Comparison of time spent writing orders on paper with computerized physician order entry.

Computerized physician order entry (CPOE) has been shown to improve quality, and to reduce resource utilization, but most available data suggest that it takes longer to enter orders using CPOE. We had previously implemented a CPOE system, and elected to evaluate its impact on physician time in the new setting. To do this, we performed a prospective study using random reminder methodology. Key findings were that interns spent 9.0% of their time ordering with CPOE, compared to 2.1% before, although CPOE saved them an additional 2% of time, so that the net difference was 5% of their total time. However, this is counterbalanced by decreased time for other personnel such as nursing and pharmacy, and by the quality and efficiency changes. We conclude that while CPOE has many benefits, it represents a major process change, and organizations must factor this in when they implement it.

Spontaneous resolution of nonimmune hydrops in a fetus with a cystic adenomatoid malformation.

Congenital cystic adenomatoid malformation (CCAM) is a rare pulmonary anomaly. It is a hamartomatous lesion characterized by a cessation of normal bronchiolar maturation, resulting in overgrowth of the terminal bronchioles. There is no preference for sex or location, and usually the lesion is confined to a single lobe. CCAMs have been classified into three subtypes according to the presence of and size of the cysts. Type I lesions have large cysts (2 to 10 cm in diameter), type II have smaller cysts (< 1 cm in diameter), and type III is noncystic. There have been several reports of diminution in size of these lesions and complete regression. However, in those cases fetal hydrops was absent. In the presence of nonimmune hydrops, fetal prognosis is extremely poor without any intervention. There are only two case reports describing fetal survival without intervention when nonimmune hydrops is present. We present a case of survival of a fetus with CCAM and nonimmune hydrops diagnosed at 24 weeks' gestation.

Acetaminophen and other risk factors for excessive warfarin anticoagulation.

CONTEXT: Warfarin is highly effective in preventing thromboembolism, but increases the risk of hemorrhage, particularly at an international normalized ratio (INR) greater than 4.0. Identifying causes of excessive anticoagulation in clinical practice could help target patients at risk for elevated INRs. OBJECTIVE: To determine causes of INRs greater than 6.0 in a clinical practice setting. DESIGN: Case-control study. SETTING: Outpatient anticoagulant therapy unit. PATIENTS: Outpatients followed up prospectively from April 1995 to March 1996 who had been taking warfarin for more than 1 month, had a target INR of 2.0 to 3.0, and were able to be interviewed within 24 hours of their reported INR. Case patients had INRs greater than 6.0; controls were randomly selected from patients having INRs between 1.7 and 3.3. MAIN OUTCOME MEASURES: Factors associated with INRs greater than 6.0, including medication use, recent diet, illness, alcohol consumption, and actual warfarin use. RESULTS: A total of 93 cases and 196 controls were interviewed; they did not differ in age, indication for warfarin, length of therapy, warfarin dose, number of prescription medications, or previous INR or long-term INR variability. Acetaminophen ingestion was independently associated in a dose-dependent manner with having an INR greater than 6.0 (P for trend <.001). For the highest-dose category of acetaminophen intake, 9100 mg/wk or more, the odds of having an INR greater than 6.0 were increased 10-fold (95% confidence interval [CI], 2.6-37.9). Other factors independently associated with an INR greater than 6.0 were new medication known to potentiate warfarin (odds ratio [OR], 8.5; 95% CI, 2.9-24.7), advanced malignancy (OR, 16.4; 95% CI, 2.4-111.0), recent diarrheal illness (OR, 3.5; 95% CI,1.4-8.6), decreased oral intake (OR, 3.6; 95% CI, 1.3-9.7), and taking more warfarin than prescribed (OR, 8.1; 95% CI, 2.2-30.0). Higher vitamin K intake (OR, 0.7; 95% CI, 0.5-0.9) and habitual alcohol consumption of from 1 drink every other day to 2 drinks a day (OR, 0.2; 95% CI, 0.1-0.7) were associated with decreased risk. CONCLUSIONS: These data suggest that acetaminophen is an underrecognized cause of overanticoagulation in the outpatient setting. Several other clinically important risk factors were identified. Increased monitoring of INR values when such risk factors are present or modification of the risk factors themselves should reduce the frequency of dangerously high levels of anticoagulation.

Successful separation of ischiopagus tripus conjoined twins with comparative analysis of methods for abdominal wall closure and use of the tripus limb.

The authors report the successful delivery, preoperative management, and postoperative courses of ischiopagus tripus twin girls successfully separated at 5 months of age. Surgical objectives were predicated on survival and optimum postseparation reconstructive potential for both girls. Each twin has subsequently undergone additional procedures, and both are doing well 2 years after separation. The authors reviewed 17 known cases of ischiopagus tripus separation, comparing anatomic findings, use of the tripus limb, operative strategies, and attainment of abdominal closure. This 18th case includes the first report of splitting the tripus limb and giving each girl a femur. The authors found that detailed systemic investigation, advanced coordinated teamwork with appropriate technical support, applications of new technologies or reapplication of existing technologies, meticulous planning, and favorable anatomy were vital in yielding favorable outcomes.

Sensitivity and specificity of rapid diagnostic tests for detection of group B streptococcal antigen in bacteremic neonates.

Latex particle agglutination (LPA) testing for antigen to group B streptococcus (GBS) has been useful in the diagnosis of GBS sepsis in newborns. However, recent reports have demonstrated that the sensitivity of LPA assays may be as low as 27 to 54%. The purposes of the present study were to directly compare the abilities of four urine antigen assays to detect GBS antigen with clinical urine samples from neonates with GBS bacteremia and to evaluate the effect of the urine concentration on the sensitivities and specificities of these assays. Urine samples were collected serially from neonates with blood cultures positive for GBS or on admission from healthy full-term infants. One milliliter of urine was removed, and the remainder was concentrated to a volume of 1 ml. Unconcentrated samples were serially diluted with normal saline and were assayed to determine the highest dilution which would produce a positive test result. The Wellcogen, Bactigen, and Directigen LPA tests and ICON immunoassay were directly compared by using concentrated and unconcentrated urine specimens and urine specimens with known titers. A total of 94 urine specimens, including 61 concentrated and 75 unconcentrated specimens, from bacteremic infants were available for sensitivity testing, and 220 urine specimens from uninfected infants were available for specificity testing. There were significant differences in sensitivity among the four assays when they were performed on concentrated urine specimens, as follows: Directigen, 98%; Bactigen, 92%; ICON, 89%; Wellcogen, 68%. When the assays were performed on unconcentrated urine specimens, the Directigen (84%) and Bactigen (76%) assays were each significantly more sensitive than the ICON (59%) or Wellcogen (43%) assay. All four assays were significantly more sensitive in detecting GBS antigen in concentrated than in unconcentrated urine. The Directigen assay detected antigen in higher dilutions (geometric mean titer, 1:5) than the ICON (1:3), Bactigen (1.2), or Wellcogen (1:1) assay. The specificity was 99.5% for all four assays when concentrated urine was used and for the Bactigen, Directigen, and ICON assays when unconcentrated urine was used; the Wellcogen assay was 100% specific when unconcentrated urine was used. We conclude that there are significant differences in sensitivity but not specificity among the commercially available assays for the detection of GBS antigenuria when concentrated and unconcentrated urine specimens are tested. These differences in sensitivity may affect the abilities of clinicians to accurately diagnose GBS sepsis before culture results are available.

Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates.

To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation < or = 34 weeks, and age < or = 12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation (R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not (R < or = 0.09). The serum IgG concentration was increased (p < 0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis.

Fryns syndrome.

We report on a premature female infant with Fryns syndrome who had several less commonly reported anomalies. She had bilateral posterior eventration of the hemidiaphragms instead of the usual diaphragmatic defects with visceral herniation into the chest cavity. She also had a unilateral cleft lip, camptodactyly, duodenal atresia, tracheomalacia, bronchomalacia, and Tetralogy of Fallot.

Intravenous immune globulin therapy for early-onset sepsis in premature neonates.

Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.

The opsonic antibody response of female rats to type III group B streptococcal immunization: a model for maternal immunity.

Group B streptococcus (GBS) remains a major cause of neonatal infection. Maternal immunization-induced GBS antibody may protect neonates from GBS disease. Since the opsonophagocytosis assay correlates well with survival in GBS infected suckling rats, we sought to determine an immunization schedule which would induce type III GBS opsonic antibody in rat dams above a predetermined level of 10 dilution-1 (dil-1). This schedule could then be used for future studies of maternal-fetal immunity. Wistar rat dams (n = 12) were given killed GBS type III using three immunization schedules (primary injection, initial booster at 7, 14 or 22 days and then weekly boosters). Opsonic GBS type III antibody and total immunoglobulin (IgG) were measured. Only the schedule with a 7-day initial booster resulted in GBS type-specific opsonic antibody consistently above 10 dil-1. The IgG (467 +/- 83 mg/100 ml) remained constant while the opsonic antibody increased significantly to 50 and 63 dil-1 (P less than 0.01 compared to day 0) after boosters on day 7 and 14 respectively. Eight pregnant dams, who received a primary immunization and boosters at 7 and 14 days, developed GBS type III opsonic antibody titers (72 dil-1) similar to non-pregnant dams and potentially adequate to protect suckling rats from GBS disease. This model may now be used to study other adjuvants, immunogens, and maternal-fetal immunity using established suckling rat models of GBS disease.

Transplacental or enteral transfer of maternal immunization-induced antibody protects suckling rats from type III group B streptococcal infection.

Deficiency of maternal group B streptococcal (GBS) type-specific IgG increases neonatal susceptibility to GBS infection. We asked if immunization-induced maternal type III GBS opsonic antibody transferred prenatally (via placenta) or postnatally (via breast milk) would affect suckling rat survival after GBS infection. Pregnant immunized dams with type III GBS opsonic antibody (20 through 320 dil-1) and nonimmunized dams without GBS antibody were matched (n = 16). Half of each litter was cross-suckled to a matching dam creating four pup groups with different exposure to maternal type III GBS opsonic antibody: none, postnatal, prenatal, and combined (pre- and postnatal). After infection with type III GBS, group survival (n) was 41% (51), 66% (47), 98% (43), and 98% (47), respectively. Type III GBS opsonic antibody in surviving pups was directly related to their immunized dam's antibody either postnatally (R = 0.85), prenatally (R = 0.84), or combined (R = 0.81). Pups exposed postnatally to high titers (80 to 320 dilution-1) of type III GBS opsonic antibody survived more often than those exposed to low titers (20 to 40 dil-1) (p less than 0.03). Immunization-induced maternal type III GBS opsonic antibody is transferred pre- and postnatally and results in improved neonatal survival after GBS infection. Survival of pups exposed to postnatal antibody appears related to the concentration of maternal type III GBS opsonic antibody. Breast milk with high titers of GBS type-specific antibody may modify the course of GBS infection. GBS vaccines and strategies could be tested in this model.