Recommendations for clinical research in children presenting to primary care out-of-hours services

BACKGROUND: Research in primary care is essential, but recruiting children in this setting can be complex and may cause selection bias. Challenges surrounding informed consent, particularly in an acute clinical setting, can undermine feasibility. The off-protocol use of an intervention nearing implementation has become common in pragmatic randomized controlled trials (RCTs) set in primary care. AIM: To describe how the informed consent procedure affects study inclusion and to assess how off-protocol medication prescribing affects participant selection in a paediatric RCT. DESIGN: A pragmatic RCT evaluating the cost-effectiveness of oral ondansetron in children diagnosed with acute gastroenteritis in primary care out-of-hours services and a parallel cohort study. METHOD: Consecutive children aged 6 months to 6 years attending primary care out-of-hours services with acute gastroenteritis were evaluated to assess the feasibility of obtaining informed consent, the off-protocol use of ondansetron, and other inclusion/exclusion criteria. RESULTS: The RCTs feasibility was reduced by the informed consent procedure because 39.0% (325/834) of children were accompanied by only one parent. General practitioners prescribed ondansetron off-protocol to 34 children (4.1%), whereof 19 children were eligible for the RCT. RCT-eligible children included in the parallel cohort had fewer risk factors for dehydration than children in the RCT despite similar dehydration assessments by general practitioners. CONCLUSION: The informed consent procedure and off-protocol use of study medication affect the inclusion rate but had little effect on selection. A parallel cohort study alongside the RCT can help evaluate selection bias, and a pilot study can reveal potential barriers to inclusion

Oral ondansetron for paediatric gastroenteritis in primary care:a randomised controlled trial

BACKGROUND: Acute gastroenteritis (AGE) affects almost all children aged ≤5 years. In secondary care, ondansetron was found to be effective at reducing vomiting. AIM: To determine the effectiveness of adding oral ondansetron to care as usual (CAU) to treat vomiting in children with AGE attending out-ofhours primary care (OOH-PC). DESIGN AND SETTING: A pragmatic randomised controlled trial at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen), with a follow-up of 7 days. METHOD: Children were included if they were: aged 6 months–6 years; AGE diagnosed by a GP; ≥4 reported episodes of vomiting in the 24 hours before presentation; ≥1 reported episode of vomiting in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated to either the control group or the intervention group. The control group received CAU, namely oral rehydration therapy. The intervention group received CAU plus one dose of oral ondansetron (0.1 mg/kg). RESULTS: In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within 4 hours from 42.9% to 19.5%, with an odds ratio of 0.37 (95% confidence interval [CI] = 0.20 to 0.72, number needed to treat: four). Ondansetron also decreased the number of vomiting episodes within 4 hours (incidence rate ratio 0.51 [95% CI = 0.29 to 0.88]) and improved overall parental satisfaction with treatment (P = 0.027). CONCLUSION: Children with AGE and increased risk of dehydration due to vomiting could be treated with ondansetron in primary care to stop vomiting more quickly and increase parental satisfaction with treatment. These results could be used to improve the quality and efficacy of general practice medicine

Focus on fatigue amongst young adults with spastic cerebral palsy

Background: This study aimed to assess fatigue amongst young adults with spastic cerebral palsy (CP), to determine subgroups at risk for fatigue and to explore the relationship between fatigue and cardiopulmonary fitness and daily physical activity level. Participants: Young adults with spastic CP, Gross Motor Function Classification System (GMFCS) levels I to III, aged 16 to 24 years. Methods: Fatigue (Fatigue Severity Scale) and self-reported daily physical activity (Physical Activity Scale for Individuals with Physical Disabilities) were assessed for 56 participants using questionnaires. Daily physical activity was objectively measured using accelerometry (Vitamove system) over 72 hours. Progressive maximal aerobic cycling was used to measure cardiopulmonary fitness. Results: The mean Fatigue Severity Scale (FSS) score was 3.7 (SD 1.4). Forty percent of participants were fatigued, including 12.5% who were severely fatigued. Participants with bilateral CP (FSS = 4.2 (SD 1.4)) were more fatigued compared to those with unilateral CP (FSS = 3.1 (SD 1.3)) (p < 0.01). Levels of cardiopulmonary fitness (2.4 L/min (SD 0.8)) and daily physical activity (8.5% (SD 3.0)) were not significantly related to fatigue (respectively p = 0.10 and p = 0.55), although for cardiopulmonary fitness a trend was found. Conclusions: Fatigue is already present at a relatively young age amongst adults with CP, and CP subtype is a determinant of fatigue. We did not find significant evidence for a cross-sectional relation of fatigue with cardiopulmonary fitness or daily physical activity. Trial registration: Nederland's trial register: NTR1785

Focus on fatigue amongst young adults with spastic cerebral palsy

textabstractBackground: This study aimed to assess fatigue amongst young adults with spastic cerebral palsy (CP), to determine subgroups at risk for fatigue and to explore the relationship between fatigue and cardiopulmonary fitness and daily physical activity level. Participants: Young adults with spastic CP, Gross Motor Function Classification System (GMFCS) levels I to III, aged 16 to 24 years. Methods: Fatigue (Fatigue Severity Scale) and self-reported daily physical activity (Physical Activity Scale for Individuals with Physical Disabilities) were assessed for 56 participants using questionnaires. Daily physical activity was objectively measured using accelerometry (Vitamove system) over 72 hours. Progressive maximal aerobic cycling was used to measure cardiopulmonary fitness. Results: The mean Fatigue Severity Scale (FSS) score was 3.7 (SD 1.4). Forty percent of participants were fatigued, including 12.5% who were severely fatigued. Participants with bilateral CP (FSS = 4.2 (SD 1.4)) were more fatigued compared to those with unilateral CP (FSS = 3.1 (SD 1.3)) (p < 0.01). Levels of cardiopulmonary fitness (2.4 L/min (SD 0.8)) and daily physical activity (8.5% (SD 3.0)) were not significantly related to fatigue (respectively p = 0.10 and p = 0.55), although for cardiopulmonary fitness a trend was found. Conclusions: Fatigue is already present at a relatively young age amongst adults with CP, and CP subtype is a determinant of fatigue. We did not find significant evidence for a cross-sectional relation of fatigue with cardiopulmonary fitness or daily physical activity. Trial registration: Nederland's trial register: NTR1785

Cost-utility of a lifestyle intervention in adolescents and young adults with spastic cerebral palsy

Objective: To evaluate the cost-utility of a lifestyle intervention among adolescents and young adults with cerebral palsy. Design: Single-blind, randomized controlled trial. Setting: Six university hospital/clinics in the Netherlands. Participants: Fifty-seven adolescents and young adults with spastic cerebral palsy classified as Gross Motor Functioning Classification System (GMFCS) level I-IV. Intervention: A 6-month lifestyle intervention consisting of physical fitness training combined with counselling sessions focusing on physical behaviour and sports participation. Main outcome measures: Data on quality of life, direct medical costs and productivity costs were collected using standardized questionnaires. Quality adjusted life years (QALYs) were derived from the Short-Form 36 questionnaire using the Short-Form 6D. Results: Quality of life remained stable over time for both groups. No significant differences between groups were found for direct medical costs or productivity costs. A cost-utility ratio of -(sic)23,664 per QALY was found for the lifestyle intervention compared with no treatment. Conclusion: The results of this study are exploratory, but indicate that implementing a lifestyle intervention for the cerebral palsy population might be cost-effective or cost-saving compared with offering no intervention to improve physical behaviour and fitness. However, the large range of uncertainty for the cost-utility ratio should be taken into account and the results interpreted with caution