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Background/aims: Peripheral neuropathies perturbate the sensorimotor system, causing difficulties in walking-related motor tasks and, eventually, falls. Falls result in functional dependency and reliance on healthcare, especially in older persons. We investigated if peripheral neuropathy is a genuine risk factor for falls in the elderly and if quantification of postural control via posturography is helpful in identifying subjects at risk of falls., Methods: Seventeen older persons with a clinical polyneuropathic syndrome of the lower limbs and converging electrophysiology were compared with 14 older persons without polyneuropathy. All participants were characterized via quantitative motor and sensory testing, neuropsychological assessment, and self-questionnaires. Video-nystagmography and caloric test excluded vestibulocochlear dysfunction. For further analysis, all subjects were stratified into fallers and non-fallers. Overall, 28 patients underwent computerized dynamic posturography for individual fall risk assessment. Regression analyses were performed to identify risk factors and predictive posturography parameters., Results: Neuropathy is an independent risk factor for falls in the elderly, while no differences were observed for age, gender, weight, frailty, DemTect test, timed "Up & Go" test, and dizziness-related handicap score. In computerized dynamic posturography, fallers stepped more often to regain postural control in challenging conditions, while the Rhythmic Weight Shift test showed a lack of anterior-posterior bidirectional voluntary control., Interpretation: Our study confirms peripheral neuropathy as a risk factor for older persons' falls. Fallers frequently used stepping to regain postural control. The voluntary control of this coping movement was impaired. Further investigations into these parameters' value in predicting the risk of falls in the elderly are warranted., (© 2024 The Author(s). Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.)

This review presents a European Federation of Pharmaceutical Industries and Association/PreClinical Development Expert Group (EFPIA-PDEG) topic group consensus on a data-driven approach to harmonized contraception recommendations for clinical trial protocols and product labeling. There is no international agreement in pharmaceutical clinical trial protocols or product labeling on when/if female and/or male contraception is warranted and for how long after the last dose. This absence of consensus has resulted in different recommendations among regions. For most pharmaceuticals, contraception recommendations are generally based exclusively on nonclinical data and/or mechanism. For clinical trials, contraception is the default position and is maintained for women throughout clinical development, whereas appropriate information can justify removing male contraception. Conversely, contraception is only recommended in product labeling when warranted. A base case rationale is proposed for whether or not female and/or male contraception is/are warranted, using available genotoxicity and developmental toxicity data. Contraception is generally warranted for both male and female subjects treated with mutagenic pharmaceuticals. We propose as a starting point that contraception is not typically warranted when the margin is 10-fold or greater between clinical exposure at the maximum recommended human dose and exposure at the no observed adverse effect level (NOAEL) for purely aneugenic pharmaceuticals and for pharmaceuticals that induce fetal malformations or embryo-fetal lethality. Other factors are discussed, including contraception methods, pregnancy testing, drug clearance, options for managing the absence of a developmental toxicity NOAEL, drug-drug interactions, radiopharmaceuticals, and other drug modalities. Overall, we present a data-driven rationale that can serve as a basis for consistent contraception recommendations in clinical trials and in product labeling across regions., (© 2022 Pfizer Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The phenomenon of temporally graded retrograde amnesia (loss of information acquired before the onset of amnesia) suggests that the hippocampus, and possibly other medial temporal lobe (MTL) structures, have a time-limited role in memory. In three experiments, we made a first attempt to use fMRI to assess activity in the hippocampal region (the CA fields of the hippocampus, the dentate gyrus, and the subiculum) and the adjacent parahippocampal gyrus (parahippocampal, entorhinal, and perirhinal cortices) during recognition memory testing as a function of study-test interval. Experiment 1 (n = 5) demonstrated activity in the hippocampal region and parahippocampal gyrus for targets relative to foils during recognition memory performance following a single study-test delay of about one-half hour. In Experiment 2, 15 participants studied line drawings at each of three different times prior to scanning: one-half hour, 1 day, and 1 week. fMRI data were then collected during recognition memory testing, using targets from all three delays and foils. While an overall effect of targets vs. foils was found in both the hippocampal region and the parahippocampal gyrus, there was no effect of study-test interval on target activity. In Experiment 3 (n = 13), behavioral performance (reaction time and accuracy) was equated across the three delays. Again, no effect of study-test interval was observed. It is possible that the time span sampled in our study (one-half hour to 1 week) was too short to observe changes in activity. Alternatively, activity in the MTL during memory testing may occur even when these structures are not necessary for retrieval.