Johan Walle - Academia.edu (original) (raw)

Papers by Johan Walle

Archives of Disease in Childhood, May 18, 2023

Archives of Disease in Childhood, May 18, 2023

Continuous high off-label use of medicines in children, estimates of 50% (90% neonatal

, +32 476 466 468 Background Acute neonatal hyperammonaemia is associated with poor neurological ... more , +32 476 466 468 Background Acute neonatal hyperammonaemia is associated with poor neurological outcomes and high mortality. As these outcomes are inversely related to the duration of the hyperammonaemic coma, prompt management that guarantees a fast decline in serum ammonia is crucial. Using our experience with different dialysis machines, we developed a kinetic model for acute neonatal hyperammonaemia to draft a dialysis prescription protocol that can ensure a fast decline in serum ammonia (goal:<400µmol/L in <4hours). Methods From all dialysis sessions performed in 2020 in our centre in newborns with hyperammonaemia, dialyzer clearance and extraction ratio were calculated using intradialytic ammonia concentration-time curves. A single compartment kinetic model with a distribution volume of 60%-80% of body weight was assumed, and generation was derived from the interdialytic concentration increase.. The calibrated single compartmental model was further used to simulate serum ammonia decline in infants of 2-5kg for different ammonia start concentrations (3000, 1500, 800, 400, 200µmol/L), dialysis machines/dialyzers and settings (blood flow QB 30-50mL/min). Results Four patients (3.24±0.40 kg) underwent 13 dialyses: 5 with the 4008 machine and FXPaed dialyzer (Fresenius Medical Care, Germany); and 8 with the CarpeDiem machine (50% with 0.15m² respectively 0.25m² dialyzer) (Medtronic, USA). QB was 30-35mL/min (4008-FXPaed), 22-35mL/min (CarpeDiem 0.15), and 30-34mL/min (CarpeDiem 0.25). Extraction ratios were 38±5% for 4008-FXPaed, 10±3% and 13±3% in the CarpeDiem 0.15m² and 0.25m² dialyzer. Generation was 0.40±0.25µmol/min, with no observed impact on dialyzer clearance and extraction ratio. For start concentrations of 3000µmol/L (3kg), the time to drop <400µmol/L was, with 4008-FXPaed, 315 and 190min for a QB of 30 and 50mL/min, respectively, while it was 205 and 125min for a start concentration of 1500µmol/L, and 110 and 65min for a start concentration of 800µmol/L. In general, for start concentrations >800µmol/L in 3kg child, the CarpeDiem machine was found inadequate to decrease serum ammonia in <4h. Increasing body weight (5kg) resulted in longer time intervals to reach target. Conclusion Kinetic models can guide our management decisions and treatment protocols by predicting which treatment goals can be reached with a particular dialysis prescription, available resources and/or dialysis modality.

Pediatric Nephrology, 2014

By providing clinicians, dealing with children with CKD, with more advanced and appropriate tools... more By providing clinicians, dealing with children with CKD, with more advanced and appropriate tools to improve management of all children with CKD, i.e. better assessment of the degree of renal dysfunction, better determination of the ideal time to start renal replacement therapy, and more accurate monitoring of the quality of that renal replacement therapy, we aim to improve neurocognitive and psychosocial functioning, growth, maturation into puberty, and social integration and survival. Children with chronic kidney disease have significant co-morbidities resulting in  a lifelong need for health care  3 times decreased life expectancy  poor quality of life and integration in society Good tools to evaluate severity and monitor adequacy of treatment of children with CKD are lacking resulting in suboptimal management. Retention of uraemic toxins is accepted to play a major role in the pathogenesis of the comorbid conditions, but studies in children are lacking.

Monosymptomatic nocturnal enuresis (MNE) is frequently related to nocturnal polyuria. Desmopressi... more Monosymptomatic nocturnal enuresis (MNE) is frequently related to nocturnal polyuria. Desmopressin (dDAVP), a synthetic vasopressin analogue, is a level A, grade I treatment option in these children. In the past years we observed 6 adolescents (3 cyclers + 3 footballers, 14-18 years) with MNE from sport schools, who had dDAVP-resistant nocturnal polyuria, especially on nights following evenings with intensive physical training. This contrasted with our initial idea that following sport and dehydration, they should have lower diuresis-volumes overnight. To investigate pathophysiological mechanisms that might explain dDAVP therapy-resistance. 24-hours urine collection with timed voidings was obtained, on a day with and without evening sport training. At least 30 to 60 minutes before sleeping, two tablets of 200 µg dDAVP was given. The use of sport drinks was avoided, but there was no absolute fluid restriction in the evening. However, fluid intake was obsolete after dDAVP intake until the next morning. Diuresis-rate overnight was in 6 of 6 patients higher on the sporting than on the non-sporting evening, mainly in the first 6 hours of the night (U5-U6) (Fig.1). This was associated with lower urinary osmolality (Fig.2) and higher osmotic and sodium excretion (Fig.3). 24-hours sodium and solute excretion was not different. However, on the sporting evening there was obvious a water-and sodiumretention during the evening urine collections.

The Australian and New Zealand Continence Journal, 2014

Neurourology and Urodynamics, 2014

Therapeutic Apheresis and Dialysis, Nov 19, 2018

Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) is associated with significant mortal... more Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) is associated with significant mortality and morbidity. Case fatalities are often associated with severe neurological involvement in children and advanced age in adults but specific treatment is currently unavailable. Plasma exchange (PE) could theoretically enable removal of Shiga toxins, pro-inflammatory cytokines, and prothrombotic factors and has been used in deteriorating patients with STEC-HUS but the efficacy remains uncertain. In order to assess efficacy of PE in STEC-HUS, a literature review was performed. PubMed, Web of Science, Embase, and LiLACS were searched for reports describing the outcomes of patients with STEC-HUS treated with PE and 16 reports were included. Reports ranged from case reports to cohort studies and one case-control study with the largest study population coming from the 2011 German STEC-HUS outbreak. Outcomes were variable but seemed to point towards lower case fatality rates in the elderly and improved outcomes in children with STEC-HUS, treated with PE early in the course. However studies were mostly of low quality with risk of observation bias and confounding. Currently no definitive answers concerning the efficacy of PE in STEC-HUS can be given, highlighting the need for well performed randomized controlled trials.

The Australian and New Zealand Continence Journal, 2014

Purpose: To investigate whether cortical arousals and periodic limb movements (PLMS) during sleep... more Purpose: To investigate whether cortical arousals and periodic limb movements (PLMS) during sleep are related to daytime psychological functioning in children with monosymptomatic nocturnal enuresis (MNE) based on nocturnal polyuria (NP). Patients and methods: Thirty children (7 girls) 6 to 16 years (mean 10.43y, SD (+/-3.08)) with MNE and NP referred to a tertiary enuresis centre were included. This multi informant multi method study includes overnight video-polysomnography, questionnaires, clinical interviews and neuropsychological testing. Results: An increase in PLMS and in cortical arousals were both associated with an increase of the score on the Pediatric incontinence Quality of life questionnaire (PinQ), indicating a lower quality of life (QoL), according to the child (respectively ρ=0.517, p<0.01; ρ=0.431, p<0.05)). There is a positive linear relationship between the PLMS and rulebreaking behaviour according to the parents (ρ=0.413, p<0.05). There is a positive linear correlation between PLMS and sustained attention (ρ=0.388, p<0.05). Cortical arousals have a negative linear relationship with planning problems, an executive function, according to the teachers (ρ=-0.409, p<0.05). Conclusion: This study clarifies the relationship between sleep parameters and psychological functioning of the child with MNE according to the child, the parents and the teachers. In children with MNE and NP, PLMS and cortical arousals are both associated with a lower QoL of the child.

Introduction and management question Acute hyperammonaemia in children is associated with poor ne... more Introduction and management question Acute hyperammonaemia in children is associated with poor neurological outcomes and high mortality. As theses outcomes are inversely correlated to the duration of the hyperammonaemic coma, prompt management with conservative treatment with/without renal replacement therapy is needed. Cardio-Renal Pediatric Dialysis Emergency CRRT Machine (CarpeDiem) is demonstrated a safe and effective CRRT machine in neonates and infants. Experience on its use in acute hyperammonaemia is limited.

Archives of Disease in Childhood, May 18, 2023

Archives of Disease in Childhood, May 18, 2023

Continuous high off-label use of medicines in children, estimates of 50% (90% neonatal

, +32 476 466 468 Background Acute neonatal hyperammonaemia is associated with poor neurological ... more , +32 476 466 468 Background Acute neonatal hyperammonaemia is associated with poor neurological outcomes and high mortality. As these outcomes are inversely related to the duration of the hyperammonaemic coma, prompt management that guarantees a fast decline in serum ammonia is crucial. Using our experience with different dialysis machines, we developed a kinetic model for acute neonatal hyperammonaemia to draft a dialysis prescription protocol that can ensure a fast decline in serum ammonia (goal:<400µmol/L in <4hours). Methods From all dialysis sessions performed in 2020 in our centre in newborns with hyperammonaemia, dialyzer clearance and extraction ratio were calculated using intradialytic ammonia concentration-time curves. A single compartment kinetic model with a distribution volume of 60%-80% of body weight was assumed, and generation was derived from the interdialytic concentration increase.. The calibrated single compartmental model was further used to simulate serum ammonia decline in infants of 2-5kg for different ammonia start concentrations (3000, 1500, 800, 400, 200µmol/L), dialysis machines/dialyzers and settings (blood flow QB 30-50mL/min). Results Four patients (3.24±0.40 kg) underwent 13 dialyses: 5 with the 4008 machine and FXPaed dialyzer (Fresenius Medical Care, Germany); and 8 with the CarpeDiem machine (50% with 0.15m² respectively 0.25m² dialyzer) (Medtronic, USA). QB was 30-35mL/min (4008-FXPaed), 22-35mL/min (CarpeDiem 0.15), and 30-34mL/min (CarpeDiem 0.25). Extraction ratios were 38±5% for 4008-FXPaed, 10±3% and 13±3% in the CarpeDiem 0.15m² and 0.25m² dialyzer. Generation was 0.40±0.25µmol/min, with no observed impact on dialyzer clearance and extraction ratio. For start concentrations of 3000µmol/L (3kg), the time to drop <400µmol/L was, with 4008-FXPaed, 315 and 190min for a QB of 30 and 50mL/min, respectively, while it was 205 and 125min for a start concentration of 1500µmol/L, and 110 and 65min for a start concentration of 800µmol/L. In general, for start concentrations >800µmol/L in 3kg child, the CarpeDiem machine was found inadequate to decrease serum ammonia in <4h. Increasing body weight (5kg) resulted in longer time intervals to reach target. Conclusion Kinetic models can guide our management decisions and treatment protocols by predicting which treatment goals can be reached with a particular dialysis prescription, available resources and/or dialysis modality.

Pediatric Nephrology, 2014

By providing clinicians, dealing with children with CKD, with more advanced and appropriate tools... more By providing clinicians, dealing with children with CKD, with more advanced and appropriate tools to improve management of all children with CKD, i.e. better assessment of the degree of renal dysfunction, better determination of the ideal time to start renal replacement therapy, and more accurate monitoring of the quality of that renal replacement therapy, we aim to improve neurocognitive and psychosocial functioning, growth, maturation into puberty, and social integration and survival. Children with chronic kidney disease have significant co-morbidities resulting in  a lifelong need for health care  3 times decreased life expectancy  poor quality of life and integration in society Good tools to evaluate severity and monitor adequacy of treatment of children with CKD are lacking resulting in suboptimal management. Retention of uraemic toxins is accepted to play a major role in the pathogenesis of the comorbid conditions, but studies in children are lacking.

Monosymptomatic nocturnal enuresis (MNE) is frequently related to nocturnal polyuria. Desmopressi... more Monosymptomatic nocturnal enuresis (MNE) is frequently related to nocturnal polyuria. Desmopressin (dDAVP), a synthetic vasopressin analogue, is a level A, grade I treatment option in these children. In the past years we observed 6 adolescents (3 cyclers + 3 footballers, 14-18 years) with MNE from sport schools, who had dDAVP-resistant nocturnal polyuria, especially on nights following evenings with intensive physical training. This contrasted with our initial idea that following sport and dehydration, they should have lower diuresis-volumes overnight. To investigate pathophysiological mechanisms that might explain dDAVP therapy-resistance. 24-hours urine collection with timed voidings was obtained, on a day with and without evening sport training. At least 30 to 60 minutes before sleeping, two tablets of 200 µg dDAVP was given. The use of sport drinks was avoided, but there was no absolute fluid restriction in the evening. However, fluid intake was obsolete after dDAVP intake until the next morning. Diuresis-rate overnight was in 6 of 6 patients higher on the sporting than on the non-sporting evening, mainly in the first 6 hours of the night (U5-U6) (Fig.1). This was associated with lower urinary osmolality (Fig.2) and higher osmotic and sodium excretion (Fig.3). 24-hours sodium and solute excretion was not different. However, on the sporting evening there was obvious a water-and sodiumretention during the evening urine collections.

The Australian and New Zealand Continence Journal, 2014

Neurourology and Urodynamics, 2014

Therapeutic Apheresis and Dialysis, Nov 19, 2018

Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) is associated with significant mortal... more Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) is associated with significant mortality and morbidity. Case fatalities are often associated with severe neurological involvement in children and advanced age in adults but specific treatment is currently unavailable. Plasma exchange (PE) could theoretically enable removal of Shiga toxins, pro-inflammatory cytokines, and prothrombotic factors and has been used in deteriorating patients with STEC-HUS but the efficacy remains uncertain. In order to assess efficacy of PE in STEC-HUS, a literature review was performed. PubMed, Web of Science, Embase, and LiLACS were searched for reports describing the outcomes of patients with STEC-HUS treated with PE and 16 reports were included. Reports ranged from case reports to cohort studies and one case-control study with the largest study population coming from the 2011 German STEC-HUS outbreak. Outcomes were variable but seemed to point towards lower case fatality rates in the elderly and improved outcomes in children with STEC-HUS, treated with PE early in the course. However studies were mostly of low quality with risk of observation bias and confounding. Currently no definitive answers concerning the efficacy of PE in STEC-HUS can be given, highlighting the need for well performed randomized controlled trials.

The Australian and New Zealand Continence Journal, 2014

Purpose: To investigate whether cortical arousals and periodic limb movements (PLMS) during sleep... more Purpose: To investigate whether cortical arousals and periodic limb movements (PLMS) during sleep are related to daytime psychological functioning in children with monosymptomatic nocturnal enuresis (MNE) based on nocturnal polyuria (NP). Patients and methods: Thirty children (7 girls) 6 to 16 years (mean 10.43y, SD (+/-3.08)) with MNE and NP referred to a tertiary enuresis centre were included. This multi informant multi method study includes overnight video-polysomnography, questionnaires, clinical interviews and neuropsychological testing. Results: An increase in PLMS and in cortical arousals were both associated with an increase of the score on the Pediatric incontinence Quality of life questionnaire (PinQ), indicating a lower quality of life (QoL), according to the child (respectively ρ=0.517, p<0.01; ρ=0.431, p<0.05)). There is a positive linear relationship between the PLMS and rulebreaking behaviour according to the parents (ρ=0.413, p<0.05). There is a positive linear correlation between PLMS and sustained attention (ρ=0.388, p<0.05). Cortical arousals have a negative linear relationship with planning problems, an executive function, according to the teachers (ρ=-0.409, p<0.05). Conclusion: This study clarifies the relationship between sleep parameters and psychological functioning of the child with MNE according to the child, the parents and the teachers. In children with MNE and NP, PLMS and cortical arousals are both associated with a lower QoL of the child.

Introduction and management question Acute hyperammonaemia in children is associated with poor ne... more Introduction and management question Acute hyperammonaemia in children is associated with poor neurological outcomes and high mortality. As theses outcomes are inversely correlated to the duration of the hyperammonaemic coma, prompt management with conservative treatment with/without renal replacement therapy is needed. Cardio-Renal Pediatric Dialysis Emergency CRRT Machine (CarpeDiem) is demonstrated a safe and effective CRRT machine in neonates and infants. Experience on its use in acute hyperammonaemia is limited.