Dennis M. Super

An organized approach to improvement in guideline adherence for acute myocardial infarction: results with the Get With The Guidelines quality improvement program.

BACKGROUND Evidence-based guidelines from the American Heart Association are voluntary, and adherence is highly variable across the country. Get With The Guidelines (GWTG) is a national quality improvement program sponsored and developed by the American Heart Association. The objective of this study was to evaluate whether participation in GWTG is associated with greater adherence to guidelines for coronary artery disease (CAD). METHODS Data on adherence to guidelines were obtained from Hospital Compare, grouping hospitals according to participation in the GWTG-CAD program on January 1, 2004: GWTG-CAD hospitals, n = 223; non-GWTG-CAD hospitals, n = 3407. The GWTG program uses a patient management tool, education, and benchmarked quality reports to improve guideline adherence. Adherence to 8 national measures, including the use of aspirin and beta-blockers early and at discharge and timeline reperfusion, was analyzed. A composite score was also calculated. Multivariable logistic regression was performed for comparing composite adherence rates between groups. RESULTS Adherence to the overall Hospital Compare composite measure was higher in GWTG-CAD hospitals than in non-GWTG-CAD hospitals (mean [SD], 89.7% [10.0%] vs 85.0 [15.0%]; absolute increase, 4.7%; P < .001). Adherence to the GWTG-CAD performance measures (PM) composite was also higher (89.5% [11.0%] vs 83.0% [18.0%]; P < .001). In multivariate analysis, GWTG-CAD participation was associated with a modest absolute increase in adherence to the PM composite by 2.52% (95% confidence interval [CI], 0.19%-4.85%). Larger acute myocardial infarction volume by quartile (absolute increase, 14.2%; 95% CI, 12.2%-16.3%), geographic location in the Northeast, and teaching hospital status (absolute increase, 2.87%; 95% CI, 0.43-5.32) were also associated with improved adherence to the PM composite. As a control, evaluation of unrelated quality measures for pneumonia, showed lower adherence among GWTG-CAD participating hospitals (74.8% [7.3%] vs 76.1% [9.7%]; P = .005). CONCLUSION Participation in GWTG-CAD was independently associated with improvements in guideline adherence beyond that associated with public reporting.

Low level lead exposure in the prenatal and early preschool periods: Intelligence prior to school entry☆

The hypothesis that low level lead exposure in the fetal and early preschool years is related to neuropsychological deficit is being examined in a prospective study of development through the preschool years. Clear and consistent support for the hypothesis was not obtained in previously reported findings relating maternal and cord blood lead level (PbB) and PbB from venous samples through age three years to a series of developmental tests. It was concluded the relationship of lead level and cognitive development was primarily a function of the dependence of each on the quality of the caretaking environment. The cohort has now been examined at age four years, ten months, an age selected to assess development just prior to school age. The test used was the Wechsler Preschool and Primary Scale of Intelligence. We found statistically significant correlations between most of the PbB measures and the intelligence test scores, but these were attenuated, not statistically significant and not consistent in direction when relevant confounding variables were considered. Possible biases or threats to validity were reviewed. Effect sizes relating both prenatal and preschool lead exposure to intellectual development were small, not statistically significant, and not consistent in direction.

A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis

To determine whether a single dose of dexamethasone (0.6 mg/kg) is useful in the treatment of acute laryngotracheitis (croup), 29 hospitalized patients with acute laryngotracheitis were randomly assigned in a double-blind fashion to receive either parenterally administered dexamethasone (n = 16) or a saline placebo (n = 13). Severity of the illness was assessed by a clinical croup score based on retractions, stridor, air entry, cyanosis, and level of consciousness. Twelve hours from the time of injection, the patients receiving the dexamethasone had a statistically significant decline in median croup score from 4.5 to 1.0 (p less than 0.001), whereas the patients receiving the placebo did not. By 24 hours, a decline of two or more points in the total croup score was noted in 85% of the patients in the dexamethasone group compared with 33% of the patients in the placebo group (p = 0.027). During this same period, only 19% of patients receiving dexamethasone required two or more racemic epinephrine treatments in comparison with 62% of patients who received the placebo (p less than 0.05). There was no statistical difference between the two groups in improvement in oxygen saturation, respiratory rates, or duration of hospitalization. We conclude that dexamethasone is beneficial in reducing the overall severity of moderate to severe acute laryngotracheitis during the first 24 hours after injection.

Bacterial polysaccharide immune globulin for prophylaxis of acute otitis media in high-risk children

We evaluated the prevention of recurrences of acute otitis media (AOM) by bacterial polysaccharide immune globulin (BPIG), a hyperimmune human immune globulin prepared by immunizing donors with bacterial polysaccharide vaccines. We used a randomized, stratified, double-blind, placebo-controlled design. Children < or = 24 months of age with 1 to 3 prior episodes of AOM received BPIG, 0.5 ml/kg, or saline placebo intramuscularly at entry and 30 days later. During the 120-day follow-up period, AOM was diagnosed by using clinical criteria and was confirmed with tympanocentesis and culture of the middle ear exudates. Eighty-eight episodes of AOM were observed in 76 patients who completed the study. The incidence of AOM during the entire 120-day study period was similar in BPIG and placebo recipients. Pneumococcal AOM was significantly less frequent in BPIG recipients (0.21 episode per patient) than in placebo recipients (0.45 episode per patient; p = 0.05). Time spent free of AOM was significantly prolonged in recipients of BPIG, in comparison with placebo recipients (51 vs 35 days; p = 0.034). This study demonstrated that circulating antibody, even without stimulation of specific local immunity, may prevent infection of the middle ear. The use of immune globulin preparations for longer periods or at a higher dosage might decrease the incidence of recurrent AOM in otitis-prone children, and deserves further evaluation.

Cefixime compared with amoxicillin for treatment of acute otitis media

Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 mg/kg of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Streptococcus pneumoniae cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were H. influenzae (five cases, two beta-lactamase-positive), S. pneumoniae (one case), and Moraxella catarrhalis (one case, beta-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (1) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating H. influenzae otitis media and should be preferred when H. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent.

Improved outcome after early fixation of acetabular fractures

This study was done in order to evaluate the effect of the timing of fixation for acetabular and pelvic ring fractures on patient outcome. Demographic, clinical and outcome data for 5821 trauma patients admitted from January 1993 through January 1996 were retrospectively reviewed. Pelvic fractures were classified according to Young and Burgess. Patients who had fixation within 24 h of admission were compared with those who had later operation. Main outcome measures were Multiple Organ Dysfunction Score according to Moore, hospital and intensive care unit length of stay and discharge disposition. Out of 416 patients with pelvic fractures, one hundred patients had fracture fixation [90 open reduction and internal fixation, 10 external fixation]. There were 59 acetabular fractures and 41 pelvic ring fractures. The overall mortality was 4%. Early fixation of acetabular fractures was associated with lower MODS (p < 0.006) and decreased total length of stay (p < 0.026). Length of hospital stay was also less with early fixation of pelvic ring fractures (p < 0.04). Functional outcome was improved in early fixation of acetabular fractures with a greater proportion of patients being discharged home rather than to rehabilitation or skilled care (p = 0.05). Patients who underwent early repair of acetabular and pelvic ring fractures had a shorter length of hospital stay compared to those with late fixation. Patients with early repair of acetabular fractures had significantly less organ dysfunction and exhibited improved functional outcome.

Diagnosis of Gestational Diabetes in Early Pregnancy

Objective To determine whether glucose intolerance can be identified early in gestation in a high-risk population so that early intervention can be planned to prevent associated morbidity. Research Design and Methods After appropriate dietary preparation, patients with a high risk for gestational diabetes underwent a 50-g oral glucose screening test during fasting. Patients were tested on enrollment and every 10 wk until delivery. Those with a 1-h plasma glucose value of ≥7.5 mM underwent a 100-g oral glucose tolerance test. Gestational diabetes was based on either a markedly abnormal 50-g screening test or abnormal 100-g oral glucose tolerance test. Results Ten of 15 (66%) patients who developed gestational diabetes were diagnosed during the first half of the pregnancy. Six were diagnosed in the first trimester. If the definition of an abnormal 1-h plasma glucose value was lowered from 7.5 to 7.2 mM, an additional 2 patients could have been identified in the first trimester with an improvement in sensitivity from 70 to 91% with only a slight drop in specificity (from 91 to 88%). Diagnosis of gestational diabetes was not enhanced by measuring plasma insulin concentrations or insulin-glucose molar ratios. Conclusions The diagnosis of gestational diabetes in a high-risk population can be made in the first half of pregnancy. Early diagnosis should permit evaluation of intervention strategies, which may result in improved perinatal outcome.

Heart rate variability in healthy newborn infants

In adults and older children, heart rate variability (HRV) is frequently used to study autonomic function noninvasively. Normal values of HRV in newborn infants, however, are not widely available. This problem may be partially attributed to the lack of standardization of different methods. This study assessed HRV in normal newborn infants using 24-hour Holter monitoring. From 1997 to 2000, we prospectively evaluated frequency- (spectral analysis), geometric-, and time-domain indexes of HRV in normal term infants. Ninety-six asymptomatic infants who were <72 hours old were studied. Frequency-domain parameters (power in the high, low, very low, ultra low, and total frequency domains), a geometric parameter (HRV triangular index), and time-domain parameters (SDNN, SDANN, SDNNi, r-MSSD, s-NN50) are reported as means +/- SD, medians, and 5th and 95th percentiles to establish the normative values for newborns. A high degree of correlation (r > or = 0.85, p <0.0001) was noted among the 3 vagal tone dependent parameters, such as high-frequency power (frequency domain), r-MSSD, and s-NN50 (time domain). Our study supports the use of vagal dependent time-domain parameters like r-MSSD and sNN50 as surrogates for high-frequency power in newborns. Because the data are reported as means +/- SD, medians, and 5th and 95th percentiles, their use facilitates the study of parasympathetic and sympathetic activity in comparable populations.

Metabolic Bone Disease: A Continued Challenge in Extremely Low Birth Weight Infants

BACKGROUND Metabolic bone disease (MBD) is an important prematurity-related morbidity, but remains inadequately investigated in extremely low birth weight (ELBW) infants, the group most at risk. The objective was to describe the incidence and associated risk factors of MBD in ELBW infants. METHODS Retrospective analysis of all ELBW infants admitted between January 2005 and December 2010 who survived > 8 weeks. MBD was defined as the presence of osteopenia or rickets in radiographs. RESULTS Of the 230 infants included in the study, 71 (30.9%) developed radiological evidence of MBD (cases) of which 24/71 (33.8%) developed spontaneous fractures. MBD and fractures were noted at mean postnatal ages of 58.2 ± 28 and 100.0 ± 61 days, respectively. Compared with controls, cases were smaller at birth (664.6 ± 146 g vs 798.1 ± 129 g), more premature (25.0 ± 1.8 vs 26.4 ± 1.9 weeks), more frequently associated with mechanical ventilation, chronic lung disease, parenteral nutrition days, cholestasis, furosemide, postnatal steroids, and antibiotics use (all P < .01). Cases had lower average weekly intake of calcium, phosphorous, vitamin D, protein, and calories during the first 8 weeks of life compared with controls. Cases with MBD, compared with controls, had higher mortality (14.1 vs 4.4%) and longer hospital stay (140.2 ± 51 vs 101.0 ± 42 days; P < .01). CONCLUSIONS MBD remains an important morbidity in ELBW infants despite advances in neonatal nutrition. Further research is needed to optimize the management of chronic lung disease and early nutrition in ELBW infants.

Relation between transamination of branched-chain amino acids and urea synthesis: evidence from human pregnancy

Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N (QN) and carbon (QC) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 +/- 1.14 vs. pregnant 3.44 +/- 1.11 micromol . kg-1 . min-1; means +/- SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. QN was also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 +/- 35 vs. 3rd trimester 135 +/- 16 micromol . kg-1 . h-1; P < 0.05). There was no significant change in QC during pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration (P < 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting (r = 0.59, P = 0.001) and during feeding (r = 0.407, P = 0. 01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as alpha-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N ( Q N) and carbon ( Q C) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 ± 1.14 vs. pregnant 3.44 ± 1.11 μmol ⋅ kg-1 ⋅ min-1; means ± SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. Q Nwas also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 ± 35 vs. 3rd trimester 135 ± 16 μmol ⋅ kg-1 ⋅ h-1; P < 0.05). There was no significant change in Q Cduring pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration ( P< 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting ( r = 0.59, P = 0.001) and during feeding ( r = 0.407, P = 0.01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as α-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.