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Biomedical subjects

J Geddes

Publications and source records attributed to J Geddes.

At least 37 records · Page 2Linked to original sources
PubMed2001

Bipolar disorder: clinical uncertainty, evidence-based medicine and large-scale randomised trials.

BACKGROUND: The increasing use of the methods of evidence-based medicine to keep up-to-date with the research literature highlights the absence of high-quality evidence in many areas in psychiatry. AIMS: To outline current uncertainties in the maintenance treatment of bipolar disorder and to describe some of the decisions involved in designing a large simple trial. METHOD: We describe some of the strategies of evidence-based medicine, and how they can be applied in practice, focusing specifically on the area of bipolar disorder. RESULTS: One of the key clinical uncertainties in the treatment of bipolar disorder is the place of maintenance drug treatments and their relative efficacy. A large-scale study, the Bipolar Affective Disorder: Lithium Anticonvulsant Evaluation (BALANCE) trial, is proposed to compare the effectiveness of lithium, valproate and the combination of lithium and valproate. CONCLUSIONS: Providing reliable answers to key clinical questions in psychiatry will require new approaches to clinical trials. These will need to be far larger than previously appreciated and will therefore need to be collaborative ventures involving front-line clinicians.

Antimanic Agents↗
PubMed2000

Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis.

OBJECTIVE: To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia. DESIGN: Systematic overview and meta-regression analyses of randomised controlled trials, as a basis for formal development of guidelines. SUBJECTS: 12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperidol or chlorpromazine) or alternative atypical antipsychotics. MAIN OUTCOME MEASURES: Overall symptom scores. Rate of drop out (as a proxy for tolerability) and of side effects, notably extrapyramidal side effects. RESULTS: For both symptom reduction and drop out, there was substantial heterogeneity between the results of trials, including those evaluating the same atypical antipsychotic and comparator drugs. Meta-regression suggested that dose of conventional antipsychotic explained the heterogeneity. When the dose was </=12 mg/day of haloperidol (or equivalent), atypical antipsychotics had no benefits in terms of efficacy or overall tolerability, but they still caused fewer extrapyramidal side effects. CONCLUSIONS: There is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotics. Conventional antipsychotics should usually be used in the initial treatment of an episode of schizophrenia unless the patient has previously not responded to these drugs or has unacceptable extrapyramidal side effects.

Amisulpride↗
PubMed2000

Suicide in psychiatric hospital in-patients. Risk factors and their predictive power.

BACKGROUND: Psychiatric hospital in-patients are known to be at high risk of suicide, yet there is little reliable knowledge of risk factors or their predictive power. AIMS: To identify risk factors for suicide in psychiatric hospital in-patients and to evaluate their predictive power in detecting people at risk of suicide. METHOD: Using a case-control design, 112 people who committed suicide while in-patients in psychiatric hospitals were compared with 112 randomly selected controls. Univariate analysis and multivariate analyses were used to estimate odds ratios and adjusted likelihood ratios. RESULTS: The rate of suicide in psychiatric in-patients was 13.7 (95% CI 11.7-16.1) per 10,000 admissions. There were five predictive factors with likelihood ratios > 2, following adjustment: planned suicide attempt, 4.1; actual suicide attempt, 4.9; recent bereavement, 4.0; presence of delusions, 2.3; chronic mental illness, 2.2; and family history of suicide, 4.6. On this basis, only two of the patients who committed suicide had a predicted risk of suicide above 5%. CONCLUSIONS: Although several factors were identified that were strongly associated with suicide, their clinical utility is limited by low sensitivity and specificity, combined with the rarity of suicide, even in this high-risk group.

Analysis of Variance↗
PubMed2000

Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations.

We describe 3 new families affected by Alzheimer's disease with spastic paraparesis. In affected individuals, including the earliest known patient with this clinical syndrome, neuropathological examination revealed large "cotton wool" plaques similar to those we have previously described in a Finnish family. In the families in which DNA was available, presenilin-1 mutations were observed. Transfection of cells with these mutant genes caused exceptionally large increases in secreted Abeta42 levels. Furthermore, brain tissue from individuals with this syndrome had very high amyloid-beta concentrations. These findings define the molecular pathogenesis of an important subgroup of Alzheimer's disease and have implications for the pathogenesis of the disease in general.

Alzheimer Disease↗
PubMed1999

p38 kinase is activated in the Alzheimer's disease brain.

The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.

Aged↗
PubMed1996

Factors associated with admission to hospital following emergency psychiatric assessment.

Psychiatric emergencies account for a large proportion of total referrals and admissions yet there has been little research in the United Kingdom into factors associated with admission after emergency psychiatric assessment. We conducted a one year prospective study of all emergency referrals from Borders Region in Scotland. Four hundred and eighty-seven emergencies were assessed and 153 (31%) of these were admitted. The main predictors of admission after stepwise logistic regression analysis were: risk to self (odds ratio 1.76 for each point increment on a five point scale, 95% confidence intervals 1.43 to 2.15), current contact with the psychiatric services (2.46; 1.52, 3.98) and psychotic diagnosis (2.38; 1.47, 3.87). Compared to subjects assessed at home, those assessed at the psychiatric hospital were more likely to be admitted (3.73; 1.99, 6.99) and self-referrals were less likely to be admitted than General Practitioner referrals (0.22; 0.08, 0.55). Our results suggest that future studies of emergency services should investigate and control for both clinical and service variables.

Adolescent↗
PubMed1994

Comparison of prevalence of schizophrenia among residents of hostels for homeless people in 1966 and 1992.

OBJECTIVE: To determine whether the prevalence of schizophrenia among the homeless population of Edinburgh resident in hostels has changed between 1966 and 1992. DESIGN: Comparison of two cross sectional surveys. SETTINGS: Hostels for homeless people in Edinburgh. SUBJECTS: In 1966 a random sample of 98 residents of three common lodging houses. In 1992 a random sample of 198 residents of nine hostels. MAIN OUTCOME MEASURE: Prevalence of schizophrenia. RESULTS: The prevalence of schizophrenia in 1992 was 12/136 (9%) compared with 20/79 (25%) in 1966 (odds ratio 0.29; 95% confidence interval 0.13 to 0.62; P = 0.001). Adjustment for confounding by age, current hostel, and duration of unemployment by means of logistic regression produced an adjusted odds ratio of 0.22 (0.08 to 0.58). CONCLUSIONS: The prevalence of schizophrenia was lower in 1992 even after other changes in the population resident in hostels occurring between 1966 and 1992 were taken into account. The findings are not consistent with an increase in the prevalence of schizophrenia among homeless people despite a 66% reduction in adult psychiatric beds in the region during 1966-92.

Adolescent↗
PubMed1994

How high is the relapse rate in schizophrenia?

Although maintenance neuroleptic treatment reduces the risk of relapse in schizophrenia, that risk remains substantial. Maintenance neuroleptics following first schizophrenic episodes are valuable in reducing the relapse rate but may be associated with occupational disadvantage. In first episodes the early introduction of neuroleptic treatment may be important in later reduction of relapse rate. Response to placebo during a psychotic episode does not predict sustained wellbeing without neuroleptics. Long-term follow-up indicates that some schizophrenic patients will remain relapse-free and that there are patients who remain well without neuroleptics, but it is not possible to select those for whom prophylactic neuroleptics will not reduce the risk of relapse.

Affective Disorders, Psychotic↗
PubMed1994

Prediction of outcome following a first episode of schizophrenia. A follow-up study of Northwick Park first episode study subjects.

BACKGROUND: Although previous studies have attempted to identify predictors of outcome in schizophrenia, few have prospectively studied first episode patients for an adequate follow-up period. METHOD: The psychopathological predictors of outcome were investigated in a subgroup of 51 subjects, originally included in the Northwick Park study of first episode schizophrenia who were followed up 7.3 years (s.d. 1.1, range 5.3-10.3) after first admission in the Harrow study. Forty-four subjects (24 men, 20 women) were traced. Outcome measures were time to first readmission, occupational level and total duration of hospital admission at five years after first admission. RESULTS: A survival analysis of time to first relapse revealed that the presence of subjective feelings of depression (CATEGO syndrome SD) during the first admission was associated with early relapse while the presence of depressive delusions (CATEGO syndrome DD) and higher educational attainment protected against early relapse. Total duration of hospitalisation at five years after first onset was positively associated with the presence of CATEGO syndromes SD and OD (biological features of depression) and negatively associated with female sex. Poor occupational outcome was not significantly associated with any psychopathological predictors. CONCLUSIONS: Our findings challenge the conventional view that symptoms of depression are associated with better outcome in schizophrenia.

Adolescent↗
PubMed1993

Perineuronal satellitosis in the human hippocampal formation.

A previously unreported example of perineuronal satellitosis in the medial CA1 and adjacent subiculum in the human hippocampal formation is described. This phenomenon is characterized by a clustering of glial cells in relation to the perikarya of a subpopulation of neurons in the deep pyramidal layer and around most neurons scattered in the stratum oriens and subcortical white matter. Most of the perineuronal satellite glia were identified as oligodendrocytes based on their nuclear chromatin patterns and antigenic properties. Satellite oligodendrocytes were mostly of the medium dense variety. A type of satellite glia with nuclear features of the dark oligodendrocyte could not be identified unequivocally using the antigenic criteria employed in this study.

Adult↗
PubMed1993

The sensory neuropathy of Friedreich's ataxia: an autopsy study of a case with prolonged survival.

Observations have been made on a patient with Friedreich's ataxia who died 52 years after the onset of symptoms. The pathology of the brain and spinal cord was typical of this disorder. Apart from loss of dorsal root ganglion cells, severe loss of secondary sensory neurons was observed, including the nucleus dorsalis in the spinal cord, the spinal and principal trigeminal nuclei and, in particular, the mesencephalic trigeminal nucleus in the brain stem. Morphometric studies on the first sacral nerve root and on the sural nerve at levels from midthigh to ankle revealed a distally accentuated axonal loss that predominantly affected larger myelinated nerve fibres. Regenerative activity was seen, mainly in the spinal root and proximally in the sural nerve. Relative myelin thickness, assessed by a g ratios, tended to be reduced. As teased fibre studies showed only limited evidence of demyelination/remyelination and of axonal regeneration, this therefore suggests the presence of a hypomyelination. The results confirm the presence of a distal axonopathy and provide no evidence that this is preceded by axonal atrophy.

Axons↗
PubMed1991

Olfactory acuity in the positive and negative syndromes of schizophrenia.

The olfactory thresholds of 46 schizophrenic subjects were measured. This group yielded 11 patients with a stringently defined positive syndrome and 12 with a negative syndrome when rated with the Positive and Negative Syndrome Scale. The negative group had a significantly (p less than 0.01) higher olfactory threshold than the positive group although neither of the groups differed significantly from a control group. Implications of this finding are discussed.

Adolescent↗
PubMed1991

DSM-III in the training of British psychiatrists: a national survey.

All 223 psychiatric clinical tutors in the UK were surveyed on their use of DSM-III in their postgraduate training programmes. Results indicate that DSM-III is widely used in clinical training to some extent in the majority of schemes (73%) and in the schemes where it is used it is rated as moderately useful by nearly everyone (93%). DSM-III is generally perceived to have positive effects on learning basic elements of psychopathology and in offering a common language for diagnostic discussion. Interestingly only 16% of users felt that DSM-III was so complicated that it impeded rather than facilitated the teaching of diagnosis. Few schemes provide specific teaching courses and case conferences provide the major forum for teaching DSM-III.

Attitude of Health Personnel↗