In a double-blind study, we examined the efficacy of allopurinol in the prevention of recurrent calcium oxalate calculi of the kidney. Sixty patients with hyperuricosuria and normocalciuria who had a history of calculi were randomly assigned to receive either allopurinol (100 mg three times daily) or a placebo. After the study, the placebo group had 63.4 percent fewer calculi (P less than 0.001), whereas the allopurinol group had 81.2 percent fewer calculi (P less than 0.001). During the study period, the mean rate of calculous events was 0.26 per patient per year in the placebo group and 0.12 in the allopurinol group. When the treatment groups were compared by actuarial analysis, the allopurinol group was found to have a significantly longer time before recurrence of calculi (P less than 0.02). We conclude that allopurinol is effective in the prevention of calcium oxalate stones in patients with hyperuricosuria. The large reduction in the frequency of calculi in the placebo group underscores the positive treatment bias that regularly occurs in trials of prophylaxis against renal calculi when historical controls are used.

The study is the first to evaluate the effects of graded normobaric hypoxia on SpO2 variability in healthy individuals. Twelve healthy males (mean (SD) age 22 (4) years) were exposed to four simulated environments (FiO2: 0.12, 0.145, 0.17 and 0.21) for 45-min, in a balanced cross-over design. Sample entropy, a tool that quantifies the irregularity of pulse oximetry fluctuations, was used as a measure of SpO2 variability. SpO2 entropy increased as the FiO2 decreased, and there was a strong significant negative correlation between mean SpO2 and its entropy during hypoxic exposure (r = -0.841 to -0.896, P < 0.001). In addition, SpO2 sample entropy, but not mean SpO2, was correlated (r = 0.630 to 0.760, P < 0.05) with dyspnoea in FiO2 0.17, 0.145, and 0.12 and importantly, SpO2 sample entropy at FiO2 0.17 was correlated with dyspnoea at FiO2 0.145 (r = 0.811, P < 0.01). These findings suggest that SpO2 variability analysis may have the potential to be used in a clinical setting as a non-invasive measure to identify the negative sequalae of hypoxaemia.

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New Findings What is the central question of this study?What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and their importance?We found that (1) performance of a complex central executive task (n‐back) was reduced at FnormalIO2 0.12; (2) there was a strong correlation between performance of the n‐back task and reductions in SnormalpO2 and cerebral oxygenation; and (3) plasma adrenaline, noradrenaline, cortisol and copeptin were not correlated with cognitive performance. Abstract It is well established that hypoxia impairs cognitive function; however, the physiological mechanisms responsible for these effects have received relatively little attention. This study examined the effects of graded reductions in fraction of inspired oxygen (FnormalIO2) on oxygen saturation (SnormalpO2), cerebral oxygenation, cardiorespiratory variables, activity of the sympathoadrenal system (adrenaline, noradrenaline) and hypothalamic–pituitary–adrenal axis (cortisol, copeptin), and cognitive performance. Twelve healthy males [mean (SD), age: 22 (4) years, height: 178 (5) cm, mass: 75 (9) kg, FEV1/FVC ratio: 85 (5)%] completed a four‐task battery of cognitive tests to examine inhibition, selective attention (Eriksen flanker), executive function (n‐back) and simple and choice reaction time (Deary–Liewald). Tests were completed before and following 60 min of exposure to FnormalIO2 0.2093, 0.17, 0.145 and 0.12. Following 60 min of exposure, response accuracy in the n‐back task was significantly reduced in FnormalIO2 0.12 compared to baseline [82 (9) vs. 93 (5)%; P < 0.001] and compared to all other conditions at the same time point [FnormalIO2 0.2093: 92 (3)%; FnormalIO2 0.17: 91 (6)%; FnormalIO2 0.145: 85 (10)%; FnormalIO2 12: 82 (9)%; all P < 0.05]. The performance of the other tasks was maintained. Δaccuracy and Δreaction time of the n‐back task was correlated with both ΔSnormalpO2 [r(9) = 0.66, P < 0.001 and r(9) = −0.36, P = 0.037, respectively] and Δcerebral oxygenation [r(7) = 0.55, P < 0.001 and r(7) = −0.38, P = 0.045, respectively]. Plasma adrenaline, noradrenaline, cortisol and copeptin were not significantly elevated in any condition or correlated with any of the tests of cognitive performance. These findings suggest that reductions in peripheral oxygen saturation and cerebral oxygenation, and not increased activity of the sympathoadrenal system and hypothalamic–pituitary–adrenal axis, as previously speculated, are responsible for a decrease in cognitive performance during normobaric hypoxia.

Peripheral capillary oxygen saturation (S pO 2) exhibits a complex pattern of fluctuations during hypoxia. The physiological interpretation of S pO 2 variability is not well understood. In this study, we tested the hypothesis that S pO 2 fluctuation carries information about integrated cardio-respiratory control in healthy individuals using a network physiology approach. We explored the use of transfer entropy in order to compute the flow of information between cardio-respiratory signals during hypoxia. Twelve healthy males (mean (SD) age 22 (4) years) were exposed to four simulated environments (fraction of inspired oxygen (F IO 2): 0.12, 0.145, 0.17, and 0.2093) for 45 min, in a single blind randomized controlled design. The flow of information between different physiological parameters (S pO 2 , respiratory frequency, tidal volume, minute ventilation, heart rate, end-tidal pressure of O 2 and CO 2) were analysed using transfer entropy. Normobaric hypoxia was associated with a significant increase in entropy of the S pO 2 time series. The transfer entropy analysis showed that, particularly at F IO 2 0.145 and 0.12, the flow of information between S pO 2 and other physiological variables exhibits a bidirectional relationship. While reciprocal interactions were observed between different cardio-respiratory parameters during hypoxia, S pO 2 remained the main hub of this network. S pO 2 fluctuations during graded hypoxia exposure carry information about cardio-respiratory control. Therefore, S pO 2 entropy analysis has the potential for non-invasive assessment of the functional connectivity of respiratory control system in various healthcare settings. K E Y W O R D S altitude, hypoxic, sample entropy, S pO 2 , transfer entropy 1 INTRODUCTION Peripheral capillary oxygen saturation (S pO 2) is measured noninvasively and is extensively used for monitoring patients in clinical This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.