Roadmap to a successful quality improvement project.

Although the benefits of quality improvement initiatives are largely understood by practicing neonatologists and perinatologists, the vast majority have not received any formal training in quality improvement methodology. Even as reporting requirements of quality metrics has increased from a number of outside agencies and public reporting entities, education for physicians regarding how to carry out quality improvement projects has largely remained the individual's responsibility. The first in a series of quality improvement education papers, we focus on the reasons why quality improvement matters and how to develop a team of stakeholders that will be functional and productive in addressing specific quality and safety concerns.

Use of neonatal simulation models to assess competency in bag-mask ventilation.

OBJECTIVE: Providing adequate bag-mask ventilation (BMV) is an essential skill for neonatal resuscitation. Often this skill is learned using simulation manikins. Currently, there is no means of measuring the adequacy of ventilation in simulated scenarios. Thus, it is not possible to ascertain proficiency. The first aim of this study was to measure the pressure generated during BMV as performed by providers with different skill levels and measure the impact of different feedback mechanisms. The second aim was to measure the pressure volume characteristics of two neonatal manikins to see how closely they reflect newborn lung mechanics. STUDY DESIGN: In Phase I to achieve the first aim, we evaluated BMV skills in different level providers including residents (n=5), fellows (n=5), neonatal nurse practitioners (n=5) and neonatologists (n=5). Each provider was required to provide BMV for 2-min epochs on the SimNewB (Laerdal), which had been instrumented to measure pressure-volume characteristics. In sequential 2-min epochs, providers were given different feedback including chest-wall movement alone compared to manometer plus chest-wall movement or chest-wall movement plus manometer plus laptop lung volume depiction. In Phase II of the study we measured pressure-volume characteristics in instrumented versions of the SimNewB (Laerdal) and NeoNatalie (Laerdal). RESULTS: In Phase I, all providers are compared with the neonatologists. All measurements of tidal volume (Vt) are below the desired 5 ml kg(-1). The greatest difference in Vt between the neonatologists and other providers occurs when only chest-wall movement is provided. A linear relationship is noted between Vt and PIP for both SimNewB and NeoNatalie. The compliance curves are not 'S-shaped' and are different between the two models (P<0.001). CONCLUSION: Phase I of this study demonstrates that the SimNewB with the feedback of chest-wall movement alone was the best method of distinguishing experienced from inexperienced providers during simulated BMV. Therefore this is likely to be the best method to ascertain proficiency. Phase II of the study shows that the currently available neonatal simulation manikins do not have pressure-volume characteristics that are reflective of newborn lung mechanics, which can result in suboptimal training.

Cranial sonography in very-low-birth-weight infants: do all infants need to be screened?

The objective of the study was to develop clinical screening criteria to diagnose infants with intraventricular hemorrhage (IVH) and cystic periventricular leukomalacia (PVL). We performed a case-control investigation of two cohorts of very-low-birth-weight infants (n = 505, combined cohorts). Univariate and multivariate analyses were performed from data obtained in cohort 1 to develop screening criteria for IVH and cystic PVL. The screening criteria were then applied to cohort 2. The screening criteria for IVH had a sensitivity of only 51%, a specificity of 62%, a positive predictive value of 31%, and a negative predictive value of 79%. Screening criteria for cystic PVL had a sensitivity of only 22%, a specificity of 58% a positive predictive value of 2%, and a negative predictive value of 95%. These data suggest that using clinical criteria to determine which infants should receive screening cranial sonography for IVH and cystic PVL would miss a substantial number of infants with these conditions.

Species differences in cis-elements of the proalpha1(I) procollagen promoter and their binding proteins.

Previous studies suggest that there may be species differences in the utilization of cis-elements of the type I collagen genes. The present study was designed to examine this possibility by focusing on two regions of the proalpha1(I) collagen promoter. One is the GC-rich A1 region (-194/168) that modulates transcriptional activity of the mouse promoter. The other contains a glucocorticoid response element (GRE) implicated in negative glucocorticoid regulation of the rat promoter. Unlike mouse A1 probes, probes representing the analogous human (-195/-168) and rat (-193/-179) regions failed to bind nuclear proteins in gel shift assays. Binding assays with mouse A1 probes containing base substitutions indicated that this behavior could be ascribed to five bases in the human, and two in the rat sequences. In addition, the pattern of expression of c-Krox, a protein that alters transcriptional activity via the mouse A1 element, differed in mouse and human tissues. Computer analysis revealed differences in the arrangement of GRE half-sites in human and rat proalpha1(I) collagen promoters. In a region of the human promoter (-700/673) analogous to the rat (-672/-633), there are three half-sites, each separated by two nucleotides, that cooperate in binding of glucocorticoid receptor. There also is a proximal half-site at position -335 of the human promoter that binds glucocorticoid receptor, but it is not present in the rat promoter. This study has defined several species-specific differences in the sequences and nuclear protein binding activity of regions involved in transcriptional activity of the proalpha1(I) collagen promoter. The results suggest that the A1 regions of the human and rat promoters examined here are unlikely to function as regulatory cis-elements, and they provide a framework for investigating the role of GREs in transcriptional regulation. They also suggest that species differences in cis-elements and transcription factors should be taken into consideration when using heterologous systems to study collagen gene regulation.

Infective endocarditis in the premature neonate.

We describe a series of 11 high-risk neonates with infective endocarditis (IE) in this retrospective review. Previously IE has rarely been diagnosed in newborns and is usually fatal. The frequency was 4.3 cases per 100 patients. Five patients survived. Microorganisms included gram positives such as S. aureus and coagulase-negative Staphylococcus, gram negatives such as Klebsiella pneumoniae, Enterobacter cloacae, Enterococcus faecalis, Serratia marcescens, and Acinetobacter calcoaceticus. Echocardiographic location of the lesions showed four left sided, five right sided, and two bilateral. We conclude that IE may be more common than previously described. Prompt diagnosis and treatment led to survival in 45% of our patients. Prospective studies are needed to identify patients at risk and to establish the true incidence of IE in high-risk neonates.

Measurement of soluble transferrin receptor in serum of healthy adults.

The concentration of soluble transferrin receptor (sTfR) in serum is reported to be useful in the diagnosis of iron deficiency, especially for patients with concurrent chronic disease, where routine tests of iron status are compromised by the inflammatory condition. A new diagnostic assay for sTfR is calibrated against natural plasma sTfR, thus minimizing calibration discrepancies that result from differences between the analyte and the cellular transferrin receptor used in other assays. Use of the new assay to measure sTfR concentrations in 225 healthy, hematologically normal adults provided a reference interval against which pathological samples could be compared. There was no difference in the reference intervals for men and women and no correlation of [sTfR] with the age of the subject. Black subjects had significantly higher concentrations than nonblacks, and people living at high altitude had higher concentrations than those living closer to sea level. These differences were additive.

The test-retest reliability of the frequency of multiple drug use in young drug users entering treatment.

Assessment of multiple drug use relies primarily on self-report. Several studies support the reliability of client self-reports of drug use but these studies have not involved assessment of the actual frequency of drug use. This test-retest reliability study assessed the frequency of drug use in a clinical sample of 103 multiple drug users, aged 16-25 years. At initial assessment, all participants completed the Drug Use History Form (DUHF) that inquired about the number of drug-using days and the daily frequency of use for 13 drug classes during four time intervals. The DUHF was readministered 2-4 weeks later. Reliability was assessed using Intra-class correlations (ICC's). The results indicated that clients do, in general, reliably report both the number of days of use and daily frequencies. The two frequency measures were not highly correlated. Reliability estimates declined over time but most markedly after 90 days, suggesting that assessments of drug use can be reliably extended beyond 30 days. Frequency estimates based solely on the number of days of use of a substance may be unreliable estimates of actual drug consumption, indicating limitations to this commonly used outcome measure.

Predicting red blood cell transfusions in very low birth weight infants based on clinical risk factors.

OBJECTIVE: To describe the clinical factors most predictive of red blood cell transfusion in very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective review of VLBW infants cared for at a single level III NICU during a two year period, n = 199. RESULTS: Overall transfusion requirement was 4.6 +/- 6.2 transfusions/infant/hospital course. Length of hospital stay, days of mechanical ventilation, requirement for dopamine support, birth weight, initial hematocrit, periventricular leukomalacia and necrotizing enterocolitis all independently correlated with number of transfusions and donors. Bronchopulmonary dysplasia and patent ductus arteriosus were associated with donor but not transfusion number. CONCLUSIONS: Our data characterize the population of VLBW infants with the greatest blood transfusion and donor requirement. Further investigation is needed to target this population for interventions to reduce blood exposure.

Translacrimal transnasal laser-assisted dacryocystorhinostomy.

Chronic dacryocystitis is due to an obstruction in the nasolacrimal duct, with subsequent infection of the lacrimal sac. The goal of surgery is to reestablish intranasal drainage of the lacrimal sac. Classic dacryocystorhinostomy (DCR) requires an external incision and drilling through the lacrimal bone into the middle meatus. In our study a 600-micron neodymium:YAG (Nd:YAG) fiber with a blunt hemispherical tip is inserted via the lacrimal puncta. An intranasal ostium is created with the laser under intranasal endoscopic control. Silicon tubes are then left in place for 6 months. We have performed 49 procedures over the past 2 1/2 years, with a success rate of 85% after one surgical procedure, which is commensurate with standard DCR. This procedure provides a simple, bloodless, incisionless alternative to standard DCR.

Characteristics of 73 patients, 1984-1993, treated by plasma exchange for Guillain-Barre syndrome.

Acute Guillain-Barre syndrome (GBS) is a demyelinating polyneuropathy which responds readily to plasma exchange (PEX). According to the North American Acute GBS PEX study there is a 50% or more reduction in the recovery time if PEX is initiated early in the course of the disease. Demyelinating antibodies are usually IgM. IgA antibodies require prolonged PEX. Patients with predominant IgG antibodies have chronic inflammatory demyelinating polyneuropathy (CIDP), which requires an even longer course of PEX, over weeks to months or years. We reviewed records of 73 patients with the initial diagnosis of GBS treated with PEX. Among these patients, 55 had classic GBS, three had the Miller-Fisher variant, two had CIDP, and 13 had demyelinating-like polyneuropathies associated with other conditions including malignancy, vaccine-related myelitis, steroid-induced myopathy, polymyositis, botulism, gram-negative sepsis, Sjogren's, and AIDS. Hughes grading system was used. Patients were graded 3 to 5, with grade 3 patients being unable to walk 5 m without support, grade 4 patients being bed or chair bound, and grade 5 patients being ventilator dependent. Of 60 unassociated (GBS) demyelinating cases receiving a mean of 6.5 PEX procedures, 13 (21%) were intubated early in the treatment, with four (6%) remaining ventilator dependent post-PEX. Of 51 non-intubated patients, 15 became ambulatory post-PEX. Patients with the Miller-Fisher variant showed improvement within 6 hours of PEX initiation. We did not investigate correlation of GBS with infection; however, we did observe a rise in CMV titer among 15% of the 58 patients with acute GBS. Considering our results we believe that intensive PEX on a daily basis for a few days is necessary for severely affected individuals. We advise five to nine procedures at consultation unless early, rapid recovery occurs.

Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2.

The gene for spinocerebellar ataxia type 2 (SCA2) has been mapped to 12q24.1. A 1.1-megabase contig in the candidate region was assembled in P1 artificial chromosome and bacterial artificial chromosome clones. Using this contig, we identified a CAG trinucleotide repeat with CAA interruptions that was expanded in patients with SCA2. In contrast to other unstable trinucleotide repeats, this CAG repeat was not highly polymorphic in normal individuals. In SCA2 patients, the repeat was perfect and expanded to 36-52 repeats. The most common disease allele contained (CAG)37, one of the shortest expansions seen in a CAG expansion syndrome. The repeat occurs in the 5'-coding region of SCA2 which is a member of a novel gene family.

Time course of endothelial dysfunction and neutrophil adherence and infiltration during murine traumatic shock.

Traumatic shock in rats has been shown to induce endothelial dysfunction, and to increase intestinal myeloperoxidase activity (MPO) indicative of neutrophil infiltration. To examine the time course of endothelial dysfunction and neutrophil adherence and infiltration, pentobarbital anesthetized rats, subjected to Noble-Collip drum trauma, were studied prior to and 15, 30, 60, 90, 120, 150, and 180 min following drum trauma. Superior mesenteric artery rings obtained from traumatized rats were tested for responsiveness to acetylcholine (ACh), a receptor-mediated endothelium-dependent vasodilator, and to NaNO2 an endothelium-independent vasodilator. ACh-induced relaxation was not impaired immediately after the induction of trauma (time 0). However, 15-30 min after trauma, responses to ACh were significantly depressed (p < .05) and were further reduced (p < .01) 90-180 min after trauma. No significant changes occurred in response to the direct vasodilator NaNO2 at any of the times studied, indicating no vascular smooth muscle injury. Moreover, the adherence of polymorphonuclear leukocytes (PMNs) to the post-traumatic mesenteric vascular endothelium also showed an increase that peaked 30 min post-trauma. Intestinal MPO activity, indicative of neutrophil infiltration, was characterized by a continuous and sustained increase from 30-180 min. Our findings suggest that endothelial dysfunction resulting in reduced NO release occurs in the early phase of murine traumatic shock, and that this phenomenon is followed by a time-dependent increase in adhesivity of neutrophils to the vascular endothelium leading to a progressive accumulation of PMNs in injured tissues (e.g., intestine).

Umbilical venous catheters: evaluation of radiographs to determine position and associated complications of malpositioned umbilical venous catheters.

To evaluate the ability of radiography to detect malpositioned umbilical venous catheters in the left atrium and to determine the frequency of associated complications, we retrospectively compared radiographs and echocardiograms of 31 infants who had malpositioned catheters in the left atrium by echocardiography (cases) and 31 infants who had properly positioned catheters (controls). The case and control infants were of similar gestational age and birthweight (gestational age, 32 +/- 5 weeks; birthweight, 1672 +/- 899 g for cases; gestational age, 31 +/- 5 weeks; birthweight, 1666 +/- 958 g for controls). Malposition was defined as the catheter tip above the seventh thoracic vertebra by radiography. Radiography had sensitivity of 45%, specificity of 87%, positive predictive value of 77%, negative predictive value of 61%, accuracy of 66%, and prevalence of 50%. Thrombus formation in the heart was detected in 8 of 31 (26%) of cases and in 1 of 31 (3%) of controls (p = 0.03). The incidence of complications, such as necrotizing enterocolitis, culture-positive sepsis, total number of sepsis cases, thrombocytopenia, embolism to extremities, and hematuria were similar in both groups (difference not significant). These results suggest that radiography is unreliable in determining incorrect catheter placement. Catheters malpositioned in the left atrium were associated with thrombus formation. There was no significant increase in systemic complications in the infants with a malpositioned catheter.

Laser-assisted uvula-palatoplasty for snoring.

Laser-assisted uvula-palatoplasty (LAUP) is a new and effective surgical method for the elimination of habitual snoring. LAUP is safely performed under local anesthesia in the office, and it provides progressive enlargement of the oropharyngeal air space by reshaping and restructuring the uvula, soft palate, and pharyngeal pillars utilizing the CO2 laser with special attachments. LAUP can also reduce oropharyngeal obstruction that may occur during sleep in patients with obstructive sleep apnea syndrome. Our experience includes over 335 patients evaluated and treated within the past year. Successive laser ablation of the vibrating structures, such as the uvula, soft palate, and posterior pharyngeal pillars, provided an 84% cure rate. In addition, 7% of the patients reported significant improvement in the loudness of their snore. The major advantage of this surgical technique is that it is a safe, simple, reliable, and bloodless procedure that can be performed in the office. This method and the results of its use are discussed.

Durable remissions following prolonged plasma exchange in thrombotic thrombocytopenic purpura.

We evaluated the efficacy of prolonged plasma exchange (PEX) for attaining durable remissions in thrombotic thrombocytopenic purpura (TTP). A recent review using steroids or PEX in initial management showed an 80% response rate but produced a relapse rate of 67-84%. Records of 50 patients starting PEX treatment for TTP/HUS were reviewed to identify and select those whose course of treatment had ended over 1 year earlier, whether or not the result was satisfactory. Records were evaluated for outcome, especially remission associated with treatment by "prolonged" plasma exchange. "Prolonged" was defined as continuing PEX beyond the stage where a normal platelet count was attained and until evidence of hemolysis was "minimal or at least compensated." If disease activity as judged by the criteria of hemolysis became accelerated or resumed, PEX was increased by volume of FFP (e.g., from 3 to 4 L) or rate (from less than daily to daily). Of 50 consecutive patients treated by PEX for TTP/HUS there were 40 cases after which at least one year had passed since the end of treatment. These 40 patients were evaluated for the results of treatment by PEX. Eight failed to achieve remission, dying in hospital within 1 month of admission. Twenty-eight achieved remission, sustained for 1 year or more in all. These are the reasons for our enthusiasm about this report. Four achieved remission lasting less than 1 year. Splenectomy was performed to obtain a sustained remission in one patient following administration of three 2 mg doses of vincristine and two relapses.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe hemolytic disease of the newborn caused by anti-Gonzales antibody.

We report on a female infant with severe hemolytic disease of the newborn (HDN) secondary to anti-Gonzales antibody (anti-Go(a)) necessitating an exchange transfusion within the first day of life. The infant was born to a mother known to be Gonzales-antigen negative and a father who was Gonzales-antigen positive. The mother had an anti-Go(a) titer of 1:256 at 35 weeks' gestation. The infant was noted to have jaundice shortly after birth, with a bilirubin of 17.8 mg/dl (total) and .05 mg/dl (direct) at 11 hours of life. Coombs' test was positive and cord cells were Gonzales-antigen positive. Eluate on cord cells demonstrated anti-Go(a). Despite aggressive phototherapy, the total bilirubin reached 23.3 mg/dl by 24 hours of age and a double-volume exchange transfusion was performed. Following the exchange transfusion, phototherapy was continued for several days. The hemoglobin, which was 19.8 gm/dl at 11 hours of age, remained stable through the hospitalization, and no further transfusions were required. History revealed that two prior pregnancies resulted in Gonzales-antigen positive infants. The first child experienced mild jaundice requiring no therapy, and the second child required phototherapy for prolonged hyperbilirubinemia. Previous reported cases of anti-Go(a) suggest that this is not a cause of severe HDN. However, in view of the current case, it may be prudent to follow women with anti-Go(a) prenatally with amniotic fluid bilirubin studies, serial antibody titers, and fetal hemoglobin levels.