Coded diagnoses from general practice electronic health records are a feasible and valid alternative to self-report to define diabetes cases in research.

AIMS: To examine the feasibility and validity of obtaining International Classification of Primary Care (ICPC)-coded diagnoses of diabetes mellitus (DM) from general practice electronic health records for case definition in epidemiological studies, as alternatives to self-reported DM. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort study of 6671 persons aged 45-65 years at baseline, included between 2008-2012. Data from electronic health records were collected between 2012-2014. We defined a reference standard using diagnoses, prescriptions and consultation notes and investigated its agreement with ICPC-coded diagnoses of DM and self-reported DM. RESULTS: After a median follow-up of 1.8 years, data from 6442 (97%) participants were collected. With the reference standard, 506 participants (79/1000 person-years) were classified with prevalent DM at baseline and 131 participants (11/1000 person-years) were classified with incident DM during follow-up. The agreement of prevalent DM between self-report and the reference standard was 98% (kappa 0.86), the agreement between ICPC-coded diagnoses and the reference standard was 99% (kappa 0.95). The agreement of incident DM between ICPC-coded diagnoses and the reference standard was >99% (kappa 0.92). CONCLUSIONS: ICPC-coded diagnoses of DM from general practice electronic health records are a feasible and valid alternative to self-reported diagnoses of DM.

Clinical experience with icodextrin in children: ultrafiltration profiles and metabolism.

Icodextrin use in adults provides sustained ultrafiltration (UF) in long-term dwells. No information is available on UF and metabolism in children. In 11 children, a volume of 1,049+/-138 ml/m2 of the study fluid (1.36% glucose, 7.5% icodextrin, 3.86% glucose) was administered for 12 h. Net UF with icodextrin (339+/-147 ml/1.73 m2) did not differ from UF with 3.86% glucose (450+/-306 ml/1.73 m2, P=0.53) and was higher than UF with 1.36% glucose (-87+/-239 ml/1.73 m2, P=0.003). Icodextrin added 0.52+/-0.07 to the weekly Kt/V. Over 6 weeks, icodextrin was used for 12-h daytime dwell. Total icodextrin reached a steady-state level of 2.91+/-1.22 g/l at 2 weeks. The main icodextrin metabolites were maltose, maltotriose, and maltotetraose. After 2 weeks, steady state levels were 2.02+/-0.66 mmol/l, 1.46+/-0.35 mmol/l, and 0.45+/-0.12 mmol/l. No icodextrin or metabolites were detectable 4 weeks after the study. We conclude that 7.5% icodextrin is capable of maintaining UF during 12-h dwell in children and is comparable to UF obtained with 3.86% glucose. Steady-state levels of icodextrin and metabolites were reached at 2 weeks and disappeared after the study.

Treatment of hyperhomocysteinemia in children on dialysis by folic acid.

Adult patients with renal failure have a high total homocysteine concentration in plasma. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Folic acid lowers the homocysteine concentrations in plasma in hyperhomocysteinemia. Whether this results in a reduced risk for cardiovascular diseases remains to be proven by intervention studies. In the present study we investigated: (1) if homocysteine concentrations are elevated in the plasma of children with renal failure and (2) the influence of folic acid administration on the plasma homocysteine concentration. The plasma homocysteine concentration was measured in 21 children, 9 on hemodialysis and 12 on peritoneal dialysis, before and 4 weeks after treatment with 2.5 mg folic acid daily. Healthy children (234) constituted the control group. In controls the median homocysteine concentration was 9.1 micromol/l (range 4.3-20.0 micromol/l). The median plasma homocysteine concentration in patients before folic acid treatment was 20.0 micromol/l (Q1-Q3 13.7-26.0; Q, quartile). After 4 weeks of folic acid treatment the median plasma homocysteine concentration was 12.0 micromol/l [Q1-Q3 9.8-14.3 (P<0.0001 Wilcoxon signed rank test)]. There was no significant difference between hemodialysis and peritoneal dialysis patients. Children with renal failure treated with hemodialysis or peritoneal dialysis have elevated plasma homocysteine concentrations, but this is significantly reduced after administration of 2.5 mg folic acid daily for 4 weeks. It is suggested that folic acid be added to the treatment of children with renal failure, although a beneficial effect still has to be proven. The required dose needs further study.

Intraperitoneal hypercoagulation and hypofibrinolysis is present in childhood peritonitis.

An increased rate of obstruction of peritoneal dialysis catheters is observed during peritonitis. Hypercoagulation and hypofibrinolysis may explain this increased occurrence. We studied plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA), D-dimer (DD), plasmin-alpha2-antiplasmin complexes (PAP), and thrombin-antithrombin III complexes (TAT) in 7 children with peritonitis (group A) and 12 children during stable peritoneal dialysis (group B). Albumin, beta2-microglobulin, IgG, and alpha2-macroglobulin were measured for baseline transperitoneal protein transport. After a dwell of 6 h with 1.36% Dianeal, dialysate and serum samples were collected. Dialysate to plasma ratios of all proteins were calculated. During peritonitis (group A) TAT was higher: 34.7 versus 22.0 (P=0.01). PAI-1 was increased in group A: 76.5 versus 22.9 (P=0.004). PAP was decreased during peritonitis (group A): 24.9 versus 39.3 (P=0.01). In group A, DD were decreased. 10.8 versus 26.7 (P=0.002). t-PA was similar in both groups (23.7 in group A vs. 27.7 in group B; P=0.26). In both groups TAT, PAI-1, t-PA, PAP, and DD were significantly higher than in baseline transperitoneal transport, suggesting intraperitoneal production. Hypercoagulability and hypofibrinolysis were present during peritonitis compared with the control situation.

Follow-up study of peritoneal fluid kinetics in infants and children on peritoneal dialysis.

OBJECTIVES: To study longitudinal changes in transcapillary ultrafiltration (TCUF) and marker clearance (MC), as a reflection of lymphatic absorption, in children on peritoneal dialysis (PD). To present data on fluid kinetics in infants younger than 2.5 years, using an intraperitoneal volume of 1200 mL/m2 body surface area (BSA). DESIGN: The study involved a 4-hour dwell of 1200 mL/m2 BSA of dialysis fluid containing 3.86% glucose with Dextran 70 as volume marker. Cumulative TCUF and cumulative MC were measured. SETTING: A tertiary-care university hospital. PATIENTS: A follow-up period of 33 months of serial (1 - 4) peritoneal equilibration tests (PETs) was studied in 20 children with a median age of 6.4 years (range 2.1 - 15.4 years). Fluid kinetics in 5 additional infants with a median age of 1.4 years (range 0.5 - 2.5 years) was measured. RESULTS: Cumulative TCUF was 1041 mL/1.73 m2 at 1 - 3 months after start of PD, 1026 mL/1.73 m2 at 7 - 9 months, 1021 mL/1.73 m2 at 11 - 13 months, and 756 mL/1.73 m2 at 26 - 33 months (NS). Cumulative MC was 235 mL/1.73 m2 at 1 - 3 months after start of PD, 311 mL/1.73 m2 at 7 - 9 months, 395 mL/1.73 m2 at 11 - 13 months, and 509 mL/1.73 m2 at 26 - 33 months (NS). In infants, cumulative TCUF was 755 +/- 237 mL/1.73 m2; cumulative MC was 400 +/- 214 mL/1.73 m2. CONCLUSIONS: Transcapillary ultrafiltration and marker clearance do not change in children > 2.5 years during the period studied. Fluid kinetics does not differ between infants < 2.5 years and older children when intraperitoneal volumes of 1200 mL/m2 BSA are used.

Peritoneal protein loss in children with nephrotic syndrome during peritoneal dialysis.

BACKGROUND: The passage of proteins across the glomerular filtration barrier is mainly determined by the size of the protein. In nephrotic syndrome (NS) the glomerular permselectivity is affected, causing proteinuria. Some authors suggest the existence of a generalized basement membrane defect. The permeability characteristics of the peritoneal basement membrane in children with NS are not known. METHODS: The transperitoneal transport of proteins with a different molecular weight (beta2-microglobulin MW 11800 D, albumin MW 69000 D, IgG MW 160000 D, and alpha2-macroglobulin MW 820000 D) was studied in a study group (group A) consisting of six stable nephrotic children (three with glomerulosclerosis and three with congenital nephrotic syndrome, one of them with mesangial sclerosis) and compared to a control group (group B) consisting of eight stable children on peritoneal dialysis. After a dwell of 6 h with Dianeal 1.36% dialysate and serum samples were collected. For each patient the dialysate to plasma (D/P) ratios of the four proteins were calculated. The D/P ratios of the nephrotic patients in group A were compared to the D/P ratios of the patients in the control group B. Data were expressed as mean +/- SD. RESULTS: The values for the D/P ratios (in percentage) of beta2-microglobulin, albumin, IgG and alpha2-macroglobulin in group A were 19.6+/-9.9, 2.7+/-1.7, 1.6+/-0.9, and 0.5+/-0.4, compared to 24.9+/-10.2, 4.0+/-2.3, 2.2 +/- 1.2, and 0.7 +/- 0.3 in the control group B. The ratios were plotted against MW on a double logarithmic scale. In all patients a linear relationship between molecular weight and D/P ratio of the proteins was obtained. The D/P ratios of the study group did not differ significantly from the control group. CONCLUSION: We conclude that the size selectivity of the capillary permeability is not affected in the peritoneal membrane in children with NS due to glomerulosclerosis and congenital nephrotic syndrome.

Increase of the bioavailability of intraperitoneal erythropoietin in children on peritoneal dialysis by administration in small dialysis bags.

OBJECTIVE: To establish the effectivity of administration of erythropoietin intraperitoneally in a small amount of fluid in children with renal anemia on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective study in which children with renal anemia on CAPD were treated with erythropoietin intraperitoneally, administered in a specially designed bag containing 50 mL NaCl 0.9%. SETTING: University hospital. PATIENTS: The patient population consisted of 9 children treated with CAPD and 1 treated with nightly intermittent peritoneal dialysis. The median age was 7.8 years (range 4.1-15.2). Four of these children had not been treated with erythropoietin before (group A), and 6 had been treated with erythropoietin administered intraperitoneally in 250 mL of dialysis fluid (group B). INTERVENTIONS: Patients in group A started on a dose of approximately 300 units/kg per week (group A). Patients in group B received their previous dose. Dosage was adjusted to achieve a target hemoglobin level of 6.5-7.0 mmol/L (104-112 g/L). Serum ferritin levels and transferrin saturation were monitored and iron supplementation was prescribed in the case of iron deficiency. MAIN OUTCOME MEASURES: Weekly erythropoietin dose in relation to hemoglobin level. RESULTS: In group A, median hemoglobin level rose from 5.3 mmol/L (85 g/L) to 6.6 mmol/L (106 g/L) after 6 months of therapy, whereas the median erythropoietin dose decreased from 266 to 234 U/kg/week. In group B, hemoglobin levels remained stable and median erythropoietin dose decreased from 262 to 194 U/kg/week. One patient in this group, for unknown reasons, never responded to erythropoietin treatment. He was excluded from further analysis. In the remaining 5 patients the median cumulative erythropoietin dose was 3250 U/kg in the 3-month period prior to the start of the study and 2713 in the 3-month period starting 6 months after the beginning of the study. This difference of 17% was statistically significant using a Wilcoxon test (p < 0.05). CONCLUSION: Intraperitoneal administration of erythropoietin in a small amount of dialysis fluid leads to a decrease in the required dose.

Immunological studies in the hyper-immunoglobulin D syndrome.

Five patients with hyper-immunoglobulin D syndrome (hyper-IgD syndrome) were followed up for 3 to 8 years. In all patients studied, serum IgG3 was high. IgM decreased during the follow-up in all patients. In four of the patients serum IgA was elevated. In four patients the serum IgD kappa/lambda ratio was measured and was found to be raised in all. However, the serum total light-chain ratio and IgG, IgA, and IgM kappa/lambda ratios separately were virtually normal. In two of the patients, clinical symptoms preceded the increase in serum IgD. All patients had a history of severe reactions on immunizations in early childhood. We conclude that in hyper-IgD syndrome, other immunoglobulins may also be affected, in particular, IgA, IgM, and IgG3. The IgD light-chain ratio is also disturbed. We emphasize that clinical symptoms may herald immunological changes. This may be the result of an underlying factor causing both the clinical symptoms and, later, the increasing serum IgD levels.

Iatrogenic IgG2 deficiency in a leukaemic child. A case report.

A girl with acute non-lymphoblastic leukaemia was treated with immunosuppressive chemotherapy. After cessation of therapy she had three consecutive episodes of infection due to Streptococcus pneumoniae from which she recovered and was shown to have developed a combined deficiency of both IgG2 and IgG4. The patient eventually relapsed and died 3 years after the initial diagnosis. The importance of measuring IgG subclasses in patients treated with immunosuppressive chemotherapy is discussed.

Mild course of mumps in patients with acute lymphoblastic leukaemia.

Few details exist on the course of mumps during cytostatic treatment. We therefore describe our observations on the course of mumps seen between 1974 and 1988 in eight children suffering from acute lymphocytic leukaemia (ALL). Our data suggest that in malignant disease the course is rarely severe and that the infection often remains subclinical, as in healthy children. Mumps was accidentally diagnosed by routine lumbar puncture in four of the eight patients. Literature data suggest that the intrinsic low cytopathological effect of the virus, together with a parallelism between T cell response and clinical severity, may explain the usual mild course in immunodepressed patients, contrasting with the severe course of measles and Varicella zoster.