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R L Davis

Publications and source records attributed to R L Davis.

At least 37 records · Page 2Linked to original sources

Molecular targets of vertebrate segmentation: two mechanisms control segmental expression of Xenopus hairy2 during somite formation.

Vertebrate hairy genes are expressed in patterns thought to be readouts of a "segmentation clock" in the presomitic mesoderm. Here we use transgenic Xenopus embryos to show that two types of regulatory elements are required to reconstitute the segmental pattern of Xenopus hairy2. The first is a promoter element containing two binding sites for Xenopus Su(H), a transcriptional activator of Notch target genes. The second is a short sequence in the hairy2 3' untranslated region (UTR), which most likely functions posttranscriptionally to modulate hairy2 RNA levels. 3' UTRs of other hairy-related, segmentally expressed genes can substitute for that of hairy2. Our results demonstrate a novel mechanism regulating the segmental patterns of Notch target genes and suggest that vertebrate segmentation requires the intersection of two regulatory pathways.

3' Untranslated Regions↗

Introduction of the new Centers for Disease Control and Prevention group B streptococcal prevention guideline at a large West Coast health maintenance organization.

OBJECTIVE: Our purpose was to assess the impact of new consensus guidelines issued by the Centers for Disease Control and Prevention, The American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics to prevent perinatal group B streptococcal disease. STUDY DESIGN: We performed a descriptive analysis and a before-and-after analysis of implementation of the group B streptococcal disease prevention guidelines among singleton-birth pregnancies in 2 Group Health Cooperative hospitals from October 1, 1995, through December 31, 1997. We studied the speed and completeness of implementation and the effect on pregnancy care practices including intrapartum antibiotic use, test ordering, and maternal and neonatal health. RESULTS: Guideline implementation occurred rapidly. The proportion of term pregnancies screened according to the guideline increased markedly, and overall intrapartum antibiotic use more than doubled. Among group B streptococci-positive women, intrapartum antibiotic prophylaxis increased from 24% before to 74% after guideline implementation. Median duration of treatment before delivery increased from 1.8 to 4.3 hours. The rate of rash did not increase, and there were no cases of anaphylaxis or pseudomembranous colitis. The proportion of infants undergoing evaluation decreased after implementation of the neonatal guidelines; among infants of group B streptococci-negative women, test ordering dropped by almost 40%. CONCLUSIONS: Implementation of the new guidelines is feasible and can be accomplished rapidly. The guidelines were associated with increased maternal intrapartum antibiotic use, particularly among women at highest risk, and with a decrease in laboratory use for infants.

Adult↗

Does influenza vaccination prevent asthma exacerbations in children?

OBJECTIVE: Influenza can exacerbate asthma, particularly in children. The effectiveness of influenza vaccine in preventing influenza-related asthma exacerbations, however, is not known. We evaluated influenza vaccine effectiveness in protecting children against influenza-related asthma exacerbations. STUDY DESIGN: We conducted a population-based retrospective cohort study with medical and vaccination records in 4 large health maintenance organizations in the United States during the 1993-1994, 1994-1995, and 1995-1996 influenza seasons. We studied children with asthma who were 1 through 6 years of age and who were identified by search of computerized databases of medical encounters and pharmacy dispensings. Main outcome measures were exacerbations of asthma evaluated in the emergency department or hospital. RESULTS: Unadjusted rates of asthma exacerbations were higher after influenza vaccination than before vaccination. After adjustment was done for asthma severity by means of a self-control method, however, the incidence rate ratios of asthma exacerbations after vaccination were 0.78 (95% CI: 0.55 to 1.10), 0.59 (0.43 to 0.81), and 0.65 (0.52 to 0.80) compared with the period before vaccination during the 3 influenza seasons. CONCLUSIONS: After controlling for asthma severity, we found that influenza vaccination protects against acute asthma exacerbations in children.

Acute Disease↗

A randomized controlled trial of point-of-care evidence to improve the antibiotic prescribing practices for otitis media in children.

CONTEXT: Prescribing practices for otitis media are not consistent with current evidence-based recommendations. OBJECTIVE: To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written. DESIGN: Randomized, controlled trial. SETTING: Primary care pediatric clinic affiliated with university training program. Intervention. A point-of-care evidence-based message system presenting real time evidence to providers based on their prescribing practice for otitis media. MAIN OUTCOME MEASURES: Proportion of prescriptions for otitis media that were for <10 days and frequency with which antibiotics were prescribed. RESULTS: Intervention providers had a 34% greater reduction in the proportion of time they prescribed antibiotics for <10 days. Intervention providers were less likely to prescribe antibiotics than were control providers. CONCLUSIONS: A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition.

Adult↗

Impact of the change in polio vaccination schedule on immunization coverage rates: a study in two large health maintenance organizations.

OBJECTIVE: In January 1997, one of the most significant changes to United States vaccine policy occurred when polio immunization guidelines changed to recommend a schedule containing inactivated polio vaccine (IPV). There were concerns that parent or physician reluctance to accept IPV into the routine childhood immunization schedule would lead to lowered coverage. We determined whether adoption of an IPV schedule had a negative impact on immunization coverage. DESIGN: A cohort study of 2 large health maintenance organizations (HMOs), Group Health Cooperative and Kaiser Permanente Northern California, was conducted. For analysis at 12 months of age, children who were born between October 1, 1996, and December 31, 1997, and were commercially insured and covered by Medicaid were continuously enrolled; for analysis at 24 months of age, children who were born between October 1, 1996, and June 30, 1997, and were commercially insured and covered by Medicaid were continuously enrolled. The 3 measures of immunization status at 12 and 24 months of age were up-to-date status, cumulative time spent up-to-date, and the number of missed opportunity visits. RESULTS: At both HMOs, children who received IPV were as likely to be up to date at 12 months as were children who received oral poliovirus vaccine (OPV), whereas at Group Health, children who received IPV were slightly more likely to be up to date at 24 months (relative risk: 1.12; 95% confidence interval [CI]: 1.05, 1.19). These findings were consistent for children who were covered by Medicaid. At Kaiser Permanente, children who received IPV spent ~3 fewer days up to date in the first year of life, but this difference did not persist at 2 years of age. At Group Health, children who received IPV were no different from those who received OPV in terms of days spent up to date by 1 or 2 years of age. At Group Health, children who received IPV were less likely to have a missed opportunity by 12 months old (odds ratio [OR] 0.46; 95% CI: 0.31, 0.70), but this finding did not persist at 24 months of age. At Kaiser Permanente, children who received IPV were more likely to have a missed opportunity by 12 months (OR 2.06; 95% CI: 1.84, 2.30), and 24 months of age (OR 1.50; 95% CI: 1.36, 1.67). CONCLUSIONS: The changeover from an all-OPV schedule to one containing IPV had little if any negative impact on vaccine coverage. Use of IPV was associated with a small increase in the likelihood of being up to date at 2 years of age at one of the HMOs and conversely was associated with a small increase in the likelihood of having a missed-opportunity visit in the other HMO.polio, poliomyelitis, vaccination, immunization coverage.

California↗

Variation in clinician recommendations for multiple injections during adoption of inactivated polio vaccine.

OBJECTIVES: To describe variation in clinician recommendations for multiple injections during the adoption of inactivated poliovirus vaccine (IPV) in 2 large health maintenance organizations (HMOs), and to test the hypothesis that variation in recommendations would be associated with variation in immunization coverage rates. DESIGN: Cross-sectional study based on a survey of clinician practices 1 year after IPV was recommended and computerized immunization data from these clinicians' patients. STUDY SETTINGS: Two large West Coast HMOs: Kaiser Permanente in Northern California and Group Health Cooperative of Puget Sound. OUTCOME MEASURES: Immunization status of 8-month-olds and 24-month-olds cared for by the clinicians during the study. RESULTS: More clinicians at Group Health (82%), where a central guideline was issued, had adopted the IPV/oral poliovirus vaccine (OPV) sequential schedule than at Kaiser (65%), where no central guideline was issued. Clinicians at both HMOs said that if multiple injections fell due at a visit and they elected to defer some vaccines, they would be most likely to defer the hepatitis B vaccine (HBV) for infants (40%). At Kaiser, IPV users were more likely than OPV users to recommend the first HBV at birth (64% vs 28%) or if they did not, to defer the third HBV to 8 months or later (62% vs 39%). In multivariate analyses, patients whose clinicians used IPV were as likely to be fully immunized at 8 months old as those whose clinicians used all OPV. At Kaiser, where there was variability in the maximum number of injections clinicians recommended at infant visits, providers who routinely recommended 3 or 4 injections at a visit had similar immunization coverage rates as those who recommended 1 or 2. At both HMOs, clinicians who strongly recommended all possible injections at a visit had higher immunization coverage rates at 8 months than those who offered parents the choice of deferring some vaccines to a subsequent visit (at Kaiser, odds ratio [OR]: 1.2; 95% confidence interval [CI]: 1.0-1.5; at Group Health, OR: 1.8; 95% CI: 1.1-2.8). CONCLUSIONS: Neither IPV adoption nor the use of multiple injections at infant visits were associated with reductions in immunization coverage. However, at the HMO without centralized immunization guidelines, IPV adoption was associated with changes in the timing of the first and third HBV. Clinical policymakers should continue to monitor practice variation as future vaccines are added to the infant immunization schedule.

Child, Preschool↗

Reducing antibiotic use in children: a randomized trial in 12 practices.

OBJECTIVE: To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old. METHODS: Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years. The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate. Confirmatory analyses at the practice level were also performed. RESULTS: The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices. Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices. Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups. The direction and approximate magnitude of effect were confirmed in practice-level analyses. CONCLUSIONS: A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.

Anti-Bacterial Agents↗

Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus.

OBJECTIVES: To evaluate suggested associations between childhood vaccinations, particularly against hepatitis B and Haemophilus influenzae type b, and risk of developing type 1 diabetes; and to determine whether timing of vaccination influences risk. METHODS: We conducted a case-control study within 4 health maintenance organizations (HMOs) that participate in the Vaccine Safety Datalink project of the Centers for Disease Control and Prevention. Study eligibility was restricted to children who met the following criteria: 1) born during 1988 through 1997; 2) HMO member since birth; 3) continuously enrolled for first 6 months of life; and 4) at least 12 months of HMO membership before diabetes incidence date (or index date for controls) unless incidence date was before 12 months of age. All 4 HMOs maintain registries of their members who have diabetes, and we used the registries to identify potential cases of diabetes. We conducted chart reviews to verify that potential cases met the World Health Organization epidemiologic case definition for type 1 diabetes mellitus (ie, a physician's diagnosis of diabetes plus treatment with daily insulin injections). We defined the incidence date of diabetes as the first date that the child received a diagnosis of diabetes. We attempted to match 3 controls to each case. Controls had the same eligibility criteria as cases and were matched to individual cases on HMO, sex, date of birth (within 7 days), and length of health plan enrollment (up to the incidence or index date). The index date for controls was defined as the incidence date of the case to which the control was matched. Chart abstraction was performed by trained chart abstractors using standardized forms. In addition to complete vaccination histories, the chart abstraction forms for both cases and controls included information on sociodemographic characteristics, selected medical conditions, history of breastfeeding, and family medical history. We used conditional logistic regression to estimate the odds ratio (OR) of diabetes associated with vaccination, with vaccine exposure defined as before the diabetes incidence date (or index date for controls). RESULTS: Two hundred fifty-two confirmed cases of diabetes and 768 matched controls met the study eligibility criteria. The OR (95% confidence interval) for the association with type 1 diabetes was 0.28 (0.07-1.06) for whole cell pertussis vaccine (predominantly in combination as diphtheria, tetanus toxoids and pertussis vaccine), 1.36 (0.70-2.63) for measles-mumps-rubella, 1.14 (0.51-2.57) for Haemophilus influenzae type b, 0.81 (0.52-1.27) for hepatitis B vaccine, 1.16 (0.72-1.89) for varicella vaccine, and 0.92 (0.53-1.57) for acellular pertussis-containing vaccines. Compared with children who had not received hepatitis B vaccine, the OR of diabetes was 0.51 (0.23-1.15) for children vaccinated at birth and 0.86 (0.54-1.35) for those first vaccinated against hepatitis B at 2 months of age or later. Race and ethnicity and family history of diabetes were independently associated with risk of type 1 diabetes, but adjustment for these factors did not materially alter the ORs for any of the vaccines. CONCLUSIONS: In this large, population-based, case-control study, we did not find an increased risk of type 1 diabetes associated with any of the routinely recommended childhood vaccines. Our study adds to previous research by providing data on newer vaccines, including hepatitis B, acellular pertussis, and varicella vaccines. For the older vaccines, our results are generally in agreement with previous studies in not finding any increased risks. Ours is the first epidemiologic study to evaluate the possibility that timing of vaccination is related to risk of clinical diabetes in children. Our results on hepatitis B vaccine do not support the hypothesis; risk of type 1 diabetes was not different between infants vaccinated at birth and those who received their first vaccination later in life. The results of our study and the preponderance of epidemiologic evidence do not support an association between any of the recommended childhood vaccines and an increased risk of type 1 diabetes. Suggestions that diabetes risk in humans may be altered by changes in the timing of vaccinations also are unfounded.

Adolescent↗

Measles vaccination and inflammatory bowel disease: controversy laid to rest?

The increasing incidence of Crohn's disease has lead to speculation about changes in exposures to environmental or infectious agents. Considerable attention has focused on the role of measles infection and/or vaccination in the pathogenesis of Crohn's disease and ulcerative colitis. Current evidence regarding the association between measles vaccination and inflammatory bowel disease (IBD) comprises analytic epidemiological studies, a case-series report and ecological studies. The first of these, a 1995 cohort study, found an association between measles vaccination and Crohn's disease and ulcerative colitis, but was widely questioned on methodological grounds. This was followed by a 1997 case-control study showing no association between measles vaccination and IBD. In 1998, public concern was rekindled by a report of 12 children with nonspecific colitis, ileal-lymphoid-nodular hyperplasia, and developmental disorders largely attributed to measles-mumps-rubella vaccine, but the nature of the report limited its scientific conclusions. Two additional studies, one case-control and one cohort, then followed and neither found an association with measles vaccination. Of the several ecological studies of measles vaccine coverage or measles schedule changes, none found an association with rates of IBD. The role of measles infection in IBD has been examined more extensively with studies of in utero measles exposure, measles infection early in life, and laboratory based investigations. An initial report of high rates of Crohn's disease among pregnancies affected by measles infection was followed by negative studies. Numerous case-control and ecological studies of children with measles infections early in life have also had discordant findings. Of three recent cohort studies, two showed no relationship between infection with early measles exposure and risk for IBD, while one found an approximate 3-fold elevation in risk. Laboratory investigations into persistent measles infection and IBD have been contentious. While some investigators have claimed to find persistent measles infection among patients with IBD, others, using highly sensitive polymerase chain reaction techniques, have not been able to replicate the findings. Recent controversy has centred on whether there is any evidence for molecular mimicry in the pathogenesis of IBD. In summary, available evidence does not support an association between measles-containing vaccines and risk of IBD, nor between measles infection and IBD. While further research is necessary into the causal factors underlying Crohn's disease and ulcerative colitis, continued public education efforts are needed to reassure the public about vaccine safety and to prevent declines in vaccine coverage.

Adult↗

Biopharmaceutical statistics in a pharmaceutical regulated environment: past, present, and future.

The practice of statistics in the pharmaceutical industry has changed markedly over the last 25 years. This paper examines the evolution of clinical trial statistics in relationship to advances in statistical methodology and computational power as well as the changing regulatory environment. The current role of the biopharmaceutical statistician is assessed along with the drivers for future change.

Biopharmaceutics↗

Integrin-mediated regulation of synaptic morphology, transmission, and plasticity.

Volado, the gene encoding the Drosophila alphaPS3-integrin, is required for normal short-term memory formation (Grotewiel et al., 1998), supporting a role for integrins in synaptic modulation mechanisms. We show that the Volado protein (VOL) is localized to central and peripheral larval Drosophila synapses. VOL is strongly concentrated in a subpopulation of synaptic boutons in the CNS neuropil and to a variable subset of synaptic boutons at neuromuscular junctions (NMJs). Mutant morphological and functional synaptic phenotypes were analyzed at the NMJ. Volado mutant synaptic arbors are structurally enlarged, suggesting VOL negatively regulates developmental synaptic sprouting and growth. Mutant NMJs exhibit abnormally large evoked synaptic currents and reduced Ca(2+) dependence of transmission. Strikingly, multiple forms of Ca(2+)- and activity-dependent synaptic plasticity are reduced or absent. Conditional Volado expression in mutant larvae largely rescues normal transmission and plasticity. Pharmacologicially disrupting integrin function at normal NMJs phenocopies features of mutant transmission and plasticity within 30-60 min, demonstrating that integrins acutely regulate functional transmission. Our results provide direct evidence that Volado regulates functional synaptic plasticity processes and support recent findings implicating integrins in rapid changes in synaptic efficacy and in memory formation.

Animals↗

The two toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase isozymes form heterotetramers.

Two isozymes of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) of the apicomplexan protozoan Toxoplasma gondii are encoded by the single HGPRT gene as a result of differential splicing. Western blotting of total T. gondii protein shows that both isozymes I and II, which differ by 49 amino acids, are expressed. Both form enzymatically active homotetramers when overexpressed in Escherichia coli. The specific activity of HGPRT-I is five times that of HGPRT-II. When both isozymes are co-expressed in E. coli, HGPRT-I.HGPRT-II heterotetramers form. The predominant heterotetramer has enzymatic activity similar to HGPRT-II, and gel filtration chromatography demonstrates that its size is intermediate between the sizes of HGPRT-I and HGPRT-II. Mass spectrometric analysis of cross-linked homo- and heterotetramers reveals species of distinct molecular mass for HGPRT-I, HGPRT-II, and HGPRT-I.HGPRT-II and suggests that the predominant heterotetramer consists of one HGPRT-I subunit and three HGPRT-II subunits. The implications of this finding are discussed.

Animals↗

Discrepancies in diagnoses of neuroepithelial neoplasms: the San Francisco Bay Area Adult Glioma Study.

BACKGROUND: Valid and reliable diagnoses of disease are key both to meaningful epidemiologic and clinical investigations and to decision-making about appropriate treatment. One previous study highlighted the lack of precision in diagnosing primary brain tumors in a neuropathology referral practice. The current study explores diagnostic discrepancies in a population-based adult glioma series by hospital of origin, specialty training of the original diagnosing pathologist, and clinical significance. METHODS: To confirm patients' eligibility for the San Francisco Adult Glioma Study, the authors obtained participants' pathology specimens and conducted a uniform secondary neuropathology review. Eligible patients were all adults age 20 years or older newly diagnosed with glioma between August 1, 1991, and March 31, 1994, who resided in 1 of 6 San Francisco Bay Area counties. RESULTS: Overall, the original and secondary diagnoses were the same (concordant) for 352 (77%) of the 457 cases available for study. Twenty-six percent of the cases from community hospitals were discordant, compared with 12% of the cases from academic hospitals P= 0.004. Of the 105 discordant diagnoses, 17 (16%) were determined to be clinically significant, defined as a difference that could significantly alter patient management and/or prognosis. Sixteen of these 17 cases originated at community hospitals, and only 1 originated at a hospital with a neuropathologist. Based on the distribution of review diagnoses, subjects presenting at nonacademic hospitals were more likely than those presenting at academic hospitals to have glioblastoma (61% vs. 52%; P = 0.07). CONCLUSIONS: The percentage of cases with discrepant original and review diagnoses was higher among those originally diagnosed at community hospitals without a neuropathologist than among those originally diagnosed at an academic hospital with a neuropathologist. Clinically significant discrepancies were much more likely to have originated at a community hospital without a neuropathologist. These data highlight the importance of review of brain tumors by a neuropathologist prior to decision-making regarding treatment. A separate implication of this study is that glioma cases selected exclusively from academic or nonacademic institutions in a particular geographic area are unlikely to be representative of all cases occurring in that area.

Adult↗

Influenza vaccination in children with asthma in health maintenance organizations. Vaccine Safety Datalink Team.

We assessed vaccination coverage and predictors of influenza vaccination in asthmatic children in four large Health Maintenance Organizations. We studied 68,839 children with asthma at four Health Maintenance Organizations (HMOs) in the 1995-1996 influenza season and 34,032 children at two HMOs in the 1996-1997 influenza season. In both seasons only 9-10% were vaccinated against influenza. Children who were hospitalized, had an emergency department visit for asthma or a prescription for a beta-agonist prior to the influenza season, were more likely to be vaccinated. Overall, 61% of the unvaccinated asthmatic children had made an outpatient clinic visit during months when influenza vaccination would have been appropriate. Vaccination coverage could be increased by taking advantage of all opportunities to vaccinate children with asthma whenever they make clinic visits in the fall and early winter.

Adolescent↗

Learning performance of normal and mutant Drosophila after repeated conditioning trials with discrete stimuli.

A new olfactory conditioning procedure is described using short training trials with discrete presentation of conditioned stimuli (CS) and unconditioned stimuli (US). A short odor presentation along with a single-shock stimulus produced modest but reliable and reproducible learning. Multiple trials presented sequentially improved performance with increasing trial number. Trial spacing had a significant impact on performance. Two trials presented with a short intertrial interval (ITI) produced no improvement over a single trial; two trials with a 15 min ITI significantly boosted performance. This effect required two associative trials, because substituting one of the trials with the CS alone, US alone, or an unpaired CS-US failed to boost performance. The increase in initial performance with two trials decayed within 15 min after training. Thus, the effect is short-lived. The utility of using a battery of tests, including a single short trial, two massed trials, and two spaced trials, to investigate parameters of memory formation in several mutants was demonstrated.

Alleles↗

Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors. Children Brain Tumor Consortium.

BACKGROUND: In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. METHODS: The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors. RESULTS: Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas. When the specific combinations of the three features were unambiguously designated, three diagnostic categories resulted. These revised diagnostic categories are consistent with WHO guidelines and have significantly different survival distributions. However, neither the original WHO diagnoses nor the revised categories adequately separated these tumors prognostically, because histologic features other than those specified by WHO were significantly associated with improved or worsened survival. CONCLUSIONS: Classifications based on small numbers of specified histologic features may not be feasible because they inadequately separate childhood astrocytic tumors into prognostically homogeneous groups. Preferable classification techniques are those that simultaneously account for all reliably recognized histologic features.

Adolescent↗