Memorial Medical Center

In Brief Purpose: Oncologic concerns from high wound recurrence rates prompted a multi-institutional randomized trial to test the hypothesis that disease-free and overall survival are equivalent, regardless of whether patients receive laparoscopic-assisted or open colectomy. Methods: Eight hundred seventy-two patients with curable colon cancer were randomly assigned to undergo laparoscopic-assisted or open colectomy at 1 of 48 institutions by 1 of 66 credentialed surgeons. Patients were followed for 8 years, with 5-year data on 90% of patients. The primary end point was time to recurrence, tested using a noninferiority trial design. Secondary endpoints included overall survival and disease-free survival. (Kaplan–Meier) Results: As of March 1, 2007, 170 patients have recurred and 252 have died. Patients have been followed a median of 7 years (range 5–10 years). Disease-free 5-year survival (Open 68.4%, Laparoscopic 69.2%, P = 0.94) and overall 5-year survival (Open 74.6%, Laparoscopic 76.4%, P = 0.93) are similar for the 2 groups. Overall recurrence rates were similar for the 2 groups (Open 21.8%, Laparoscopic 19.4%, P = 0.25). These recurrences were distributed similarly between the 2 treatment groups. Sites of first recurrence were distributed similarly between the treatment arms (Open: wound 0.5%, liver 5.8%, lung 4.6%, other 8.4%; Laparoscopic: wound 0.9%, liver 5.5%, lung 4.6%, other 6.1%). Conclusion: Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on long-term oncologic endpoints from a prospective randomized trial. A multicenter prospective trial of 872 patients randomly assigned to undergo laparoscopic or open colectomy for curable cancer was performed. Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on 5-year overall survival, disease-free survival, and overall and site-specific rates of recurrence.

BACKGROUND: Computed tomographic (CT) colonography is a noninvasive option in screening for colorectal cancer. However, its accuracy as a screening tool in asymptomatic adults has not been well defined. METHODS: We recruited 2600 asymptomatic study participants, 50 years of age or older, at 15 study centers. CT colonographic images were acquired with the use of standard bowel preparation, stool and fluid tagging, mechanical insufflation, and multidetector-row CT scanners (with 16 or more rows). Radiologists trained in CT colonography reported all lesions measuring 5 mm or more in diameter. Optical colonoscopy and histologic review were performed according to established clinical protocols at each center and served as the reference standard. The primary end point was detection by CT colonography of histologically confirmed large adenomas and adenocarcinomas (10 mm in diameter or larger) that had been detected by colonoscopy; detection of smaller colorectal lesions (6 to 9 mm in diameter) was also evaluated. RESULTS: Complete data were available for 2531 participants (97%). For large adenomas and cancers, the mean (+/-SE) per-patient estimates of the sensitivity, specificity, positive and negative predictive values, and area under the receiver-operating-characteristic curve for CT colonography were 0.90+/-0.03, 0.86+/-0.02, 0.23+/-0.02, 0.99+/-<0.01, and 0.89+/-0.02, respectively. The sensitivity of 0.90 (i.e., 90%) indicates that CT colonography failed to detect a lesion measuring 10 mm or more in diameter in 10% of patients. The per-polyp sensitivity for large adenomas or cancers was 0.84+/-0.04. The per-patient sensitivity for detecting adenomas that were 6 mm or more in diameter was 0.78. CONCLUSIONS: In this study of asymptomatic adults, CT colonographic screening identified 90% of subjects with adenomas or cancers measuring 10 mm or more in diameter. These findings augment published data on the role of CT colonography in screening patients with an average risk of colorectal cancer. (ClinicalTrials.gov number, NCT00084929; American College of Radiology Imaging Network [ACRIN] number, 6664.)

Abstract Engineering as a profession faces the challenge of making the use of technology ubiquitous and transparent in society while at the same time raising young learners' interest and understanding of how technology works. Educational efforts in science, technology, engineering, and mathematics (i.e., STEM disciplines) continue to grow in pre‐kindergarten through 12th grade (P‐12) as part of addressing this challenge. This article explores how engineering education can support acquisition of a wide range of knowledge and skills associated with comprehending and using STEM knowledge to accomplish real world problem solving through design, troubleshooting, and analysis activities. We present several promising instructional models for teaching engineering in P‐12 classrooms as examples of how engineering can be integrated into the curriculum. While the introduction of engineering education into P‐12 classrooms presents a number of opportunities for STEM learning, it also raises issues regarding teacher knowledge and professional development, and institutional challenges such as curricular standards and high‐stakes assessments. These issues are considered briefly with respect to providing direction for future research and development on engineering in P‐12.

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 x 10(9)/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P <.01) and CR rate after one course (74% v 55%, P <.01) and better survival (P <.01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P =.01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

BACKGROUND: Despite improving arterial oxygen saturation and pH, bystander cardiopulmonary resuscitation (CPR) with chest compressions plus rescue breathing (CC+RB) has not improved survival from ventricular fibrillation (VF) compared with chest compressions alone (CC) in numerous animal models and 2 clinical investigations. METHODS AND RESULTS: After 3 minutes of untreated VF, 14 swine (32+/-1 kg) were randomly assigned to receive CC+RB or CC for 12 minutes, followed by advanced cardiac life support. All 14 animals survived 24 hours, 13 with good neurological outcome. For the CC+RB group, the aortic relaxation pressures routinely decreased during the 2 rescue breaths. Therefore, the mean coronary perfusion pressure of the first 2 compressions in each compression cycle was lower than those of the final 2 compressions (14+/-1 versus 21+/-2 mm Hg, P<0.001). During each minute of CPR, the number of chest compressions was also lower in the CC+RB group (62+/-1 versus 92+/-1 compressions, P<0.001). Consequently, the integrated coronary perfusion pressure was lower with CC+RB during each minute of CPR (P<0.05 for the first 8 minutes). Moreover, at 2 to 5 minutes of CPR, the median left ventricular blood flow by fluorescent microsphere technique was 60 mL. 100 g(-1). min(-1) with CC+RB versus 96 mL. 100 g(-1). min(-1) with CC, P<0.05. Because the arterial oxygen saturation was higher with CC+RB, the left ventricular myocardial oxygen delivery did not differ. CONCLUSIONS: Interrupting chest compressions for rescue breathing can adversely affect hemodynamics during CPR for VF.

PURPOSE: To test the hypothesis that absence of statistically significant lung nodule enhancement (< or =15 HU) at computed tomography (CT) is strongly predictive of benignity. MATERIALS AND METHODS: Five hundred fifty lung nodules were studied. Of these, 356 met all entrance criteria and had a diagnosis. On nonenhanced, thin-section CT scans, the nodules were solid, 5-40 mm in diameter, relatively spherical, homogeneous, and without calcification or fat. All patients were examined with 3-mm-collimation CT before and after intravenous injection of contrast material. CT scans through the nodule were obtained at 1, 2, 3, and 4 minutes after the onset of injection. Peak net nodule enhancement and time-attenuation curves were analyzed. Seven centers participated. RESULTS: The prevalence of malignancy was 48% (171 of 356 nodules). Malignant neoplasms enhanced (median, 38.1 HU; range, 14.0-165.3 HU) significantly more than granulomas and benign neoplasms (median, 10.0 HU; range, -20.0 to 96.0 HU; P < .001). With 15 HU as the threshold, the sensitivity was 98% (167 of 171 malignant nodules), the specificity was 58% (107 of 185 benign nodules), and the accuracy was 77% (274 of 356 nodules). CONCLUSION: Absence of significant lung nodule enhancement (< or = 15 HU) at CT is strongly predictive of benignity.

OBJECTIVE: To describe the epidemiology, antimicrobial susceptibility, and control of widespread ceftazidime-resistant Klebsiella pneumoniae infections in a North American hospital and circumstances that led to delayed detection. DESIGN: A 2-year epidemiologic, microbiologic, and clinical cohort study. SETTING: A 487-bed general hospital in New York City. PATIENTS AND CLINICAL ISOLATES: Patient records were reviewed retrospectively and prospectively. Isolates were obtained from the Clinical Microbiology Laboratory. RESULTS: Four hundred thirty-two isolates of ceftazidime-resistant Klebsiella pneumoniae were recovered during a 19-month study period. The peak incidence reached 17.3% of all Klebsiella isolates. One hundred fifty-five patients were colonized or infected, representing more than 70 per 1000 average daily census. Infections occurred in 39% of patients from whom ceftazidime-resistant Klebsiella was isolated. These included 14 bacteremias and 17 pulmonary infections among 52 infected patients. The outbreak coincided with increasing use of ceftazidime therapy for multiresistant Acinetobacter infections. Reduction in ceftazidime use and barrier precautions markedly reduced the incidence of colonization and infection. Ceftriaxone, ceftizoxime, cefotaxime, and cephamycins were inhibitory, but not bactericidal, against ceftazidime-resistant Klebsiella and appeared effective by routine disc diffusion tests. In contrast, imipenem provided consistent bactericidal activity. Preliminary studies indicated that the outbreak was caused by one or more plasmid-mediated beta lactamases. CONCLUSIONS: Nosocomial ceftazidime-resistant Klebsiella pneumoniae may be resistant to the bactericidal activity of all cephalosporins and cephamycins. Such isolates appear susceptible to cephalosporins other than ceftazidime by routine disc diffusion testing. Ineffective therapy, delayed detection of resistance, and epidemic spread are potential consequences. Imipenem provides consistent bactericidal activity. Ceftazidime restriction and barrier precautions for colonized and infected patients are effective control measures.

OBJECTIVES: To determine the prevalence of symptoms associated with gastroesophageal reflux (GER) in 3- to 17-year-old children, to describe the prevalence of factors associated with GER in these children, and to determine the percentage of symptomatic children who have been treated. DESIGN: A cross-sectional survey. SETTING: Sixteen pediatric practice research group practices in the Chicago, Ill, area (urban, suburban, and semirural). PARTICIPANTS: A total of 566 parents of 3- to 9-year-old children, 584 parents of 10- to 17-year-old children, and 615 children aged 10 to 17 years. INTERVENTION: None. MAIN OUTCOME MEASURE: Reported frequency of symptoms associated with GER. RESULTS: Parents of 3- to 9-year-old children reported that their children experienced a sensation of heartburn ("burning/painful feeling in middle of chest"), epigastric pain ("stomachache above belly button"), and regurgitation ("sour taste or taste of throw up") 1.8%, 7.2%, and 2.3% of the time, respectively. Parents of 10- to 17-year-old children reported that their children experienced the same symptoms 3.5%, 3.0%, and 1.4% of the time, while children aged 10 to 17 years reported the symptoms 5.2%, 5.0%, and 8.2% of the time, respectively. Complaints of abdominal pain ("stomachache") were most common, reported by 23.9% and 14.7% of parents of 3- to 9-year-old and 10- to 17-year-old children and by 27.9% of children aged 10 to 17 years. In those aged 10 to 17 years, heartburn reported by the children was associated with reported cigarette use (odds ratio, 6.5; 95% confidence interval, 2-21); no other complaint was associated with cigarette, alcohol, or caffeine consumption or passive smoking exposure. In 3- to 9-year-old children, no complaint was associated with caffeine consumption or passive smoking exposure. Reported treatment in the past week with antacids was 0.5% according to parents of children aged 3 to 9 years and 1.9% and 2.3% according to parents of children aged 10 to 17 years and children aged 10 to 17 years, respectively. Treatment with over-the-counter histamine receptor blockers was 0% for children aged 3 to 9 years and 10 to 17 years, as reported by their parents, and 1.3% for those aged 10 to 17 years, as reported by themselves. CONCLUSIONS: Symptoms suggestive of GER are not rare in childhood, yet only a fraction of children with symptoms are treated with over-the-counter antacids or histamine2 antagonists. Prospective longitudinal data are needed to determine which children with symptoms of GER actually have GER disease and are at risk of developing complications.

The cause of the Chiari II hindbrain deformity in children born with a myelomeningocele can be explained by the lack of distention of the embryonic ventricular system. Defective occlusion and an open neural tube precludes the accumulation of fluid and pressure within the cranial vesicles. This distention is critical to normal brain development. The small posterior fossa, cerebral disorganization, and lückenschädel are the result.

BACKGROUND: Controversy exists as to the risk for postoperative apnea in former preterm infants. The conclusions of published studies are limited by the small number of patients. METHODS: The original data from eight prospective studies were subject to a combined analysis. Only patients having inguinal herniorrhaphy under general anesthesia were included; patients receiving caffeine, regional anesthesia, or undergoing other surgical procedures were excluded. A uniform definition for apnea was used for all patients. Eleven risk factors were examined: gestational age, postconceptual age, birth weight, history of respiratory distress syndrome, bronchopulmonary dysplasia, neonatal apnea, necrotizing enterocolitis, ongoing apnea, anemia, and use of opioids or nondepolarizing muscle relaxants. RESULTS: Two hundred fifty-five of 384 patients from eight studies at four institutions fulfilled study criteria. There was significant variation in apnea rates and the location of apnea (recovery room and postrecovery room) between institutions (P < 0.001). There was considerable variation in the duration and type of monitoring, definitions of apnea, and availability of historical information. The incidence of detected apnea was greater when continuous recording devices were used compared to standard impedance pneumography with alarms or nursing observations. Despite these limitations, it was determined that: (1) apnea was strongly and inversely related to both gestational age (P = 0.0005) and postconceptual age (P < 0.0001); (2) an associated risk factor was continuing apnea at home; (3) small-for-gestational-age infants seemed to be somewhat protected from apnea compared to appropriate- and large-for-gestational-age infants; (4) anemia was a significant risk factor, particularly for patients > 43 weeks' postconceptual age; (5) a relationship to apnea with history of necrotizing enterocolitis, neonatal apnea, respiratory distress syndrome, bronchopulmonary dysplasia, or operative use of opioids and/or muscle relaxants could not be demonstrated. CONCLUSIONS: The analysis suggests that, if it is assumed that the statistical models used are equally valid over the full range of ages considered and that the average rate of apnea reported across the studies analyzed is accurate and representative of actual rates in all institutions, the probability of apnea in nonanemic infants free of recovery-room apnea is not less than 5%, with 95% statistical confidence until postconceptual age was 48 weeks with gestational age 35 weeks. This risk is not less than 1%, with 95% statistical confidence, for that same subset of infants, until postconceptual age was 56 weeks with gestational age 32 weeks or postconceptual age was 54 weeks and gestational age 35 weeks. Older infants with apnea in the recovery room or anemia also should be admitted and monitored. The data do not allow prediction with confidence up to what age this precaution should continue to be taken for infants with anemia. The data were insufficient to allow recommendations regarding how long infants should be observed in recovery. There is additional uncertainty in the results due to the dramatically different rates of detected apnea in different institutions, which appear to be related to the use of different monitoring devices. Given the limitations of this combined analysis, each physician and institution must decide what is an acceptable risk for postoperative apnea.

RATIONALE: Considerable confusion exists regarding nomenclature, classification, and management of pediatric diffuse lung diseases due to the relative rarity and differences in the spectrum of disease between adults and young children. OBJECTIVES: A multidisciplinary working group was formed to: (1) apply consensus terminology and diagnostic criteria for disorders presenting with diffuse lung disease in infancy; and (2) describe the distribution of disease entities, clinical features, and outcome in young children who currently undergo lung biopsy in North America. METHODS: Eleven centers provided pathologic material, clinical data, and imaging from all children less than 2 years of age who underwent lung biopsy for diffuse lung disease from 1999 to 2004. MEASUREMENTS AND MAIN RESULTS: Multidisciplinary review categorized 88% of 187 cases. Disorders more prevalent in infancy, including primary developmental and lung growth abnormalities, neuroendocrine cell hyperplasia of infancy, and surfactant-dysfunction disorders, constituted the majority of cases (60%). Lung growth disorders were often unsuspected clinically and under-recognized histologically. Cases with known surfactant mutations had characteristic pathologic features. Age at biopsy and clinical presentation varied among categories. Pulmonary hypertension, presence of a primary developmental abnormality, or ABCA3 mutation was associated with high mortality, while no deaths occurred in cases of pulmonary interstitial glycogenosis, or neuroendocrine cell hyperplasia of infancy. CONCLUSIONS: This retrospective cohort study identifies a diverse spectrum of lung disorders, largely unique to young children. Application of a classification scheme grouped clinically distinct patients with variable age of biopsy and mortality. Standardized terminology and classification will enhance accurate description and diagnosis of these disorders.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

PURPOSE: Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with a historic median survival ranging from 6 to 11 months. Based on a previous pilot series, a prospective multi-institutional trial was conducted for patients with newly diagnosed CNS ATRT. PATIENTS AND METHODS: Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy (RT) was prescribed, either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on age and extent of disease at diagnosis. RESULTS: Between 2004 and 2006, 25 patients were enrolled; 20 were eligible for evaluation. Median age at diagnosis was 26 months (range, 2.4 months to 19.5 years). Gross total resection of the primary tumor was achieved in 11 patients. Fourteen patients had M0 disease at diagnosis, one patient had M2 disease, and five patients had M3 disease. Fifteen patients received radiation therapy: 11 focal and four craniospinal. Significant toxicities, in addition to the expected, included radiation recall (n = 2) and transverse myelitis (n = 1). There was one toxic death. Of the 12 patients who were assessable for chemotherapeutic response (pre-RT), the objective response rate was 58%. The objective response rate observed after RT was 38%. The 2-year progression-free and overall survival rates are 53% +/- 13% and 70% +/- 10%, respectively. Median overall survival has not yet been reached. CONCLUSION: This intensive multimodality regimen has resulted in a significant improvement in time to progression and overall survival for patients with this previously poor-prognosis tumor.

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI. 1. Ischemic symptom improvement is the primary indication for CTO-PCI. 2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI. 3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges. 4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs. 5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use. 6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation. 7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training.

OBJECTIVE: This study explored parents' perceptions about their child's appearance and health and evaluated a tool to determine parents' visual perception of their child's weight. METHODS: Parents of children aged 2 to 17 years were surveyed concerning their child's appearance and health and opinions about childhood overweight. They also selected the sketch (from 7 choices) that most closely matched the body image of their child using 1 of 8 gender-and age-range-specific panels of sketches. Children's height and weight were measured. Respondents were grouped by child body mass index (BMI) percentile (<5th, 5-84th, 85-94th [at risk for overweight (AROW)], and > or =95th [overweight]). Those with BMI > or =5th percentile were analyzed. Logistic regression was used to examine factors influencing parental perceptions and levels of worry about their overweight or AROW child. RESULTS: Of the 223 children, 60% were <6 years old, 42% were male, 17% were black, 35% were Hispanic, 42% were white, and 7% were other; 19% were AROW, and 20% were overweight. Few parents (36%) identified their overweight or AROW child as "overweight" or "a little overweight" using words, but more (70%) selected a middle or heavier sketch. Among parents of overweight and AROW children, 18% recalled a doctor's concern and 26% were worried about their child's weight. If the overweight or AROW child was age > or =6 years, parents were more likely to identify their child as "overweight" or "a little overweight" using words, select a middle or heavier sketch, and to be worried. Parents of older children were more likely to be worried if they perceived their child as less active/slower than other children or recalled a doctor's concern. CONCLUSIONS: Few parents of overweight and AROW children recognized their child as overweight or were worried. Recognition of physical activity limitations and physicians' concerns may heighten the parent's level of concern. Sketches may be a useful tool to identify overweight children when measurements are not available.

Twenty-nine patients with necrotizing fasciitis were treated from 1980 to 1988. This study evaluates how the addition of hyperbaric oxygen (HBO) therapy to surgical treatment has affected mortality and the number of debridements required to achieve wound control in these patients. Two groups of patients were viewed: group 1 (n = 12) received surgical debridement and antibiotics only; group 2 (n = 17) received HBO (90 minutes at 2.5 atm, average 7.4 treatments) in addition to surgery and antibiotics. Both groups were similar in age, race, sex, wound bacteriology, and antimicrobial therapy. Body surface area affected was similar, however, perineal involvement was more common in group 2 (53%) than in group 1 (12%). The admitting conditions of patients in group 1 (non-HBO) were diabetic, 33%; white blood cell count more than 12,000, 50%; and shock, 8%. The admitting conditions of patients in group 2 (HBO) were diabetic, 47%; white blood cell count more than 12,000, 59%; and shock, 29%. Although group 2 patients receiving HBO were more seriously ill on admission, mortality was significantly lower (23%) compared to group 1 (66%) (p less than 0.02). In addition, only 1.2 debridements per group 2 patient were required to achieve wound control versus 3.3 debridements per group 1 patient (p less than 0.03). The addition of HBO therapy to the surgical and antimicrobial treatment of necrotizing fasciitis significantly reduced mortality and wound morbidity (number of debridements) in this study, especially among nonclostridial infections. We conclude that HBO should be used routinely in the treatment of necrotizing fasciitis.

OBJECTIVE: This study was designed to assess the relation of exclusive breast-feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life. METHODS: Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children's Respiratory Study were reviewed. Detailed prospective information about the duration and exclusiveness of breast-feeding was obtained, as was information relative to potential risk factors (socioeconomic status, gender, number of siblings, use of day care, maternal smoking, and family history of allergy). Acute otitis media and recurrent otitis media, defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months, were the outcome variables. RESULTS: Of the 1013 infants followed for their entire first year, 476 (47%) had at least one episode of otitis and 169 (17%) had recurrent otitis media. Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. This protection was independent of the risk factors considered. CONCLUSION: These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media.

Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with > 95% specificity. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.

The Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium Protocol 95-01 was designed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy. Patients participated in randomized comparisons of (1) doxorubicin given with or without dexrazoxane, a cardioprotectant (high-risk patients), (2) intensive intrathecal chemotherapy and cranial radiation (standard-risk patients), and (3) Erwinia and Escherichia coli asparaginase (all patients). Between 1996 and 2000, 491 patients (aged 0-18 years) were enrolled (272 standard risk and 219 high risk). With a median of 5.7 years of follow-up, the estimated 5-year event-free survival (EFS) for all patients was 82%+/-2%. Dexrazoxane did not have a significant impact on the 5-year EFS of high-risk patients (P=.99), and there was no significant difference in outcome of standard-risk patients based on type of central nervous system (CNS) treatment (P=.26). Compared with E coli asparaginase, Erwinia asparaginase was associated with a lower incidence of toxicity (10% versus 24%), but also an inferior 5-year EFS (78%+/-4% versus 89%+/-3%, P=.01). We conclude that (1) dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2) intensive intrathecal chemotherapy is as effective as cranial radiation in preventing CNS relapse in standard-risk patients, and (3) once-weekly Erwinia is less toxic than E coli asparaginase, but also less efficacious.

The purpose of this study was to record prospectively the frequency of and potential harm caused by errant medication orders at two large pediatric hospitals. The objective of the study was to assess the impact of pharmacist intervention in preventing potential harm. The study was conducted during a 6-month period. A total of 281 and 198 errors were detected at the institutions. The overall error rates for the two hospitals were 1.35 and 1.77 per 100-patient days, and 4.9 and 4.5 per 1,000 medication orders, respectively. Pediatric patients aged 2 years and less and pediatric intensive care unit patients received the greatest proportion of errant orders. Neonatal patients received the lowest rate of errant orders. The most common type of error was incorrect dosage, and the most prevalent type of error was overdosage. Antibiotics was the class of drugs for which errant orders were most common. Orders for theophylline, analgesics, and fluid and electrolytes, including hyperalimentation, were also frequently in error. In general, the error rate was greatest among physicians with the least training, but no physician group was error free. Involving pharmacists in reviewing drug orders significantly reduced the potential harm resulting from errant medication orders.