Systematic review of hematuria and acute renal failure with tranexamic acid.

OBJECTIVES: To conduct a systematic review of tranexamic acid (TXA) and the risk of renal failure from urinary clots in adult patients with hematuria. METHODS: A systematic review of Medline, Embase, CENTRAL, www. CLINICALTRIALS: gov, and Google Scholar were searched. Randomized control trials (RCTs) and observational studies that assessed the risk of renal failure with use of TXA among adults with hematuria were included. The primary outcome was renal failure due to urinary tract clots with TXA compared to no TXA (or placebo) or comparator. RESULTS: We identified three RCTs (N = 466 patients) and three retrospective cohort studies (N=220 patients), and a total of 342 patients that had hematuria and received TXA. The patient population of the six studies included medical and surgical patients, with two of the three RCTs comprised patients undergoing percutaneous nephrolithotomy, and the third RCT comprised patients undergoing transurethral resection of the prostate. Documentation of renal function before and after TXA administration was documented in only two studies (N = 28 patients), and neither identified worsening renal function in those exposed to TXA. CONCLUSIONS: There are limited studies evaluating the risk of renal failure in patients with hematuria who were exposed to TXA, and the available data does not suggest an increased risk.

Sodium-Glucose Cotransporter-2 Inhibitors and Risk of Diabetic Ketoacidosis Among Adults With Type 2 Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVES: The magnitude and precision regarding the risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear. Thus, we examined the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials. METHODS: Searches were performed in PubMed, Embase, CENTRAL and Google Scholar (from inception to April 15, 2019) without language restrictions, including conference proceedings and reference lists. Study selection consisted of randomized controlled trials and observational studies that quantified the rate of DKA with an SGLT2 inhibitor in comparison to other diabetes medications or placebo. Two independent investigators abstracted the study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method. Absolute event rates and hazard ratios for DKA were extracted from each study. RESULTS: Seven randomized trials encompassing 42,375 participants and 5 cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1,000 person years. Four randomized trials were included in the meta-analysis and, compared with placebo or comparator medication, SGLT2 inhibitors had a 2.5-fold higher risk of DKA (relative risk [RR], 2.46; 95% confidence interval [CI], 1.16 to 5.21]; I2=0%; p=0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1,000 person years and a 1.7-fold higher rate of DKA compared with another diabetes medication (RR, 1.74; 95% CI, 1.07 to 2.83; I2=45%; p=0.12). CONCLUSIONS: In adults with type 2 diabetes, SGLT2 inhibitors were found to increase the risk of DKA in both observational studies and large randomized clinical trials.

Resonance Raman measurements of carotenoids using light-emitting diodes.

We report on the development of a compact commercial instrument for measuring carotenoids in skin tissue. The instrument uses two light-emitting diodes (LEDs) for dual-wavelength excitation and four photomultiplier tubes for multichannel detection. Bandpass filters are used to select the excitation detection wavelengths. The f1.3 optical system has high optical throughput and single photon sensitivity, both of which are crucial in LED-based Raman measurements. We employ a signal processing technique that compensates for detector drift and error. The sensitivity and reproducibility of the LED Raman instrument compares favorably to laser-based Raman spectrometers. This compact, portable instrument is used for noninvasive measurement of carotenoid molecules in human skin with a repeatability better than 10%.

External influences and priority-setting for anti-cancer agents: a case study of media coverage in adjuvant trastuzumab for breast cancer.

BACKGROUND: Setting priorities for the funding of new anti-cancer agents is becoming increasingly complex. The funding of adjuvant trastuzumab for breast cancer has brought this dilemma to the fore. In this paper we review external factors that may influence decision-making bodies and present a case study of media response in Ontario, Canada to adjuvant trastuzumab for breast cancer. METHODS: A comprehensive search of the databases of Canadian national and local newspapers and television was performed. Articles pertaining to trastuzumab in adjuvant breast cancer as well as 17 other anti-cancer drugs and indications were retrieved. The search period was from the date when individual trial results were announced to the date funding was made available in Ontario. RESULTS: During the 2.6 months between the release of the trastuzumab results to funding approval in Ontario, we identified 51 episodes of media coverage. For the 17 other drugs/indications (7 breast and 10 non-breast), the median time to funding approval was 31 months (range 14-46). Other recent major advances in oncology such as adjuvant vinorelbine/cisplatin for resected NSCLC and docetaxel for advanced prostate cancer received considerably less media attention (17 media reports for each) than trastuzumab. The median number of media reports for breast cancer drugs was 4.5 compared to 2.5 for non-breast cancer drugs (p = 0.56). CONCLUSION: Priority-setting for novel anti-cancer agents is a complex process that tries to ensure fair use of constrained resources to fund therapies with the best evidence of clinical benefit. However, this process is subject to external factors including the influence of media, patient advocates, politicians, and industry. The data in this case study serve to illustrate the significant involvement one (or all) of these external factors may play in the debate over priority-setting.