The prevalence of co-prescription of clinically relevant CYP enzyme inhibitor and substrate drugs in community-dwelling elderly Australians.

WHAT IS KNOWN AND OBJECTIVE: The elderly are at increased risk of adverse effects resulting from drug interactions due to decreased drug clearance and polypharmacy. This study examines the prevalence of the co-administration of clinically relevant cytochrome P450 (CYP) enzyme inhibitors with drugs that are substrates for these enzymes, in the community-dwelling elderly in Australia. METHODS: Participants aged 75 years or older (n = 1045) were recruited via their general practitioners at four Australian sites (Newcastle, Sydney, Melbourne and Adelaide). A research nurse visited the home of each patient to compile a list of all prescription medications (including doses) currently used by the patient, and to complete assessments for depression, quality of life and cognitive status. The medication data were searched for the co-prescription of clinically relevant CYP inhibitor and corresponding substrate drugs. RESULTS AND DISCUSSION: Potentially inappropriate CYP inhibitor-substrate combinations were found in 6·2% (65/1045) of patients. These patients were on significantly more medications (6·1 ± 3·0 vs. 3·9 ± 2·5; P = 0·001) and had a significantly lower physical quality of life (P = 0·047) than those who were not on any CYP inhibitor-substrate combinations. The most commonly prescribed inhibitor-substrate combinations involved the CYP 3A4 inhibitors, diltiazem and verapamil, with the substrates simvastatin or atorvastatin. Only 1 of 41 patients on a CYP3A4 inhibitor and a statin was prescribed a non-CYP 3A4 metabolized statin. Metoprolol was another substrate commonly co-prescribed with a CYP2D6 inhibitor. In many cases, the risks and benefits of potential interactions may have been considered by the GP as the prescribed doses of both the inhibitor and substrate were relatively low. There were, however, some notable exceptions, also involving the substrates simvastatin, atorvastatin and metoprolol. There were no GP factors that were associated with co-prescription of CYP inhibitors and substrates. WHAT IS NEW AND CONCLUSION: There is not a particular GP demographic that should be targeted for education regarding CYP interactions, but a focus on particular medications such as the statins may reduce the potential for clinically significant drug-drug interactions. As CYP drug-drug interactions are more common in patients on higher number of medications, particular vigilance is required at the time of prescribing and dispensing medications for elderly patients with multiple conditions.

Acne's relationship with psychiatric and psychological morbidity: results of a school-based cohort study of adolescents.

BACKGROUND: There is a considerable number of studies linking acne with psychological and psychiatric morbidities, although this literature is not entirely consistent and is largely cross-sectional in methodology. OBJECTIVE: This study aims to establish the relationship of acne and psychological and psychiatric morbidity in adolescents in a community setting and, via a longitudinal methodology, provide evidence for causality in the relationship. METHODS: The study was a 12-month cohort study. Two hundred and forty-four students in Years 8, 9 and 11 (ages 14-17) at four Australian high schools were assessed at baseline 6 months and 12 months. Presence and severity of acne were assessed, along with a number of psychological and psychiatric morbidities and personality traits (depression, anxiety, overall psychiatric morbidity, self-consciousness, neuroticism and introversion/extraversion) and other demographic variables. RESULTS: Of the 244 participating students, 209 (86%) completed all three rounds of data collection. A further 26 (11%) completed two rounds. The study failed to demonstrate an association of the presence of acne or of acne severity with the examined measures of psychological and psychiatric morbidity, and no evidence for an effect of acne in their causation. CONCLUSION: The relationship of acne and psychological morbidities found in previous health care settings was not found in this community sample. This may be due to differences between community and clinical acne populations. Other possible reasons for this finding are attenuation of psychological morbidity in subjects in this study by successful acne treatment, and the role of personality traits in the complex relationship between acne and psychological morbidities. It is suggested that this relationship would be best investigated by means of longer-term cohort studies enlisting subjects at an early age, prior to the onset of acne.

Making the most of Papua New Guinea's biodiversity: Establishment of an integrated set of programs that link botanical survey with pharmacological assessment in "The Land of the Unexpected"

An integrated and coordinated set of programs has been established to meet ICBG goals in Papua New Guinea (PNG). Here we give an overview of the PNG ICBG and focus on the key elements and major steps taken to establish a program necessary for the pharmacological assessment of botanicals and traditional medicines in PNG and, by extrapolation, in other developing countries.

A cross-sectional study of psychological morbidity in patients with acne, psoriasis and atopic dermatitis in specialist dermatology and general practices.

BACKGROUND: There is considerable evidence for an association of skin diseases with psychological morbidity. This relationship is best established for acne, psoriasis and atopic eczema. Previous studies have mostly been performed in specialist dermatological practice, and there is a lack of studies that include patients from general practice and a lack of controlled studies employing multivariate analysis. AIMS/OBJECTIVES: This study aims to examine the relationship of acne, psoriasis and atopic eczema with psychological morbidities in patients recruited from general practice as well as specialist dermatology practice. METHODS AND SUBJECTS: In this cross-sectional study, 108 patients from general and specialist dermatology practices with the three diseases had disease severity assessed and completed measures of minor psychological disturbance (General Health Questionnaire-12), anxiety and depression (Hospital Anxiety and Depression Scale), public self-consciousness and social anxiety (Fenigstein Self-Consciousness Scale), and neuroticism and extraversion/introversion (Eysenck Personality Inventory). Demographic data were also collected, along with self-ratings of disease severity. Control subjects were 96 patients without skin disease recruited from the same general practices as the subjects. RESULTS: On univariate analyses, patients with skin disease had higher levels of minor psychological disturbance, public self-consciousness and neuroticism than did controls. There were no differences in psychological measures between specialist and general practice patients or between patients with different skin diseases. On multivariate analyses, the significant differences did not persist. CONCLUSIONS: This study demonstrates confounding in the relationship of skin diseases with psychological morbidity. The complex relationship of skin disease and psychological morbidity should be re-examined.

Topical and oral CAM in acne: a review of the empirical evidence and a consideration of its context.

INTRODUCTION: Acne is one of the commonest diseases to afflict humanity. Anecdotally, the use of CAM in acne is widespread. In this review the empirical evidence for the efficacy of CAM modalities is examined and the context for their use discussed. METHODS: Searches were made of the MEDLINE, EMBASE, AMED (Allied and Complementary Medicines), Cochrane, and DARE databases using the search terms "acne" and "acne vulgaris" together with "alternative" and "complementary". RESULTS: The identified studies examined a broad range of CAM modalities but were of generally poor methodological quality. Evidence suggests that many of these therapies are biologically plausible. DISCUSSION AND CONCLUSION: Complementary therapies in acne should be viewed in a wider context than that of the very limited empiric evidence base that exists for their use. Further rigorously conducted trials should be conducted to define efficacy and adverse effect profiles of currently used CAM acne therapies.

Four-year follow-up of mortality and sleep-related respiratory disturbance in non-demented seniors.

To ascertain whether sleep-disordered breathing (SDB) in the elderly is associated with increased mortality, a prospective cohort study with 4-year follow-up was conducted at a retirement village complex in Sydney, Australia. The subjects were 163 non-demented retirement village residents. Logistic regression was used to assess SDB and co-morbidity as independent predictors of mortality. Respiratory disturbance index (RDI) was measured in the home; those subjects with RDIs > or = 15 were classified as having SDB. Co-morbidity was measured by an index of Burden of Illness based on the medical history obtained at baseline. At 4 years, 27% (4/15) of those subjects with RDIs > or = 15 and 22% (33/148) of those with RDIs < 15 were dead. RDI had an odds ratio (OR) of 1.00 (95% CI: 0.96, 1.04). Burden of Illness had an OR of 1.90 (95% CI: 1.34, 2.71). Adjustment for age and sex did not alter these findings. Significant predictors of mortality from the illness measure were a history of hypertension, Parkinson's disease and other severe illnesses (usually cancer). RDI was not a predictor of mortality in this population of non-demented seniors, where the prevalence of high levels of RDI was low.

Accumulation, activation and interindividual variation of the epidermal TP53 protein in response to ionizing radiation in organ cultured human skin.

In this study, we examined effects of low-dose ionizing radiation on organ cultured human foreskin and, in particular, on the epidermis. Diagnostic, therapeutic, natural environmental and incidental exposures to moderate to low doses of radiation are inevitable and, although information on cultured cells continues to accumulate, little is known about the effects of low-dose radiation on human tissues. Our hypothesis is that ex vivo organ cultured foreskin is a simple and reliable model to study the biochemical effects of low-dose radiation exposure on skin. A model such as this will aid in the identification and quantification of low-dose radiation-induced changes in proteins in human skin and may be useful in the development of a precise, non-invasive, and reliable assay of exposure. In this work, several aspects of skin responses to culture conditions and radiation were examined. The responses of epidermal TP53 from organ cultured skin irradiated in medium with and without serum were found to be similar. TP53 levels in organ cultured neonatal foreskin epidermis were then examined for baseline TP53 expression. After an initial increase at 4 h, the TP53 D01 signal returned to low steady-state levels for at least 72 h. Irradiated skin samples from different individuals revealed variations in the TP53 D01 signal. The dose and temporal response of dermis and epidermis to radiation were examined by Western blotting from 0 to 24 h after exposure. After irradiation and incubation, the epidermis was removed and assayed by Western blotting and was found to have increases in the TP53 D01 epitope and the TP53 phosphoserine 15 (TP53-S15p) epitope that reached a maximum at about 3 h. In the epidermis, doses of 1-5 cGy of radiation were detectable with the TP53 D01, and CDKN1A antibodies and doses greater than 10 cGy were detectable with the TP53-S15p antibody. When the dermis was compared to epidermis, it was found that dermis had a smaller response to radiation and more phosphorylated TP53.

Use of medications by the elderly.

Our study confirms that multiple medications are frequently taken by relatively healthy residents of a retirement village, the more so when they are less socially active during the day, and when they are living in hostel accommodation. There were few drug combinations that caused a potential interaction, suggesting that safe use of medication by the elderly should be an achievable goal.

Surface plasmon resonance analysis of topoisomerase I-DNA binding: effect of Mg2+ and DNA sequence.

Surface plasmon resonance detection was used to characterize interactions of human topoisomerase I and DNA. The disassociation of topoisomerase I and DNA is characterized by two rate constants. This suggests two parallel but independent pathways of release. DNA association appears to be complex. Mg2+ was found to increase both disassociation rate constants and may have a detectable effect on topoisomerase I-DNA association. DNA base content did not affect disassociation rate constants or the rate of association.

General practitioner diagnosis of depression and dementia in the elderly: can academic detailing make a difference?

The objective was to improve the ability of general practitioners (GPs) to diagnose depression and dementia compared with standard screening measures. The setting was a retirement village on the outskirts of Sydney, Australia. The study used a prepost design with a 6 month follow-up. The intervention involved a visit to the GP by an academic detailer who spent 15 minutes discussing the diagnosis of depression and dementia. Ratings of depression and dementia on two occasions by GPs, and by independent interviews were made using the Geriatric Depression Scale, Mini-mental State Examination and Canberra Interview for the Elderly. In the case of depression, the level of agreement (Kappa) between the GPs and all instruments increased significantly by a factor of between 2.3 and 3.3. The doctors did not significantly improve in their agreement with the instruments on the diagnosis of dementia. An academic detailing approach to improving GPs' abilities in the diagnosis of depression can be effective. A controlled trial would be justified to confirm this finding.

Effects of mutations in the F361 to R364 region of topoisomerase I (Topo I), in the presence and absence of 9-aminocamptothecin, on the Topo I-DNA interaction.

Steady-state levels and rates of DNA binding and release of wild-type and mutant topoisomerase I (Topo I) proteins were quantified by surface plasmon resonance analysis. The proteins were constructed and expressed as GST fusion proteins. The Topo I mutations analyzed were F361S, R362L and R364G, all altering a highly conserved region of wild-type eukaryotic Topo I. The R362L and R364G mutations resulted in much lower steady-state levels of DNA binding than wild-type. This was due to a large increase in the k(d). The F361S mutation increased the steady-state levels of the protein-DNA interaction by increasing the k(a) 2-fold, while having little effect on the k(d). The F361S mutation has been shown to confer resistance to camptothecin and its analogs. The camptothecin analog 9-aminocamptothecin decreased greatly the overall k(d) of the wild-type Topo I, but had little effect on the F361S mutant. Both the wild-type and the F361S mutant exhibited decreased steady-state levels in the presence of the drug, and this was attributable to decreased association.

Dementia and abnormal breathing during sleep.

We have examined a group of cognitively impaired elderly people who already showed some increase in indices of sleep-disordered breathing and applied standard criteria for dementia to them. This resulted in a subgroup of truly demented subjects who showed significantly more abnormal breathing during sleep than either normal subjects or those whose cognitive impairment may not have been due to a dementing illness.

Sleep-related respiratory disturbance and dementia in elderly females.

Sleep-related respiratory disturbance was studied with a microprocessor-based portable monitoring system in female residents of a retirement village aged greater than or equal to 75 years. Comparisons were made between 29 demented subjects Mini-Mental State Examination Score (MMSE) less than 21 and 48 controls (MMSE greater than 25). Respiratory disturbance index (RDI, the number of episodes of apnea and hypopnea/hour of total sleep time) was higher in the demented subjects: mean RDI (+/- SD) 18.5 +/- 18.6 vs 7.3 +/- 10.8, p = .004. The number of minutes per hour of sleep spent with disturbed breathing was greater in demented subjects than in controls (p = .01). These differences between demented subjects and controls persisted after adjustment for age and relevant medical history. Other possible confounders, namely body mass index and use of sedatives, were not significant. We conclude that respiratory disturbance during sleep is more prevalent in elderly demented females than in controls.

Neuropsychological functioning and sleep patterns in the elderly.

OBJECTIVE: To discover whether reported sleep-wake disturbances in the elderly (more frequent nocturnal awakenings, earlier waking and more day time naps) are associated with neuropsychological dysfunction. DESIGN AND SETTING: A sample of 124 residents of a retirement village complex were interviewed about their sleep patterns and given neuropsychological assessments. Reported sleep-wake difficulties were combined to form two variables, "night sleep" and "day sleep". Additional sleep variables analysed were reported sleep duration and time of wakening. Principal components analysis of the neuropsychological test scores yielded four factors: "general ability", "memory", "motor", and "cerebral efficiency". MAIN OUTCOME MEASURES: A correlation analysis was performed for sleep variables, neuropsychological factors and age, mood scale and scores on indices of participation in physical and passive activities. RESULTS: There was no correlation between "night sleep" and the factor scores derived from the neuropsychological tests. "Day sleep" was correlated with "cerebral efficiency" only. Age was correlated with the "memory" and "motor" factors, the latter also being associated with participation in physical activities. CONCLUSION: Night sleep problems are not associated with neuropsychological deficits in a non-clinic population.

Recognition of depression in the elderly: a comparison of general practitioner opinions and the Geriatric Depression Scale.

As part of a larger study, 133 subjects aged 70 years and over were screened for depression using the Geriatric Depression Scale, a 30-item questionnaire, as the screening instrument. Cognitive status was assessed using the Mini Mental State Examination. The subject's own general practitioner was asked his/her opinion as to whether the subject was depressed. Poor agreement was found between depression as measured by the Geriatric Depression Scale and the general practitioner's assessment. Possible reasons for this include the difficulty of finding a satisfactory operational definition of depression for use by general practitioners, the problems of identifying depression in the elderly, the arbitrary definition provided by the scale and the confounding of depression, as measured by the scale, with cognitive status.

Anxiety and depression in general practice patients: prevalence and management.

OBJECTIVE: To determine the prevalence of anxiety and depression in general practice patients and assess management of these conditions by general practitioners (GPs). METHOD: A random sample of 212 GPs were approached to be interviewed and to conduct a patient survey and audit on 50 consecutive patient consultations during 1993. PARTICIPANTS: 117 GPs (55% response rate) and 4867 patients (85%) who completed questionnaires suitable for analysis. SETTING: General practices in two areas (divisions of general practice) in Sydney, New South Wales. RESULTS: Thirty-six per cent of patients had abnormal scores on a General Health Questionnaire (GHQ-12); they were more likely to be women or to be unemployed. Twenty per cent of these patients had been treated for depression or anxiety in the previous 12 months; 52% were prescribed drug therapy, and were more likely to be older, male or unemployed. Seventy per cent of patients reported having been offered therapy by their GP that did not involve drugs. Twenty-four per cent had been referred to another health professional; they were more likely to be younger, or men, or patients attending their usual doctor. CONCLUSIONS: A brief screening instrument may improve GPs' detection rate of patients with anxiety or depression. The high prevalence of these conditions in unemployed people deserves particular attention by GPs. Both drug and non-drug therapies are being more appropriately applied in general practice than previously.

How to help depressed older people living in residential care: a multifaceted shared-care intervention for late-life depression.

OBJECTIVE: To describe a population-based, multifaceted shared-care intervention for late-life depression in residential care as a new model of geriatric practice, to outline its development and implementation, and to describe the lessons learned during the implementation process. SETTING: A large continuing-care retirement community in Sydney, Australia, providing three levels of care (independent living units, assisted-living complexes, and nursing homes). PARTICIPANTS: The intervention was implemented for the entire non-nursing home population (residents in independent and assisted living: N = 1,466) of the facility and their health care providers. Of the 1,036 residents whowere eligible and agreed to be interviewed, 281 (27.1%) were classified as depressed according to the Geriatric Depression Scale. INTERVENTION DESCRIPTION: The intervention included: (a) multidisciplinary collaboration between primary care physicians, facility health care providers, and the local psychogeriatric service; (b) training for primary care physicians and other facility health care providers about detecting and managing depression; and (c) depression-related health education/promotion programs for residents. CONCLUSIONS: The intervention was widely accepted by residents and their health care providers, and was sustained and enhanced by the facility after the completion of the study. It is possible to implement and sustain a multifaceted shared-care intervention for late-life depression in a residential care facility where local psychogeriatric services are scarce, staff-to-resident ratios are low, and the needs of depressed residents are substantial.

The formation of professional and consumer solutions: ethics in the general practice setting.

A general practice research project on ethics is underway at the University of New South Wales, funded by GPEP (General Practice Evaluation Program, Commonwealth Department of Human Services and Health, GPEP 386). Ethical issues, as defined and explored by general practitioners and consumers, are being examined across four areas of Sydney. So far, telephone interviews have been conducted (64% response rate) with a random sample of general practitioners (GPs). Face-to-face interviews have been conducted with 107 consumers, randomly sampled using ABS collection district information. Focus groups have been formed to discuss acceptable solutions to GP and consumer identified ethical issues. This report will report on some preliminary findings to date and will explore professional and consumer roles in the formation of ethical solutions.