Clinical researchers often propose (or review committees demand) pilot studies to determine whether a study is worth performing and to guide power calculations. The most likely outcomes are that (1) studies worth performing are aborted and (2) studies that are not aborted are underpowered. There are many excellent reasons for performing pilot studies. The argument herein is not meant to discourage clinical researchers from performing pilot studies (or review committees from requiring them) but simply to caution against their use for the objective of guiding power calculations.

The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.

ClinicalTrials.gov Identifier: NCT01191333.

We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG.

Kappa coefficients are measures of correlation between categorical variables often used as reliability or validity coefficients. We recapitulate development and definitions of the K (categories) by M (ratings) kappas (K x M), discuss what they are well- or ill-designed to do, and summarize where kappas now stand with regard to their application in medical research. The 2 x M(M>/=2) intraclass kappa seems the ideal measure of binary reliability; a 2 x 2 weighted kappa is an excellent choice, though not a unique one, as a validity measure. For both the intraclass and weighted kappas, we address continuing problems with kappas. There are serious problems with using the K x M intraclass (K>2) or the various K x M weighted kappas for K>2 or M>2 in any context, either because they convey incomplete and possibly misleading information, or because other approaches are preferable to their use. We illustrate the use of the recommended kappas with applications in medical research.

Background-Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance.

No abstract

Objectives-To determine if bright light can improve sleep in older individuals with insomnia.Design-Single-blind, placebo-controlled, twelve-week, parallel-group randomized design comparing four treatment groups representing a factorial combination of two lighting conditions and two times of light administration.Setting-At-home light treatment, eight office therapy sessions.Participants-Thirty six females, fifteen males (63.6 ± 7.1 years) meeting primary insomnia criteria, recruited from the community.Interventions-A 12-week program of sleep hygiene and exposure either to bright (∼4000 lux) or dim light (∼65 lux) scheduled daily in the morning or evening for 45 minutes.Measurements and Results-Within group changes were observed for subjective sleep measures (sleep logs, questionnaires) after morning or evening bright light, but were not significantly different from those observed after exposure to scheduled dim light. Objective sleep changes (actigraphy, polysomnography) after treatment were not significantly different between bright and dim light groups. Scheduled light exposure was able to shift circadian phase predictably, but was unrelated to changes in objective or subjective sleep measures. A polymorphism in CLOCK predicted morningness, but did not moderate the effects of light on sleep. The phase angle between the circadian system (melatonin midpoint) and sleep (darkness) Address correspondence to: Jerome Yesavage, M.D., Palo Alto VA Health Care System (151Y),