An open-label study of citalopram for major depression following traumatic brain injury.

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti-depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of < or =7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of TBI.

An international study of the quality of national-level guidelines on driving with medical illness.

BACKGROUND: Medical illnesses are associated with a modest increase in crash risk, although many individuals with acute or chronic conditions may remain safe to drive, or pose only temporary risks. Despite the extensive use of national guidelines about driving with medical illness, the quality of these guidelines has not been formally appraised. AIM: To systematically evaluate the quality of selected national guidelines about driving with medical illness. DESIGN: A literature search of bibliographic databases and Internet resources was conducted to identify the guidelines, each of which was formally appraised. METHODS: Eighteen physicians or researchers from Canada, Australia, Ireland, USA and UK appraised nine national guidelines, applying the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: Relative strengths were found in AGREE II scores for the domains of scope and purpose, stakeholder involvement and clarity of presentation. However, all guidelines were given low ratings on rigour of development, applicability and documentation of editorial independence. Overall quality ratings ranged from 2.25 to 5.00 out of 7.00, with modifications recommended for 7 of the guidelines. Intra-class coefficients demonstrated fair to excellent appraiser agreement (0.57-0.79). CONCLUSIONS: This study represents the first systematic evaluation of national-level guidelines for determining medical fitness to drive. There is substantive variability in the quality of these guidelines, and rigour of development was a relative weakness. There is a need for rigorous, empirically derived guidance for physicians and licensing authorities when assessing driving in the medically ill.

Controlled release of a model antibacterial drug from a novel self-lubricating silicone biomaterial.

There is considerable interest in developing medical devices that provide controlled delivery of biologically active agents, for example, to reduce the incidence of device-related infection. Silicone elastomers are one of the commonest biomaterials used in medical device production. However, they have a relatively high coefficient of friction and the resulting lack of lubricity can cause pain and tissue damage on device insertion and removal. Novel silicone cross-linking agents have recently been reported that produce inherently 'self-lubricating' silicone elastomers with very low coefficients of friction. In this study, the model antibacterial drug metronidazole has been incorporated into these self-lubricating silicone elastomers to produce a novel bioactive biomaterial. The in vitro release characteristics of the bioactive component were evaluated as a function of cross-linker composition and drug loading. Although conventional matrix-type release kinetics were observed for metronidazole from the silicone systems, it was also observed that increasing the concentration of the cross-linking agent responsible for the lubricious character (tetra(oleyloxy)silane) relative to that of the standard non-lubricious cross-linking agent (tetrapropoxysilane) produced an increase in the metronidazole flux rate by up to 65% for a specified drug loading. The results highlight the potential for developing lubricious silicone medical devices with enhanced drug release characteristics.

Pathological laughing and crying in amyotrophic lateral sclerosis: an association with prefrontal cognitive dysfunction.

Pathological laughing and crying (PLC) frequently occurs in amyotrophic lateral sclerosis (ALS). The etiology of the syndrome is unclear, but frontal-subcortical circuits are implicated, given their known association with mood and affect regulation. Ten ALS patients with PLC, eight patients without, and ten healthy controls were compared on a number of psychometric measures. Three indices of prefrontal cortical function were given: the Wisconsin Card Sort Test (WCST), the novel 'Gambling task' and a measure of olfactory discrimination. Global cognitive ability, psychiatric symptoms, and illness variables were also examined. No significant between-groups differences emerged with respect to global cognitive ability, mood, olfaction, and performance on the Gambling task. On the WCST, however, patients with PLC made significantly more total errors than the other two groups, and showed a strong trend in a similar direction for perseverative errors. A discriminant function analysis revealed that the WCST variable 'total errors' correctly predicted the presence or absence of pathological affect in 75% of cases. Thus, PLC appears to be associated with impairment in the functional integrity of the prefrontal cortex. Although this was not found for all prefrontal measures, further investigation of this area appears warranted.

Outcome after mild traumatic brain injury: an examination of recruitment bias.

OBJECTIVES: Research concerning the natural history after mild traumatic brain injury (TBI) faces a number of methodological challenges, including those related to subject recruitment. The aim of this study was to determine whether subjects who agree to participate in longitudinal research differ from those who do not. The presence of identifiable, selective factors operating during recruitment may be an important source of systematic bias. In Canada, given the presence of universal healthcare coverage, this issue can be examined using population based, administrative databases to obtain information about a cohort that was approached for study enrollment, regardless of whether they ultimately agreed to participate. METHODS: A sample of 626 consecutive patients with mild TBI was invited to enroll in TBI outcome research. Those who agreed to participate (n=272) were compared with those who refused (n=354) on demographic, past health, and injury related variables. Thereafter, using encrypted health card data, the two groups were contrasted with respect to pre-injury and post-injury healthcare utilisation. RESULTS: No premorbid differences between the groups emerged. However, all early indices of TBI severity were significantly worse for the participants group (p<0.001). Consistent with these findings, healthcare utilisation rates were no different before injury, but were significantly increased after injury for the participants (p<0.001), even beyond the period of study enrollment (p<0.001). Differences remained even after controlling for those with significant non-TBI injuries. CONCLUSIONS: Premorbid factors did not predict whether patients comply with, or refuse study participation. However, the participants group was biased toward those with more significant injuries, which translated into higher rates of healthcare utilisation after injury. These results strike a cautionary note, given the apparent systematic bias influencing enrollment in longitudinal studies of mild TBI.

Treatment of pathological affect: variability of response for laughter and crying.

Pathological laughing and crying (PLC) is increasingly recognized to accompany diverse neurologic conditions, although it remains poorly understood. The authors describe 3 cases of amyotrophic lateral sclerosis (ALS) with an unusual change from a predominance of pathological crying to laughter following drug treatment. Possible explanations for this phenomenon are discussed.

Vital capacity and one-second forced expiratory volume in Australian male factory workers.

The vital capacity (VC) and one-second forced expiratory volume (FEV1) of 482 men were measured and corrected for temperature but not pressure. The relationship between both VC and FEV1 and height and age was examined and found to be linear. In using these relationships for significance testing the 95% confidence limit is 1.65 standard deviations below the predicted value. Our results are expressed in graphical form to facilitate interpolation and will thus be of use to the clinical practitioner in Australia. Neither weight nor smoking habit was found to influence the relationship of VC or FEV1 with age or height.

Prediction of neuropsychiatric outcome following mild trauma brain injury: an examination of the Glasgow Coma Scale.

The relationship between the Glasgow Coma Scale (GCS) and neuropsychiatric outcome was examined in 57 consecutive subjects with mild traumatic brain injury (TBI) attending a follow-up clinic. Subjects were grouped according to initial GCS score (15 versus 13-14) and contrasted at an average of 5-6 months post-injury. As expected, those with GCS 13-14 had longer PTA (p = 0.001) and a higher rate of abnormal brain CT scans (p = 0.005). However, no significant differences emerged for indices of neuropsychiatric status, including measures of neurobehavioural symptoms/signs, overall psychological distress, psychiatric 'caseness', functional and psychosocial outcome, frequency of common somatic complaints, and rate of return to work. Subsidiary analyses based upon the presence/absence of CT abnormalities and the duration of PTA (<1 hour versus 1-24 hours) also failed to predict outcome, although a trend associating longer PTA with lower functional outcome was observed. Thus, despite early neurosurgical differences, the results suggest that initial GCS scores do not clearly translate into neuropsychiatric sequelae at follow-up within the rubric of GCS 13-15.