The effects of multivitamin supplementation on mood and general well-being in healthy young adults. A laboratory and at-home mobile phone assessment.

Previous research has suggested that multivitamin (MV) supplementation may be associated with beneficial effects for mood and general well-being, although treatment durations have typically been less than 90 days, samples have often been restricted to males only and acute effects have not been adequately differentiated from chronic effects. In the current study a MV supplement containing high levels of B-vitamins was administered daily to 138 healthy young adult participants between the ages of 20 and 50 years over a 16-week period. Chronic mood measures (GHQ-28, POMS, Chalder fatigue, PILL, Bond-Lader and custom visual analogue scales) were administered pre-dose at baseline, 8- and 16-weeks. Changes in Bond-Lader and VAS in response to a multi-tasking framework (MTF) were also assessed at 8- and 16-weeks. For a subset of participants, at-home mobile-phone assessments of mood were assessed on a weekly basis using Bond-Lader and VAS. No significant treatment effects were found for any chronic laboratory mood measures. In response to the MTF, a significant treatment x time interaction was found for STAI-S, with a trend towards a greater increase in stress ratings for male participants in the MV group at 16 weeks. However, this finding may have been attributable to a larger proportion of students in the male MV group. In contrast, at-home mobile-phone assessments, where assessments were conducted post-dose, revealed significantly reduced stress, physical fatigue and anxiety in the MV group in comparison to placebo across a number of time points. Further research using both acute and chronic dosing regimens are required in order to properly differentiate these effects.

Neurocognitive and mood effects of alcohol in a naturalistic setting.

OBJECTIVE: The current pilot study aimed to assess the effects of drinking alcohol in a naturalistic setting on aspects of performance. METHODS: Thirty individuals were approached and tested individually in a university campus bar. They provided details regarding alcoholic drinks consumption. Each was breathalysed before and after completion of a computerised test battery administered on a handheld device. The battery consisted of visual analogue mood scales, a series of alcohol-sensitive psychomotor and cognitive tests. RESULTS: There were highly significant correlations between measured blood alcohol concentrations, estimated units of alcohol consumed and scores on a 'sober-drunk' VAS (p < 0.001 in all cases). For performance, there was a characteristic alcohol-associated shift in the speed/accuracy trade-off (SATO), which was reflected as significantly more errors with less effect on speed across several measures (including maze performance and Serial Sevens). Individuals who were more intoxicated were also significantly less alert. CONCLUSIONS: The data suggest that controlled laboratory tests into the effects of alcohol intoxication may have ecological validity, with SATO shifts amongst the characteristic impairments seen in both controlled and naturalistic settings.

Evaluation of a new method of assessing depth of sedation using two-choice visual reaction time testing on a mobile phone.

The utility of two-choice visual reaction time testing using a specially programmed mobile telephone as a measure of sedation level was investigated in 20 healthy patients sedated with target controlled infusions of propofol. At gradually increasing target concentrations visual reaction time was compared with patient-assessed visual analogue scale sedation scores and an observer-rated scale. Propofol sedation caused dose-dependent increases in visual reaction time and visual analogue scale scores that were statistically significant when the calculated effect-site concentration reached 0.9 microg.ml(-1) (p < 0.05) and 0.5 microg.ml(-1) (p < 0.01) respectively. While visual analogue scale scores were more sensitive at lower levels of sedation than visual reaction time, the latter demonstrated marked increase in values at higher levels of sedation. Visual reaction time may be useful for identifying impending over-sedation.

Comparison of the sedative, cognitive, and analgesic effects of nitrous oxide, sevoflurane, and ethanol.

BACKGROUND: Anaesthetics which work by different mechanisms may have different patterns of effect. Measurement of these patterns thus may elucidate their mechanisms of action and allow therapeutic choices between the agents. METHODS: We compared the effects of ethanol (approximately 80 mg per 100 ml), and different end-tidal concentrations of nitrous oxide (15% and 25%) and sevoflurane (0.3% and 0.5%) in volunteers. We measured speed and accuracy in psychomotor tests, reaction time and memory, touch and pain sensitivity to von Frey filaments, and subjective mood for a range of descriptors. RESULTS: All treatments caused the same degree of overall abnormal feelings, but sevoflurane caused more obtunding (subjective drowsiness, slow reaction times, and loss of memory function) and nitrous oxide was more analgesic. Ethanol caused a marked feeling of drunkenness, but little drowsiness or analgesia. CONCLUSIONS: In the same volunteer subjects, direct comparison of sub-anaesthetic doses of these agents showed a clear and characteristic pattern of effects. These support the possible mechanisms for these disparate agents and may help choose appropriate agents for specific desired anaesthetic outcomes such as sedation or analgesia.

Cognitive functioning in polycystic ovary syndrome.

To date there have been no published studies of cognitive functioning in polycystic ovary syndrome (PCOS). This large internet-based study compared neuropsychological functioning in right-handed women with (minimum n=135) and without PCOS (minimum n=322), stratified according to use of anti-androgen medication and level of depression. Women with PCOS are thought to have hyperandrogenism and hyperestrogenism which was hypothesized to differentially influence cognitive function across cognitive domains. Performance did not differ according to diagnosis on mental rotation and spatial location tasks. Hence, no evidence to support the view that women with PCOS display a more masculine cognitive profile due to hyperandrogenism. Despite presumed hyperestrogenism, women with PCOS demonstrated impaired performance in terms of speed and accuracy, on reaction time and word recognition tasks. These findings are intriguing given the well-documented roles of estrogen and testosterone in cognitive function. Overall, these findings suggest that PCOS is not associated with masculinized cognitive functioning, and, although associated with impaired performance on tasks considered to demonstrate female-advantage, such impairments are subtle and are unlikely to affect daily functioning.

Assessment of postsurgical recovery after discharge using a pen computer diary.

We assessed patients after their return home following gynaecological surgery, using a daily electronic diary. Thirty-two females aged 27-77 years took part. After a hospital stay of 1-6 days (mean 2.3), they were given a pen-based electronic diary and asked to record symptoms and other data over one month. They also completed a questionnaire at the end of the study. Substantial effects on quality and duration of sleep, pain during both the night and day, interference with daily activities, energy, and ability to concentrate were recorded, mostly during the first week of treatment. Symptoms reported in the final questionnaire correlated significantly with diary data. Most patients found the electronic diary easy to use, and none found it difficult. Daily electronic diaries are an acceptable method of obtaining better information on the extent and duration of symptoms and other difficulties after discharge following surgery.

Errors in performance testing: a comparison of ethanol and temazepam.

Both ethanol and benzodiazepines impair psychomotor function. Previous work has suggested that ethanol may have a greater effect on errors while benzodiazepines may cause greater slowing, but this has not been tested in a direct comparison. We assessed the effects of ethanol, at blood concentrations of approximately 80-100 mg/100 ml, compared to two doses of temazepam (20 mg and 30 mg) on psychomotor speed and accuracy and on long-term memory. Sixteen healthy volunteers (eight male, aged 20-25 years) took part in a four-period, placebo-controlled cross-over study. Performance was evaluated using analysis of covariance (critical significance level, p = 0.05) comparing the areas under the response-time curves. Performance on a psychomotor maze showed an almost complete dissociation, with ethanol leading to a substantial and significant increase in errors with little effect on speed, while temazepam slowed performance with no significant change in accuracy. Other tasks showed a similar pattern, but the dissociation was less complete. Handwriting size was substantially increased by ethanol, but not by temazepam. Information processing capacity and long-term memory formation were reduced by a similar amount both for ethanol and 30 mg temazepam. The faster, more error-prone, behaviour on ethanol than with a similarly impairing dose of temazepam has clear implications for the relative potential of the two drugs to contribute to accidents. The results are also important in understanding the differential effects of drugs with different mechanisms of action on human performance.

A comparison of target-controlled therapy with patient-controlled administration of propofol combined with midazolam for sedation during dental surgery.

Forty anxious day case patients undergoing extraction of third molar teeth under local anaesthesia with sedation, were studied in a randomised double-blind controlled trial. A target-controlled infusion of propofol was compared with patient-controlled propofol for sedation, combined with a small dose of midazolam to improve amnesia. The objectives of the study were to measure the total dose of propofol used by the two groups and assess recovery and patient satisfaction. The mean dose of propofol used in the patient-controlled sedation group was significantly less than the target-controlled group (p < 0.00007). Five patients became over-sedated in the target-controlled group compared with none in the patient-controlled group. Only one of the three tests of performance showed that the target-controlled patients were more sedated. Patient satisfaction was high in both groups despite a greater recollection of events in the patient-controlled group.

Effect of ethanol on psychomotor performance and on risk taking behaviour.

Ethanol may increase the willingness to take risks, but this issue remains controversial. We used a risk-taking paradigm in which volunteers answered a series of general knowledge questions with numerical answers and were asked to judge the length of a line that would just fit into a given gap. A maximum score was given for an exactly correct answer. For answers that were less than the correct value, the score was reduced gradually to zero, while answers even slightly over the correct value were penalized considerably. Total points were rewarded by cash payments, so volunteers were taking real risks when making their responses. Performance was assessed in a two-period, double-blind crossover study, comparing ethanol (0.7 g/kg) with placebo in 20 female volunteers aged 19-20 years. Tests were carried out before and at 45 min after dosing. Mean (SD) ethanol blood alcohol concentrations were 65 (10.5) mg/100 ml. Ethanol impaired the skill/ability measure of the length estimation test (SD of difference between length of line and gap), which increased from 5.9 to 6.6 (p < 0.05), indicating a reduced accuracy of estimation. The risk measures in both tasks were not significantly affected. The skill/ability measure in the general knowledge task was not significantly affected. Other performance tests showed that ethanol produced the expected impairment of both speed and accuracy. These results suggest that risk-taking is not increased by ethanol at doses approaching the UK legal limit for driving.

Ethanol, errors, and the speed-accuracy trade-off.

Ethanol has been shown to have a relatively greater effect on error rates in speeded tasks than temazepam, and this may be due to a differential effect on the speed-accuracy trade-off (SATO). This study used different instruction sets to influence the SATO. Forty-nine healthy volunteers (24 males, aged 18-41 years) were allocated at random to one of three instruction conditions--emphasising accuracy, neutral, and emphasising speed. After familiarisation, they took part in two sessions spaced at least 4 days apart in which they received either ethanol (0.8 g/kg, max 60 g males, 50 g females) or placebo in randomised order. Tests were administered starting at 30 and 75 min postdrug. Instructions significantly affected performance. In two maze tasks, one on paper, the other on a pen computer, the pattern of instruction effects was as expected. A significant increase in errors with ethanol was seen for both maze tasks, and there was a tendency to speed up with ethanol (significant only for the pen computer task). Responses to fixed stimulus sequences on the Four-Choice Reaction Test also showed a tendency to speed up and an increase in errors with ethanol, while all other tests showed both slowing and increases in errors with ethanol compared to placebo. Error scores are consistently increased by ethanol in all test situations, while the effects of ethanol on speed are variable across tests.

Validity and sensitivity of a pen computer battery of performance tests.

This study compared administration of performance tests and visual analogue scales (VAS) using a newly developed pen computer (PenC) battery with established tests using either pencil-and-paper (PP) or conventional computer. The performance of 47 subjects (23 male, age 18-45 years, weight 51-112 kg) was compared on the two systems after a dose of ethanol (0.8 g/kg up to a maximum of 60 g for males, 50 g for females) or placebo in a double-blind two-period randomized crossover study. Mean (SD) blood ethanol concentrations (breathalyser) were 94.5 mg/100 ml (21.9) at the start of the test battery (30 min post-drink) and 80.2 (13.0) at the end of the battery (75 min post-drink). Ethanol effects were found in all tests, with most outcome measures showing significant slowing or loss of accuracy. Results from the Rapid Visual Information Processing, Sentence Verification and Continuous Attention tasks show that the ethanol-placebo difference and the statistical significance of this difference are in close correspondence for the two modes of administration. The pen computer versions of these tasks may therefore be used as direct replacements for the previous versions. Digit-Symbol and maze tasks did not correspond so closely both showing differences in the speed-accuracy trade-off between the two modes. These tests, however, are sensitive to the effects of ethanol, and may be useful in their own right. Principal component analysis suggested that VAS may be grouped into two factors: (1) 'functional integrity', including measures of alertness and perceived proficiency, and (2) 'mood', including happiness and sociability. Factor 1 showed substantial effects of ethanol, while factor 2 was unchanged. There was close agreement between the results from PP and PenC for both factors as well as for the Sober-Drunk scale, which showed the expected effects of ethanol. Thus pen computer VAS perform in a similar way to the PP versions.

Single dose pharmacodynamics of thioridazine and remoxipride in healthy younger and older volunteers.

Phenothiazines are widely used in older patients, but little experimental work has been carried out in this age group. Two groups of healthy volunteers, a younger group (Y: six males and six females, aged 20-42 years) and an older group (O: six males and eight females, aged 65-77 years) took part in a randomized double-blind three-period crossover study in which they received by mouth single doses of thioridazine (Y: 50 mg; O: 25 mg) remoxipride (Y: 100 mg; O: 50 mg) or placebo. Measures of central nervous system (CNS) and haemodynamic function were carried out before drug administration and at 1.5-h intervals up to 9 h post-dose, and blood samples were collected over a 24-h period. No significant differences in dose-corrected pharmacokinetic variables were found between the two groups. There was evidence of marked CNS depressant effects of thioridazine from both objective and subjective measures. The effects for remoxipride were similar, though generally less marked. After allowance was made for dose, there was little indication of any difference in degree of CNS depression between the two age groups. Haemodynamic measures showed orthostatic reductions in blood pressure with thioridazine which were particularly marked in the older group, who also showed lower compensatory increases in pulse rate. These results indicate potential problems with orthostatic hypotension with thioridazine in older patients. CNS depression may also be a problem, especially in patients with compromised cholinergic function.

Computer anxiety: a comparison of pen-based personal digital assistants, conventional computer and paper assessment of mood and performance.

The recent growth of pen-based devices, such as the Personal Digital Assistant (PDA), offer mobility and a more natural interface than that of a conventional computer. The feasibility and application of the PDA for mood and cognitive assessment were investigated by examining possible interactions of individual characteristics and administration medium. Previous studies have provided evidence that individual characteristics of 'computer anxiety' and 'private self-consciousness' divergently covaried with mood scores measured by computer and paper methods. To investigate the relationship between individual characteristics and medium effects, 136 paid participants were allocated to and completed mood assessment tasks and a short battery of cognitive tasks by either the computer, PDA or the paper method. Self-ratings of mood measured by these three modalities covaried divergently with measures of computer anxiety and private self-consciousness. In addition, computer anxiety covaried with reaction time on the visual search task obtained on computers, but there was no such relationship when measured by a PDA. These results show that computer anxiety can affect the results of assessments of cognitive function as well as of mood ratings, and suggest that pen-based systems may have advantages over conventional computers in this respect.

Psychomotor performance: investigating the dose-response relationship for caffeine and theophylline in elderly volunteers.

OBJECTIVE: The aim of the study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers. METHODS: In a randomized, double-blind, placebo-controlled, six-period cross-over study we compared the effect of three doses of theophylline (predicted peak concentrations of 3, 6 mg. 1(-1) and 12 mg . 1(-1), two doses of caffeine (predicted peak concentrations of 4.5 mg. 1(-1) and 9 mg. 1 (-1) and placebo on ten healthy elderly volunteers. Psychomotor performance was measured using a continuous attention task, symbol digit substitution test and choice reaction time. Subjective effects were assessed using visual analogue scales. Following drug administration, subjects received the test battery at 30-min intervals, up to 150 min. Maximum and mean effects from baseline on each variable were included in the analysis. RESULTS: Significant improvement on the continuous attention task was seen at the lowest concentration of caffeine and theophylline used, while at higher concentrations there was a non-significant trend towards placebo scores. There was little effect of either drug on the subjective effects measured by visual analogue scales. CONCLUSION: Caffeine and theophylline increase psychomotor performance measures of attention at low plasma concentrations in healthy elderly volunteers. This effect is not increased by higher drug concentrations and there is trend towards a return to placebo scores. The lack of effect of both caffeine and theophylline on subjective measures is consistent with previous studies of caffeine in the elderly.

Validity and sensitivity of visual analogue scales in young and older healthy subjects.

BACKGROUND: Previous findings from studies on the acute effects of drugs indicate that older subjects report less change on visual analogue scales than do younger subjects, when the observed drug effects on objective performance measures are as great or greater. AIM: To validate the use of visual analogue scales independently of internal perceptions. SUBJECTS AND METHODS: 50 younger and 50 older subjects rated attributes of four animals--tortoise, crow, tiger and wasp--on a series of 10 cm lines. The attributes rated included physical qualities (size, noise) and psychological aspects (danger). RESULTS: Ratings were generally similar for the two groups, although older subjects tended to rate slightly greater differences between animals, but the variability was also slightly greater. Thus the mean difference between tiger and wasp for size was 60.1 (SD 15.6) in the younger group and 68.8 (SD 18.4) in the older group. CONCLUSIONS: These results support the validity of the use of visual analogue scales in both groups. Explanations for the previously observed discrepancy may need to be sought in terms of an effect of age on the perception of internal changes rather than on any difference in the use of the scales.

Electronic quality of life questionnaires: a comparison of pen-based electronic questionnaires with conventional paper in a gastrointestinal study.

The use of pen-based electronic questionnaires and conventional paper questionnaires was compared in a randomized crossover study. Forty-six patients, aged 17-81 years, suffering from gastro-intestinal disorders, initially filled in a paper quality of life questionnaire for familiarization purposes, then on two subsequent visits completed electronic and paper questionnaires in randomized order. At the last visit they completed a preference survey. The results showed a high degree of acceptability of the electronic questionnaire, with 57% of patient preferring electronic and 13% preferring paper, while the remaining 30% expressed no preference. Neither age, gender nor familiarity with technology showed any marked association with patients' preferences. All patients found both paper and electronic questionnaires easy to use. Data were more complete on the electronic questionnaire (100%) than on the paper (99.1%). Data handling procedures were greatly simplified. These results show that major benefits in completeness of data, speed of data flow, and data handling workload can be obtained from the use of pen-based electronic questionnaires.

Effects of nitrous oxide on psychological performance. A dose-response study using inhalation of concentrations up to 15%.

In this six-period randomised double-blind study, 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0% (placebo); 3%, 5%, 7%, 10%, and 15% in oxygen. Each concentration was inhaled for 55 min, each period being on a separate day. The order of treatments was randomised using a Latin-Square design. The effects of nitrous oxide were assessed using a battery of performance tests which included measures of attention, psychomotor function, memory and cognition. Mood was assessed using visual analogue scales. Measures of attention and psychomotor performance showed impairment at 15% nitrous oxide, and subjective measures showed sedation at this dose. The Buschke Selective Reminding Task showed impairment to long-term recall at all doses of nitrous oxide compared to placebo, while short-term recall was impaired only at 15%. These results suggest that consolidation of memory may be particularly sensitive to disruption as a result of CNS depression.

The effects of inhaled nitrous oxide on some measures of attention.

This study compared the sensitivity of various measures of attention to the effects of CNS depression, using a randomised single-blind two-period cross-over study. Nineteen healthy volunteers, 10 males and nine females, aged 20-49 took part in a single session in which they inhaled 15% nitrous oxide in oxygen or 100% oxygen (placebo) through a face-mask for 45 min, followed by a 10-min interval after which they received the other treatment in counterbalanced order. They performed a battery of five attention tasks and completed visual analogue scales starting 10 min after the beginning of each inhalation period. The most sensitive measures of the effects of this dose of nitrous oxide were letter cancellation, which had three target letters to cancel, and an auditory attention task with different stimuli to the two ears. Measures of concentrated attention without distractors (continuous attention task and continuous performance task) were less sensitive, though clear effects were seen at these doses. Tests of differing complexities may involve distinct functions which could be differentially affected by different classes of drug. Thus both simple and more complex tasks should be represented in studies assessing attentional function in detail.

The effects of remoxipride and chlorpromazine on eye movements and psychomotor performance in healthy volunteers.

Fifteen healthy male volunteers received single doses of 100 mg immediate release remoxipride (IR), 150 mg controlled release remoxipride (CR), 50 mg chlorpromazine (CPZ), 2 mg lorazepam (LZ), and placebo in a randomised, five-period cross-over study. Both saccadic (SEM) and smooth pursuit eye movements (SPEM) as well as a battery of psychomotor performance tests were assessed at 1.5-h intervals over 9 h following drug administration. The areas under the response-time curves and the maximum effect during the study period were analysed by analysis of variance. The most consistent impairments were produced by LZ. The neuroleptics caused impairments to SEM, and tended to impair critical flicker fusion, continuous attention and both paced and unpaced versions of the digit-symbol substitution test as well as subjective measures of sedation. Only LZ impaired SPEM. Neither paced nor unpaced psychomotor tests distinguished between neuroleptics and benzodiazepines. The low therapeutic doses of IR and CR produced similar impairments to a sub-therapeutic dose of CPZ. Selectivity of pharmacological action does not appear to predict selectivity of effect on psychomotor function.