Improvement in walking impairment following surgical and endovascular revascularization: Insights from VOYAGER PAD.

BACKGROUND: Peripheral artery disease (PAD) affects 200 million people worldwide and is associated with impaired quality of life, increased morbidity, and mortality. Supervised exercise therapy (SET) and lower-extremity revascularization (LER) are both proven strategies to improve patient symptoms. Short and long-term functional outcomes after LER for symptomatic PAD in a large, international cohort have not previously been described. METHODS: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2-6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter. The primary outcome analysis was degree of difficulty walking two blocks at each of the aforementioned time points. Difficulty walking three blocks and climbing one flight of stairs at these time points was also analyzed. Data about supervised and home exercise therapy before or after revascularization were not collected in the VOYAGER PAD trial. RESULTS: Of the 5614 VOYAGER PAD participants completing the WIQ at baseline, three-quarters presented with claudication and one-quarter with critical limb ischemia. Of these, the majority (62% with claudication and 74% with CLI) reported inability or much difficulty walking two blocks prior to LER. Walking improved after LER regardless of revascularization strategy, but one-fifth with claudication and one-third with CLI reported continued inability or much difficulty walking two blocks 1 month after LER. Participants who reported improved walking ability 1 month after LER experienced a durable functional result out to 3 years. Although the proportion of participants reporting significant baseline difficulty climbing one flight of stairs or walking three blocks differed, the trend in immediate and sustained improvement after LER was similar to that observed for walking two blocks. CONCLUSION: In this large, international cohort undergoing LER for symptomatic PAD, nearly two-thirds reported inability or much difficulty walking two blocks at baseline. Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled. These observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after LER.

Improving the power of long term rodent carcinogenicity bioassays by adjusting the experimental design.

Since long term rodent carcinogenicity studies are used to test a very large number of potential tumor endpoints, finding a balance between the control of Type 1 and Type 2 error is challenging. As a result, these studies can suffer from very low power to detect effects of regulatory significance. In the present paper, a new design is proposed in order address this problem. This design is a simple modification of the existing standard designs and uses the same number of animals. Where it differs from the currently used designs is that it uses just three treatment groups rather than four, with the animals concentrated in the control and high dose groups, rather than being equally distributed among the groups. This new design is tested, in a pair of simulation studies over a range of scenarios, against two currently used designs, and against a maximally powerful two group design. It consistently performs at levels close to the optimal design, and except in the case of relatively modest effects and very rare tumors, is found to increase power by 10%-20% over the current designs while maintaining or reducing the Type 1 error rate.

A quantitative study of vapor diffusions for crystallizations: rates and solvent parameter changes.

Vapor diffusion crystallizations are among the most versatile methods for growing X-ray quality crystals. While many experimental sections describe the successful use of various solvent combinations, the literature has been entirely lacking in quantitative data (rates, measures of solvent strength changes) that might allow more informed planning rather than simple trial-and-error approaches. We here report the diffusion-induced volume changes for 44 solvent combinations over the first 60 h under standardized conditions, plus six more combinations that exhibit little or no volume changes. Additionally, the inner and outer vial compositions at 24 h were determined, and the resulting changes in solvation parameters were quantified using Hansen solubility parameters. Some general preliminary effects of changes in volume ratios and scale are described. These results identify two dozen solvent combinations with larger changes in solvent parameters than the very commonly used diethyl ether/dichloromethane example. These results should allow a more informed approach to the execution of vapor diffusion crystallizations than has previously been possible.