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Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 91 records · Page 5Linked to original sources

Early and late onset depression in old age: different aetiologies, same phenomenology.

BACKGROUND: Phenomenological differences between older patients with early onset (EO; onset of first major depressive episode before 60 years) and late onset (LO) depression have been inconsistent but, if real, may reflect differences in aetiology. We aimed to compare aetiological factors, phenomenology and cognitive function in older patients with depression by age of onset. METHODS: Subjects were all patients > or =60 years old (n=73) from 407 consecutive attenders to a Mood Disorders Unit, diagnosed with DSM-III-R Major Depressive Episode, at or close to the nadir of their episode. Putative risk factors were assessed by structured interview. Psychological morbidity and depressive symptoms were assessed by the 21-item Hamilton Rating Scale for Depression, CORE rating of psychomotor disturbance, Newcastle Endogeneity Scale, Zung Depression Scale and General Health Questionnaire. Cognition was assessed by tests of memory, attention, executive function and motor speed. RESULTS: Personality abnormalities, a family history of psychiatric illness and dysfunctional past maternal relationships were significantly more common in EO depression. The two age of onset groups were essentially similar in terms of depressive sub-type and severity, phenomenology, history of previous episode, and in neuropsychological performance. LIMITATIONS: Use of self-report data, moderate sample size, sample not age-matched, tertiary referral patients. CONCLUSIONS: EO and LO depression are similar phenotypically, but differ aetiologically. The pursuit of mechanisms which predispose depressive episodes may be heuristically more valuable than further investigation of individual depressive features in distinguishing early from late onset depression.

Aged↗

Phase II study of paclitaxel and oral etoposide in patients with locally advanced or metastatic non-small cell lung cancer.

The combination of paclitaxel and etoposide was evaluated in a phase II study in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC). Thirty-five patients, median age 61, received treatment with paclitaxel 200 mg/m (2) intravenous over 3 h on day 1, and oral etoposide, 100 mg daily on days 1-5. Cycles were repeated every 21 days for a maximum of nine cycles, or until progression occurred. Twenty-eight patients had stage IV disease, and seven patients had stage IIIA or B disease. There was one complete and seven partial responses (overall response rate, 23%). Two of these responses were in patients with stage III disease (29%) and six in patients with stage IV disease (21%). Median survival was 8.7 months, and 36% of patients were alive at 1 year. There were no treatment-related deaths and little grade 3 or 4 non-haematological toxicity although grade 3 or 4 neutropenia occurred in 60% of patients (33% of cycles). There were four episodes of febrile neutropenia. The combination of paclitaxel and oral etoposide is active in advanced NSCLC and can be delivered with acceptable toxicity.

Administration, Oral↗

mRNA turnover.

Nuclear RNA-binding proteins can record pre-mRNA processing events in the structure of messenger ribonucleoprotein particles (mRNPs). During initial rounds of translation, the mature mRNP structure is established and is monitored by mRNA surveillance systems. Competition for the cap structure links translation and subsequent mRNA degradation, which may also involve multiple deadenylases.

Alternative Splicing↗

The differential impact of age on the phenomenology of melancholia.

BACKGROUND: We pursue an observation that age may influence the clinical features of melancholia and, in particular, psychomotor disturbance. METHODS: Two large clinical databases were amalgamated allowing the clinical features of 124 depressed subjects meeting DSM-III-R and clinical criteria for melancholia to be contrasted with 218 subjects diagnosed as having a non-melancholic depression by both criteria sets. Psychomotor disturbance was assessed by the CORE measure and by seven classical endogeneity symptoms of melancholia which, when summed, created a ENDOG score. RESULTS: There was no impact of age on ENDOG scores in either the melancholics or non-melancholics. In the melancholics, increasing age was associated with increasing CORE scores and with agitation scale scores in particular. In a set of discriminant function analyses seeking to identify the comparative utility of a set of predictors of melancholic (versus non-melancholic) groups, age was significant, and while CORE and ENDOG scores were individual predictors, their combined entry established that the CORE score alone made the ENDOG score redundant, and that the addition of age then made little impact. CONCLUSIONS: Melancholia appears to have a later age of onset than non-melancholic depression, while its phenotypic expression appears to change with age, with psychomotor disturbance being more distinct in older subjects. Such an effect may have a number of clinical implications, including possible differential effects of varying antidepressant treatments.

Adult↗

Late-onset depression: genetic, vascular and clinical contributions.

BACKGROUND: Neuropsychiatric research needs to examine the relationships between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders. METHODS: Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 549 years, S.D. = 14.1) and 22 healthy control subjects (mean age = 55.5 years, S.D. = 9.6). RESULTS: Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0.01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0.05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0.05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3.8, 95% CI = 1.1-12.9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression. CONCLUSIONS: Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Adult↗

Folate fortification: potential impact on folate intake in an older population.

OBJECTIVE: To examine the potential impact of different models of folate fortification of Australian foods on the folate intakes of older Australians. DESIGN: Dietary data were collected using a food frequency questionnaire from people attending a population-based health study. SETTING: Two postcode areas west of Sydney, Australia. SUBJECTS: A total of 2895 people aged over 49 y, obtained from a door knock census (79% of 3654 subjects examined). MAIN OUTCOME MEASURES: The folate intake in this population was estimated using four different models: (1) pre-fortification folate values; (2) current voluntary folate fortification in Australia; (3) universal fortification of all foods permitted to add folate, at 25% recommended dietary intake (RDI) per reference serve; and (4) universal fortification of all foods permitted to add folate, at 50% RDI per reference serve. The increased bioavailability of synthetic folic acid (SFA) was included in the analysis. RESULTS: At current voluntary folate fortification, approximately 65% of this population consume 320 microg dietary folate equivalents (DFE) or more per day from diet and supplements, and 0.4% (n=10) consume greater than the recommended upper safety level of 1000 microg from SFA. More than 95% of this older population would be expected to consume more than 320 microg DFE from diet and supplements with universal fortification at 50% of the RDI, and 0.5% (n=14) may consume greater than 1000 microg/day of SFA. CONCLUSIONS: There is unlikely to be a large increase in the proportion of older persons who are likely to consume more than the upper safety level of intake with universal folate fortification. As most of those who currently or are predicted to consume over 1000 microg SFA take supplements containing folic acid, it is highly recommended that vitamin B12 be included in any vitamin supplements containing folate. SPONSORSHIP: This study was supported by the Australian National Health and Medical Research Council (NHMRC).

Aged↗

Co-prescribing of SSRIs and TCAs in Australia: how often does it occur and who is doing it?

AIMS: To determine the frequency with which the selective serotonin re-uptake inhibitor (SSRI) antidepressants are used as add-on therapy to the tricyclic antidepressants (TCA) rather than as replacement therapy. METHODS: The data analysed were profiles of prescription records by date of supply to the patient. From within the national administrative dispensing claims database, the subset eligible for social security entitlements was identified as individuals by means of their coded permanent identification numbers (PINs). Following the initial supply of an SSRI in January 1996, the subsequent 6 months dispensing of SSRI and TCA antidepressants to these individuals was examined. The main outcome measure was the proportion of individuals to whom SSRIs and TCAs were dispensed concurrently, as an indirect measure of coprescription. In instances where a patient was receiving prescriptions for SSRIs and TCAs that had been written by the one doctor only, the major specialty of the doctor was investigated. RESULTS: 55 271 PINs were dispensed 63 865 SSRI prescriptions in January 1996 which represented over half (52%) of the total community SSRI prescriptions dispensed in that month. The number of these patients meeting the criteria for coprescription of SSRIs and TCAs over the next 6 months was 2773 (5%). The coprescribing instances were highest in Queensland and the prescribers most frequently involved had psychiatry major specialty codes. CONCLUSIONS: Among SSRI users there is a cohort of patients who, within the same time frame, are receiving supplies of a TCA, the nonselective drug that the SSRIs were designed to replace. This is indirect evidence of probable coprescription. Such combination use is of uncertain clinical and cost effectiveness, and carries additional risks. The SSRIs were included on the subsidy list in Australia on the basis of reasonable cost effectiveness as monotherapy compared with the TCAs. Our data imply that for some patients, antidepressant prescribing is inconsistent with the basis on which government subsidy was approved.

Adult↗

Depression and smoking: examining correlates in a subset of depressed patients.

OBJECTIVE: The objective of this study was to examine for associations between depression and cigarette smoking. METHOD: A sample of 92 depressed smokers was compared with a control sample of depressed non-smokers, matched for age, gender and diagnostic variables. Comparisons were made across a range of demographic, depression, family history, developmental factors, anxiety and personality style variables, as well as use of alcohol and illicit drugs. RESULTS: We failed to find any difference between smokers and non-smokers in history or severity of depression. Cigarette smokers were distinguished principally by greater exposure to aversive experiences in childhood, disordered personality function, greater use of illicit drugs, anxiolytics and alcohol. Logistic regression identified dysfunctional personality 'domains', physical violence in childhood, long-term anxiolytic use and illicit drug use as the most significant predictor set. CONCLUSIONS: Results favour a model of cigarette smoking and depression as linked by shared early deprivational variables, rather than cigarette smoking causing depression or the converse.

Adult↗

The increasing prevalence of myopia: implications for Australia.

Myopia is often regarded as a minor priority in public health research, yet the public health costs of myopia are considerable, both due to the costs of optical correction and from the costs imposed by the morbidity resulting from myopia in terms of associated eye disease (glaucoma, posterior subcapsular cataract), and the visual impairment and blindness that can result from myopia due to myopic retinal degeneration and retinal detachment. There is clear evidence for a high and increasing prevalence of myopia in East Asia, apparently driven by increasing educational pressures and urbanization. Data from the USA, Europe and Australia are consistent with the data from Asia in terms of the role of these risk factors. However, the evidence for an increasing prevalence of myopia is more problematic, due to the lack of adequate longitudinal studies, and the confounding effects of age-related hypermetropization. It is concluded that the prevalence of myopia is probably increasing in Australia, although the changes are of much lower magnitude than n East Asia. Longitudinal studies are, therefore, clearly required to quantify changes in the prevalence of myopia in Australia, for accurate assessment of the public health impacts and to assist with the development of preventive approaches.

Adult↗

Impaired vision and other factors associated with driving cessation in the elderly: the Blue Mountains Eye Study.

The aim of present study was to review vision and other factors associated with the cessation of driving. As part of the Blue Mountains Eye Study, detailed demographic information, driving status and medical history were taken. Visual acuity was measured during a standardized refraction and visual fields documented. Potential risk factors were decided a priori. Among the 3654 Eye Study participants, 2831 (77.5%) had driven a motor vehicle in the past, of whom 2379 (84.0%) were current drivers and 452 (16.0%, 95% CI 14.6-17.4%) said they had stopped driving. Older persons and women were more likely to have stopped driving. After adjusting for age and sex, sensory impairment affecting vision and hearing, plus chronic medical conditions and benzodiazepine use were significantly associated with cessation of driving. The study found that sensory impairment, particularly visual parameters, was associated with the decision to stop driving by older subjects.

Aged↗

Prevalence and associations with ectropion in an older population: the Blue Mountains Eye Study.

The aim of this study was to describe the prevalence of eyelid ectropion and its associations with sunlight-related and other ocular variables, plus systemic factors, in an older Australian population. The Blue Mountains Eye Study examined 3654 persons aged 49-97 years. Examination recorded ectropion and other ocular signs. The questionnaire assessed sunlight-related and systemic variables. Ectropion was present in either eye of 143 subjects (3.9%) and was bilateral in 101 (70.6%). A marked age-related increase in prevalence was observed with ectropion found in 0.3% of persons aged < 60 years, 1.2% of ages 60-69 years, 6.7% of ages 70-79 years and 16.7% of those aged 80 years or older Ectropion prevalence was higher in men (5.1%) than women (3.0%), age-adjusted odds ratio 2.1 (95% confidence interval 1.5-3.0). Statistically significant associations were found between ectropion and history of skin cancer removal, increased skin sun sensitivity, lighter iris colour and presence of pingueculum, as well as current smoking, hypertension, diabetes and stroke.

Age Distribution↗

Lower nasal distribution of cortical cataract: the Blue Mountains Eye Study.

Previous reports have indicated that cortical cataract commences in the lower nasal lens, possibly due to sunlight exposure because of the shallow brow temporally. The present study aimed to assess the lens sector distribution of cortcal cataract in a population. The Blue Mountains Eye Study assessed 3654 residents aged 49-97 years; 3270 phakic subjects had retroillumination lens photographs graded using the Wisconsin method, which divides the lens into eight radial sectors with a grid overlay. Graders estimated percentage of cortical opacity in each sector. The lower nasal area consistently had the greatest opacity, a pattern present at each age and similar in both sexes, despite the 20% greater cortical cataract in women. The mean area of lens cortex involved by opacities in the lower nasal hemisphere was four fold greater than in the upper temporal hemisphere at each age. The lower nasal distributon was highly symmetrical when both eyes were affected. When > 20% of the lower nasal lens quadrant had cortical opacity, 88% of bilaterally affected subjects had cortical cataract n the same quadrant of the fellow eye. The lower nasal distribution may indicate a role for sunlight in the aetiology of cortcal cataract, which could be considered when examining other cortical cataract risk factors, such as diabetes, vascular disease and hormonal factors in women.

Age Distribution↗

Validation of self-reported hearing loss. The Blue Mountains Hearing Study.

PURPOSE: Large-scale epidemiological studies have often used self-report to estimate prevalence of age-related hearing loss. However, few large population-based studies have validated self-report against measured hearing loss. Our study aimed to assess the performance of a single question and a brief hearing handicap questionnaire in identifying individuals with hearing loss, against the gold standard of pure-tone audiometry. METHODS: We examined 2015 residents, aged 55-99 years, living in the west of Sydney, Australia, who participated in the Blue Mountains Hearing Study during 1997-1999. Audiologists administered a comprehensive questionnaire, including the question: 'Do you feel you have a hearing loss?' The Shortened Hearing Handicap Inventory for Elderly (HHIE-S) was also administered during the hearing examination, which included pure-tone audiometry. The single question and HHIE-S were compared with measured losses at levels >25, >40 and >60 decibels hearing level (dBHL) to indicate mild, moderate and marked hearing impairment, for pure-tone averages (PTA) of responses to 500, 1000, 2000 and 4000 Hz. RESULTS: The single question yielded reasonable sensitivity and specificity for hearing impairment, and was minimally affected by age and gender. HHIE-S scores >8 had lower sensitivity but higher specificity and positive predictive value. The HHIE-S performed slightly better in younger than older subjects and performed better for moderate hearing impairment. CONCLUSIONS: In this older population with a high prevalence of hearing loss (39.4%), both a question about hearing and the HHIE-S appeared sufficiently sensitive and specific to provide reasonable estimates of hearing loss prevalence. Both could be recommended for use in epidemiological studies that aim to assess the magnitude of the burden caused by age-related sensory impairment but cannot measure hearing loss by audiometry.

Aged↗