The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group.

OBJECTIVE: To analyze the change in the age distribution at onset of type 1 diabetes in boys and girls aged 1-14 years during a 32-year period (from 1965 to 1996). RESEARCH DESIGN AND METHODS: Data on the incidence of type 1 diabetes in Finland were obtained from the Central Drug Registry of the Social Insurance Institution for 1965-1986 (6,195 cases) and from the Prospective Childhood Diabetes Registry for 1987-1996 (3,613 cases). The change in age- and sex-specific incidence was estimated by fitting the linear regression with the logarithm of the annual incidence data. Analysis of variance was used to compare the trends between the various age-groups (1-4, 5-9, and 10-14 years) and sexes. RESULTS: The incidence of type 1 diabetes increased predominantly in the younger age-groups. In children aged 1-4 years, the increase was 4.2% per year, and the overall 32-year relative increase was 338%. For children aged 5-9 and 10-14 years, the increase was 2.5 and 1.3% per year, respectively, and the overall relative increase was 116 and 49%, respectively. In boys aged 1-9 years, the increase was greatest from 1965 to 1984, whereas in girls aged 1-9 years, the statistically significant increase occurred between 1985 and 1996. In children aged 10-14 years, the only significant increase was seen in boys from 1965 to 1974 (3.7% per year). CONCLUSIONS: The greatest increase in the incidence of type 1 diabetes mainly occurred in children aged < 5 years. The incidence in young boys has been increasing since the mid-1960s, whereas in young girls, the significant increase began later, around the mid-1970s. In children aged 10-14 years, the increase in incidence has leveled off.     

Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group

OBJECTIVE: To evaluate whether the increased risk of type 1 diabetes conferred by an early introduction of cow's milk supplements can be mediated by accelerated growth in formula-fed infants. RESEARCH DESIGN AND METHODS: All children < or = 14 years of age who were diagnosed with type 1 diabetes from September 1986 to April 1989 were invited to participate in the study. Birth date- and sex-matched control children were randomly selected from the Finnish Population Registry. At least three weight measurements from the first year of life were obtained for 435 full-term diabetic subjects and 386 control subjects from well-baby clinics and school health care units. RESULTS: Increase in body weight was greater in the diabetic girls than in the control girls, and the difference increased from 111 g (95% CI 0-218, P = 0.04) at 1 month of age to 286 g (95% CI 123-450, P = 0.0006) at 7 months. For boys, the difference in weight between the diabetic subjects and the control subjects remained stable during infancy (difference 95 g, 95% CI-2-205, P = 0.09). Increased weight was associated on average with a 1.5-fold risk of type 1 diabetes. Early introduction of formula feeding (< 3 vs. > or = 3 months) was also associated with an increased risk of type 1 diabetes after adjustment for the individual weight gain curve (adjusted odds ratio 1.53, 95% CI 1.1-2.2). No evidence for interaction was observed. CONCLUSIONS: These observations indicate that an early exposure to cow's milk formula-feeding and rapid growth in infancy are independent risk factors of childhood type 1 diabetes.     

Increasing trend of outpatient management of children with newly diagnosed IDDM. Colorado IDDM Registry, 1978-1988.

OBJECTIVE--To examine the management of newly diagnosed insulin-dependent diabetes mellitus (IDDM) in Colorado over time and to determine the prevalence of outpatient care at IDDM diagnosis on a statewide basis. RESEARCH DESIGN AND METHODS--The Colorado IDDM Registry was used to assess medical care at the diagnosis of IDDM in 1182 patients less than 18 yr of age between 1978 and 1988. RESULTS--Twenty-three percent of children with IDDM in Colorado reported never being hospitalized during the diagnosis period. Treatment of IDDM at diagnosis (outpatient vs. inpatient) did not differ by age, sex, or ethnicity/race. Patients living in rural counties were less likely to have been treated as outpatients at diagnosis than those living in urban counties. Physicians at specialized diabetes clinics (e.g., The Barbara Davis Center for Childhood Diabetes and The Childrens Hospital) were more likely to treat newly diagnosed children in an outpatient setting than physicians not affiliated with these clinics. The proportion of patients receiving only outpatient care at IDDM diagnosis increased from 6% in 1978 to 35% in 1988. This increase can be attributed to three factors: 1) an increase in the number of Colorado children diagnosed at The Barbara Davis Center, where outpatient care is strongly advocated; 2) a change in treatment practices at The Childrens Hospital away from routine hospitalization at onset; and 3) a steady increase in outpatient care for newly diagnosed diabetic children by physicians who were not affiliated with the aforementioned specialized diabetes clinics. CONCLUSIONS--The relatively new practice of outpatient care at diagnosis of IDDM increased between 1978 and 1988 in Colorado, in both specialized diabetes clinics and physicians' practices not affiliated with specialized clinics.     

Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group.

An unselected population of 755 siblings of children with insulin-dependent diabetes mellitus (IDDM) was studied to evaluate the predictive characteristics of islet cell antibodies (ICA), antibodies to the IA-2 protein (IA-2A), antibodies to the 65-kD isoform of glutamic acid decarboxylase (GADA), insulin autoantibodies (IAA), and combinations of these markers. We also evaluated whether the histochemical ICA test could be replaced by the combined detection of other markers. 32 siblings progressed to IDDM within 7.7 yr of the initial sample taken at or close to the diagnosis of the index case (median follow-up, 9.1 yr). The positive predictive values of ICA, IA-2A, GADA, and IAA were 43, 55, 42, and 29%, and their sensitivities 81, 69, 69, and 25%, respectively. In contrast to the other three antibody specificities, GADA levels were not related to the risk for IDDM. The risk for IDDM in siblings with four, three, two, one, or no antibodies was 40, 70, 25, 2, and 0.8%, respectively. Combined screening for IA-2A and GADA identified 70% of all ICA-positive siblings, and all of the ICA-positive progressors were also positive for at least one of the three other markers. The sensitivity of the combined analysis of IA-2A and GADA was 81%, and the positive predictive value was 41%. In conclusion, combined screening for IA-2A and GADA may replace the ICA assay, giving comparable sensitivity, specificity, and positive predictive value. Accurate assessment of the risk for IDDM in siblings is complicated, as not even all those with four antibody specificities contract the disease, and some with only one or no antibodies initially will progress to IDDM.     

Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM

OBJECTIVE: In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS: Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulin-dependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6-wk screening phase with conventional dietary treatment. During the follow-up, the control group (n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group (n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity. RESULTS: Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P less than 0.01). The better glycemic control was achieved with fewer antidiabetic drugs. After 5 yr, antidiabetic drugs were prescribed to 47% of the control subjects, 28% of the IHE group, and 34% of the IHE plus clofibric acid group (cutoff limit for drug application was postprandial blood glucose of greater than or equal to 13.87 mM). The ratio of polyunsaturated to saturated fatty acids (0.26 vs. 0.40, P less than 0.01) and physical activity (174 vs. 327 scores, P less than 0.01) were increased, and blood pressure, tobacco, and alcohol consumption were significantly reduced by IHE. However, IHE had no effect on calorie intake, percentage of fat in the diet (45%), and body weight. The most important finding was the significant increase of blood cholesterol in all three groups (+0.47, +0.36, and +0.34 mM, respectively). Clofibric acid only prevented the increase of triglyceride levels (+0.56, +0.24, and +0.05 mM, respectively). The incidence rate per 1000 for myocardial infarction was 30.3 for control subjects, 53.6 for the IHE group, and 55.6 for the IHE plus clofibric acid group. The corresponding rates for IHD incidence were 90.9, 97.8, and 98.8, respectively. Men suffered more frequently from myocardial infarction, whereas women developed ECG criteria for IHD more frequently. Among the 35 cases of death, besides cardiovascular diseases, liver cirrhosis and neoplasia were the predominant causes. The death rate per 1000 in control subjects was 46.2, 30.6 in the IHE group, and 27 among patients with IHE plus clofibric acid. CONCLUSIONS: IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides.     

Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group

OBJECTIVE: To study the characteristics of type 1 diabetes in very young children. RESEARCH DESIGN AND METHODS: Clinical outcome, islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies against GAD (GADA), IA-2 antibodies (IA-2A), and HLA-DQB1-defined genetic risk were analyzed in 35 children diagnosed with type 1 diabetes before 2 years of age and compared with those in 146 children who were diagnosed between 2.0 and 4.9 years of age and with those in 620 children diagnosed between 5.0 and 14.9 years of age. RESULTS: The youngest age-group had severer metabolic decompensation at clinical onset, and their serum C-peptide levels, compared with those of older children, were lower at the time of diagnosis and during the first 2 years after the diagnosis. The levels of ICA and IAA were highest in children < 2 years of age, but there were no differences in GADA levels among the three age-groups. The youngest age-group had the lowest IA-2A levels. The HLA DQB1*02/*0302 genotype associated with strong genetic susceptibility was more frequent in children diagnosed < 5 years of age, whereas the proportion of children carrying a genotype, which includes protective alleles, was higher among those diagnosed at > or = 5 years of age. CONCLUSIONS: The clinical presentation of type 1 diabetes at a very young age is associated with severe metabolic decompensation, poorly preserved residual beta-cell function, strong humoral autoimmunity against islet cells and insulin, and strong HLA-defined disease susceptibility.     

Colorado IDDM Registry. Incidence and validation of IDDM in children aged 0-17 yr

The purpose of this study was to determine the incidence of insulin-dependent diabetes mellitus (IDDM) among children aged 0-17 yr for age, sex, season, and urban and rural residence of onset in Colorado. Retrospective registration of new-onset cases was conducted from 1978 to 1980, and then prospective registration continued through 1983 with the use of physician reporting with hospital validation. The annual incidence of IDDM was 15.2/100,000 per year (95% confidence interval [CI] 14.1, 16.3), with little difference between the sexes. The highest incidence was in the 10- to 14-yr age-group for both sexes. There was a seasonal peak of winter onset in those aged 10-17 yr, with similar patterns between sex and ethnic groups. No temporal trend over the 6 yr was seen, although an excess of cases was seen for 15- to 17-yr-old boys in 1980-1982. Rates were similar for urban and rural areas of the state. Case ascertainment was estimated to be 93.2% complete (95% CI 91.5, 95.5). Incidence was similar in Colorado to other populations in the United States at similar latitudes. These data serve as a baseline for evaluation of changes in incidence over time, by region, and for the identification of possible outbreaks.     

Diabetes complications and glycemic control. The Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report after 5 yr of IDDM

The relationship between glycemic control and complications of insulin-dependent diabetes mellitus (IDDM) remains controversial. With the use of glycosylated hemoglobin (HbA1) to assess glycemic control from diagnosis onward, the Pittsburgh Prospective Insulin-Dependent Diabetes Mellitus Cohort Study prospectively evaluated 80 new cases of IDDM diagnosed at Children's Hospital of Pittsburgh. This study presents findings in 62 patients at 5 yr postdiagnosis. Only 7 patients, all girls, had any retinopathy (microaneurysms). These subjects had an elevated 5-yr mean HbA1 compared to those with no retinopathy (13.0 vs. 11.7%; P less than .05). Six female subjects who had an elevated albumin excretion rate (AER; greater than or equal to 20 micrograms/min) had a higher 5-yr mean HbA1 (13.3%) than the 26 subjects with AER less than 20 micrograms/min (11.8%; P less than .05). Current HbA1 was correlated with AER (r = +.36, P less than .05) and systolic blood pressure (r = +.49, P less than .01) in females. However, these associations were not observed in males. Positive correlations were found between HbA1 (5-yr mean and current) and serum triglyceride and cholesterol, but only in females was HbA1 inversely related to high-density lipoprotein cholesterol. However, HbA1 was independent of sex, HLA-DR type, and urine C-peptide status. Age adjustment did not change the above results. These analyses suggest that glycemic control is related to AER, systolic blood pressure, presence of microaneurysms, and serum triglyceride and cholesterol concentrations during the first 5 yr of IDDM. However, these associations appear to be predominant in girls.     

Factors associated with avoidance of severe complications after 25 yr of IDDM. Pittsburgh Epidemiology of Diabetes Complications Study I

To identify characteristics associated with long-term avoidance of insulin-dependent diabetes mellitus (IDDM) complications, subjects taking part in an epidemiologic natural history study of childhood-onset IDDM, with a duration of disease greater than or equal to 25 yr, were studied. Nineteen percent of 175 subjects had avoided overt nephropathy, definite cardiovascular and peripheral vascular disease, clinical neuropathy, and proliferative retinopathy. Approximately half of the nonrenal complications occurred in the absence of renal disease. Subjects free of these advanced complications were characterized by a longer duration of disease (P less than 0.05), better lipid profile and blood pressure (P less than 0.01), and considerably lower glycosylated hemoglobin levels (P less than 0.001). Health-related behaviors, including recent medical contact, regular glucose monitoring, physical activity in youth, and avoidance of cigarette smoking, did not relate to complication status, although regular (at least weekly) alcohol consumption was more prevalent (P less than 0.05) in those without complications. We conclude that a lower mean glycosylated hemoglobin level is strongly related to the avoidance of all IDDM complications.     

Limb fractures and nonaccidental injury in children less than 24 months of age.

AIM: The pattern of limb fractures in children aged 24 months or younger is poorly understood. This age group is particularly vulnerable to nonaccidental injury, which can be difficult for inexperienced clinicians to detect. The aim of this study is to identify fracture patterns in children below the age of 24 months. METHODS: Data was collected prospectively. For all fractures, the mechanism of injury including height of fall (cm), severity of injury, outcome and deprivation scores were collected. Information on children referred for child-protection review was also noted. RESULTS: During the 12 months of the year 2003, 122 new patients aged less than 24 months presented with limb fractures directly to the Emergency Department of the Royal Hospital for Sick Children, giving an incidence of 4.55 per 1000 in the 0-12-month group and 17 per 1000 in the 13-24-month group. Sixty-three (52%) children sustained the injury during a fall and only 7% of children were admitted, the rest being followed up as outpatients. Thirty-eight (31%) had simple distal radius/ulna fractures. Five children with unclear histories or mechanisms of injury underwent formal child-protection procedures. All were less than 14 months of age. CONCLUSIONS: Fractures are relatively rare in the first 2 years of life. Child protection needs to be considered in all children, but specifically in those patients with atypical fractures presenting with an unclear mechanism of injury.     

Physical activity and proliferative retinopathy in people diagnosed with diabetes before age 30 yr.

OBJECTIVE--To examine the relationships of past and current physical activity to the prevalence of PDR. RESEARCH DESIGN AND METHODS--Individuals diagnosed with diabetes less than 30 yr of age (n = 818), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984-1986. Stereoscopic fundus photographs were graded for presence of PDR. Physical activity was assessed by an interviewer-administered standardized questionnaire. RESULTS--Women diagnosed with diabetes less than 14 yr of age who reported a history of participation in team sports in high school or college were less likely to have PDR at examination (OR 0.46, 95% CI 0.23, 0.93). Those women who reported current strenuous activity levels were less likely to have PDR (OR 0.34, 95% CI 0.13, 0.87). There were no significant associations between past or current physical activity and PDR in men. Current levels of energy expenditure were not related to PDR in either sex. CONCLUSIONS--Higher levels of physical activity may be associated with a reduced risk of having PDR in women. However, the lack of similar findings in men suggests that physical activity may be a relatively unimportant factor in the etiology of PDR.     

阶段性经口喂养促进方案在胎龄小于32周早产儿中的应用研究

目的 探讨阶段性经口喂养促进方案在胎龄<32周早产儿中的应用效果。方法 连续选取2020年1月—12月上海市某三级甲等儿科医院NICU收治的128例胎龄<32周的早产儿作为研究对象,采用随机区组法分为试验组和对照组。试验组采用阶段性经口喂养促进方案进行喂养,对照组采用NICU常规喂养方法。比较两组达到完全经口喂养时、开始经口喂养时及首次经口摄入50%医嘱奶量时的日龄、纠正胎龄和体重,住院时间以及喂养相关并发症的发生情况。结果 共脱落5例,最终试验组纳入61例,对照组纳入62例。试验组达到完全经口喂养时的纠正胎龄小于对照组;开始经口喂养及首次经口摄入50%医嘱奶量时的日龄、纠正胎龄小于对照组,体重低于对照组,差异具有统计学意义（P<0.05）。两组住院时间比较,差异无统计学意义（P>0.05）。两组均未发生喂养相关并发症。结论 实施阶段性经口喂养促进方案有利于胎龄<32周的早产儿更早达到完全经口喂养。     

Increased insulin action and clearance in hyperthyroid newly diagnosed IDDM patient. Restoration to normal with antithyroid treatment

In a patient with hyperthyroidism and newly diagnosed insulin-dependent diabetes mellitus (IDDM), insulin action and clearance were studied before the initiation of antithyroid treatment and at 3-mo intervals for 1 yr thereafter. The sequential euglycemic clamp technique (5 mM) was used with insulin infusion rates of 0.5, 1.0, 2.0, and 5.0 mU.kg-1.min-1 in four steps of 2 h. The data were compared with nine control subjects and nine newly diagnosed euthyroid IDDM patients treated with insulin for 0.5 mo. Insulin sensitivity was increased in the patients (ED50 40 vs. 52 mU/L, range 43-70, in controls and 70 mU/L, range 59-120, in IDDM subjects). Insulin responsiveness was markedly elevated; the steady-state glucose infusion rate (SSGIR) of step 4 was 104 vs. 64 mumol.kg-1.min-1 (range 50-79) in controls and 61 mumol.kg-1.min-1 (range 47-69) in IDDM subjects. Insulin clearance was elevated in all steps (1-3, 20-23 vs. 9-15 ml.kg-1.min-1; 4, 18 vs. 6-12 ml.kg-1.min-1 in control and IDDM subjects). Parallel to the normalization of thyroid metabolism, insulin action (ED50 60 mU/L, SSGIR in step 4, 51 mumol.kg-1.min-1) and insulin clearance (steps 1-3, 11-14 ml.kg-1.min-1; step 4, 7 ml.kg-1.min-1) returned to the normal range in 6 mo. Both remained within the normal range until 12 mo. In the patient with newly diagnosed IDDM, the initial marked increases of insulin action and clearance were due to coexistent hyperthyroidism. With the amelioration of the hyperthyroid state, both processes became normal. The parallelism between insulin action and clearance suggests a functional relationship.     

Incidence of IDDM in Western Australia in children aged 0-14 yr from 1985 to 1989.

OBJECTIVE--To document the incidence of insulin-dependent diabetes mellitus (IDDM) in Western Australia in children aged 0-14 yr between 1985 and 1989 and to test for differences in incidence by year of diagnosis, age of diagnosis, and sex. RESEARCH DESIGN AND METHODS--A population-based register that used a primary source of case ascertainment (diabetes clinics at teaching hospitals and direct approach to general practitioners and general physicians) and a secondary source (Western Australian Hospital Morbidity Data System) established numerator data. Denominator data were obtained from the Australian Bureau of Statistics. RESULTS--From 1985 to 1989 inclusive, 235 children in the 0- to 14-yr age-group were diagnosed with IDDM in Western Australia. Case ascertainment was estimated at 99% complete. The mean age-adjusted (developed-world population) annual incidence of IDDM was 13.2 per 100,000 person-yr and there was no evidence of an increasing incidence over the 5 yr. However, girls were more likely than boys to be diagnosed with IDDM in this period (P = 0.006). CONCLUSIONS--The incidence of IDDM in Western Australia is in the middle range of IDDM incidence in countries throughout the world. The unexpected finding of an increased incidence of IDDM in girls compared with boys needs to be confirmed in a future study.     

A 13-year review of lisinopril ingestions in children less than 6 years of age

Abstract

Background. Lisinopril is an angiotensin converting enzyme inhibitor used for treatment of hypertension, congestive heart failure, and acute myocardial infarction. Reports of clinical experience with pediatric ingestions are minimal. Method. A 13-year retrospective study of lisinopril ingestions in children reported to the California Poison Control System was analyzed and case notes were reviewed. Institutional Review Board approval was obtained and cases were blinded. Inclusion criteria were lisinopril as a single ingestant, age less than 6 years, treatment in a health care facility, case followed to a known outcome. Results. Inclusion criteria were met in 296 cases. Demographics include 51% of male patients and the mean age was 1.97 years (range: 9 months–5 years). Of the 296 patients, 8 patients (2.7%) developed hypotension (ranges: 55–74 mm Hg systolic and 22–48 mm Hg diastolic). The lowest blood pressure of 55/22 mm Hg was recorded in a 22-month old male who ingested an estimated 120-mg lisinopril (13.3 mg/kg). The lowest dose of lisinopril causing hypotension was with an estimated dose of approximately 50 mg or 3.9 mg/kg in a 2-year old. Two hundred and eighty-two patients (95.3%) were treated and released from the emergency department and 14 patients (4.7%) were admitted. The dose ingested was reported in 189 cases and an exact-dose of lisinopril was reported in 61 patients (20.6%); mean amount ingested was 3.0 mg/kg, median amount ingested was 2.1 mg/kg (range: 0.1–10.9 mg/kg, N = 38); and mean total dose was 33.4 mg, median total dose was 20 mg (range: 2.5–160 mg, N = 61). None of the patients with exact-dose lisinopril ingestions developed hypotension, received intravenous fluids, or were admitted. Conclusion. The lowest estimated dose of lisinopril to cause hypotension was 50 mg or 3.9 mg/kg. Although continued evaluation of pediatric lisinopril ingestions is essential to determine more specific thresholds of toxicity, the lack of effect on blood pressure in children with exact-dose ingestions indicate that pediatric lisinopril ingestions (for ages > 9 months) ≤ 4 mg/kg up to 40 mg total may be safely managed at home.     

An 11-year review of levetiracetam ingestions in children less than 6 years of age

Background. Levetiracetam is a new anticonvulsant, which works to block high-voltage-activated Ca⁺⁺ channels in children, for partial-onset seizures. Reports of clinical experience with pediatric ingestions are minimal. The purpose of this study was to characterize the toxicity of accidental levetiracetam exposures in children less than 6 years of age. Methods. This was an 11-year retrospective observational case series of pediatric (< 6 years old) levetiracetam ingestions reported to a Poison Control System from 2002 to 2013. Case narratives were individually reviewed to collect desired information on exposure and clinical course. Inclusion criteria were levetiracetam as a single ingested medication, age less than 6 years, treatment in a health care facility, and followed to a known outcome. Results. Eighty-two cases met inclusion criteria with 55% female patients and overall median age of 2.0 years (range: 1–60 months). The levetiracetam dose ingested was reported in 69 (84.1%) cases, with exact dose (median dose, 45.0 mg/kg; range, 10.5–1429 mg/kg) reported in 33 cases (40.2%). Of these, twenty-nine cases (88%) involved the oral solution formulation and 28 cases (85%) had unintentional therapeutic error as the cause of the exposure. No dose–response relationship was demonstrated; however, the odds of a levetiracetam-naive patient, (median dose, 26.9 mg/kg; N = 15) with an unintentional exposure, developing drowsiness or ataxia was 6 times that of a patient who was not naïve to levetiracetam (median dose, 70.1 mg/kg; N = 20) (Odds ratio [OR], 6.0; 95% confidence interval [CI], 1.03–35.91).Of the 82 cases, 17 (20.7%) developed untoward clinical effects of drowsiness and/or ataxia. Eighty patients (97.6%) were treated and discharged from the emergency department, and two patients (2.4%) were admitted. The two patients admitted included a two-month old who was accidentally given a dose 10 times that of her usual dose and a 3-year old who was lethargic on arrival to the hospital after ingestion of an unknown dose. Of all patients, 66 patients (80.5%) had no effect from the drug exposure. The medical outcome was considered to be minor in 15 cases (18.3%), and moderate in 1 case (1.2%). There were no cases with major outcomes and no deaths. Conclusions. Pediatric levetiracetam exposures were associated with few transient clinical effects. Poison Control Centers may wish to consider acuity of ingestion when developing send-in protocols.     

Preliminary experience with nesiritide in pediatric patients less than 12 months of age

The natriuretic peptide system plays an active role in the regulation of fluid balance and systemic vascular resistance. Advances in recombinant technology have provided the opportunity for the exogenous administration of a recombinant form of B-type natriuretic peptide (nesiritide). To date, reports of its use in the pediatric population are limited, with limited information regarding its use in patients less than 12 months of age. We retrospectively reviewed our experience with nesiritide in infants less than 12 months of age to determine its efficacy and adverse effect profile. The study cohort included 22 patients, ranging in age from 4 days to 12 months. The starting dose of the nesiritide infusion ranged from 0.01 to 0.05 microg/kg/min (0.015+/-0.01microg/ kg/min) and was administered for a total of 3 to 264 hours (85.2+/-75.0 hours). Nesiritide resulted in a significant increase in urine output even in the face of decreased fluid intake. Mean urine output increased from 3.1+/-2.5 mL/kg/h before nesiritide to 5.7+/-4.5 mL/kg/h (P = .03) during the initial 24 hours after starting the infusion. Fluid intake before and after the infusion were 126 +/- 60 mL/kg/d and 108+/-56 mL/kg/d, respectively. There were no statistically or clinically significant changes in hemodynamic parameters (heart rate, blood pressure, and central venous pressure) during the nesiritide infusion. No change in electrolytes, blood urea nitrogen, and creatinine were noted. No adverse effects of the nesiritide infusion were noted. No infusion was stopped due to adverse effects. These data suggest that nesiritide is a safe method of improving urine output in pediatrics patients less than 12 months of age and that the adverse effect profile does not appear to be different than that reported in older children.     

HLA-DQB1-defined genetic susceptibility, beta cell autoimmunity, and metabolic characteristics in familial and nonfamilial insulin-dependent diabetes mellitus. Childhood Diabetes in Finland (DiMe) Study Group.

Familial aggregation of insulin-dependent diabetes mellitus (IDDM) is a common phenomenon, but the reasons behind it are poorly understood. To investigate whether there is heterogeneity between familial and nonfamilial forms of IDDM we compared genetic, immunological, and clinical characteristics of diabetic children with and without an affected first-degree relative in a population-based series of Finnish children with IDDM. The frequencies of HLA-DQB1 genotypes known to be associated with high (DQB1*0302/0201) or moderate (*0302/x) IDDM risk in the Finnish population were increased, while the proportions of DQB1 genotypes associated with low or decreased risk for IDDM were reduced in the 121 familial cases as compared with the 574 nonfamilial cases (32.7 vs. 21.3%, 41.3 vs. 35.9%, 18.3 vs. 31.4%, and 7.7 vs. 11.4%, respectively; P = 0.002). The frequencies and serum concentrations of islet cell antibodies, insulin autoantibodies, and antibodies to the 65-kD isoform of glutamic acid decarboxylase were similar at diagnosis in the familial and nonfamilial cases. The 31 first-affected cases in the multiple case families were younger at diagnosis than the nonfamilial cases (6.9 vs. 8.5 yr; P < 0.05). The 90 second-affected familial cases had less severe metabolic decompensation at diagnosis than either the first-affected familial or nonfamilial cases. In conclusion, familial aggregation of IDDM in Finland is at least partly explained by a higher frequency of IDDM susceptibility genes in families with multiple affected individuals. The lack of differences in autoantibody levels between the familial and nonfamilial cases indicates homogeneity rather than heterogeneity in the pathogenetic process of beta cell destruction.