Coping with defeat : acute glucocorticoid and forebrain responses to social defeat vary with defeat episode behaviour

Individuals vary in the way in which they cope with stressful situations. It has been suggested that ‘active’ coping behaviour, characterised by aggression and territorial control, is more effective in moderating the stress associated with social defeat than ‘passive’ coping behaviour, as characterised by immobility, decreased reactivity, and low aggression. We used the rodent ‘resident/intruder’ paradigm to determine whether individual differences in coping behaviour modulate the acute adrenocortical response to social defeat. During the 10 min conflict episode, behaviours displayed by the intruder were recorded and subsequently scored. Intruders that engaged in large numbers of fights and/or frequently used physical structures to block the resident's approach (a behaviour referred to as ‘guarding’), displayed smaller corticosterone responses to defeat than other intruders. Corticosterone responses to defeat were unrelated to a measure of coping style preferences (defensive burying test) obtained prior to the defeat encounter. We further chose to investigate the neurobiological basis of this observation by comparing the patterns of defeat-induced neuronal activation in the forebrains of intruders that displayed high versus low numbers of defensive behaviours during the defeat episode. The results of this analysis indicated that ‘low fight’ and ‘low guard’ intruders, i.e. those that achieved a fight or a guard score below the 20th percentile, had significantly higher numbers of Fos-positive neurons in forebrain regions such as the medial prefrontal cortex and the amygdala than did control animals exposed to an empty resident's cage. In summary, the present data suggest that ‘active’ coping behaviour is associated with both a smaller adrenocortical response and a lower level of ‘neural activation’ following social defeat. This outcome differs from that of earlier studies, a difference that we suggest is due to the fact that the present study is the first to assess coping on the basis of behaviour actually displayed during the conflict interaction.

Stressor categorization : acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups

It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category-specific. Data from previous immediate–early gene expression mapping studies have hinted that this is the case, but interstudy differences in methodology render conclusions tenuous. In the present study, immunolabelling for the expression of c-fos was used as a marker of neuronal activity elicited in the rat brain by haemorrhage, immune challenge, noise, restraint and forced swim. All stressors elicited c-fos expression in 25–30% of hypothalamic paraventricular nucleus corticotrophin-releasing-factor cells, suggesting that these stimuli were of comparable strength, at least with regard to their ability to activate the hypothalamic–pituitary–adrenal axis. In the amygdala, haemorrhage and immune challenge both elicited c-fos expression in a large number of neurons in the central nucleus of the amygdala, whereas noise, restraint and forced swim primarily elicited recruitment of cells within the medial nucleus of the amygdala. In the medulla, all stressors recruited similar numbers of noradrenergic (A1 and A2) and adrenergic (C1 and C2) cells. However, haemorrhage and immune challenge elicited c-fos expression in subpopulations of A1 and A2 noradrenergic cells that were significantly more rostral than those recruited by noise, restraint or forced swim. The present data support the suggestion that the brain recognizes at least two major categories of stressor, which we have referred to as ‘physical’ and ‘psychological’. Moreover, the present data suggest that the neural activation footprint that is left in the brain by stressors can be used to determine the category to which they have been assigned by the brain.

Thalamic paraventricular nucleus lesions facilitate central amygdala neuronal responses to acute psychological stress

The thalamic paraventricular nucleus (PVT) is activated by stress and projects to forebrain structures directly implicated in processing stress-related information. Accordingly, it seems likely the PVT plays an important role in modulating stress responses. We examined effects of excitotoxic PVT lesions on forebrain Fos expression patterns normally elicited by an acute psychological stressor. PVT lesions significantly increased stress-induced Fos in a key stress-processing region, the central amygdala.

Descriptive analysis of emergency department oxygen use in acute exacerbation of chronic obstructive pulmonary disease

Background: Inconsistencies in oxygen therapy recommendations in acute exacerbation of chronic obstructive pulmonary disease (COPD) may result in variability in emergency department (ED) oxygen management of patients with COPD. The aim of this study was to describe oxygen management in the first 4 h of ED care for patients with exacerbation of COPD.
Methods: A retrospective medical record audit was conducted at four public and one private ED in Melbourne, Australia. Participants were 273 adult ED patients with COPD presenting with a primary complaint of shortness of breath from July 2006 to July 2007. Outcome measures were physiological data, including oxygen saturation (SpO2), oxygen delivery devices and flow rates on ED arrival, 1 and 4 h.
Results: Oxygen was used in 82.0% of patients. Patients who required oxygen had higher incidence of ambulance transport (P < 0.001), triage category 2 (P = 0.006), home oxygen use (P < 0.001), and increased work of breathing on ED arrival (P < 0.001), and higher median respiratory rate (P < 0.001) and heart rate (P = 0.001). SpO2 > 90% occurred in the majority of patients (87.5%; 96.4%; 95.6%); however, a considerable number of patients with SpO2 < 90% were not given oxygen (61.8%; 30%; 45.5%).
Conclusions: A number of patients with documented hypoxaemia were not given oxygen and there may be variables other than oxygen saturation that may influence oxygen use. Future research should focus on increasing the evidence-based supporting
oxygen use and better understanding of clinicians’ oxygen decision-making in patients with COPD.

Clinical outcomes associated with screening and referral for depression in an acute cardiac ward

Aim.  The aim of this paper is to describe the implementation of a depression screening and referral tool in two cardiac wards of a major metropolitan public hospital. The tool consisted of two sections: (1) screening for depression risk (Cardiac Depression Scale-5) and (2) consequential referral actions.

Background.  Prior research has shown that depression in patients with heart disease is associated with significantly impaired quality of life, decreased medication adherence, increased morbidity and increased use of healthcare services.

Design.  A prospective in-patient study design.

Method.  A consecutive sample of 202 patients admitted to either the cardiac medical (n = 145) or surgical (n = 57) wards of a major Melbourne metropolitan hospital were recruited into the study over an 18-week period.

Results.  Just over half (54%) of the patients were identified as ‘at risk’ of depression. Of these, 19% were assessed as moderate risk and 35% high risk. Of those patients, 91% had the risk score documented in their medical history, 90% had engaged in discussions with clinicians regarding their risk score, 85% had their risk score communicated formally to the medical team and 25% were formally referred for appropriate follow-up – significantly more than prior to implementation of the screening and referral tool.

Conclusions.  By providing a formalised mechanism for detecting depression, documented screening and referral rates improved for those with comorbid depression and heart disease affording an opportunity for early intervention. These findings support a move towards integrated approaches to screening of depression to become standard practice in the acute cardiac setting.

Relevance to clinical practice.  Such mechanisms also have the potential to initiate the development of new models of care that acknowledge the complexity of comorbid depression and heart disease and provide pathways from speciality to primary care which integrate the physical and psychosocial domains inclusive of screening, referral, systematic monitoring and streamlined behavioural and physical care.

Content validity of visual analog scales to assess symptom severity of acute angioedema attacks in adults with hereditary angioedema : an interview study

Background: Hereditary angioedema (HAE) is a rare, debilitating, potentially life-threatening condition characterized by recurrent acute attacks of edema of the skin, face/upper airway, and gastrointestinal and urogenital tracts. During a laryngeal attack, people with HAE may be at risk of suffocation, while other attacks are often associated with intense pain, disfigurement, disability, and/or vomiting. The intensity of some symptoms is known only to the person experiencing them. Thus, interview studies are needed to explore such experience and patient-reported outcome measures (PROMs) are required for systematic assessment of symptoms in the clinical setting and in clinical trials of treatments for acute HAE attacks.

Objective: The aim of this interview study was to assess the content validity and suitability of four visual analog scale (VAS) instruments for use in clinical studies. The VAS instruments were designed to assess symptoms at abdominal, oro-facial-pharyngeal-laryngeal, peripheral, and urogenital attack locations. This is the first known study to report qualitative data about the patient's experience of the rare disorder, HAE.

Methods: Semi-structured exploratory and cognitive debriefing interviews were conducted with 27 adults with a confirmed clinical/laboratory diagnosis of HAE (baseline plasma level of functional plasma protein C1 esterase inhibitor [C1INH] <50% of normal without evidence for acquired angioedema). There were 17 participants from the US and 10 from Italy, with mean age 42.5 (SD 14.5) years, range 18–72 years, mean HAE duration 21.3 (SD 14.1) years, range 1–45 years, 67% female, and 44% VAS-naïve. Experience of acute angioedema attacks was first explored, noting spontaneous mentions by participants of HAE symptomatology. Cognitive debriefing of the VAS instruments was undertaken to assess the suitability, comprehensibility, and relevance of the VAS items. Asymptomatic participants completed the VAS instruments relevant to their angioedema experience, reporting as if they were experiencing an acute angioedema attack at the time. Interviews were conducted in the clinic setting in the US and Italy over an 8-month period.

Results: Participants mentioned spontaneously almost all aspects of acute angioedema attacks covered by the four VAS instruments, thus providing strong support for inclusion of nearly all VAS items, with no important symptoms missing. Predominant symptoms found to be associated with acute angioedema attacks were edema and pain, and there was evidence of varying degrees of disruption to everyday activities supporting the inclusion of an overall severity item reflecting the disabling effects of HAE symptoms. VAS item wording was understood by participants.

Conclusion: This interview study explored and reported the patient experience of HAE attacks. It demonstrated the content validity of the four anatomical location HAE VAS instruments and their suitability for use in clinical trials of recombinant human C1INH (rhC1INH) treatment for ascertaining trial participants' assessments of the severity of acute angioedema symptoms.

Acute rheumatic fever associated with household crowding in a developed country

Background: Acute rheumatic fever (ARF) and its sequelae, chronic rheumatic heart disease, remain important causes of morbidity and mortality worldwide, but there is little recent information about risk factors. The aim of this study was to examine the association between ARF and household crowding in New Zealand between 1996 and 2005.

Methods: This ecologic study used hospitalization data and census data to calculate incidence rates by census area unit (CAU). Rates of ARF were examined in relation to individual factors (age, ethnicity) and area factors based on the CAU of home address (household crowding, New Zealand deprivation index, household income, and proportion of children aged 5–14 years). The multivariate relationship between ARF incidence and CAU-based variables was assessed using a zero-inflated negative binomial model.

Results: This study included 1249 new cases of ARF between 1996 and 2005. At the univariate level, ARF rates were associated with household crowding across all age groups and ethnicities. ARF rates were significantly and positively related to household crowding after controlling for age, ethnicity, household income, and the density of children in the neighborhood. The incidence rate ratio was 1.065 (95% confidence interval, 1.052–1.079) for the total population.

Conclusions: In New Zealand, ARF rates are associated with household crowding at the CAU level. This finding supports action to reduce household crowding to improve health and reduce health inequalities. Our conclusion could be further investigated using a case-control study.

Human brain structural change related to acute single exposure to sarin

Objective This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin.

Methods Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated.

Results The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05).

Interpretation Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

A randomised, feasibility trial of a tele-health intervention for acute coronary syndrome patients with depression (‘MoodCare’): study protocol

Background Coronary heart disease (CHD) and depression are leading causes of disease burden globally and the two often co-exist. Depression is common after Myocardial Infarction (MI) and it has been estimated that 15-35% of patients experience depressive symptoms. Co-morbid depression can impair health related quality of life (HRQOL), decrease medication adherence and appropriate utilisation of health services, lead to increased morbidity and suicide risk, and is associated with poorer CHD risk factor profiles and reduced survival. We aim to determine the feasibility of conducting a randomised, multi-centre trial designed to compare a tele-health program (MoodCare) for depression and CHD secondary prevention, with Usual Care (UC).

Methods Over 1600 patients admitted after index admission for Acute Coronary Syndrome (ACS) are being screened for depression at six metropolitan hospitals in the Australian states of Victoria and Queensland. Consenting participants are then contacted at two weeks post-discharge for baseline assessment. One hundred eligible participants are to be randomised to an intervention or a usual medical care control group (50 per group). The intervention consists of up to 10 × 30-40 minute structured telephone sessions, delivered by registered psychologists, commencing within two weeks of baseline screening. The intervention focuses on depression management, lifestyle factors (physical activity, healthy eating, smoking cessation, alcohol intake), medication adherence and managing co-morbidities. Data collection occurs at baseline (Time 1), 6 months (post-intervention) (Time 2), 12 months (Time 3) and 24 months follow-up for longer term effects (Time 4). We are comparing depression (Cardiac Depression Scale [CDS]) and HRQOL (Short Form-12 [SF-12]) scores between treatment and UC groups, assessing the feasibility of the program through patient acceptability and exploring long term maintenance effects. A cost-effectiveness analysis of the costs and outcomes for patients in the intervention and control groups is being conducted from the perspective of health care costs to the government.

Discussion This manuscript presents the protocol for a randomised, multi-centre trial to evaluate the feasibility of a tele-based depression management and CHD secondary prevention program for ACS patients. The results of this trial will provide valuable new information about potential psychological and wellbeing benefits, cost-effectiveness and acceptability of an innovative tele-based depression management and secondary prevention program for CHD patients experiencing depression.

Parent initiated prednisolone for acute asthma in children of school age : randomised controlled crossover trial

Objective To evaluate the efficacy of a short course of parent initiated oral prednisolone for acute asthma in children of school age.

Design Double blind, randomised, placebo controlled, crossover trial in which episodes of asthma, rather than participants, were randomised to treatment.

Setting The Barwon region of Victoria, Australia.

Participants Children aged 5-12 years with a history of recurrent episodes of acute asthma.

Intervention A short course of parent initiated treatment with prednisolone (1 mg/kg a day) or placebo.

Main outcome measures The primary outcome measure was the mean daytime symptom score over seven days. Secondary outcome measures were mean night time symptom score over seven days, use of health resources, and school absenteeism.

Results 230 children were enrolled in the study. Over a three year period, 131 (57%) of the participants contributed a total of 308 episodes of asthma that required parent initiated treatment: 155 episodes were treated with parent initiated prednisolone and 153 with placebo. The mean daytime symptom score was 15% lower in episodes treated with prednisolone than in those treated with placebo (geometric mean ratio 0.85, 95% CI 0.74 to 0.98; P=0.023). Treatment with prednisolone was also associated with a 16% reduction in the night time symptom score (geometric mean ratio 0.84, 95% CI 0.70 to 1.00; P=0.050), a reduced risk of health resource use (odds ratio 0.54, 95% CI 0.34 to 0.86; P=0.010), and reduced school absenteeism (mean difference −0.4 days, 95% CI −0.8 to 0.0 days; P=0.045).

Conclusion A short course of oral prednisolone initiated by parents when their child experiences an episode of acute asthma may reduce asthma symptoms, health resource use, and school absenteeism. However, the modest benefits of this strategy must be balanced against potential side effects of repeated short courses of an oral corticosteroid.

Epidemiology of acute rheumatic fever in New Zealand 1996-2005

Aim: Acute rheumatic fever (ARF) and its sequela chronic rheumatic heart disease remain significant causes of morbidity and mortality in New Zealand, particularly among Māori and Pacific peoples. Despite its importance, ARF epidemiology has not been reviewed recently. The aims of this study were to assess trends in ARF incidence rates between 1996 and 2005 and the extent to which ARF is concentrated in certain populations based on age, sex, ethnicity and geographical location.

Methods: This descriptive epidemiological study examined ARF incidence rates using hospitalisation data (1996–2005) and population data from the 1996 and 2001 censuses. Rates were compared by using rate ratios and 95% confidence intervals.

Results: New Zealand's annual ARF rate was 3.4 per 100 000. ARF was concentrated in certain populations: 5- to 14-year-olds, Māori and Pacific peoples and upper North Island areas. From 1996 to 2005, the New Zealand European and Others ARF rate decreased significantly while Māori and Pacific peoples’ rates increased. Compared with New Zealand European and Others, rate ratios were 10.0 for Māori and 20.7 for Pacific peoples. Of all cases, 59.5% were Māori or Pacific children aged 5–14 years, yet this group comprised only 4.7% of the New Zealand population.

Conclusion: ARF rates in New Zealand have failed to decrease since the 1980s and remain some of the highest reported in a developed country. There are large, and now widening, ethnic disparities in ARF incidence. ARF is so concentrated by age group, ethnicity and geographical area that highly targeted interventions could be considered, based on these characteristics.

Parent-initiated oral corticosteroid therapy for acute asthma: a survey of current practice

Aim: To determine (i) the proportion of doctors who recommend parent-initiated oral corticosteroids (PIOCS) for acute asthma; and (ii) the proportion of parents who have received this advice.

Methods: (i) An internet-based survey of doctors involved in the care of children with asthma; and (ii) a questionnaire-based survey of parents of children aged 4–13 years who were identified from a random sample of primary schools within the Barwon region of Victoria.

Results: Eight-five per cent (95% confidence interval 80.0–89.1%) of responding doctors reported recommending PIOCS to parents of children with asthma. However, only 16.5% (95% confidence interval 14.2–18.7%) of parents of children with recent asthma symptoms report that they have received such advice.

Conclusion: The majority of responding doctors involved in the care of children with asthma report recommending PIOCS to parents. By contrast, a minority of parents of children with asthma report that they have received such advice.