INHIBITION OF THE CAUDAL PRESSOR AREA REDUCES CARDIORESPIRATORY CHEMOREFLEX RESPONSES

The caudal pressor area (CPA) is a brainstem area located close to the spinal cord. The activation of the CPA increases sympathetic activity and mean arterial pressure (MAP) by mechanisms dependent on the commissural nucleus of the solitary tract (commNTS) and rostroventrolateral medulla, however, the signals that activate the CPA to produce these responses are still unknown. Therefore, in the present study, we investigated the activity of glutamatergic and GABAergic mechanisms from the CPA and commNTS in rats exposed to hypoxia and the effects of the inhibition of CPA neurons on cardiorespiratory responses to peripheral chemoreceptor activation with i.v. sodium cyanide (NaCN). Male Sprague-Dawley rats (250-280 g, n=5-8/group) were used. In conscious rats, most of the commNTS neurons (66 +/- 11%) and part of the CPA neurons (36 +/- 7%) activated by hypoxia (8% O2) were glutamatergic (contained VGLUT2mRNA). Small part of the neurons activated during hypoxia was GABAergic (contained GAD-67mRNA) in the commNTS (9 +/- 4%) or the CPA (6 +/- 2%). In urethane anesthetized rats, the inhibition of CPA neurons with bilateral injections of muscimol (GABA-A agonist, 2 mM) reduced baseline MAP, splanchnic sympathetic nerve discharge (SND) and phrenic nerve discharge (PND). Muscimol into the CPA also reduced by around 50% the pressor and sympathoexcitatory responses and the increase in PND to peripheral chemoreceptor activation with NaCN (50 mu g/kg i.v.), without changing sympathetic baroreflex responses. These data suggest that CPA mechanisms facilitate cardiorespiratory responses to peripheral chemoreflex activation. Immunohistochemistry results also suggest that at least part of the CPA mechanisms activated by hypoxia is glutamatergic. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

The Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venom

Pyroglutamyl proline-rich oligopeptides, present in the venom of the pit viper Bothrops jararaca (Bj-PROs), are the first described naturally occurring inhibitors of the angiotensin I-converting enzyme (ACE). The inhibition of ACE by the decapeptide Bj-PRO-10c (inhibition alone is not sufficient for explaining the antihypertensive actions exerted by these peptides. In this study, we show that intracerebroventricular injection of Bj-PRO-10c induced a significant reduction of mean arterial pressure (MAP) together with a decrease of heart rate (HR) in spontaneously hypertensive rats, indicating that Bj-PRO-10c may act on the central nervous system. In agreement with its supposed neuronal action, this peptide dose-dependently evoked elevations of intracellular calcium concentration ([Ca(2+)](i)) in primary culture from postnatal rat brain. The N-terminal sequence of the peptide was not essential for induction of calcium fluxes, while any changes of C-terminal Pro or Ile residues affected Bj-PRO-10c`s activity. Using calcium imaging by confocal microscopy and fluorescence imaging plate reader analysis, we have characterized Bj-PRO-10c-induced [Ca(2+)](i) transients in rat brain cells as being independent from bradykinin-mediated effects and ACE inhibition. Bj-PRO-10c induced pertussis toxin-sensitive G(i/o)-protein activity mediated through a yet unknown receptor, influx and liberation of calcium from intracellular stores, as well as reduction of intracellular cAMP levels. Bj-PRO-10c promoted glutamate and GABA release that may be responsible for its antihypertensive activity and its effect on HR. (C) 2010 International Society for Advancement of Cytometry

Different mechanisms underlie the effects of acute and long-term inhibition of nitric oxide synthases in antigen-induced pulmonary eosinophil recruitment in BALB/C mice

Nitric oxide synthase (NOS) inhibitors are largely used to evaluate the NO contribution to pulmonary allergy, but contrasting data have been reported. In this study, pharmacological, biochemical and pharmacokinetic assays were performed to compare the effects of acute and long-term treatment of BALB/C mice with the non-selective NOS inhibitor L-NAME in ovalbumin (OVA)-challenged mice. Acute L-NAME treatment (50 mg/kg, gavage) significantly reduced the eosinophil number in bronchoalveolar lavage fluid (BALF). The inducible NOS (iNOS) inhibitor aminoguanidine (20 mg/kg/day in the drinking water) also significantly reduced the eosinophil number in BALF In contrast, 3-week L-NAME treatment (50 and 150 mg/kg/day in the drinking water) significantly increased the pulmonary eosinophil influx. The constitutive NOS (cNOS) activity in brain and lungs was reduced by both acute and 3-week L-NAME treatments. The pulmonary iNOS activity was reduced by acute L-NAME (or aminoguanidine), but unaffected by 3-week L-NAME treatment. Acute L-NAME (or aminoguanidine) treatment was more efficient to reduce the NO(x) levels compared with 3-week L-NAME treatment. The pharmacokinetic study revealed that L-NAME is not bioavailable when given orally. After acute L-NAME intake, serum concentrations of the metabolite N(omega)-nitro-L-arginine decreased from 30 min to 24 h. In the 3-week L-NAME treatment, the N(omega)-nitro-L-arginine concentration was close to the detection limit. In conclusion, 3-week treatment with L-NAME yields low serum N(omega)-nitro-L-arginine concentrations, causing preferential inhibition of cNOS activity. Therefore, eosinophil influx potentiation by 3-week L-NAME treatment may reflect removal of protective cNOS-derived NO, with no interference on the ongoing inflammation due to iNOS-derived NO. (c) 2008 Elsevier Ltd. All rights reserved.

Inhibition of myeloperoxidase-mediated protein nitration by tempol: Kinetics, mechanism, and implications

Despite the therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetra-methyl-1-piperidinyloxy) and related nitroxides as antioxidants, their effects on peroxidase-mediated protein tyrosine nitration remain unexplored. This posttranslational protein modification is a biomarker of nitric oxide-derived oxidants, and, relevantly, it parallels tissue injury in animal models of inflammation and is attenuated by tempol treatment. Here, we examine tempol effects on ribonuclease (RNase) nitration mediated by myeloperoxidase (MPO), a mammalian enzyme that plays a central role in various inflammatory processes.. Some experiments were also performed with horseradish peroxidase (HRP). We show that tempol efficiently inhibits peroxidase-mediated RNase nitration. For instance, 10 mu M tempol was able to inhibit by 90% the yield of 290 mu M 3-nitrotyrosine produced from 370 mu M RNase. The effect of tempol was not completely catalytic because part of it was consumed by recombination with RNase-tyrosyl radicals. The second-order rate constant of the reaction of tempol with MPO compound I and 11 were determined by stopped-flow kinetics as 3.3 x 10(6) and 2.6 x 10(4) M-1 s(-1), respectively (pH 7.4, 25 degrees C); the corresponding HRP constants were orders of magnitude smaller. Time-dependent hydrogen peroxide and nitrite consumption and oxygen production in the incubations were quantified experimentally and modeled by kinetic simulations. The results indicate that tempol inhibits peroxidase-mediated RNase nitration mainly because of its reaction with nitrogen dioxide to produce the oxammonium cation, which, in turn, recycles back to tempol by reacting with hydrogen peroxide and superoxide radical to produce oxygen and regenerate nitrite. The implications for nitroxide antioxidant mechanisms are discussed.

Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia

Methylmalonic acidemia is one of the most prevalent inherited metabolic disorders involving neurological deficits. In vitro experiments, animal model studies and tissue analyses from human patients suggest extensive impairment of mitochondrial energy metabolism in this disease. This review summarizes changes in mitochondrial energy metabolism occurring in methylmalonic acidemia, focusing mainly on the effects of accumulated methylmalonic acid, and gives an overview of the results found in different experimental models. Overall, experiments to date suggest that mitochondrial impairment in this disease occurs through a combination of the inhibition of specific enzymes and transporters, limitation in the availability of substrates for mitochondrial metabolic pathways and oxidative damage.

The role of nurses in preventing adverse events related to respiratory dysfunction: literature review

Aims. This paper reports a literature review examining the relationship between specific clinical indicators of respiratory dysfunction and adverse events, and exploring the role of nurses in preventing adverse events related to respiratory dysfunction.

Background. Adverse events in hospital are associated with poor patient outcomes such as increased mortality and permanent disability. Many of these adverse events are preventable and are preceded by a period during which the patient exhibits clearly abnormal physiological signs. The role of nurses in preserving physiological safety by early recognition and correction of physiological abnormality is a key factor in preventing adverse events.

Methods. A search of the Medline and CINAHL databases was conducted using the following terms: predictors of poor outcome, adverse events, mortality, cardiac arrest, emergency, oxygen, supplemental oxygen, oxygen therapy, oxygen saturation, oxygen delivery, assessment, patient assessment, physical assessment, dyspnoea, hypoxia, hypoxaemia, respiratory assessment, respiratory dysfunction, shortness of breath and pulse oximetry. The papers reviewed were research papers that demonstrated a relationship between adverse events and various clinical indicators of respiratory dysfunction.

Results. Respiratory dysfunction is a known clinical antecedent of adverse events such as cardiac arrest, need for medical emergency team activation and unplanned intensive care unit admission. The presence of respiratory dysfunction prior to an adverse event is associated with increased mortality. The specific clinical indicators involved are alterations in respiratory rate, and the presence of dyspnoea, hypoxaemia and acidosis.

Conclusions. The way in which nurses assess, document and use clinical indicators of respiratory dysfunction is influential in identifying patients at risk of an adverse event and preventing adverse events related to respiratory dysfunction. If such adverse events are to be prevented, nurses must not only be able to recognise and interpret signs of respiratory dysfunction, but must also take responsibility for initiating and evaluating interventions aimed at correcting respiratory dysfunction.

Bitterness suppression with zinc sulfate and na-cyclamate: a model of combined peripheral and central neural approaches to flavor modification

Purpose Zinc sulfate is known to inhibit the bitterness of the antimalarial agent quinine [R. S. J. Keast. The effect of zinc on human taste perception. J. Food Sci. 68:1871–1877 (2003)]. In the present work, we investigated whether zinc sulfate would inhibit other bitter-tasting compounds and pharmaceuticals. The utility of zinc as a general bitterness inhibitor is compromised, however, by the fact that it is also a good sweetness inhibitor [R. S. J. Keast, T. Canty, and P. A. S. Breslin. Oral zinc sulfate solutions inhibit sweet taste perception. Chem. Senses 29:513–521 (2004)] and would interfere with the taste of complex formulations. Yet, zinc sulfate does not inhibit the sweetener Na-cyclamate. Thus, we determined whether a mixture of zinc sulfate and Na-cyclamate would be a particularly effective combination for bitterness inhibition (Zn) and masking (cyclamate).

Method We used human taste psychophysical procedures with chemical solutions to assess bitterness blocking.

Results Zinc sulfate significantly inhibited the bitterness of quinine–HCl, Tetralone, and denatonium benzoate (DB) (p < 0.05), but had no significant effect on the bitterness of sucrose octa-acetate, pseudoephedrine (PSE), and dextromethorphan. A second experiment examined the influence of zinc sulfate on bittersweet mixtures. The bitter compounds were DB and PSE, and the sweeteners were sucrose (inhibited by 25 mM zinc sulfate) and Na-cyclamate (not inhibited by zinc sulfate). The combination of zinc sulfate and Na-cyclamate most effectively inhibited DB bitterness (86%) (p < 0.0016), whereas the mixture's inhibition of PSE bitterness was not different from that of Na-cyclamate alone.

Conclusion A combination of Na-cyclamate and zinc sulfate was most effective at inhibiting bitterness. Thus, the combined use of peripheral oral and central cognitive bitterness reduction strategies should be particularly effective for improving the flavor profile of bitter-tasting foods and pharmaceutical formulations.

Does interpersonal psychotherapy improve clinical care for adolescents with depression attending a rural child and adolescent mental health service? Study protocol for a cluster randomised feasibility trial

Background: Depression amongst adolescents is a costly societal problem. Little research documents the effectiveness of public mental health services in mapping this problem. Further, it is not clear whether usual care in such services can be improved via clinician training in a relevant evidence based intervention. One such intervention, found to be effective and easily learned amongst novice clinicians, is Interpersonal Psychotherapy (IPT). The study described in the current paper has two main objectives. First, it aims to investigate the impact on clinical care of implementing Interpersonal Psychotherapy for Adolescents for the treatment of adolescent depression within a rural mental health service compared with Treatment as Usual (TAU). The second objective is to record the process and challenges (i.e. feasibility, acceptability, sustainability) associated with implementing and evaluating an evidence-based intervention within a community service. This paper outlines the study rationale and design for this community based research trial.

Methods/design: The study involves a cluster randomisation trial to be conducted within a Child and Adolescent Mental Health Service in rural Australia. All clinicians in the service will be invited to participate.  Participating clinicians will be randomised via block design at each of four sites to (a) training and delivery of IPT, or (b) TAU. The primary measure of impact on care will be a clinically significant change in depressive  symptomatology, with secondary outcomes involving treatment satisfaction and changes in other symptomatology. Participating adolescents with significant depressive symptomatology, aged 12 to 18 years, will complete assessment measures at Weeks 0, 12 and 24 of treatment. They will also complete a depression inventory once a month during that period. This study aims to recruit 60 adolescent participants and their parent/guardian/s. A power analysis is not indicated as an intra-class correlation coefficient will be calculated and used to inform sample size calculations for subsequent large-scale trials. Qualitative data regarding process implementation will be collected quarterly from focus groups with participating clinicians over 18 months, plus phone interviews with participating adolescents and parent/guardians at 12 weeks and 24 weeks of treatment. The focus group qualitative data will be analysed using a Fourth Generation Evaluation methodology that includes a constant comparative cyclic analysis method.

Discussion: This study protocol will be informative for researchers and clinicians interested in considering, designing and/or conducting cluster randomised trials within community practice such as mental health services.

Chronic intermittent hypoxia and incremental cycling exercise independently depress muscle in vitro maximal Na+-K+-ATPase activity in well-trained athletes

Athletes commonly attempt to enhance performance by training in normoxia but sleeping in hypoxia [live high and train low (LHTL)]. However, chronic hypoxia reduces muscle Na⁺-K⁺-ATPase content, whereas fatiguing contractions reduce Na⁺-K⁺-ATPase activity, which each may impair performance. We examined whether LHTL and intense exercise would decrease muscle Na⁺-K⁺-ATPase activity and whether these effects would be additive and sufficient to impair performance or plasma K⁺ regulation. Thirteen subjects were randomly assigned to two fitness-matched groups, LHTL (n = 6) or control (Con, n = 7). LHTL slept at simulated moderate altitude (3,000 m, inspired O₂ fraction = 15.48%) for 23 nights and lived and trained by day under normoxic conditions in Canberra (altitude ~600 m). Con lived, trained, and slept in normoxia. A standardized incremental exercise test was conducted before and after LHTL. A vastus lateralis muscle biopsy was taken at rest and after exercise, before and after LHTL or Con, and analyzed for maximal Na⁺-K⁺-ATPase activity [K⁺-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase)] and Na⁺-K⁺-ATPase content ([³H]ouabain binding sites). 3-O-MFPase activity was decreased by –2.9 ± 2.6% in LHTL (P < 0.05) and was depressed immediately after exercise (P < 0.05) similarly in Con and LHTL (–13.0 ± 3.2 and –11.8 ± 1.5%, respectively). Plasma K⁺ concentration during exercise was unchanged by LHTL; [3H]ouabain binding was unchanged with LHTL or exercise. Peak oxygen consumption was reduced in LHTL (P < 0.05) but not in Con, whereas exercise work was unchanged in either group. Thus LHTL had a minor effect on, and incremental exercise reduced, Na⁺-K⁺-ATPase activity. However, the small LHTL-induced depression of 3-O-MFPase activity was insufficient to adversely affect either K⁺ regulation or total work performed.

Investigating the Effects of Mifepristone (RU486) in the Behavioral, Hormonal and Central Responses to Acute Stress

Depression is associated with glucocorticoid hypersecretion, due to dysfunction of the hypothalamo-pituitary-adrenocorticol axis (HPA-axis). Because excess glucocorticoids are associated with depressive-like features in humans, glucocorticoid receptor antagonists are currently being tested for antidepressant efficacy in clinical trials. In the current study the hypothesis that mifepristone (RU486), a glucocorticoid receptor antagonist, would decrease the neuroendocrine and central HPA-axis responses to an acute stressor and attentuate depressive like behavior in an animal model of behavioral helplessness (forced swim test) was tested. Adult male rats were treated with 10 mglkg RU486 (subcutaneous) for five days and then exposed to a IO-minute forced swim test (FST), conducted in Plexiglas cylinders. FST sessions were videotaped for later analysis of behavioral immobility. Plasma ACTH and corticosterone CORT were measured at 15min and 90min after FST cessation. Animals were perfused and brains were collected for immunocytochemical assessment of c-Fos expression in the medial prefrontal cortex (mPFC), a brain region implicated in both depression and central control of the HPA axis. RU486 significantly decreased peak ACTH and CORT concentrations following FST exposure. In addition, glucocorticoid negative feedback was at1enuated in RU486-treated animals exposed to the FST. Exposure to FST alone induced c-FOS expression in the mPFC, as measured by the number of c-Fos positive neurons. Treatment with RU486 significantly increased the number of rnPFC c-Fos positive cell following FST exposure. The behavioral data obtained from FST paradigm, demonstrated that RU486 decreased immobility in the FST illustrating the potential efficacy of this drug as an antidepressant. Collectively these data suggest that RU486 dampens HPA-axis responses to stress, possibly by enhancing the excitability of stress-inhibitory neurons in the mPFC. This is particularly exciting, given the fact that this neural region is associated with decreased neural activity during depression in humans.

The cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children

Background : Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children.
Methods : We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs.
Results : Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95% confidence interval $263 to $354). Influenza illnesses had a mean cost of $904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories.
Conclusion : From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.

Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle

The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no L-NAME ingestion and acute exercise, rest plus L-NAME, and rest without L-NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly (P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor-{gamma} coactivator 1beta (PGC-1beta) mRNA levels and tended (P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or beta-hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor-{gamma} coactivator 1{alpha} (PGC-1{alpha}) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL.

Exploring optimistic and pessimistic attributions in depression-specific mood

Cognitive theories of depression include maladaptive thinking styles as depressive vulnerabilities. The hopelessness theory of depression (Abramson, Metalsky, & Alloy, 1989) particularly implicates stable and global attributions for negative events as influences upon depression. Positive event attributions are considered less influential, yet they have shown equal predictiveness to negative event attributions for depression-specific mood. Previous research has provided equivocal results largely because of cross-sectional design and modest psychometric properties of the measures. The present research aimed to: create a new instrument to measure optimistic and pessimistic attributions; test the relatedness of attributions for positive and negative events; and, clarify relationships of the scales with optimism and mood. Three studies were undertaken, all of which used structural equation modeling. Two cross-sectional studies, using 342 and 332 community participants respectively, developed and validated the Questionnaire of Explanatory Style (QES). A final longitudinal study with 250 community participants tested the predictive validity of the QES. Overall, six scales were developed, three of which were optimistic and three of which were negative. The scales were acceptable to community samples and had adequate psychometric properties. The optimistic scales were attributions for positive events and the negative scales were attributions for negative events rather than pessimistic scales. Cross-sectional results indicated that only one of the negative scales weakly directly predicted depression-specific mood, but all predicted general psychological distress. By contrast, the optimistic scales were more directly predictive of depression-specific mood, particularly the Positive Disposition scale. Longitudinal results indicated that two of the optimistic scales were the most important QES predictors of depression-specific mood two months later. The optimistic scale Positive Disposition appears most central to the prediction of both concurrent and subsequent depression-specific mood. The scale content represents explanations for positive events that are internal and stable characteristics. These may be construed as personal competencies to bring about positive outcomes. This scale is closely allied to measures of optimism. Findings affirm the importance of optimistic attributions to the understanding of depression-specific mood and provide a productive focus for therapeutic intervention and future research.

The TrueBlue study : is practice nurse-led collaborative care effective in the management of depression for patients with heart disease or diabetes?

Background: In the presence of type 2 diabetes (T2DM) or coronary heart disease (CHD), depression is under diagnosed and under treated despite being associated with worse clinical outcomes. Our earlier pilot study demonstrated that it was feasible, acceptable and affordable for practice nurses to extend their role to include screening for and monitoring of depression alongside biological and lifestyle risk factors. The current study will compare the clinical outcomes of our model of practice nurse-led collaborative care with usual care for patients with depression and T2DM or CHD.

Methods: This is a cluster-randomised intervention trial. Eighteen general practices from regional and metropolitan areas agreed to join this study, and were allocated randomly to an intervention or control group. We aim to recruit 50 patients with co-morbid depression and diabetes or heart disease from each of these practices. In the intervention group, practice nurses (PNs) will be trained for their enhanced roles in this nurse-led collaborative care study. Patients will be invited to attend a practice nurse consultation every 3 months prior to seeing their usual general practitioner. The PN will assess psychological, physiological and lifestyle parameters then work with the patient to set management goals. The outcome of this assessment will form the basis of a GP Management Plan document. In the control group, the patients will continue to receive their usual care for the first six months of the study before the PNs undergo the training and switch to the intervention protocol. The primary clinical outcome will be a reduction in the depression score. The study will also measure the impact on physiological measures, quality of life and on patient attitude to health care delivered by practice nurses.

Conclusion: The strength of this programme is that it provides a sustainable model of chronic disease management with monitoring and self-management assistance for physiological, lifestyle and psychological risk factors for high-risk patients with co-morbid depression, diabetes or heart disease. The study will demonstrate whether nurse-led collaborative care achieves better outcomes than usual care.

The Cool Little Kids randomised controlled trial population-level early prevention for anxiety disorders

Background: The World Health Organization predicts that by 2030 internalising problems (e.g. depression and anxiety) will be second only to HIV/AIDS in international burden of disease. Internalising problems affect 1 in 7 school aged children, impacting on peer relations, school engagement, and later mental health, relationships and employment. The development of early childhood prevention for internalising problems is in its infancy. The current study follows two successful ‘efficacy’ trials of a parenting group intervention to reduce internalising disorders in temperamentally inhibited preschool children. Cool Little Kids is a population-level randomised trial to determine the impacts of systematically screening preschoolers for inhibition then offering a parenting group intervention, on child internalising problems and economic costs at school entry.
Methods/Design: This randomised trial will be conducted within the preschool service system, attended by more than 95% of Australian children in the year before starting school. In early 2011, preschool services in four local government areas in Melbourne, Australia, will distribute the screening tool. The ≈16% (n≈500) with temperamental inhibition will enter the trial. Intervention parents will be offered Cool Little Kids, a 6-session group program in the local community, focusing on ways to develop their child’s bravery skills by reducing overprotective parenting interactions. Outcomes one and two years post-baseline will comprise child internalising diagnoses and symptoms, parenting interactions, and parent wellbeing. An economic evaluation (costconsequences framework) will compare incremental differences in costs of the intervention versus control children to incremental differences in outcomes, from a societal perspective. Analyses will use the intention-to-treat principle, using logistic and linear regression models (binary and continuous outcomes respectively) to compare outcomes between the trial arms.
Discussion: This trial addresses gaps for internalising problems identified in the 2004 World Health Organization Prevention of Mental Disorders report. If effective and cost-effective, the intervention could readily be applied at a population level. Governments consider mental health to be a priority, enhancing the likelihood that an effective early prevention program would be adopted in Australia and internationally.