Can a management pathway for chronic cough in children improve clinical outcomes: protocol for a multicentre evaluation.

BACKGROUND: Chronic cough is common and is associated with significant economic and human costs. While cough can be a problematic symptom without serious consequences, it could also reflect a serious underlying illness. Evidence shows that the management of chronic cough in children needs to be improved. Our study tests the hypothesis that the management of chronic cough in children with an evidence-based management pathway is feasible and reliable, and improves clinical outcomes. METHODS/DESIGN: We are conducting a multicentre randomised controlled trial based in respiratory clinics in 5 major Australian cities. Children (n = 250) fulfilling inclusion criteria (new patients with chronic cough) are randomised (allocation concealed) to the standardised clinical management pathway (specialist starts clinical pathway within 2 weeks) or usual care (existing care until review by specialist at 6 weeks). Cough diary, cough-specific quality of life (QOL) and generic QOL are collected at baseline and at 6, 10, 14, 26, and 52 weeks. Children are followed-up for 6 months after diagnosis and cough resolution (with at least monthly contact from study nurses). A random sample from each site will be independently examined to determine adherence to the pathway. Primary outcomes are group differences in QOL and proportion of children that are cough free at week 6. DISCUSSION: The clinical management pathway is based on data from Cochrane Reviews combined with collective clinical experience (250 doctor years). This study will provide additional evidence on the optimal management of chronic cough in children. TRIAL REGISTRATION: ACTRN12607000526471.

Improving response rates to primary and supplementary questionnaires by changing response and instruction burden: cluster randomised trial.

OBJECTIVE: Supplementary questionnaires provide additional information from subgroups, but may have an attritional effect on response rates. We examined the effects of different instruction methods on response rates to a two-part questionnaire. METHODS: The ACT Kindergarten Health Survey comprises a health questionnaire for all school-entry children. A supplementary questionnaire targets children with respiratory symptoms. We cluster-randomised 109 schools in the ACT (4,494 children) to two instruction groups. Group 1 (instruction burden) had instructions to complete the supplementary questionnaire if certain questions in the primary questionnaire were answered. Group 2 (response burden) had instructions to complete both questionnaires irrespective of answers to the primary questionnaire. RESULTS: Instructing all respondents to complete both questionnaires regardless of eligibility resulted in a statistically significantly lower primary questionnaire response rate (82% vs. 87%), but a statistically significantly higher response rate to the supplementary questionnaire (99% vs. 91%). The net effect was a small overall gain (82% vs. 79%) for the response burden group. CONCLUSION: Increasing the response burden had a minor impact on response rate to the primary questionnaire, but increased the response rate for most items to the supplementary questionnaire. IMPLICATIONS: Large surveys may be broken into primary and supplementary questionnaires, if strategies to maximise response rates are used. Questionnaires may need to be modified to take into account the likely attrition on response to either questionnaire resulting from instruction and response burdens.

Respiratory health in Aboriginal and Torres Strait Islander children in the Australian Capital Territory.

OBJECTIVES: To measure the prevalence of respiratory symptoms and atopic disease in Aboriginal and Torres Strait Islander (indigenous) and non-indigenous children in the Australian Capital Territory (ACT). METHODS: A two-stage questionnaire survey of children in the ACT with stage two completed for children identified by parents as having respiratory symptoms or asthma in the first stage cross-sectional survey. Participants in the study were: (i) all new entrant primary schoolchildren aged 4-6 years in 1999, 2000 and 2001, 217 being indigenous children and 10 604 being non-indigenous children (80% of eligible); and (ii) Year 1-6 primary schoolchildren in 2000, with 216 being indigenous children and 14 202 being non-indigenous children (52% of eligible). Respiratory symptoms (including recent wheeze and parent-reported asthma) and other factors were measured by parental questionnaire. RESULTS: Indigenous kindergarten children had more recent wheeze (21%, odds ratio (OR) 1.4 95% confidence interval (CI) 1.0-2.0)) and parent-reported asthma (24%, OR 1.8 95% CI 1.3-2.5) than non-indigenous children (both 15%). However, indigenous children had less eczema (25%, OR 0.7 95% CI 0.5-0.9) and hayfever (14%, OR 0.7 95% CI 0.5-1.0) than non-indigenous children (32% and 19%, respectively). Among children with respiratory symptoms, the symptom severity did not differ between groups, but indigenous children were exposed to more environmental tobacco smoke (ETS) (63%, OR 3.5 95% CI 2.1-5.9) than non-indigenous children (32%). CONCLUSIONS: Indigenous children in the ACT have more respiratory morbidity but less of the atopic diseases of hayfever and eczema than non-indigenous children. Whether the respiratory morbidity represents 'asthma' or results from increased ETS exposure is unclear and needs to be further explored.

Loss of interstitial cells of Cajal and development of electrical dysfunction in murine small bowel obstruction.

1. Partial obstruction of the murine ileum led to changes in the gross morphology and ultrastructure of the tunica muscularis. Populations of interstitial cells of Cajal (ICC) decreased oral, but not aboral, to the site of obstruction. Since ICC generate and propagate electrical slow waves in gastrointestinal muscles, we investigated whether the loss of ICC leads to loss of function in partial bowel obstruction. 2. Changes in ICC networks and electrical activity were monitored in the obstructed murine intestine using immunohistochemistry, electron microscopy and intracellular electrophysiological techniques. 3. Two weeks following the onset of a partial obstruction, the bowel increased in diameter and hypertrophy of the tunica muscularis was observed oral to the obstruction site. ICC networks were disrupted oral to the obstruction, and this disruption was accompanied by the loss of electrical slow waves and responses to enteric nerve stimulation. These defects were not observed aboral to the obstruction. 4. Ultrastructural analysis revealed no evidence of cell death in regions where the lesion in ICC networks was developing. Cells with a morphology intermediate between smooth muscle cells and fibroblasts were found in locations that are typically populated by ICC. These cells may have been the redifferentiated remnants of ICC networks. 5. Removal of the obstruction led to the redevelopment of ICC networks and recovery of slow wave activity within 30 days. Neural responses were partially restored in 30 days. 6. These data describe the plasticity of ICC networks in response to partial obstruction. After obstruction the ICC phenotype was lost, but these cells regenerated when the obstruction was removed. This model may be an important tool for evaluating the cellular/molecular factors responsible for the regulation and maintenance of the ICC phenotype.

Asthma screening as part of a routine school health assessment in the Australian Capital Territory.

OBJECTIVE: To determine the feasibility and performance of a routine screen for childhood asthma in new entrants to primary school relative to diagnosis by a paediatrician. DESIGN: Cross-sectional study with a validation substudy. PARTICIPANTS AND SETTING: All 4539 new primary school entrants (mean age, 5.72 years; 95% CI, 5.71-5.74) in the Australian Capital Territory (ACT) in 1999; 180 of these children (73% of the 248 contacted) participated in the validation substudy. MAIN OUTCOME MEASURE: Performance of the screening test relative to a paediatrician's diagnosis of current asthma (defined as a history of wheeze suggestive of a clinical diagnosis of asthma within the past 12 months) based on history and examination. RESULTS: 3748 of the 4539 new primary school entrants (83%) returned completed asthma and respiratory questions. The screening test was positive in 38% of children. Estimated sensitivity was 92% (95% CI, 75%-99%); specificity, 76% (95% CI, 72%-80%); positive predictive value, 51% (95% CI, 41%-63%); negative predictive value, 98% (95% CI, 90%-100%); positive likelihood ratio, 3.8 (95% CI, 2.8-4.8); and negative likelihood ratio, 0.14 (95% CI, 0.02-0.33). CONCLUSIONS: It is feasible to conduct population screens for asthma that have good diagnostic test performance against a specialist paediatrician's diagnosis through school health programs. This approach could facilitate monitoring changes in asthma prevalence over time.

Regulation of pacemaker currents in interstitial cells of Cajal from murine small intestine by cyclic nucleotides.

1. Electrical rhythmicity (slow waves) in gastrointestinal muscles (GI) is generated by interstitial cells of Cajal (ICC). Cultured ICC from the murine small intestine were studied with the patch-clamp technique to characterize regulation of pacemaker currents by cyclic nucleotides. Cyclic nucleotide agonists were also tested on intact strips of murine small intestine. 2. Nitric oxide donors slowed the frequency of pacemaker currents in a concentration-dependent manner. These effects depended on cGMP formation and were reduced by 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The effects of nitric oxide donors were mimicked by membrane-permeable analogues of cGMP. The specific cGMP phosphodiesterase inhibitor zaprinast reduced the frequency of spontaneous pacemaker currents. 3. The cGMP-dependent effects on pacemaker currents were not affected by okadaic acid or KT-5823, an inhibitor of protein kinase G. 4. Forskolin, but not dideoxy forskolin, reduced the frequency of spontaneous pacemaker activity and activated a sustained outward current. The latter was likely to be due to ATP-dependent K+ channels because it was blocked by glibenclamide. 5. The effects of forskolin were not mimicked by membrane-permeable cAMP analogues. A membrane-permeable inhibitor of protein kinase A, myristoylated PKA inhibitor, and the adenylyl cyclase inhibitor SQ-22536, had no effect on responses to forskolin. 6. Responses of intact muscles to cGMP and cAMP agonists were similar to the responses of pacemaker cells. Changes in resting membrane potential and slow wave amplitude, however, were noted in intact jejunal muscles that were not observed in ICC. Differences in responses may have been due to the effects of cyclic nucleotide agonists on smooth muscle cells that would sum with responses of ICC in intact jejunal muscle strips. 7. A cGMP-dependent mechanism regulates slow wave frequency, but this occurs through direct action of cGMP not via protein phosphorylation. Regulation of pacemaker currents by cAMP-dependent mechanisms was not observed.

When doctors lack knowledge and deal with uncertainty.

General practitioners are often confronted with problems, where their knowledge base may be lacking and/or diagnostic uncertainty exists, but competent management is still needed. Sometimes a case brings these issues very much to the fore, and in this case study the problem of familial Mediterranean fever is used to highlight some of the issues involved. This article also summarises this unusual condition which, with recent immigration patterns, may become more frequent in Australasia.

Doing randomized controlled trials in a developing country: some practical realities.

BACKGROUND: Formal randomized controlled trial results are often reported. The difficulties of doing such trial are not. Developing countries represent a new field in which trials can be undertaken. In this context even less is known about the practicalities involved. METHOD AND RESULTS: A randomized, double-blind, parallel study took significantly longer than expected to complete and subject recruitment and participation fell short of expectations. Different recruitment strategies were used and these performed differently in terms of enrolling trialists. Subjects most frequently left the trial in its early stages. CONCLUSIONS: Possible explanations for these findings include the demography of the country, cultural factors, and the existence of an established doctor-patient relationship.