverse reactions in patients treated with PD-1 inhibitors. @*Methods@#The study included patients who had been administered PD-1 inhibitors (either nivolumab or pembrolizumab) at the Samsung Medical Center between October 1, 2016 and June 30, 2017. Data was collected from electronic medical records and tested using Mann-Whitney tests and Chi-Square tests for statistical significance. Associations between PD-1 inhibitors and incidence of adverse events were tested using Cox regression for age, gender, BMI, ECOG PS and medication. @*Results@#Two hundred fifteen patients were identified as eligible for analyses. Thyroid-related adverse events occurred in 20% of patients (n=43). Thyroid function tests (TFTs) was performed in 109 patients (50.7%). Positive results of PD-L1 testing were found in 53.2% of the 94 patients who had the test. Approved doses of nivolumab (3 m/kg) and pembrolizumab (200 mg) were administered in 70.4% and 53% of patients, respectively. The analysis of risk factor of thyroid-related adverse reaction did not show statistically significant differences (Cox regression). @*Conclusion@#Thyroid-related adverse events are common in patients treated with PD-1 inhibitors and hypothyroidism is the most frequent adverse reaction. Routine TFTs monitoring is strongly recommended to evaluate thyroid function in real-world clinical practice.

Usage Patterns and Incidence of Thyroid-related Adverse Events in Patients Treated with PD-1 Inhibitors

Objective@#PD-1 inhibitors have demonstrated improved health outcomes in cancer patients. PD-1 inhibitors are well-tolerated and associated with immune-related adverse events. The objectives of this study are to analyze use patterns of PD-1 inhibitors in patients with cancer and to investigate the incidence of thyroid-related adverse reactions in patients treated with PD-1 inhibitors. @*Methods@#The study included patients who had been administered PD-1 inhibitors (either nivolumab or pembrolizumab) at the Samsung Medical Center between October 1, 2016 and June 30, 2017. Data was collected from electronic medical records and tested using Mann-Whitney tests and Chi-Square tests for statistical significance. Associations between PD-1 inhibitors and incidence of adverse events were tested using Cox regression for age, gender, BMI, ECOG PS and medication. @*Results@#Two hundred fifteen patients were identified as eligible for analyses. Thyroid-related adverse events occurred in 20% of patients (n=43). Thyroid function tests (TFTs) was performed in 109 patients (50.7%). Positive results of PD-L1 testing were found in 53.2% of the 94 patients who had the test. Approved doses of nivolumab (3 m/kg) and pembrolizumab (200 mg) were administered in 70.4% and 53% of patients, respectively. The analysis of risk factor of thyroid-related adverse reaction did not show statistically significant differences (Cox regression). @*Conclusion@#Thyroid-related adverse events are common in patients treated with PD-1 inhibitors and hypothyroidism is the most frequent adverse reaction. Routine TFTs monitoring is strongly recommended to evaluate thyroid function in real-world clinical practice.

Osteoporotic Fractures of the Spine, Hip, and Other Locations after Adjuvant Endocrine Therapy with Aromatase Inhibitors in Breast Cancer Patients: a Meta-analysis

Background@#Aromatase inhibitors (AIs) play an important role in the endocrine therapy of postmenopausal breast cancer patients, with a recent tendency to extend the duration of their use. However, AIs may increase the risk of osteoporotic bone fractures. This meta-analysis evaluated the risk of osteoporotic fractures of the hip, spine, and other locations in breast cancer patients using AIs. @*Methods@#We performed a systematic search to identify randomized controlled clinical trials that investigated osteoporotic fractures in breast cancer patients on AI therapy. The main outcomes were the incidence and risk of osteoporotic fractures in general and of hip, vertebral, and non-vertebral fractures in AI users and controls. @*Results@#The systematic review found a total of 30 randomized controlled trials including 117,974 participants. The meta-analysis showed a higher incidence of osteoporotic fracture in AI users: The crude risk ratio for all osteoporotic fractures was 1.35 (95% confidence interval [CI], 1.29–1.42;P < 0.001), for hip fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), for vertebral fractures 1.84 (95% CI, 1.36–2.49; P < 0.001), and for non-vertebral fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), respectively, compared to the controls. @*Conclusion@#Our meta-analysis suggested an increased risk of osteoporotic fractures for AI therapy in patients with breast cancer that was most expressed for vertebral fractures. Breast cancer patients on AIs need to be monitored for osteoporosis and osteoporotic fractures, and active prevention measures should be implemented.

Costs Attributable to Overweight and Obesity in Working Asthma Patients in the United States

PURPOSE: To estimate annual health care and productivity loss costs attributable to overweight or obesity in working asthmatic patients. MATERIALS AND METHODS: This study was conducted using the 2003–2013 Medical Expenditure Panel Survey (MEPS) in the United States. Patients aged 18 to 64 years with asthma were identified via self-reported diagnosis, a Clinical Classification Code of 128, or a ICD-9-CM code of 493.xx. All-cause health care costs were estimated using a generalized linear model with a log function and a gamma distribution. Productivity loss costs were estimated in relation to hourly wages and missed work days, and a two-part model was used to adjust for patients with zero costs. To estimate the costs attributable to overweight or obesity in asthma patients, costs were estimated by the recycled prediction method. RESULTS: Among 11670 working patients with a diagnosis of asthma, 4428 (35.2%) were obese and 3761 (33.0%) were overweight. The health care costs attributable to obesity and overweight in working asthma patients were estimated to be $878 [95% confidence interval (CI): $861–$895] and $257 (95% CI: $251–$262) per person per year, respectively, from 2003 to 2013. The productivity loss costs attributable to obesity and overweight among working asthma patients were $256 (95% CI: $253–$260) and $26 (95% CI: $26–$27) per person per year, respectively. CONCLUSION: Health care and productivity loss costs attributable to overweight and obesity in asthma patients are substantial. This study's results highlight the importance of effective public health and educational initiatives targeted at reducing overweight and obesity among patients with asthma, which may help lower the economic burden of asthma.

Daily Mean Temperature and Urolithiasis Presentation in Six Cities in Korea: Time-Series Analysis

Seasonal variation in urinary stone presentation is well described in the literature. However, previous studies have some limitations. To explore overall cumulative exposure-response and the heterogeneity in the relationships between daily meteorological factors and urolithiasis incidence in 6 major Korean cities, we analyzed data on 687,833 urolithiasis patients from 2009 to 2013 for 6 large cities in Korea: Seoul, Incheon, Daejeon, Gwangju, Daegu, and Busan. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of mean daily urolithiasis incidence (MDUI) associated with mean daily meteorological factors, including the cumulative RR for a 20-day period. The estimated location-specific associations were then pooled using multivariate meta-regression models. A positive association was confirmed between MDUI and mean daily temperature (MDT), and a negative association was shown between MDUI and mean daily relative humidity (MDRH) in all cities. The lag effect was within 5 days. The multivariate Cochran Q test for heterogeneity at MDT was 12.35 (P = 0.136), and the related I2 statistic accounted for 35.2% of the variability. Additionally, the Cochran Q test for heterogeneity and I2 statistic at MDHR were 26.73 (P value = 0.148) and 24.7% of variability in the total group. Association was confirmed between daily temperature, relative humidity and urolithiasis incidence, and the differences in urolithiasis incidence might have been partially attributable to the different frequencies and the ranges in temperature and humidity between cities in Korea.

Enhanced In Vitro Skin Deposition Properties of Retinyl Palmitate through Its Stabilization by Pectin

The purpose of this study was to examine the effect of stabilization of retinyl palmitate (RP) on its skin permeation and distribution profiles. Skin permeation and distribution study were performed using Franz diffusion cells along with rat dorsal skin, and the effect of drug concentration and the addition of pectin on skin deposition profiles of RP was observed. The skin distribution of RP increased in a concentration dependent manner and the formulations containing 0.5 and 1 mg of pectin demonstrated significantly increased RP distributions in the epidermis. Furthermore, it was found that skin distribution of RP could be further improved by combined use of pectin and ascorbyl palmitate (AP), due largely to their anti-oxidative effect. These results clearly demonstrate that the skin deposition properties of RP can be improved by stabilizing RP with pectin. Therefore, it is strongly suggested that pectin could be used in the pharmaceutical and cosmetic formulations as an efficient stabilizing agent and as skin penetration modulator.

Enhanced In Vitro Skin Deposition Properties of Retinyl Palmitate through Its Stabilization by Pectin

The purpose of this study was to examine the effect of stabilization of retinyl palmitate (RP) on its skin permeation and distribution profiles. Skin permeation and distribution study were performed using Franz diffusion cells along with rat dorsal skin, and the effect of drug concentration and the addition of pectin on skin deposition profiles of RP was observed. The skin distribution of RP increased in a concentration dependent manner and the formulations containing 0.5 and 1 mg of pectin demonstrated significantly increased RP distributions in the epidermis. Furthermore, it was found that skin distribution of RP could be further improved by combined use of pectin and ascorbyl palmitate (AP), due largely to their anti-oxidative effect. These results clearly demonstrate that the skin deposition properties of RP can be improved by stabilizing RP with pectin. Therefore, it is strongly suggested that pectin could be used in the pharmaceutical and cosmetic formulations as an efficient stabilizing agent and as skin penetration modulator.