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.

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.

Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.

Five hundred four outpatients suffering from a major depressive episode were randomly assigned to receive either amitriptyline, doxepin, alprazolam, or placebo. The study was conducted in three treatment centers during a six-week period. All three active medications produced significantly more clinical improvement than did placebo, irrespective of the patient's initial anxiety, depression, and psychomotor retardation and irrespective of the patient's assignment to various subtypes of depression, including the DSM-III melancholia subtype. Compared with placebo, sedation was reported more frequently with all three medications, whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants, but not for alprazolam.

Short-term augmentation of fluoxetine with clonazepam in the treatment of depression: a double-blind study.

OBJECTIVE: Because selective serotonin reuptake inhibitors (SSRIs) require 2-4 weeks to reach efficacy, the authors determined whether clonazepam augmentation of fluoxetine is superior to fluoxetine alone at the beginning of treatment for major depression. METHOD: Eighty adult outpatients with major depression who were rated as "moderately ill" or "markedly ill" on the Clinical Global Impression of Severity underwent 8 weeks of double-blind, randomized treatment with fluoxetine, 20 mg/day for all patients initially and 40 mg/day if needed after 6 weeks. One-half of these patients received clonazepam, 0.5 mg h.s. adjusted to two tablets by day 10 if needed, and the remainder received placebo, likewise adjusted. Clonazepam/placebo was gradually discontinued during days 21-33. Efficacy was evaluated by means of the Hamilton Depression Rating Scale, the Clinical Global Impression of Improvement, and a patient rating of global improvement. RESULTS: The patients taking clonazepam improved significantly more during the first 3 weeks of treatment according to ratings on the Hamilton scale (> or =50% improvement) and the clinician- and patient-rated global improvement measures ("much" or "very much" improved). Analysis of variance confirmed a significant effect of clonazepam for average Hamilton depression scores. No serious adverse events were found in either treatment group. Taper effects appeared modest and transitory. CONCLUSIONS: Clonazepam augmentation of fluoxetine was superior to fluoxetine alone in the first 3 weeks of treatment. This strategy may reduce suffering during early SSRI treatment, may partially suppress SSRI side effects, may increase compliance, and could possibly reduce the risk of suicide.

Undergraduate education about cancer.

The quality, quantity and balance of undergraduate cancer teaching in Australian Medical Schools were investigated by a survey, using a self-administered questionnaire, of recent graduates from all Australian medical schools. Stratified random cluster sampling was used and a response rate of 84% (389 respondents) was achieved. The results revealed substantial differences in knowledge, experience in, and rating of teaching between the medical, surgical, radiotherapeutic and palliative components of cancer management. The proportions of graduates who had never attended radiotherapy and palliative care clinics or units (42.3% and 49.9%, respectively) were more than double the proportion who had never attended medical and surgical cancer clinics or units (17.5% and 10.9%, respectively). More than twice as many graduates rated their instruction in the palliative management of cancer as poor or very poor (29.4%) compared with those rating their instruction as poor or very poor in both cancer prevention (8.4%) and treatment for cure (14.6%). The respondents displayed a considerable lack of knowledge about radiotherapy treatment options, and reported a lack of perceived competence in doing cervical smears. Their answers to questions about 5-year survival of selected cancers, about the existence of screening tests validly shown to reduce mortality, and the ages at which breast and cervical cancers are likely to develop all revealed worrying levels of incorrect knowledge. There was some important disturbing variation in levels of knowledge, experience and rating of cancer instruction between states and between universities.

A placebo-controlled trial of paroxetine in the treatment of major depression.

Paroxetine is a phenylpiperidine compound that selectively inhibits neuronal serotonin uptake in man. In this study, the efficacy of paroxetine was compared with that of placebo in the treatment of 66 outpatients with the diagnosis of moderate-to-severe major depression. The research was a 6-week, prospective, double-blind design after a 1-week placebo baseline phase. Paroxetine was associated with a consistent pattern of greater improvement on the primary efficacy scales, but the differences were not statistically significant. Paroxetine did produce significantly greater improvement than placebo for patients whose illness had lasted more than 1 year, and there was a significant reduction in suicidal ideation. Significantly fewer dropouts were due to lack of efficacy in those patients treated with paroxetine compared with those in the placebo group. Paroxetine was well tolerated. There was no difference between paroxetine and placebo in the rate of adverse effects or in the number of patients who dropped out because of adverse effects.

Paroxetine versus placebo: a double-blind comparison in depressed patients.

BACKGROUND: Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI). The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed outpatients. METHOD: A double-blind, parallel-group study was undertaken in four stand-alone centers. Patients aged 18-65 years, meeting DSM-III criteria for major depression, and having a Hamilton Rating Scale for Depression (HAM-D) score > or = 18 on the first 17 items of the HAM-D-21 were randomized to paroxetine or placebo for 6 weeks of treatment. Efficacy outcome variables included the HAM-D, the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impressions Scale (CGI), and the Covi Anxiety Scale. Tolerability was assessed by asking a non-leading question. Routine laboratory safety and vital sign data from all four centers were pooled. The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried-forward data set was employed. Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables. RESULTS: Significant differences (p < or = .05) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4. Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor. Similar results were obtained when an adequate treatment group (therapy for > or = 28 days) was considered. A full clinical response (CGI-severity of illness score 1 or 2) was seen in over 40% of subjects. Adverse events were more common for paroxetine compared with placebo (p < or = .01). Somnolence was twice more common than nervousness. Dropout due to adverse events was similar between therapies. Paroxetine had no clinically significant effect on laboratory safety data or vital signs. CONCLUSION: Paroxetine was an effective, well tolerated, and safe antidepressant. Side effects were typical of the SSRI class of drugs. Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects.

Comparison of two dosage regimens of fluoxetine in major depression.

The effect of dose frequency on fluoxetine efficacy and safety was evaluated in a double-blind study in patients with major depressive disorder. The patients received fluoxetine once a day (in the morning) or twice a day (in the morning and at noon). There were no significant differences between the two groups in the mean measures of efficacy, all of which showed significant improvement over baseline (p less than .001). Adverse experience profiles were not significantly different, with nervousness/anxiety predominating in both groups. In the subsequent 48-week open-label study, the percentage of patients reporting adverse experiences decreased greatly.

Acute effects of low levels of ambient ozone on peak expiratory flow rate in a cohort of Australian children.

BACKGROUND: We enrolled a cohort of primary schoolchildren with a history of wheeze (n = 148) in an 11-month longitudinal study to examine the relationship between ambient ozone concentrations and peak expiratory flow rate. METHODS: Enrolled children recorded peak expiratory flow rates (PEFR) twice daily. We obtained air pollution, meteorological and pollen data. In all, 125 children remained in the final analysis. RESULTS: We found a significant negative association between daily mean deviation in PEFR and same-day mean daytime ozone concentration (beta-coefficient = 0.88; P = 0.04) after adjusting for co-pollutants, time trend, meteorological variables, pollen count and ALTERNARIA: count. The association was stronger in a subgroup of children with bronchial hyperreactivity and a doctor diagnosis of asthma (beta-coefficient = -2.61; P = 0.001). There was no significant association between PEFR and same-day daily daytime maximum ozone concentration. We also demonstrated a dose-response relationship with mean daytime ozone concentration. CONCLUSIONS: Moderate levels of ambient ozone have an adverse health effect on children with a history of wheezing, and this effect is larger in children with bronchial hyperreactivity and a doctor diagnosis of asthma.

Acute stimulation of ornithine decarboxylase in neonatal rat brain regions by nicotine: a central receptor-mediated process?

Nicotine exposure during development alters central nervous system structure and function. In the current study, we examined the acute effects of nicotine (3 mg/kg) on developing rat brain by monitoring ornithine decarboxylase (ODC), a marker for perturbed cell development; ODC controls polyamine biosynthesis and thus regulates cell differentiation. Three brain regions were selected that differ both in their timetables for maturation and in nicotinic receptor concentrations: midbrain + brainstem (earliest development, highest receptor concentration), forebrain (intermediate profiles) and cerebellum (latest development and lowest receptor concentration). Nicotine caused stimulation of ODC within 1 h after drug administration, an effect that displayed both age- and region-dependence corresponding to the development of central nicotinic receptors: effects appeared earliest and were largest in magnitude in midbrain + brainstem and forebrain, and appeared last and with smaller magnitude in the cerebellum. Central receptor involvement was confirmed at 8 days postpartum by demonstrating desensitization of the response after repeated nicotine administration, and by evoking equivalent effects with direct introduction of a small dose of nicotine into the central nervous system. Later in development, acute stimulation of ODC by nicotine became less selective, reflecting secondary actions mediated through systemic hypoxia caused by the drug; this conclusion was confirmed by the absence of desensitization after repeated nicotine administration, and by the failure of centrally administered nicotine to evoke a full stimulatory response. Nicotine-induced ischemia did not contribute to stimulation of ODC seen at the 1 h time point: pretreatment with chlorisondamine, a ganglionic nicotinic antagonist, failed to alter the central stimulatory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Telephone reminders are a cost effective way to improve responses in postal health surveys.

STUDY OBJECTIVE: To assess the effectiveness of a telephone reminder in increasing responses to postal surveys and to calculate the differential costs per completed questionnaire. DESIGN: Randomised controlled trial. SETTING: Australian university and rehabilitation medicine practice. PARTICIPANTS: The trial was conducted in 1999 among the 143 non-respondents to a questionnaire about work related neck and upper body disorders. The questionnaire was sent to two Australian female samples: 200 office workers (Sample A) and 92 former rehabilitation medicine patients (Sample B). A reminder letter, another copy of the questionnaire and a final letter were sent at two week intervals. Half of the non-respondents within each sample were randomly selected to receive a telephone reminder just after the second mailout of the questionnaire. All direct costs were calculated. MAIN RESULTS: Responses were significantly higher among those who received the telephone reminder intervention (relative risk 2.54, 95% confidence intervals 1.43 to 4.52). Analysed by intention to phone, 47% of non-respondents in Sample A and 38% in Sample B returned a complete questionnaire after the intervention, compared with 21% and 10%, respectively, in the control groups. For the 112 women (combined samples) who returned completed questionnaires before randomisation, the average cost per respondent was AUD14. There was a higher total cost for the intervention groups (AUD851 versus AUD386 for controls), but the significantly higher number of additional completed responses (31 versus 12) resulted in a 15% lower marginal cost per completed questionnaire in those groups. CONCLUSION: Telephone reminders are cost effective in improving responses to postal surveys.

Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance and core symptoms of depression.

BACKGROUND: SSRIs resolve depression slowly and may increase anxiety or insomnia. Adding clonazepam to fluoxetine sped response, raising the question of mechanism of action: reducing symptoms co-existing with depression, suppressing side-effects, and/or alleviating core depressive symptoms. METHOD: Adult outpatients randomly assigned to double-blind treatment with fluoxetine 20 mg+placebo or fluoxetine+clonazepam 0.5-1.0 mg were assessed by a HAM-D anxiety cluster, sleep disturbance cluster, and core symptoms cluster. RESULTS: No serious AEs were noted; no cotherapy patients dropped for AEs. Cotherapy proved superior (HAM-D total, anxiety cluster, sleep disturbance cluster ANOVA P<0.001; core symptoms P<0.011). Treatment-emergent anxiety was reported for 25% of placebo patients and 7% of cotherapy patients (P<0.037); sleep disturbance for 10% of placebo patients and no cotherapy patients (P<0.055). Sedation and dry mouth were more common for cotherapy treatment (P>0.20). LIMITATIONS: Extended treatment and refractory depression were not addressed. CONCLUSIONS: Low-dose cotherapy of fluoxetine with clonazepam was safe and accelerated response over 21 days of treatment, decreasing anxiety and sleep disturbance as symptoms and partially suppressed them as SSRI side-effects; it also modestly reduced core symptoms of low mood and loss of interest.

Effects of low cobalamin diet and chronic cyanide toxicity on cobalamin distribution in baboons.

This paper reports the bodily distribution of total cobalamin and individual cobalamins at the termination of an experiment on the effects of a low cobalamin diet and chronic cyanide or thiocyanate administration in baboons. The results show that the distribution of cobalamins in the tissues of the baboon can be altered by a low cobalamin diet and also by chronic intoxication with cyanide, whether or not the animals are on a low cobalamin diet. All animals on the low cobalamin diet showed a reduction in total and individual cobalamins. In blood plasma and erythrocytes, kidney, spleen, testis and brain, the proportion of methylcobalamin tended to be disproportionately reduced in cobalamin-depleted animals. This reduction was lessened or prevented by the administration of cyanide. Neither cyanide not thiocyanate produced a significant increase in the proportion of cyanocobalamin in plasma, though thiocyanate produced a large increase in cyanocobalamin in erythrocytes. In liver, cyanocobalamin was more than doubled by the administration of cyanide to cobalamin-depleted animals.

Effects of low cobalamin diet and chronic cyanide toxicity in baboons.

The effects of a low cobalamin (Cbl) diet, together with chronic cyanide or thiocyanate administration in some animals have been investigated in baboons over a period of 42 months. All animals remained healthy throughout the study and gained weight at a similar rate. None became anaemic or showed major haematological changes and there were no major neurological changes. Plasma total Cbl in the animals on the low Cbl diet fell within 9 months to values below the lower limit in man and were lowest at 24 months in baboons not receiving cyanide or thiocyanate. A striking feature in all animals, however, was an apparently seasonal increase in the plasma total Cbl each autumn with a corresponding decrease the following spring. This fluctuation was detected by radioisotopic assay but not by Euglena. Methylmalonic (MMA) excretion after oral valine ranged from 0.1--8.4 mg/24 h and was greatest in animals on the low Cbl diet and not receiving cyanide or thiocyanate. The results suggested an inverse relationship between MMA excretion and plasma total Cbl. Plasma thiocyanate was consistently higher in animals receiving cyanide or thiocyanate and at the end of the study plasma cyanide was highest in animals on the low Cbl diet receiving cyanide. The results support the suggestions that cyanide affects bodily handling of Cbl and that hydroxo-cobalamin plays a part in detoxication of cyanide.

Stereospecificity of 2-methylpiperidine binding to a nicotinic up-regulatory site in the rat brain P2 preparation.

(+/-)-2-Methylpiperidine has a high degree of specificity in enhancing the binding of (-)-[3H]nicotine in the rat brain P2 preparation. (-)- and (+)-2-Methylpiperidine have been resolved. The (+) but not the (-) isomer increased the binding of (-)-[3H]nicotine. The two isomers were equally effective in inhibiting the binding of (-)-[3H]nicotine in high concentrations. These data provide additional support for a stereospecific nicotinic up-regulatory site.

Evaluation of multiple doses of milacemide in the treatment of senile dementia of the Alzheimer's type.

A multicenter, double-blind, placebo-controlled, parallel group study was conducted to assess the safety and efficacy of three doses of milacemide in the treatment of patients with senile dementia of the Alzheimer type of mild to moderate severity. Patients were randomly assigned to receive one of three dosages of milacemide (400, 800, or 1200 mg/day) or placebo for 4 weeks followed by a single-blind 4-week placebo period. One hundred forty-eight men and women older than 50 years of age were enrolled, and 129 patients completed the study. The differences among treatment groups were not statistically different with respect to total scores on the Alzheimer's Disease Assessment Scale or any items and subscales that were examined, nor were significant differences on the Clinical Global Impression Scale found. Clinically significant increases in liver function tests, specifically aspartate aminotransferase and alanine aminotransferase (AST and ALT), were reported for five of the patients receiving milacemide, requiring their withdrawal from the study.

The asthma health outcome indicators study.

Health outcomes have become an important public health policy focus in Australia. The New South Wales Health Department's Health Outcomes Program includes asthma as one of its priority areas. This study combined a survey of a non-random sample of 14 asthma researchers and clinicians and the results of a literature review to determine the current status and validity of outcome indicators used in relation to asthma. A written questionnaire was used to present individual patient, clinical trial, school intervention and public health scenarios, and respondents were asked to nominate asthma outcome indicators they would use in each scenario as well as their estimate of the indicators' validity. The results provide a critical appraisal of a variety of asthma outcome indicators with regard to their repeatability, and their concurrent and predictive validity.

Risk factors for asthma deaths: a population-based, case-control study.

OBJECTIVES: To investigate risk factors for death from asthma using a case-control study design with two control groups. METHODS: Cases (n = 42) comprised subjects aged 10-59 years who died from asthma. Two control groups were selected: a random sample of asthmatics from the community (n = 132) and age and sex matched patients recently admitted to hospital for asthma (n = 89). We obtained information from proxies of cases and controls, and their general practitioners, by a structured telephone survey. Matched and unmatched logistic regression analyses were used to determine odds ratios for risk factors for asthma deaths. RESULTS: Compared to community controls, important risk factors for asthma deaths included indicators of asthma severity, use of three or more groups of asthma medications, more extensive use of health services for asthma, poor compliance with asthma medications and regularly missing hospital and general practitioner appointments for asthma. Compared to hospital controls, risk factors for asthma deaths were previous visits to emergency department for asthma, knowledge about asthma medications and regularly missing general practitioner appointments. CONCLUSIONS: In this study, severity of asthma, increased health service utilisation and suboptimal asthma self-management were associated with increased risks for asthma death. IMPLICATIONS: People with severe asthma or poorly controlled asthma have a greater risk of dying from their asthma. Both clinicians and non-clinicians managing asthma should regularly assess the appropriateness of management to prevent deaths.

Food and nutrient consumption trends in older Australians: a 10-year cohort study.

BACKGROUND/OBJECTIVES: Few longitudinal population-based cohort studies of older people have described dietary intakes over time. The objective of this study was to assess changes in the food and nutrient intake in a cohort of older Australians, using longitudinal data collected over 10 years. SUBJECTS/METHODS: Population-based cohort of people aged 49 years and over at baseline (82% of those eligible) living in two postcode areas, west of Sydney. In 1992-1994, 3654 people were examined; 2334 were reexamined after 5 years and 1952 after 10 years (75% survivors at both examinations). A 145-item food frequency questionnaire was used to assess food and nutrient intake on each occasion, and 1166 participants provided usable dietary data at all three examinations. RESULTS: Energy and sugar intake significantly increased among women over the 10-year period (P-value for trend <0.0001). Long-chain omega-3 fatty acid and fish intake significantly increased in both men and women (P-value for trend <0.0001). Folate intake significantly increased in both men and women (women: 325 dietary folate equivalents (DFE) vs 403 DFE; men: 346 DFE vs 425 DFE, P<0.0001). Wholemeal/grain bread consumption decreased in both men and women (P-value for trend <0.0001). CONCLUSIONS: Many of the observed changes in diet over the 10-year period were consistent with current population dietary recommendations. Some changes, however, appear to have been due to poorer dietary choices. This information could be used to inform nutrition policy and programs targeted to older persons. These data highlight the need to identify barriers to better food choices.