Lost in Time: Temporal Monitoring Elicits Clinical Decrements in Sustained Attention Post-Stroke.

OBJECTIVES: Mental fatigue, 'brain fog', and difficulties maintaining engagement are commonly reported issues in a range of neurological and psychiatric conditions. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory or visual domains. However, with this approach, discrete target stimuli may exogenously capture attention to aid detection, thereby masking deficits in the ability to endogenously sustain attention over time. METHODS: To address this, we developed the Continuous Temporal Expectancy Task (CTET) where individuals continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690 ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020 ms or longer). As such, sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration. Using the CTET, we assessed stroke survivors with unilateral right hemisphere damage (N = 14), a cohort in which sustained attention deficits have been extensively reported. RESULTS: Stroke survivors had overall lower target detection accuracy compared with neurologically healthy age-matched older controls (N = 18). Critically, stroke survivors performance was characterised by significantly steeper within-block performance decrements, which occurred within short temporal windows (˜3 ½ min), and were restored by the break periods between blocks. CONCLUSIONS: These findings suggest that continuous temporal monitoring taxes sustained attention processes to capture clinical deficits in this capacity over time, and outline a precise measure of the endogenous processes hypothesised to underpin sustained attention deficits following right hemisphere stroke.

An MRI method for parcellating the human striatum into matrix and striosome compartments in vivo.

The mammalian striatum is comprised of intermingled tissue compartments, matrix and striosome. Though indistinguishable by routine histological techniques, matrix and striosome have distinct embryologic origins, afferent/efferent connections, surface protein expression, intra-striatal location, susceptibilities to injury, and functional roles in a range of animal behaviors. Distinguishing the compartments previously required post-mortem tissue and/or genetic manipulation; we aimed to identify matrix/striosome non-invasively in living humans. We used diffusion MRI (probabilistic tractography) to identify human striatal voxels with connectivity biased towards matrix-favoring or striosome-favoring regions (determined by prior animal tract-tracing studies). Segmented striatal compartments replicated the topological segregation and somatotopic organization identified in animal matrix/striosome studies. Of brain regions mapped in prior studies, our human brain data confirmed 93% of the compartment-selective structural connectivity demonstrated in animals. Test-retest assessment on repeat scans found a voxel classification error rate of 0.14%. Fractional anisotropy was significantly higher in matrix-like voxels, while mean diffusivity did not differ between the compartments. As mapped by the Talairach human brain atlas, 460 regions were significantly biased towards either matrix or striosome. Our method allows the study of striatal compartments in human health and disease, in vivo, for the first time.

A registration method for improving quantitative assessment in probabilistic diffusion tractography.

Diffusion MRI-based probabilistic tractography is a powerful tool for non-invasively investigating normal brain architecture and alterations in structural connectivity associated with disease states. Both voxelwise and region-of-interest methods of analysis are capable of integrating population differences in tract amplitude (streamline count or density), given proper alignment of the tracts of interest. However, quantification of tract differences (between groups, or longitudinally within individuals) has been hampered by two related features of white matter. First, it is unknown to what extent healthy individuals differ in the precise location of white matter tracts, and to what extent experimental factors influence perceived tract location. Second, white matter lacks the gross neuroanatomical features (e.g., gyri, histological subtyping) that make parcellation of grey matter plausible - determining where tracts "should" lie within larger white matter structures is difficult. Accurately quantifying tractographic connectivity between individuals is thus inherently linked to the difficulty of identifying and aligning precise tract location. Tractography is often utilized to study neurological diseases in which the precise structural and connectivity abnormalities are unknown, underscoring the importance of accounting for individual differences in tract location when evaluating the strength of structural connectivity. We set out to quantify spatial variance in tracts aligned through a standard, whole-brain registration method, and to assess the impact of location mismatch on groupwise assessments of tract amplitude. We then developed a method for tract alignment that enhances the existing standard whole brain registration, and then tested whether this method improved the reliability of groupwise contrasts. Specifically, we conducted seed-based probabilistic diffusion tractography from primary motor, supplementary motor, and visual cortices, projecting through the corpus callosum. Streamline counts decreased rapidly with movement from the tract center (-35% per millimeter); tract misalignment of a few millimeters caused substantial compromise of amplitude comparisons. Alignment of tracts "peak-to-peak" is essential for accurate amplitude comparisons. However, for all transcallosal tracts registered through the whole-brain method, the mean separation distance between an individual subject's tract and the average tract (3.2 mm) precluded accurate comparison: at this separation, tract amplitudes were reduced by 74% from peak value. In contrast, alignment of subcortical tracts (thalamo-putaminal, pallido-rubral) was substantially better than alignment for cortical tracts; whole-brain registration was sufficient for these subcortical tracts. We demonstrated that location mismatches in cortical tractography were sufficient to produce false positive and false negative amplitude estimates in both groupwise and longitudinal comparisons. We then showed that our new tract alignment method substantially reduced location mismatch and improved both reliability and statistical power of subsequent quantitative comparisons.

Detecting depression in elderly outpatients: findings from depression symptom scales and the Dartmouth COOP charts.

BACKGROUND: The diagnosis and treatment of depression in elderly adults is a serious concern in outpatient settings, where it is well known that practicing physicians often overlook the possibility of depression in adult patients of all ages. Detecting depression in elderly patients can present different problems than detection in younger patients, and special instruments have been developed to screen for depressive symptoms in the elderly. These instruments are not commonly used in family practice settings because of time constraints and confusion about details on how to use them. METHODS: This study compared four commonly accepted depression scales: the Geriatric Depression Scale (GDS), the Beck Depression Inventory Short Form, the Durham GRECC, and the Brief Carroll Scale, and one functional assessment instrument, the Dartmouth COOP Functional Assessment Charts/WONCA, in identifying depressive symptoms in 100 patients 65 years and older (mean 71.6 years) attending an outpatient family practice residency clinic. These results were compared with actual chart records relating to depression and depression symptoms. RESULTS: The prevalence of depressive symptoms in this elderly outpatient population fell within the range of 16.5%-34.7%, according to scores on the various depression scales. Review of the same patients' medical records revealed that only 7% had been given a diagnosis of or were being treated for depression by their physician. The three shorter depression scales correlated well with the longer GDS, indicating that they may be substitutable for the more lengthy GDS. The Dartmouth COOP Functional Assessment Charts/WONCA proved to have a high level of consistency between the findings from its emotional condition component and the results of the depression symptom scales. CONCLUSION: This study affirms the potential utility of depression symptom screening scales in the outpatient setting. It also points to the possible utility of the emotional condition component of the Dartmouth COOP Functional Assessment Charts/WONCA as a screening question to be followed, as appropriate, by more formal instruments or clinical interview for depression in elderly outpatients.

Attitudes of part-time community internal medicine faculty about their teaching.

The authors sent a six-item questionnaire regarding attitudes about teaching to 130 part-time community internal medicine faculty at the University of Illinois College of Medicine at Rockford in August 1991; of the 90 (69%) who responded, 53 were salaried and 37 nonsalaried. Substantial numbers of the salaried faculty responded (1) that teaching is important for their career development (25, 48%), compared with nine (22%) of the nonsalaried faculty, and (2) that they expected to increase their commitments to the medical school (50, 75%), compared with 24 (65%) of the nonsalaried faculty. Of all the faculty, fewer than the authors expected--22 (24%)--felt that their teaching interfered with their clinical practices. As expected, most (76, 84%) responded that salary was necessary. The authors suggest that their results may be helpful to other medical schools, because with the setting of medical education changing from the hospital to the community, the importance of part-time faculty is increasing.

Clarithromycin versus penicillin in the treatment of streptococcal pharyngitis.

The safety and efficacy of oral clarithromycin 250 mg every 12 h treatment and of oral penicillin VK (the potassium salt of phenoxymethylpenicillin) 250 mg every 6 h were compared in the treatment of streptococcal pharyngitis caused by Streptococcus pyogenes in an eight centre in-vivo study. A total of 243 patients were enrolled in the study and 125 patients were evaluated for efficacy; evaluable patients included 67 patients in the clarithromycin treatment group and 58 patients in the penicillin VK group. Both antibiotic regimens were effective in the treatment of streptococcal pharyngitis. The clinical cure rate during the initial post-treatment period (between two and ten days post-treatment) for the penicillin VK treated group was 98% (57/58) and for the clarithromycin treated group was 96% (64/67). The bacteriological cure rate during the initial post-treatment period for the penicillin VK treated group was 97% (56/58) and for the clarithromycin treated group was 100% (67/67). A total of 17 patients reported adverse events; seven patients were in the clarithromycin treatment group and ten patients in the penicillin VK treatment group. One patient in the penicillin VK group was withdrawn because of the severity of the adverse advent (balanitis). No clinically significant differences were reported between the two treatment groups for haematology, blood chemistry, or urinalysis evaluations. Oral clarithromycin 250 mg 12-hourly treatment was as safe and effective as penicillin VK 250 mg 6-hourly in the treatment of streptococcal pharyngitis.

Comparison of cefixime and co-trimoxazole in acute uncomplicated urinary tract infection. A double-blind general practice study.

Five hundred and twenty-eight patients with presumptive acute uncomplicated urinary tract infection (UTI) were randomly assigned to receive cefixime 400 mg once daily, cefixime 200 mg twice daily or co-trimoxazole 2 tablets twice a day for 10 days; 477 completed at least 5 days of therapy. Of the patients 342 (65%) had positive baseline urine cultures, yielding 353 pathogens. A microbiological response was determined for 280 pathogens (79%), eradication being observed in over 94% of isolates; 153 pathogens (43%) were sensitive to both cefixime and co-trimoxazole and eradication was observed in over 96% of cases. Clinical response correlated well with microbiological response. The incidence of diarrhoea and stool changes was higher (P less than 0.005) in the patients who received cefixime once daily than in the other groups. There was a significantly higher incidence of stool changes with cefixime twice daily than with co-trimoxazole (P less than 0.05), but these did not necessitate discontinuation of therapy. Nausea was commoner with co-trimoxazole (P less than 0.05). The majority of pathogens isolated were Escherichia coli, Proteus mirabilis and staphylococci. Approximately 24% of E. coli were resistant in vitro to co-trimoxazole (P less than 0.005). Cefixime 200 mg twice daily is an effective and safe alternative to co-trimoxazole in the management of acute uncomplicated UTI.

The patient-centred clinical method. 3. Changes in residents' performance over two months of training.

A method for assessing the patient-centred approach was used to identify changes taking place in the interviewing behaviour of 13 residents during two months in a teaching practice. The descriptive study confirmed the prediction that the residents' approach would become more patient-centred. A statistically significant change from August to October was found in the number of facilitating behaviours shown by residents (P less than 0.05) and there was a change in the number of fears expressed by patients (P less than 0.10). Increases in the number of expectations, feelings and prompts were noted but were not significant. The frequency with which residents cut off patients' expressions increased on the whole, although not significantly. The findings suggest that while these residents had succeeded in increasing their facilitating behaviours over two months (one-sixth of their family medicine experience) they had not yet found ways of responding to the many problems elicited.

The patient-centred clinical method. 2. Definition and application.

In this article, the patient-centred clinical method is described in operational terms. Definitions are given for the patient's expectations, feelings and fears. The physician behaviours described are: facilitations, acknowledgements, cut-offs and returns. Using the definitions, a method was devised for scoring video-taped interviews for the degree of 'patient-centredness'. The method proved to have good inter-observer reliability.

The patient-centred clinical method. 1. A model for the doctor-patient interaction in family medicine.

This article describes a patient-centred clinical method appropriate for family medicine. The method is designed to attain an understanding of the patient as well as his disease. This two-fold task is described in terms of two agendas: the physician's and the patient's. The key to an understanding of the patient's agenda is the physician's receptivity to cues offered by the patient, and behaviour which encourages him to express his expectations, feelings and fears. The physician's agenda is the explanation of the patient's illness in terms of a taxonomy of disease. In the patient-centred clinical method, both agendas are addressed by the physician and any conflict between them dealt with by negotiation. This is contrasted with the disease-centred method in which only the doctor's agenda is addressed. Further articles will describe the patient-centred method in operational terms.

Isoxicam and indomethacin in acute osteo-arthritis. A GP multicentre double-blind comparison.

A study was conducted in general practice to assess the efficacy and safety of isoxicam 200 mg once daily compared with indomethacin 25 mg 3 times a day in the treatment of acute exacerbations of osteo-arthritis. The trial was conducted as a multicentre, double-blind, randomized parallel-group study with 'dummy loading' of the medications. Thirty-one general practitioners entered 309 patients in the study. Of these, 139 patients on isoxicam and 137 on indomethacin completed the treatment. The most common sites of osteo-arthritis were the knee (100 patients) and the hip (79 patients). On examination at 7 days and 14 days there was a significant improvement in both treatment groups. After 7 days the reduction of pain and clinical symptoms of osteo-arthritis of the hip and knee was significant for both drugs at the P less than 0,001 level. There thus appeared to be no difference in clinical efficacy between the drugs. Eight patients in the isoxicam group experienced definite drug-related adverse reactions as against 19 in the indomethacin group. A total of 38 patients (18 on isoxicam and 20 on indomethacin) suffered probably drug-related effects. Isoxicam therefore appeared to be better tolerated than indomethacin.

Faecal occult blood testing in the detection of colorectal cancer.

5012 asymptomatic patients over the age of 40 years were asked by their general practitioners to perform a Hemoccult faecal blood test over 3 days. 3422 patients on a normal diet completed the test (a compliance rate of 67 per cent). Ninety-nine patients (3 per cent) had a positive result. Those patients with a positive result then underwent a second Hemoccult test over 6 days on a restricted diet. Thirty-two patients had a positive result on repeat testing (1 per cent). Only those patients who were positive on the second testing were fully investigated (including double contrast barium enema and colonoscopy). Twenty-seven patients on investigation were found to have neoplastic disease (84 per cent). Twelve had invasive carcinomas (nine Dukes' A, two Dukes' B, one Dukes' C) and thirty-seven adenomas were identified and removed at colonoscopy (barium enema missed three carcinomas--all dukes' A and only identified sixteen of the thirty-seven adenomas, 43 per cent). Those patients found to be negative after the second Hemoccult test are being followed up.

Early detection of colorectal cancer using faecal occult blood tests.

Five thousand and twelve asymptomatic patients over the age of 40 years who were on a normal diet were asked by their general practitioners to perform a Hemoccult (Röhn Pharma (Noristan] faecal occult blood test over 3 days. Of the 3 422 patients (68%) who completed the test, 99 (3%) had a positive result. The patients with a positive result then again performed the Hemoccult test, this time over 6 days on a restricted diet. Thirty-two of these patients had a positive result on the second test. Only the 32 patients who had a positive result for the second test were fully investigated (including double-contrast barium enema and colonoscopy); 27 patients (84%) were found to have neoplastic disease. Twelve had invasive carcinoma (9 Dukes' A, 2 Dukes' B and 1 Dukes' C), 6 of these also having 10 adenomas, while the other 15 had 27 adenomas which were identified and removed at colonoscopy. Barium enema missed 3 carcinomas (all Dukes' A) and identified only 16 (43%) of the 37 adenomas. Those patients found to have a negative result for the second Hemoccult test are being followed up.

Efficacy and tolerability of an amoxycillin/clavulanic acid combination in the treatment of common bacterial infections. A general practitioner trial.

The efficacy and tolerability of a combination of amoxycillin 250 mg and clavulanic acid 125 mg (A-CA) (Augmentin; Beecham) was evaluated under general practice conditions. One hundred and sixty-four patients were treated with either A-CA tablets or amoxycillin 250 mg capsules, taken 3 times daily for 7 days at the start of a meal. Ten patients with treatment failure on amoxycillin were re-treated with A-CA. In the initial stage of the trial 102 patients were randomly allocated to either amoxycillin or A-CA treatment; of these 89 could be assessed clinically and 63 could be assessed bacteriologically, of whom 32 had received amoxycillin and 31 A-CA treatment. Subsequently a further 62 patients were treated with A-CA; 50 were assessed clinically and 40 bacteriologically. Bacteriological assessment was possible in 109 patients, 71 on A-CA, 32 on amoxycillin, and 6 who received A-CA after having failed on amoxycillin treatment. In this study A-CA was bacteriologically significantly superior to amoxycillin in treating urinary tract infections (P less than 0,024), skin and soft tissue infections (P less than 0.05) and all infections caused by amoxycillin-resistant organisms (P less than 0.013). No difference was shown in infections caused by amoxycillin-sensitive organisms. Side-effects most commonly associated with A-CA treatment were gastro-intestinal (6,7%) and consisted of nausea and diarrhoea. This trial has a special significance for general practitioners in that it shows a high incidence of penicillin-resistant organisms (51%). This observation, as yet limited to one area in South Africa, has wide implications for general practice management of infections.

The natural history of acute heart attacks. Cape general practitioner series.

One hundred and twenty-nine Cape Town general practitioner participated in an emergency coronary care project in which one of the main aims was to survey the natural history of acute heart attacks in their practices over a 14-month period. Although the 1-month community mortality rate (28% of 445 patients of all ages and 23% of 356 patients under the age of 70 years) compared favourably with those of other series, the proportion of patients dying before hospitalization was similar to that of other series (approximately two-thirds). Of the 140 deaths in patients of all ages over a 3-month period, 71 (51%) took place before hospitalization or emergency treatment (pretreatment phase); 85 (60,7%) were due to probable or recorded arrhythmias and 47 (33,6%) to pump failure. Of the 71 deaths in the pretreatment phase, 67 (94%) were caused by a probable arrhythmia. Forty-four of the 69 deaths that occurred after treatment and up to 3 months after the onset of symptoms were due to pump failure. Thus, it is concluded that the commonest post-treatment cause of death is pump failure. Conversely, deaths due probable arrhythmias are most common in the absence of medical intervention, when failure deaths are arae. Of the 140 who died, 37% (52 patients) died within 1 hour of the onset of symptoms and 51% (72 patients) within 4 hours after the onset of symptoms. When therapeutic intervention occurred even within the first 2 hours of symptoms, deaths due to probable arrhythmias could be avoided, with only 3 occurring in 188 treated patients. This natural history survey of acute heart attacks is the first of its kind in South Africa.