Cerebral blood flow and heart rate variability in chronic fatigue syndrome : a randomized cross-over study

Background: Pain, fatigue, and concentration difficulties are typical features of chronic fatigue syndrome (CFS). The exact underlying mechanisms of these symptoms are still unknown, but available evidence suggests an important role for impaired pain modulation. As evidence also suggests that pain modulation is related to cardiovascular mechanisms, it seems logical to investigate whether cerebral blood flow (CBF) and heart rate variability (HRV) are altered in these patients. Objectives: We aimed to investigate the role of the cardiovascular system in pain modulation and symptoms of CFS; the response of CBF and HRV to physical stress and their relation to the change in temporal summation (TS) of pressure pain and self-reported symptoms was evaluated. Study Design: A controlled, randomized cross-over trial. Setting: University Hospital Brussels. Methods: Twenty CFS patients and 20 sedentary healthy controls were included in this study. In both of the groups, the change in TS of pressure pain, CBF (using transcranial Doppler), and HRV (using finger plethysmography) was examined during physical and emotional stress (to control for potential bias), as well as their association mutually and with self-reported symptoms of pain, fatigue, and concentrations difficulties. Results: There was no significant interaction or group (F-values ranging from .100 to 1.862, P-values ranging from .754 to .181) effect in CBF or HRV parameters. HRV and CBF did change during physical exercise, but the changes did not differ between patients and controls. While pain scores during TS at the trapezius site reduced in the control group after the physical exercise protocol (P=.037), they did not change in the CFS group (P=.108), suggesting impaired pain modulation. There were no significant correlations between CBF, HRV, TS, and self-reported symptoms (all P-values of correlation analyses > .01). Limitations: Although effect sizes were medium to large, the study sample was relatively low. Also, the mild nature of the exercise bout is discussable. Nonetheless, this mild exercise was able to provoke endogenous pain modulation in the control group, which endorsed a proper execution of the cycling exercise. Moreover, mild exercises are more applicable to daily physical activities in CFS patients than vigorous exercises. Conclusion: These results seem to refute the previously suggested alterations of CBF/HRV in CFS patients. These cardiovascular parameters appear not to explain pain before, during, and following exercise

Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial)

Background: Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. Methods: The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18–24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. Discussion: Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. Trial registration: ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020

Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial)

Abstract Background Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. Methods The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18–24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. Discussion Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. Trial registration ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020

Endogenous pain modulation in children with functional abdominal pain disorders

Functional abdominal pain disorders (FAPDs) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry, and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age- and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds (PPTs) at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. Conditioned pain modulation was recorded as an increase in the PPT at the trapezius test site in response to experimental conditioning pain imposed by the cold pressor task (12 +/- 1 degrees C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear, and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower PPTs at all test sites (P 0.05), nor was there a significant correlation between the child- and parent-reported questionnaires and the CPM effect (P > 0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia

Central pain modulation in children with functional abdominal pain related disorders

Introduction:Functional abdominal pain related disorders (FAPD) are common among young individuals. To date, relatively little is known regarding the function of the central pain mechanisms in this vulnerable group. Therefore, this study aimed to compare conditioned pain modulation (CPM), pressure algometry and psychosocial variables in young children (aged 6-12 years) with FAPD and healthy controls. Methods:Thirty-nine children diagnosed with FAPD were compared with 36 age –and sex matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds at both symptomatic (umbilicus) and non-symptomatic (trapezius and tibia) test sites. CPM was recorded as an increase in the pain pressure threshold at the trapezius test site in response to experimental conditioning pain imposed by the cold pressure task (12°C ± 1°C). The assessors were blinded to the type of subject assessed. Parent-proxy and/or self-reported questionnaires were used to assess pain intensity, functional disability, pain-related fear and parental pain catastrophizing. Results:Compared with pain-free controls, young children with FAPD showed lower pressure pain thresholds at all test sides (P<.5), a less efficient CPM response (P=.2), more functional disability (P<.1) and pain related fear (P<.1). Parents of children with FAPD catastrophized more about their child’s pain than parents of healthy controls (P<.1). Discussion:Young children with FAPD demonstrated less efficient central pain modulation. Future research should control for psychosocial variables while testing CPM, given their direct effect on descending pain modulation through activation of the facilitatory pathways. Process evaluation: The full-out written manuscript of this study is currently under review by all co-authors prior to the submission process. Developing a standardized CPM paradigm for our study population, as well as selecting the proper questionnaires to assess for psychosocial variables was challenging, given their young age (6-12 years). Other experienced problems related to this study can mainly be categorized as practical problems, such as patient recruitment and availability of the assessors and the testing room. References: Morris MC, Walker LS, Bruehl S, Stone AL, Mielock AS, Rao U. Impaired conditioned pain modulation in youth with functional abdominal pain. Pain [Internet]. 216;157(1):2375–81. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27389918 Williams AE, Heitkemper M, Self MM, Czyzewski DI, Shulman RJ. Endogenous inhibition of somatic pain is impaired in girls with irritable bowel syndrome compared with healthy girls. J Pain [Internet]. Elsevier Ltd; 213;14(9):921–3. Available from: http://dx.doi.org/1.116/j.jpain.213.3.3 Pas R, Ickmans K, Oosterwijck S Van, Van Der Cruyssen K, Foubert A, Leysen L, et al. Hyperexcitability of the Central Nervous System in Children with Chronic Pain: A Systematic Review. Pain Med [Internet]. 217;(January):1–11. Available from: https://academic.oup.com/painmedicine/advance-article-abstract/doi/1.193/pm/pnx32/47831

The Impact of the COVID-19 Pandemic on Lifestyle and Wellbeing of Children, Adolescents and Their Parents:A Qualitative Study

Prior studies have shown that changes in daily structure and habits due to the COVID-19 pandemic affected the lifestyle and wellbeing of families. This study aimed to obtain in-depth information on children's and adolescents' experiences regarding their lifestyle and wellbeing during the pandemic. Semi-structured interviews with fifteen families were carried out between May and November 2021. Directed content analysis was used to analyze the transcripts and fundamental qualitative description to describe the results. Children and adolescents revealed an overall unhealthier lifestyle and decreased wellbeing. These negative effects were even larger in adolescents and children with overweight or psychosocial complaints. Our results revealed that parents were actively involved in maintaining a normal daily structure. Furthermore, diet changes were inconsistent and dependent on food availability. An increase in screen time was experienced as inevitable, and external influences were necessary to keep children and adolescents active. Almost no effects were reported on physical health, whereas negative emotions were experienced in varying degrees. Moreover, the decrease in social interactions was reported as the most negative effect of the pandemic. The above-mentioned insights may contribute to the development of preventive measures to promote a healthy lifestyle and wellbeing of children and adolescents during future pandemics

The Effect of a Multidisciplinary Lifestyle Intervention on Health Parameters in Children versus Adolescents with Severe Obesity

Lifestyle interventions are the common treatment for children and adolescents with severe obesity. The efficacy of these interventions across age groups remain unknown. Therefore, this study aimed to compare the effectiveness of a lifestyle intervention on health parameters between children and adolescents with severe obesity. A longitudinal design was carried out at the Centre for Overweight Adolescent and Children's Healthcare (COACH) between December 2010 and June 2020. Children (2-11 years old, n = 83) and adolescents (12-18 years old, n = 77) with severe obesity received a long-term, tailored, multidisciplinary lifestyle intervention. After 1 year, 24 children (28.9%) and 33 adolescents (42.9%) dropped out of the intervention. The primary outcome was the change in body mass index (BMI) z-score after one and two years of intervention. The decrease in BMI z-score over time was significantly higher in children compared to adolescents, the mean decrease was 0.15 (0.08-0.23) versus 0.03 (-0.05-0.11) after one year and 0.25 (0.15-0.35) versus 0.06 (-0.06-0.17) after two years of intervention; p values for the difference between children and adolescents were 0.035 and 0.012. After two years, multiple improvements in cardio metabolic health parameters were observed, especially in children. In conclusion, during our tailored lifestyle intervention, a positive and maintained effect on health parameters was observed in children with severe obesity. Compared to children, the effect on health parameters was less pronounced in adolescents