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This trial assessed the effect of tolvaptan on cognition, gait, and postural stability in adult patients with mild to moderate asymptomatic hyponatremia.Phase 3b, multicenter, randomized, double-blind, placebo-controlled, parallel-group pilot study.57 men and women 50 years or older with chronic asymptomatic euvolemic or hypervolemic hyponatremia (serum sodium concentration120-135 mEq/L) at 16 sites.Patients were randomly assigned 1:1 to receive tolvaptan or matching placebo beginning at a dose of 15mg/d, with titration to 30 or 60mg/d based on change in serum sodium concentration and tolerance.Primary: change from baseline in the neurocognitive composite score of speed domains. Secondary: changes from baseline in individual neurocognitive domain scores, overall neurocognitive composite score, gait and postural stability test results, and serum sodium concentrations.Mean serum sodium concentration increased from 129 to 136 mEq/L in the tolvaptan group and from 130 to 132 mEq/L in the placebo group (P0.001). There was no difference in overall neurocognitive composite scores of speed domains between groups, except for the psychomotor speed domain, which was statistically improved following hyponatremia correction with tolvaptan (treatment effect, 0.27; 95% CI, 0.04-0.51; P=0.03).There were some imbalances between treatment groups in baseline neurocognitive function scores and some baseline test results were near normal, leaving little opportunity for improvement. Formal sample size calculations were not performed because this was a pilot study. The study population was small (n=57) and treatment was of short duration (3 weeks). The primary end point of the study was not significant; thus, subgroup analyses are subject to errors of multiplicity and should be regarded as hypothesis generating.Tolvaptan was effective in reversing chronic hyponatremia, and this correlated with improvements in results of a variety of neurocognition tests, particularly rapid motor movements, which tended to reverse following return to a low baseline serum sodium concentration after treatment withdrawal.

Chronic conditions carry with them strong emotions and often lead to charged relationships between patients and their health providers and, by extension, patients and health researchers. Persons are both autonomous and relational and a purely cognitive model of autonomy neglects the social and relational basis of chronic illness. Ensuring genuine informed consent in research requires a thorough understanding of how participants perceive a study and their reasons for participation. Surveys may not capture the complexities of reasoning that underlies study participation. Contradictory reasons for participation, for instance an initial claim of altruism as rationale and a subsequent claim of personal benefit (therapeutic misconception), affect the quality of informed consent. Individuals apply principles through the filter of personal values and lived experience. Authentic autonomy, and hence authentic consent to research, occurs within the context of patients- unique life narratives and illness experiences.

The formation of the National Center for Advancing Translational Sciences (NCATS) brings new promise for moving basic and discoveries to clinical practice, ultimately improving the health of the nation. The CTSA sites, now housed with NCATS, are organized and prepared to support in this endeavor. The CTSAs provide a foundation for capitalizing on such promise through provision of a disease-agnostic infrastructure devoted to C&T science, maintenance of training programs designed for C&T investigators of the future, by incentivizing institutional reorganization and by cultivating institutional support.

Summary: We describe a case of presumed postpartum infundibuloneurohypophysitis, which is a rare inflammatory process involving the pituitary stalk and posterior pituitary. Only one case has been previously reported in a postpartum woman. Serial MR images obtained in our patient revealed spontaneous regression of inflammation. The critical position of the inflammation leads to hormonal deficiencies, mostly involving the posterior pituitary. Treatment options include hormone replacement; the role of pharmacological steroids is controversial.