Outcomes of a randomized trial of hyperfractionated cranial radiation therapy for treatment of high-risk acute lymphoblastic leukemia: therapeutic efficacy and neurotoxicity.

PURPOSE: We evaluated 8-year survival and late neuropsychologic toxicity in children with acute lymphoblastic leukemia treated in a randomized clinical trial to test whether hyperfractionated (twice daily) cranial radiation therapy (CRT) can reduce incidence and severity of late toxicities associated with 18 Gy of CRT. PATIENTS AND METHODS: Between 1987 and 1995, 369 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for high-risk acute lymphoblastic leukemia were randomly assigned to conventionally fractionated CRT (CFX) or hyperfractionated CRT (HFX) to a total dose of 18 Gy. Neuropsychologic testing was completed for 125 of 287 children in continuous complete remission. Event-free and overall survival, as well as neuropsychologic function, were compared for the two arms of the protocol. RESULTS: Eight-year event-free survival (+/- SE) was 80% +/- 3% for children randomly assigned to CFX and 72% +/- 3% for HFX (P =.06). Overall survival was 85% +/- 3% for CFX and 78% +/- 3% for HFX (P =.06). CNS relapses occurred in 2.8% of patients receiving CFX and 2.7% receiving HFX (P =.99). Cognitive function for both groups was solidly in the average range, with no group differences in intelligence, academic achievement, visuospatial reasoning, or verbal learning. Children on the HFX arm exhibited a modest advantage for visual memory (P <.05). CONCLUSION: HFX provides no benefit in terms of cognitive late effects and may compromise antileukemic efficacy. HFX should not be substituted for conventionally dosed CRT in children who require radiation therapy for treatment of acute lymphoblastic leukemia.     

Changes in the expression of the type-2 but not the type-1 cyclo-oxygenase enzyme in chorion-decidua with the onset of labour

Objective To determine the relative expression of cyclo-oxygenase (COX)-1 and COX-2 in the chorion-decidual part of human fetal membranes following delivery at term and to identify any changes in expression associated with labour.
Methods Fetal membranes were collected from 12 term pregnancies before labour following elective caesarean section and from 12 spontaneous vaginal deliveries. Expression of COX-1 and COX-2 mRNA was measured using a previously validated quantitative RT-PCR assay.
Results COX-2 expression exceeded that of COX-1 by approximately eight-fold. COX1 expression did not change but COX-2 expression was found to increase four-fold with labour.
Conclusions Chorion-decidua has the capacity to contribute to the increase in prostaglandin synthesis within the uterus associated with labour. As in the amnion, it is COX-2 and not COX-1 which is upregulated with labour. COX-2 selective anti-prostaglandins should therefore be as effective as nonselective drugs in inhibition of fetal membrane prostaglandin synthesis.     

Patterns and predictors of inpatient falls and fall-related injuries in a large academic hospital.

OBJECTIVES: Most research on hospital falls has focused on predictors of falling, whereas less is known about predictors of serious fall-related injury. Our objectives were to characterize inpatients who fall and to determine predictors of serious fall-related injury. METHODS: We performed a retrospective observational study of 1,082 patients who fell (1,235 falls) during January 2001 to June 2002 at an urban academic hospital. Multivariate analysis of potential risk factors for serious fall-related injury (vs no or minor injury) included in the hospital's adverse event reporting database was conducted with logistic regression to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CI95) RESULTS: The median age of patients who fell was 62 years (interquartile range, 49-77 years), 50% were women, and 20% were confused. The hospital fall rate was 3.1 falls per 1,000 patient-days, which varied by service from 0.86 (women and infants) to 6.36 (oncology). Some (6.1%) of the falls resulted in serious injury, ranging by service from 3.1% (women and infants) to 10.9% (psychiatry). The most common serious fall-related injuries were bleeding or laceration (53.6%), fracture or dislocation (15.9%), and hematoma or contusion (13%). Patients 75 years or older (aOR, 3.2; CI95, 1.3-8.1) and those on the geriatric psychiatry floor (aOR, 2.8; CI95, 1.3-6.0) were more likely to sustain serious fall-related injuries. CONCLUSIONS: There is considerable variation in fall rates and fall-related injury percentages by service. More detailed studies should be conducted by floor or service to identify predictors of serious fall-related injury so that targeted interventions can be developed to reduce them.     

Preservice early childhood students' perceptions of written feedback on their essays

Lecturer feedback on students' essays is important to the quality of the experience students have at university (Norton & Norton, 2001). The aim of the present study was to investigate whether early childhood students at one university actually read lecturer feedback on their essays and, if they did, what they found helpful and not helpful to their learning. Feedback was defined as 'giving students information on how well or how poorly they are doing in their academic work' (Hounsell, 1987, p. 109). Using the Vygotskian concept of learning as a socially shared activity, qualitative data were collected from second-year students from a four-year early childhood degree programme via an anonymous survey and four focus groups. Major findings were that, in contrast with studies of students in other programmes, early childhood students read lecturer feedback on their essays and used feedback that was detailed and explanatory as a learning tool. Types of feedback students found to be most and least useful were identified.     

Occurrence of co-colonization or co-infection with vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in a medical intensive care unit.

OBJECTIVE: To determine the occurrence of co-colonization or co-infection with VRE and MRSA among medical patients requiring intensive care. DESIGN: Prospective, single-center, observational study. SETTING: A 19-bed medical ICU in an urban teaching hospital. PATIENTS: Adult patients requiring at least 48 hours of intensive care and having at least one culture performed for microbiologic evaluation. RESULTS: Eight hundred seventy-eight consecutive patients were evaluated. Of these patients, 402 (45.8%) did not have microbiologic evidence of colonization or infection with either VRE or MRSA, 355 (40.4%) were colonized or infected with VRE, 38 (4.3%) were colonized or infected with MRSA, and 83 (9.5%) had co-colonization or co-infection with VRE and MRSA. Multiple logistic regression analysis demonstrated that increasing age, hospitalization during the preceding 6 months, and admission to a long-term-care facility were independently associated with colonization or infection due to VRE and co-colonization or co-infection with VRE and MRSA. The distributions of positive culture sites for VRE (stool, 86.7%; blood, 6.5%; urine, 4.8%; soft tissue or wound, 2.0%) and for MRSA (respiratory secretions, 34.1%; blood, 32.6%; urine, 17.1%; soft tissue or wound, 16.2%) were statistically different (P < .001). CONCLUSIONS: Co-colonization or co-infection with VRE and MRSA is common among medical patients requiring intensive care. The recent emergence of vancomycin-resistant Staphylococcus aureus and the presence of a patient population co-colonized or co-infected with VRE and MRSA support the need for aggressive infection control measures in the ICU.     

What do pediatric primary care providers think are important research questions? A perspective from PROS providers.

OBJECTIVE: To describe what pediatric primary care providers involved in the Pediatric Research in Office Settings (PROS) research network think are important yet inadequately addressed questions in pediatric primary care research. METHODS: A total of 1785 pediatric primary care providers in the PROS network were asked what they thought were important yet inadequately addressed areas of primary care research. We used a single, open-ended question in a mail survey. Written answers to this question were analyzed by qualitative methods to determine the main themes of interest to pediatric primary care providers. RESULTS: Overall survey response rate was 48.7%; the open-ended question yielded 1109 individual answers. Six lines of inquiry were identified as being important to these providers: (1) effective counseling techniques to use in anticipatory guidance; (2) strategies to prevent and treat obesity; (3) the effectiveness of well-child care; (4) ongoing management of patients with attention-deficit/hyperactivity disorder; (5) the role of the primary care provider in caring for children with mental health needs; and (6) optimal organization of office practices. CONCLUSIONS: The translation of research into practice may be improved by a better understanding of the needs and interests of those who see pediatric patients in the primary care setting.     

Novel histone deacetylase inhibitors in the treatment of thyroid cancer.

Histone deacetylases (HDAC) and histone acetyltransferases exert opposing enzymatic activities that modulate the degree of acetylation of histones and other intracellular molecular targets, thereby regulating gene expression, cellular differentiation, and survival. HDAC inhibition results in accumulation of acetylated histones and induces differentiation and/or apoptosis in transformed cells. In this study, we characterized the effect of two HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and m-carboxycinnamic acid bis-hydroxamide, on thyroid carcinoma cell lines, including lines originating from anaplastic and medullary carcinomas. In these models, both SAHA and m-carboxycinnamic acid bis-hydroxamide induced growth arrest and caspase-mediated apoptosis and increased p21 protein levels, retinoblastoma hypophosphorylation, BH3-interacting domain death agonist cleavage, Bax up-regulation, down-regulation of Bcl-2, A1, and Bcl-x(L) expression, and cleavage of poly(ADP-ribose) polymerase and caspase-8, -9, -3, -7, and -2. Transfection of Bcl-2 cDNA partially suppressed SAHA-induced cell death. SAHA down-regulated the expression of the apoptosis inhibitors FLIP and cIAP-2 and sensitized tumor cells to cytotoxic chemotherapy and death receptor activation. Our studies provide insight into the tumor type-specific mechanisms of antitumor effects of HDAC inhibitors and a framework for future clinical applications of HDAC inhibitors in patients with thyroid cancer, including histologic subtypes (e.g., anaplastic and medullary thyroid carcinomas) for which limited, if any, therapeutic options are available.     

Environmental risk factors and colorectal neoplasia: Recent developments

The vast majority of new cases of colorectal cancer, the second most common cause of death in men and women in the United States, are attributable to environmental rather than genetic causes. Recent research has clarified inconsistencies in the literature and has explored new pathways through which risk factors may act. This review discusses newly published, selected interesting and important findings in colorectal cancer etiology; these include postmenopausal hormone use, nonsteroidal anti-inflammatory drug use, obesity, physical activity, diet, and other confirmed epidemiologic associations. This research provides insight into mechanisms and offers opportunities for prevention.     

Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown. PATIENTS AND METHODS: Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily; (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily. RESULTS: No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% CI, 2% to 42%) achieved a confirmed partial response. CONCLUSION: The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted.