Objective assessment of the damaging effect of glucocorticoids (toxicity index) in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multisystem disease characterized by chronic inflammation and damage to vital organs and systems. Despite the great success achieved in the treatment of SLE, glucocorticoids (GC) remain one of the main methods of therapy. The GC toxicity index is an objective method for assessing adverse events associated with their use, and in future studies can be actively used to monitor the safety of various therapy regimens. Wider introduction of this index in the management of patients with SLE will allow to optimize approaches to the selection of GC doses, to consider earlier prescription of biologic disease modifying antirheumatic drugs, before the development of severe irreversible damage.

Toxicity Index, Patient-Reported Outcomes, and Early Discontinuation of Endocrine Therapy for Breast Cancer Risk Reduction in NRG Oncology/NSABP B-35

PURPOSE The US National Cancer Institute Moonshot initiative calls for improving analysis and reporting of toxicity to inform treatment tolerability. We used existing clinician-reported adverse event (AE) and patient-reported outcome (PRO) questionnaire data from the randomized, double-blind NSABP B-35 clinical trial to explore reasons for anastrozole and tamoxifen discontinuation. METHODS Postmenopausal women with ductal carcinoma in situ treated with breast-conserving therapy were randomly assigned to anastrozole or tamoxifen for 5 years. The primary outcome for this analysis was time to treatment discontinuation. AEs were collected every 6 months post–random assignment from all 3,104 participants and summarized using the Toxicity Index (TI). PRO data were collected at baseline and every 6 months from 1,194 participants. Univariate and multivariable analyses of time to treatment discontinuation were performed using Cox regression models with TIs and PROs as time-dependent covariates. RESULTS Of 3,046 analyzed participants, 869 (28.5%) discontinued treatment prematurely. In multivariable analysis, when both baseline PROs and on-treatment AEs were considered, thrombosis and arthralgia AEs were associated with discontinuation of both tamoxifen and anastrozole; additional AEs associated with discontinuation varied by drug. In addition, baseline pain interference, hot flashes, and unhappiness were associated with tamoxifen discontinuation (n = 589; overall Harrell's C-statistic 0.686 [95% CI, 0.640 to 0.732]); no baseline PROs were associated with anastrozole discontinuation (n = 589; overall Harrell's C-statistic 0.656 [95% CI, 0.630 to 0.681]). When only baseline PROs were examined, pain interference, hot flashes, and unhappiness were associated with shorter time to discontinuation of tamoxifen; only hot flashes were associated with discontinuation of anastrozole. CONCLUSION Analysis of AEs using the TI yielded important insights into reasons for discontinuation of endocrine therapy that was enhanced by the addition of PRO baseline and treatment-emergent symptoms.

Safety assessment of residual amounts of disinfectants based on quaternary ammonium compounds on medical devices

Has been made an assessment of the toxicity of residual amounts of disinfectants after using them on products, made from various materials, with DS solutions based on QAC. The working solutions were used in concentrations from 0.3 to 7 % (by DV). The safety of the studied samples was assessed by the toxicity index "It" (in%) on an AT-05 Image Analyzer. Washing out of the residual amounts of DS in concentrations of 0.3–0.7 % (by DW) did not significantly affect the total time of disinfection treatment or pre-sterilization cleaning. At higher concentrations of solutions, there were differences in the time of washing test items and dishes for receiving safe amounts of DS. It is concluded that it is inexpedient to use solutions based on QAC in a concentration of more than 4.5 % (in terms of DV) for disinfection treatment and pre-sterilization cleaning of products made of natural and silicone rubber. Keywords: disinfectants, quaternary ammonium compounds, product washing, AT-05 image analyzer, to­xicity index.

Glucocorticoid toxicity reduction with Mepolizumab using the glucocorticoid toxicity index

Reduction in glucocorticoid exposure is the primary benefit of new biologic treatments in severe asthma, but there is currently no evidence that reduction in glucocorticoid exposure corresponds to a proportionate reduction in associated toxicity.ObjectivesTo use the validated Glucocorticoid Toxicity Index (GTI) to assess change in glucocorticoid toxicity after 12 months treatment with mepolizumab, and compare toxicity change to glucocorticoid reduction and change in patient reported outcome measures (PROMs).MethodsA longitudinal, real world prospective cohort of 101 consecutive patients with severe asthma commenced on mepolizumab in a Specialist UK Regional Severe Asthma clinic. GTI toxicity assessment, cumulative glucocorticoid exposure and PROMs were recorded on commencing mepolizumab (V1), and after 12 months treatment (V2).ResultsThere was significant reduction in oral glucocorticoid exposure (V1 4280 mg prednisolone/year [interquartile range (IQR) 3083, 5475] versus V2 2450 mg prednisolone/year [1243, 3360], p<0.001). Substantial improvements in individual toxicities were observed but did not correlate with oral glucocorticoid reduction. Mean GTI Aggregate Improvement Score (AIS) was −35.7 (sd 57.8) with a wide range in toxicity change at individual patient level (AIS range −165 to +130); 70% (71/101) had a reduction in toxicity (AIS <0), 3% (3/101) had no change (AIS=0) and 27% (27/101) an increase in overall toxicity. Sixty-two (62/101) patients met the AIS minimally clinically important difference of ≤−10, but AIS did not correlate with glucocorticoid reduction or change in PROMs.ConclusionMepolizumab resulted in substantial oral glucocorticoid reduction but this did not correlate with reduction in oral glucocorticoid toxicity, which varies widely at the individual patient level. Oral glucocorticoid reduction is not a comprehensive measure of response to mepolizumab.

Comparison of Landfill Leachate Properties by LPI and Phytotoxicity-A Case Study

The formation of leachate is one of the inevitable consequences associated with the operation of landfills. In addition to the study of physicochemical composition, toxicity is an important parameter taken into account, among others because of the need to subject leachate to treatment before discharge into the environment. The aim of this study was to determine the degree of leachate contamination using LPI and toxicity index. An analysis of the relationship between the toxic effect on plants and the calculated LPI values was also carried out to assess whether they could provide a measure of leachate toxicity when selecting a treatment method. The research conducted was to determine the degree of leachate contamination using LPI and toxicity index. An analysis of the relationship between the toxic effect on plants and the calculated LPI values was also carried out to assess whether they could provide a measure of leachate toxicity when selecting a treatment method. Calculated values of the leachate pollution index showed that leachates from selected Polish landfills are characterized by low and medium levels of LPI values. The variation in index values obtained was particularly evident between active and closed landfills and was related to the physicochemical composition of leachates. In closed landfills this value ranged from 7.4 to 11.1, while in active landfills from 12.9 to 15.9. The variation in index values obtained was particularly evident between active and inactive landfills and was related to the physicochemical composition of leachates. Phytotoxicity tests showed that leachate at low concentrations can promote plant growth. At higher concentrations (50 and 100%), leachates caused inhibition of root and shoot growth, which correlated with high LPI values. The results confirmed the relationship between the toxic effect on plants and the LPI values, so it can be considered as a reliable indicator of leachate toxicity.