Failure of intravenous immunoglobulin to prevent congenital heart block: Findings of a multicenter, prospective, observational study.

OBJECTIVE: Congenital heart block (CHB) is presumed to be caused by transplacental passage of maternal immunoglobulin against Ro and La ribonucleoproteins. The recurrence rate in subsequent pregnancies following the birth of a child with CHB is approximately 19%. The purpose of this study was to determine whether intravenous immunoglobulin (IVIG) therapy could prevent the development of CHB in the fetuses of high-risk pregnant women. METHODS: A total of 24 pregnancies in 22 women who had a previous pregnancy in which CHB developed, were over the age of 18 years, were <12 weeks pregnant, and had anti-Ro, anti-La, or both antibodies were monitored in this multicenter, prospective, observational study. Fifteen patients received infusions of IVIG. The 9 pregnancies in the remaining 7 patients served as controls. IVIG was administered at a dose of 400 mg/kg at weeks 12, 15, 18, 21, and 24 of pregnancy. Echocardiograms were performed at least every 3 weeks from week 15 to week 30 of gestation. Electrocardiograms were obtained at birth. The outcome measure was the development of third-degree CHB detected by fetal echocardiogram. RESULTS: CHB developed in 3 babies among the 15 pregnancies in the treatment group (20%) and in 1 baby among the 9 pregnancies in the control group (11%). CHB was detected at weeks 18, 23, and 26, respectively, in the 3 babies in the treated group and at week 19 in the baby in the control group. Three of the affected pregnancies ended in termination; 2 for reasons related to the fetal disease and 1 for reasons related to both maternal (severe pulmonary hypertension) and fetal disease (at 21 weeks of gestation). CONCLUSION: IVIG at the dose and frequency used in this study was not effective as prophylactic therapy for CHB in high-risk mothers.

[Conversion of fast insulin intensive therapy to lispro insulin in type I diabetes. Pharmacoeconomic analysis of cost-effectiveness]. / Conversión de la terapia intensiva con insulina rápida a insulina lispro en la diabetes tipo 1. Análisis farmacoeconómico de coste-efectividad.

In order to analyze the initial cost-effectiveness of transfer to two treatments with insulin lispro in type 1 diabetes, a pharmaco-economic study was conducted for nine months. After an educational reinforcement, a group of 30 C-peptide-negative patients (31.8 +/- 11.5 years [mean +/- SD], time since diagnosis of diabetes of 9.2 +/- 7.1 years, and on intensive therapy for 5.3 +/- 3.1 years) initiated a 3-month basal period with their usual therapy (preprandial rapid insulin and nocturnal NPH). Patients were then randomly assigned to one of the two groups, changing rapid insulin to either lispro (L1) or lispro combined with 15% to 20% NPH insulin (L2). Cross-over was made 3 months after the first treatment. Efficacy and safety were established by the assessment of HbA1c, self-monitoring blood glucose and hypoglycemia rates. Therapy cost was measured by systematic examination of the injection devices and wastage of insulin. The mean prescribed and actually consumed doses for R, L1, L2 groups were 52.9, 57.1, 55.2 U and 60.3, 64.1, 63 U per day, respectively (p < 0.001). The average of postprandial peak glucose (9.7, 8.4, 8.3 mM; p < 0.001) and HbA1c (7.6%, 7.2%, 7.1%; p < 0.01) were significantly lower after L1 or L2 lispro therapy. Although no statistical differences in overall hypoglycemia rates were observed, fewer nocturnal episodes were detected (0.72, 0.37, 0.41 events/month). The mean daily cost for regular insulin treatment was lower (186.8, 241.8; 215.7 pts and 53.7 pts per day. Efficacy and safety for two MIT regimens containing lispro were similar in the short run. Nevertheless, the preprandial use of the fast-acting insulin analog lispro in combination with a 15%-20% intermediate-acting NPH seemed to be more cost-effective than the premeal lispro therapy alone.

Conversión de la terapia intensiva con insulina rápida a insulina lispro en la diabetes tipo 1. Análisis farmacoeconómico de coste-efectividad / Conversión of intensive therapy with rapid insulin to lispro insulin in type-1 diabetes. A cost-effectiveness assessment

Para analizar el coste y la efectividad inicial de la transferencia a dos tratamientos con insulina lispro en la diabetes tipo 1 se desarrolló un estudio farmacoeconómico durante 9 meses. Después del refuerzo educativo, un grupo de 30 pacientes con péptido-C negativo, de 31,8 ñ 11,5 años (x- ñ DE), duración de la diabetes de 9,2 ñ 7,1 años y en terapia intensiva desde hacía 5,3 ñ 3,1 años inició un período basal de 3 meses con su tratamiento habitual (insulina rápida preprandial y NPH nocturna). Luego se asignaron aleatoriamente a uno de los dos grupos, sustituyendo la insulina rápida por lispro (L1) o bien por lispro mezclada con un 15 por ciento-20 por ciento de insulina NPH (L2), cruzándose a los 3 meses. La eficacia se valoró por la HbA1c y el autoanálisis de la glucemia capilar; la seguridad por el registro minucioso de la hipoglucemia. El coste consideró el consumo real de insulina (teórico y desperdicio) y material de inyección.La dosis total prescrita fue menor en el período basal que en L1 y L2 (52,9; 57,1; 55,2 UI/día; p < 0,001) y también la realmente consumida (60,3, 64,1, 63 UI/día; p < 0,01), sin diferencias entre L1 y L2. La glucemia posprandial (9,7, 8,4, 8,3 mM; p < 0,001) y la HbA1c (7,6 por ciento, 7,2 por ciento, 7,1 por ciento; p < 0,01) disminuyeron en L1 y L2 sin incremento global de la hipoglucemia. Las crisis durante el sueño fueron más infrecuentes (0,72, 0,37, 0,41 crisis/mes; p < 0,05). El coste bruto diario del tratamiento con insulina rápida fue menor (186,8, 241,8, 215,7 pts; p < 0,001). El sobrecoste diario estimado para reducir un 1 por ciento la HbA1c fue 134,1 pts durante L1 y 53,7 en L2. La efectividad y seguridad de ambas terapias con lispro fue parecida, pero la mezcla preprandial de lispro con NPH fue más coste-efectiva (AU)

The relationship between spinal and peripheral osteoarthritis and bone density measurements.

OBJECTIVE: To determine the influence of osteoarthritis (OA) on bone density measurements and whether OA at one site is associated with OA at other sites. METHODS: Nonrandomized, cross sectional observational study; secondary analysis of a general population database. Sixty-four subjects derived from a longitudinal study of long distance runners and community controls had a complete peripheral radiographic evaluation for osteoarthritic changes in hands, knees, and lumbar spine. Forty-four of these were studied in 1984 with quantitative computed tomography (QCT) of L1, and 54 were studied in 1988 with 153-Gd dual photon absorptiometry (DPA) in the spine and total body. Thirty-four subjects had all measurements done. RESULTS: Total body and lumbar spine DPA were positively correlated with radiological scores of OA in the spine and knees, with coefficients ranging between 0.467 to 0.530 (p < 0.001 in all cases). This correlation was principally associated with spinal spurs and knee sclerosis. Results of stepwise multiple linear regression modeling for QCT included age, spine sclerosis, knee sclerosis and knee spurs as the main predictors of bone mineral density (BMD). For DPA measurements, spine spur score was a useful regressor for all the models. Altogether, the percentage of variance accounted for by individual radiological OA variables was 27.4% for lumbar QCT, 27.3% for lumbar BMD, 7.3% for total spine BMD, and 45.2% for total body BMD. OA scores at different sites were not correlated, although repeated assessment at the same site showed very close correlation. CONCLUSIONS: All methods used to determine BMD showed a highly significant positive correlation between lumbar and knee radiological OA and bone mineral content both in the spine and the total body. Thus, our results support the hypothesis that OA is negatively correlated with osteopenia. OA, as seen in this population, was not a generalized condition, but rather, was site specific.