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Purpose: To determine long-term survival and predictors of recurrence in a retrospective cohort of patients with epithelial ovarian cancer treated with intraperitoneal (IP) chemotherapy., Patients and Methods: Records were reviewed of 433 patients who received IP therapy for ovarian cancer between 1984 and 1998; follow-up data were available for 411 patients. IP therapy was provided as consolidation therapy (n = 89), or for treatment of persistent (n = 310) or recurrent (n = 12) disease after surgery and initial systemic therapy; therapy usually consisted of platinum-based combination therapy. Statistical analysis included tests for associations between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox proportional hazard model., Results: The mean age of patients was 52 years (range, 25 to 76 years). Distribution by stage and grade was as follows: stage I, 7; II, 24; III, 342; IV, 52; not available (NA), 8; and grade 1, 30; 2, 99; and 3, 289; NA, 15. The median survival from initiation of IP therapy by residual disease was none, 8.7 years; microscopic, 4.8 years; less than 1 cm, 3.3 years; more than 1 cm, 1.2 years. In a multivariate analysis, the only significant predictors of long-term survival were grade and size of residual disease at initiation of IP therapy., Conclusion: Prolonged survival was observed in selected patients receiving IP platinum-based therapy. It is not possible to determine the contribution of IP therapy to survival in this study. A relationship between size of disease at the initiation of IP therapy and long-term survival was demonstrated.

Acute exacerbations of asthma are frequently caused by viral infections, but the inflammatory mechanisms in virus-induced asthma are poorly understood. The aim of the present study was to determine whether viral infection in acute asthma was associated with increased sputum neutrophil degranulation and increased cellular lysis and whether these changes are related to clinical severity. Adults (n=49) presenting to the emergency department with acute asthma were examined for infection by means of sputum direct-fluorescence antigen detection, sputum culture, and sputum polymerase chain reaction for Mycoplasma, Chlamydia and Legionella pneumophila, and all common respiratory viruses. Subjects infected with one of these agents were classed as having an infective exacerbation. Spirometry and sputum induction were performed on presentation and 4-5 weeks later. Thirty-seven subjects (76%) had virus infection and acute asthma. Those with virus infection had increased sputum neutrophils (p<0.05) and increased neutrophil elastase (p<0.05), this was related to increased elevated sputum lactate dehydrogenase (LDH). Subjects with noninfective asthma had an increase in the proportion of sputum eosinophils. Both groups had elevated sputum eosinophil cationic protein (ECP) concentrations. Higher levels of sputum LDH and ECP were associated with a longer hospital stay. Virus infection and acute asthma is associated with neutrophilic inflammation, cell lysis and more severe clinical disease.

Background: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. At its simplest level, education is limited to the transfer of information about asthma, its causes and its treatment. This review focused on the effects of limited asthma education., Objectives: The objective of this review was to assess the effects of limited (i.e. information only) asthma education on health outcomes in adults with asthma., Search Strategy: We searched the Cochrane Airways Group trials register and reference lists of articles., Selection Criteria: Randomised and controlled trials of individual asthma education involving information transfer only in adults over 16 years of age., Data Collection and Analysis: Trial quality was assessed and two reviewers extracted data independently. Study authors were contacted for missing information., Main Results: Twelve trials were included. They were of variable quality. Limited asthma education did not reduce hospitalisation for asthma (weighted mean difference -0.03 average hospitalisations per person per year, 95% confidence interval -0.09 to 0.03). There was no significant effect on doctor visits, lung function and medication use. The effects on asthma symptoms were variable. There was no reduction in days lost from normal activity, but in two studies, perceived asthma symptoms did improve after limited asthma education (odds ratio 0.44, 95% confidence interval 0.26 to 0.74). In one study, limited asthma education was associated with reduced emergency department visits (reduction of -2.76 average visits per person per year, 95% confidence interval -4.34 to 1.18)., Reviewer's Conclusions: Use of limited asthma education as it has been practiced does not appear to improve health outcomes in adults with asthma although perceived symptoms may improve. Provision of information in the emergency department may be effective, but this needs to be confirmed.

The role of eosinophilic airway inflammation in the variant asthma syndromes of cough and chest colds is not well defined. We tested the hypothesis that children with persistent cough and chest colds have increased sputum eosinophils, similar to those with wheeze. The parents of 390 primary school children completed a symptoms questionnaire. Children with wheeze (n = 28), cough (n = 12), recurrent chest colds (n = 17), and no symptoms (control subjects, n = 26), underwent allergy skin prick tests, spirometry, hypertonic saline inhalation challenge, and sputum induction, and then completed a peak expiratory flow (PEF) and symptoms diary over a 2-mo period. Children with wheeze had significantly reduced PEF (p = 0.001) and higher sputum eosinophils when compared with the cough, chest cold, and control groups (3.1% versus 0.5%, 0%, 0%; p = 0.03). The prevalence of eosinophilic bronchitis (sputum eosinophils > 2.5%) was 45% in the wheeze group, which was significantly higher than the control group (9.35%, p = 0.04). Eosinophilic bronchitis was present in two children with cough (20%) and two with chest colds (15%, p > 0.05 versus control). In these groups, eosinophilic bronchitis was not associated with airway hyperresponsiveness (AHR) to hypertonic saline (p > 0.05). Children with cough and chest colds reported greater exposure to environmental tobacco smoke. In conclusion, this community-based survey of children with chronic respiratory symptoms has shown that wheeze is a good discriminator for the presence of eosinophilic bronchitis, and that persistent cough and recurrent chest colds without wheeze should not be considered a variant of asthma. Eosinophilic bronchitis did occur in a significant minority of these "variant asthma" syndromes.

Objective: The Gynecologic Oncology Group (GOG) has demonstrated that age, tumor grade, and size and number of residual lesions after primary cytoreductive surgery are significant prognostic factors in advanced ovarian carcinoma. Recent studies have reported numerous other clinical features as having prognostic value. We sought to identify the independent prognostic factors for survival in a cohort of patients with advanced ovarian cancer., Methods: We performed a retrospective chart review of all patients with stage III and IV ovarian carcinoma who received their primary treatment at our institution between 1987 and 1994., Results: A total of 295 patients were identified, 282 of whom were evaluable. Of these 282 patients, 214 (76%) have died of disease or other causes. The median follow-up is 32 months (range: 1-139). Eighteen factors were evaluated for prognostic significance. Significant factors in univariate analysis included patient age, gravidity (0 vs > 0), parity (0 vs > 0), preoperative albumin level, preoperative total protein level, ascites (presence vs absence), disease stage (IIIA/IIIB vs IIIC vs IV), number of residual lesions (< or =20 vs >20), and diameter of largest residual tumor nodule (< or = 1 cm vs 1-2 cm vs > 2 cm). However, on multivariate analysis, only patient age (P < 0.001), ascites (P = 0.001), and size of residual disease (P = 0.005) retained prognostic significance. Substage of disease was of borderline significance (P = 0.086)., Conclusion: Although numerous clinical variables have recently been reported to have prognostic value in advanced ovarian carcinoma, only patient age, presence or absence of ascites, and diameter of the largest residual tumor nodule proved to be of statistical significance in our analysis., (Copyright 2001 Academic Press.)

Objective: In clinical practice, chemotherapy agents demonstrating modest second-line activity against platinum-refractory epithelial ovarian cancer (PROC) are frequently used in patients who have received multiple prior chemotherapy agents. Whether the response rates reported in selected patients can be expected in heavily pretreated patients is not known. Similarly, the costs of palliative chemotherapy are not known. We sought to determine the response, survival, and predictors of response in an unselected cohort of PROC patients receiving liposomal doxorubicin (LD) for relapsed disease, and the overall costs of delivering liposomal doxorubicin in this setting., Methods: In a cohort of 62 consecutive patients who initiated LD as second- or greater-line therapy for PROC, the following variables were examined: age, number of prior regimens for relapse disease, duration of first clinical remission, time from last prior treatment, dose intensity of LD received, response/clinical benefit, time to progression, toxic effects, and survival. Multivariate analyses were used to identify predictors of clinical benefit and overall survival. Direct medical charges were calculated and converted to costs, and major cost drivers determined., Results: Sixty-two patients received a total of 174 cycles of LD. The mean number of cycles per patient was 2 (range, 1-8); the median number of prior regimens for recurrent PROC was 2 (range, 0-8); and the median duration of the first clinical remission was 6 months. Median dose intensity of LD delivered was 11.4 mg/m(2)/week (range, 2.8-16.7 mg/m(2)/week). Nine of sixty-two patients (14.5%) had an objective clinical response by CA-125 and/or CT scan (95% confidence interval, 6-23%). Grade 3/4 toxicity occurred in 11% of patients. In the full cohort, median time to progression was 2.2 months, and median overall survival, 9.6 months (range, 0.2-26 months). Dose intensity was the only independent predictor of overall response. Duration of first clinical remission and number of prior salvage regimens were associated with longer overall survival. The mean total direct medical cost per cycle of LD was $5763, and the major cost drivers were hospitalizations and drug acquisition/delivery costs., Conclusion: LD is an active agent in PROC, even when used as greater-than-second-line therapy. Among heavily pretreated patients, delivering a dose intensity of at least 9.0 mg/m(2)/week was associated with a higher probability of response. The cost per cycle of LD is driven by hospitalizations and drug acquisition/delivery costs., (Copyright 2001 Academic Press.)

Objective: Anemia requiring red blood cell (RBC) transfusion is common in ovarian cancer (OC) patients receiving post-debulking surgery chemotherapy. Erythropoietin use has been shown to decrease transfusion requirements in patients receiving chemotherapy. We sought to identify pretreatment risk factors that could identify patients at increased risk for requiring RBC transfusion during first-line treatment for ovarian cancer., Methods: One hundred seventy-five consecutive patients who received chemotherapy with either carboplatin-paclitaxel or cisplatin-paclitaxel following debulking surgery for epithelial OC from 1993 to 1996 were identified. No patient received erythropoietin. Patient characteristics recorded included: age, stage, prechemotherapy hemoglobin, nadir hemoglobin, number of cycles and doses of chemotherapy received. The outcome was requiring RBC transfusion. Independent predictors of requiring RBC transfusion were identified using multivariate analyses., Results: Median age of the cohort was 62 years (range, 28-86). Seventy-one and four-tenths percent had FIGO stage III/IV disease. Median prechemotherapy hemoglobin was 11 g/dL (range, 7.1-15.4); median nadir hemoglobin was 9.3 g/dL (range, 6.6-11.1). One hundred nineteen (66%) patients received cisplatin-paclitaxel, and 61 (34%) received carboplatin-paclitaxel. Of 175 patients, 31 (18%, 95% CI = 12-23%) required RBC transfusion. Independent risk factors for RBC transfusion were prechemotherapy hemoglobin <10 g/dL (P < 0.01, odds ratio = 3.78, 95% CI = 1.52-9.44) and carboplatin-paclitaxel versus cisplatin-paclitaxel treatment (P = 0.01, odds ratio = 3.14, 95% CI = 1.27-7.76). Of 175 patients, 40 (22.8%) had a prechemotherapy hemoglobin <10 g/dL. Fifty percent of patients with prechemotherapy hemoglobin <10 g/dL who received carboplatin-paclitaxel required RBC transfusion, compared with 7.7% of patients with hemoglobin >10 g/dL who received cisplatin-paclitaxel., Conclusion: Ovarian cancer patients frequently require RBC transfusion during postdebulking platinum-paclitaxel chemotherapy. Patients with prechemotherapy hemoglobin <10 g/dL and those receiving carboplatin-paclitaxel are at increased risk of requiring RBC transfusion. Early initiation of erythropoietin use in such patients may reduce transfusion needs., (Copyright 2001 Academic Press.)

Objective: The objective of this study was to determine the clinical outcomes of patients with fallopian tube carcinoma treated with paclitaxel-based combination chemotherapy following primary cytoreductive surgery., Methods: Twenty-four patients with the diagnosis of primary tubal adenocarcinoma treated between 1993 and 1998 were identified through the gynecology service database and the Memorial Sloan-Kettering Cancer Center tumor registry. Medical records were reviewed for information on age, stage, chemotherapy regimen, surgical intervention, relapse, and survival. All patients had their histologic material initially read or reviewed at Memorial Sloan-Kettering Cancer Center prior to treatment. The original slides were reviewed again by one of the authors (P.E.S.) to confirm the diagnosis of primary fallopian tube cancer., Results: The mean age of the patients was 63 years (range, 44-76). Distribution by stage was as follows: four patients (17%) were Stage I, three patients (12%) were Stage II, 16 patients (67%) were Stage III, one patient (4%) was Stage IV. Four patients had grade 2 tumors, 20 had grade 3. Sixteen patients (67%) had optimal cytoreduction at the time of initial surgery with residual disease less than 1 cm. Eight patients (33%) had suboptimal cytoreduction. Following initial surgery, all patients were treated with paclitaxel-based chemotherapy for a median of five cycles. Twenty-three patients received paclitaxel at the dose of 135-175 mg/m(2) in combination with carboplatin or cisplatin; the majority, 17 of 23 (74%), received carboplatin. One patient received paclitaxel alone. Median follow-up from time of initial surgery was 24 months (range, 1-73 months). Two patients are dead of disease. Overall survival for the entire group was 96% at 12 months by Kaplan-Meier analysis, and 90% at 3 years. The overall median progression-free survival was 27 months (range, 5-57 months) for the entire group. The median disease progression-free survival at 3 years was 67% (95% CI, 45-100) in the optimally debulked group as compared with 45% in the suboptimally debulked group (95% CI, 27-57). Twelve patients (50%) had evidence of recurrence or persistent disease. There were fewer recurrences in the optimally debulked group: 5 of the 16 patients (31%) versus 7 of the 8 patients (88%) with suboptimal cytoreduction., Conclusion: Optimally cytoreduced patients with primary fallopian tube carcinoma treated with a paclitaxel-based chemotherapy regimen have an excellent possibility of survival., (Copyright 2001 Academic Press.)

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus that may progress to bronchiectasis. The aim of the present study was to characterize airway inflammation in patients with clinically stable ABPA and asthma, and to correlate this with bronchiectasis severity. Subjects with ABPA and central bronchiectasis (ABPA-CB; n=16) and ABPA with serological evidence alone (ABPA-S; n=10) were studied. Comparison groups were A. fumigatus-sensitized asthma (n=19), non-A. fumigatus-sensitized asthma (n=15) and healthy controls (n=8). Hypertonic saline challenge, sputum induction and high-resolution computed tomography (HRCT) of the chest were performed. Sputum eosinophil numbers were markedly elevated in ABPA-CB (median 8.4%) compared to ABPA-S (2.4%), A. fumigatus-sensitized asthma (1.8%), asthma (1.8%) and controls (0.3%) (p<0.01); sputum eosinophil cationic protein levels were higher in ABPA-CB (median 13,706 ng.mL(-1)), compared to ABPA-S (1,633.5 ng.mL(-1)), A. fumigatus-sensitized asthma (1,550.7 ng.mL(-1)), asthma (309.2 ng.mL(-1)), and controls (110 ng.mL(-1)) (p<0.001). ABPA-CB also showed increased sputum neutrophil number (median 60.3%) compared to the other groups (controls 29.3%) (p=0.01). The severity of bronchiectasis on HRCT correlated with sputum neutrophil (r=0.6) and eosinophil number (r=0.5) but not serum immunoglobulin-E levels. In conclusion, clinically stable allergic bronchopulmonary aspergillosis with bronchiectasis is characterized by an intense heterogenous inflammatory infiltrate consisting of eosinophils and neutrophils, which correlates closely with the severity of bronchiectasis on high-resolution computed tomography. Sputum analysis may be useful in monitoring the course of allergic bronchopulmonary aspergillosis.

The majority of women with ovarian cancer present with advanced-stage disease. Women with early-stage ovarian cancer have a much better chance of achieving a cure than do women with late-stage disease. This difference makes screening for ovarian cancer, with the hope of detecting it in its presymptomatic state, an attractive concept. Unfortunately, efforts to demonstrate that screening for ovarian cancer in the general population can decrease mortality have been disappointing. Current screening techniques do not have high enough sensitivity and specificity to be applied to the general population, because the low prevalence of the disease in the general population leads to very low positive predictive values for the available screening tests. However, applying current screening strategies to certain high-risk populations (women who carry mutations in the BRCA1 or BRCA2 genes, or with strong family histories of breast/ovarian cancer) is a reasonable approach and may result in acceptably high positive predictive values. This article discusses the results of screening studies using serum CA-125, sonography, other serum markers, and combinations of these tests. Screening for women of average risk is not recommended, although such women should be encouraged to participate in clinical trials whose end points are either the demonstration of the impact of screening on mortality, or the development of novel screening strategies. Screening with twice yearly transvaginal sonography and serum CA-125 testing is recommended for women at high risk for ovarian cancer, although prospective data are needed regarding the impact of such screening on stage of cancer detected, quality of life, and psychological distress, as well as the costs--both personal and societal--of screening.

Purpose: Recombinant interferon alfa-2b (rIFNalpha2b) is a standard therapy for chronic myelogenous leukemia (CML). Severe neuropsychiatric toxicity has been described in patients receiving rIFNalpha2b, although the frequency of and the risk factors for developing this toxicity are not well described. The purpose of this study was to identify predictors for the development of severe neuropsychiatric toxicity in CML patients receiving rIFNalpha2b-based therapy., Patients and Methods: From a prospective cohort of 91 Philadelphia chromosome-positive, previously untreated, chronic-phase CML patients treated on Cancer and Leukemia Group B (CALGB) 9013, a phase II trial of rIFNalpha2b plus cytarabine, the following were recorded at baseline: age, sex, race, pretreatment history of neurologic or psychiatric diagnosis, spleen size, blood counts, and peripheral blast count. Best response to treatment, rIFNalpha2b cumulative dose, dose duration, and dose-intensity were recorded during follow-up. Severe neuropsychiatric toxicity was defined as grade 3 or 4 events, according to CALGB expanded common toxicity criteria. Univariate and multivariate logistic regression analyses were used to identify variables that were associated with the development of severe neuropsychiatric toxicity., Results: Severe neuropsychiatric toxicity developed in 22 patients (24.0%; 95% confidence interval [CI], 15.2% to 32.8%). Toxicity resolved after withdrawal of treatment in all patients. Five of six patients developed recurrence of symptoms with rechallenge. Twelve (63%) of 19 patients with a pretreatment neurologic or psychiatric diagnosis developed severe neuropsychiatric toxicity, as compared with 10 (14%) of 72 patients without a pretreatment neurologic or psychiatric diagnosis (P =.001), resulting in a relative risk of 4. 55 (95% CI, 2.33 to 8.88) for developing severe neuropsychiatric toxicity. No other variables were independently associated with the development of neuropsychiatric toxicity., Conclusion: CML patients with a pretreatment history of a neurologic or psychiatric diagnosis are at significantly increased risk of developing severe neuropsychiatric toxicity during therapy with rIFNalpha2b plus cytarabine. Monitoring for neuropsychiatric symptoms and avoiding rechallenge are recommended measures for such patients receiving rIFNalpha2b-based therapy.

Background: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. This review was conducted to examine the strength of evidence supporting Step 6 of the Australian Asthma Management Plan: "Educate and Review Regularly"; to test whether health outcomes are influenced by education and self-management programmes., Objectives: The objective of this review was to assess the effects of asthma self-management programmes, when coupled with regular health practitioner review, on health outcomes in adults with asthma., Search Strategy: We searched the Cochrane Airways Group trials register and reference lists of articles., Selection Criteria: Randomised trials of self-management education in adults over 16 years of age with asthma., Data Collection and Analysis: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation., Main Results: Twenty-five trials were included. Self-management education was compared with usual care in 22 studies. Self-management education reduced hospitalisations (odds ratio 0.57, 95% confidence interval 0.38 to 0.88); emergency room visits (odds ratio 0.71, 95% confidence interval (0.57 to 0.90); unscheduled visits to the doctor (odds ratio 0.57, 95% confidence interval 0.40 to 0.82); days off work or school (odds ratio 0.55, 95% confidence interval 0.38 to 0. 79); and nocturnal asthma (odds ratio 0.53, 95% confidence interval 0.39 to 0.72). Measures of lung function were little changed. Self-management programmes that involved a written action plan showed a greater reduction in hospitalisation than those that did not (odds ratio 0.35, 95% confidence interval 0.18 to 0.68). People who managed their asthma by self-adjustment of their medications using an individualised written plan had better lung function than those whose medications were adjusted by a doctor., Reviewer's Conclusions: Training in asthma self-management which involves self-monitoring by either peak expiratory flow or symptoms, coupled with regular medical review and a written action plan appears to improve health outcomes for adults with asthma. Training programmes which enable people to adjust their medication using a written action plan appear to be more effective than other forms of asthma self-management.

Background: Lung volume reduction surgery (LVRS) has been re-introduced for treating patients with severe diffuse emphysema., Objectives: To assemble evidence from randomised controlled trials for the effectiveness of LVRS, and identify optimal surgical techniques, those patients who benefit most and those for whom it should be avoided., Search Strategy: Randomised controlled trials were identified using the Cochrane Airways Group COPD register using the terms: emphysema AND (emphysema surgery OR lung volume reduction surgery OR LVRS OR volume reduction surgery OR pneumectomy OR reduction pneumoplasty OR lung reduction surgery). The Cochrane Controlled Clinical Trials Register was also searched using these terms., Selection Criteria: Randomised controlled trials that studied the safety and efficacy of LVRS in patients with diffuse emphysema were included. Studies were excluded if they investigated giant or bullous emphysema., Data Collection and Analysis: Two independent reviewers assessed trials for inclusion and extracted data., Main Results: Only one randomised trial of LVRS for diffuse emphysema was identified. This compared stapled unilateral thoracoscopic lung reduction coupled with bovine pericardium reinforcement with a unilateral neodymium:yttrium aluminium garnet laser contact reduction. A total of 72 patients were studied. Both arms included post-operative rehabilitation and appeared to be well matched at randomisation. Improvement in FEV1 & FVC at six months was significantly greater in the staple treated group (p < 0.01 & p < 0. 07 respectively), but absolute increases were small. Need for supplemental oxygen was reduced significantly more in the staple treated group; Peto Odds Ratio (OR) 4.05; 95% confidence interval (CI) 1.40, 11.71. Quality of life improved more in the staple treated group (OR 5.36; 95% CI 2.13,13.47). The rate of delayed pneumothorax in the laser treated group was significantly higher (OR 10.46; 95% CI 1.98, 55.30)., Reviewer's Conclusions: There is no randomised controlled trial evidence concerning the efficacy of LVRS for diffuse emphysema compared to optimal conservative medical therapy. Stapling is more effective than laser resection and has a lower complication rate. LVRS should not be applied routinely until results of large trials currently underway become available.

Background: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. At its simplest level, education is limited to the transfer of information about asthma, its causes and its treatment. This review focused on the effects of limited asthma education., Objectives: The objective of this review was to assess the effects of limited (i.e. information only) asthma education on health outcomes in adults with asthma., Search Strategy: We searched the Cochrane Airways Group trials register and reference lists of articles., Selection Criteria: Randomised and controlled trials of individual asthma education involving information transfer only in adults over 16 years of age., Data Collection and Analysis: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing information., Main Results: Eleven trials were included. They were of variable quality. Limited asthma education did not reduce hospitalisation for asthma (weighted mean difference -0.03 average hospitalisations per person per year, 95% confidence interval -0.09 to 0.03). There was no effect on doctor visits, lung function and medication use. The effects on asthma symptoms were variable. There was no reduction in days lost from normal activity, but perceived asthma symptoms did improve after limited asthma education (odds ratio 0.40, 95% confidence interval 0.18 to 0.86). In one study, limited asthma education was associated with reduced emergency department visits (weighted mean difference -2.76 average visits per person per year, 95% confidence interval -4.34 to 1.18)., Reviewer's Conclusions: Use of limited asthma education as it has been practiced does not appear to improve health outcomes in adults with asthma. However the use of information in the emergency department may be effective, but this needs to be confirmed.

Problem: A perception that the reliability of our oral assessments of clinical competence was vitiated by lack of consistency in questioning., Design: Parallel group controlled trial of a Structured Question Grid for use in clinical assessments. The Structured Question Grid required assessors to see the patient personally in advance of the student and to write down for each case the points they wished to examine. The Structured Question Grid limited assessors to two questions on each point, one designated a pass question and one at a higher level. Three basic science and three clinical reasoning issues were required, so that a total of 12 questions was allowed., Setting: Small (70 students/year) undergraduate medical school with an integrated, problem-based curriculum., Subjects: Sixty-seven students in the fourth year of a 5-year course were assessed, each seeing one patient and being examined by a pair of assessors. Assessor pairs were allocated to use the Structured Question Grid or to assess according to their usual practice., Results: After the assessment but before being informed of the result the students completed a questionnaire on their experience and gave their performance a score between 0 and 100. The questions asked were based on focus group discussions with a previous student cohort, and concerned principally the perceived fairness and subjective validity of the assessment. The assessors independently completed a similar questionnaire, gave the student's performance a score between 0 and 100, and assigned an overall pass/fail grade., Conclusions: No difference was detected between students' or assessors' views of the fairness of the assessment for assessors who had used the Structured Question Grid compared to those who had not. Students whose assessors used the Structured Question Grid considered the assessment less representative of their ability. No difference was detected in the chance of students being assessed as failing or on the likelihood of a discrepancy between students' and assessors' ratings of students as passing or failing.

Purpose: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials., Methods: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection., Results and Conclusion: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Individual variability in care practices traditionally has been a strong force in oncology practice in the United States. Such variability has necessarily led to inconsistencies in resource utilization and quality of care. The concept of outcomes management has grown from a recognition of this variability and from a desire to both optimize the quality of care and control costs. Disease management guidelines are based on the current best evidence and expert opinion. Designed to outline appropriate frameworks for care, guidelines reduce variability, minimize underutilization and overutilization of resources, provide compliance information, and ultimately lead to improved quality of care. Guidelines also can form a critical framework for cost estimation. The development of guidelines for salvage therapy of ovarian cancer at our institution has led to an excellent ability to estimate costs. Institution of these guidelines has led to several findings, including the realization that the use of more expensive drugs does not necessarily lead to an increase in the overall costs of care. The use of oral agents was found to be far less expensive than the use of intravenous agents, however. Efficacy analyses are ongoing. The goals for the management of advanced ovarian cancer in traditional care and managed care settings are the same: high-quality care with attention to costs. Such an approach can increase the number of patients with this challenging disease who have access to high-quality care.

Objective: To investigate the relationship between outdoor air pollution and the respiratory health of children aged 8 to 10 years., Design: A cross-sectional survey (between October 1993 and December 1993) of children's health and home environment. Summary measures of particulate pollution (levels of particles with an aerodynamic diameter less than 10 microns [PM10] each 6th day) and SO2 (daily mean and maximum hourly values) were estimated for each area (using air quality monitoring station data from July 1993 to June 1994). SETTING AND SURVEY PARTICIPANTS: Parents of 3023 primary school children (Years 3, 4 and 5) from industrial and non-industrial areas with air quality monitoring stations in the Hunter and Illawarra regions of New South Wales., Main Outcome Measures: Reported occurrence of four or more chest colds, four or more attacks of wheezing, and night-time cough without a cold for more than two weeks, all within the previous 12 months., Results: 77% response rate, ranging by area from 66% to 88%. The average annual outdoor air pollution for the nine areas was 18.6-43.7 micrograms/m3 for PM10 and 0.16-0.90 parts per hundred million for SO2. The proportion of children reported to have the main outcome symptoms were: chest colds, 3.0%-9.7%; night cough, 12.3%-30.5%; and wheeze, 3.4%-11.3%. There was no significant association with SO2, but a significant increase in the odds of symptoms per 10 micrograms/m3 increase in PM10 on chest colds (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.12-1.82) and night-time cough (OR, 1.34; 95% CI, 1.19-1.53), but not wheeze. Passive smoking was significantly associated with chest colds but not with the other symptoms. Maternal allergy was associated with all three respiratory symptoms, most strongly with wheeze., Conclusion: These results provide evidence of health effects at lower than expected levels of outdoor air pollution in the Australian setting. They also suggest differences in contributions of environmental and hereditary factors to cough and chest colds compared with wheeze.

The role of airway inflammation in childhood asthma is not well defined, despite modern treatment approaches recommending potent anti-inflammatory therapy for an increasing number of children. In this study, induced sputum analysis was used to investigate the relationships among sputum inflammatory cells (eosinophils and mast cells), asthma symptoms, and airway hyperresponsiveness to hypertonic saline in a cohort of 170 children aged 8-14 years. Children who reported asthma symptoms in the past 2 wk had a 2. 25-fold (95% to CI, 1.20-4.24) increased odds of having significant sputum eosinophilia. Hyperresponsiveness to hypertonic saline was strongly associated with higher levels of sputum eosinophils ([OR] 4. 36, 1.70-11.20), sputum mast cells (OR 7.46, 2.48-22.75), and nasal eosinophils (OR 4.73, 1.89-11.86). Interestingly, boys were more likely than girls to have features of airway inflammation (sputum mast cells, OR 3.33, 1.15-9.65; nasal eosinophils, OR 3.25, 1.72-5. 97), which is consistent with the known increase in asthma prevalence in boys in this age group. Airway inflammation with eosinophils and mast cells is likely to be important in the pathogenesis of asthma in childhood. Induced sputum analysis can be used to evaluate this problem and has the potential to be a useful tool for monitoring therapy.

Bed-side teaching is the process of active learning in the presence of a patient. A cross-sectional study was conducted in a teaching hospital to obtain the opinions of clinical teachers about bed-side teaching including perceived hindrances to its implementation. Of 152 teachers, 78% responded to the questionnaire. Ninety-five per cent reported that bed-side teaching is an effective way to teach professional skills. Time constraints, noisy wards and patients not being available were reported as the most frequently experienced hindrances to bed-side teaching. The survey found strong support for bed-side teaching but a substantial number of barriers to its implementation. Further research is required to study methods that will improve bed-site teaching.

Objective: Establish and compare the safety and tolerance of three medical nutritional products when used as sole sources of nutrition in stable hemodialysis patients., Design: Prospectively randomized, controlled, single blind, parallel design., Setting: Three outpatient hemodialysis clinics., Participants: Seventy-nine normally nourished, stable, anuric, adequately dialyzed, adult outpatients with end-stage renal disease (ESRD) and requiring thrice weekly hemodialysis., Intervention: A 3-week trial was conducted. During the first week, baseline medical history and physical examination, gastrointestinal symptom, urea kinetic, bowel habit, and biochemical data were collected while participants ingested their usual diet. During the last 2 weeks, the same data were collected while participants orally ingested 35 kcal/kg actual weight/d of one of three medical nutritional products as a sole source of nutrition. Products were a standard medical nutritional (EN-9527) and two renal nutritionals (EN-9528 and EN-9529). The latter product was a reformulation of EN-9528 and contained added beta-carotene and fructooligosaccharides., Main Outcome Measures: Gastrointestinal symptoms, bowel habits (stool frequency and consistency), routine blood chemistries, urea kinetics, and normalized protein catabolic rate (nPCR) RESULTS: All three groups achieved a mean energy and protein intake of approximately 35 kcal/kg/d and 1.25 g protein/kg/d during the last 10 days of the sole source feeding period. Adherence with the formula ingestion targets was assessed using both a patient-completed product consumption log and nPCR. By intent to treat analysis, there were no changes in number or severity of gastrointestinal symptoms, stool frequency or stool consistency, or urea kinetics between the baseline week and during product consumption. In comparison to the standard formulation, the disease-specific formulations resulted in improved serum phosphorus and calcium-phosphorus product. Patients receiving the fructooligosaccharide-containing product (EN-9529), by Chi-squared analysis, had less constipation than for the comparable product without oligosaccharides (EN-9528) or the standard medical nutritional (EN-9527)., Conclusion: Use of enteral nutritionals as a sole source of nutrition is both possible and well tolerated in hemodialyzed patients. Selection of a disease-specific formulation offered advantages over a standard formulation in the management of biochemical complications of renal disease when the products were used as a sole source of nutrition.

Objective: Our objective was to explore the effectiveness of community action as a strategy for health promotion, through a critical review of five years of community action evaluation literature., Methods: Community action was defined as a health promotion, program that involved the community in implementation and control of the process of the program. Criteria for scientific evaluation of programs were proposed for sampling and control procedures, reliability and validity of instruments, analysis techniques, and specification of details of the intervention. A critical review of the literature, located by an on-line and related reference search, was undertaken for community action aimed at reducing cancer and cardiovascular disease, between January 1990 and May 1995., Results: None of seven community action studies (17 articles) that examined cancer risk factors fulfilled all the criteria for rigorous scientific evaluation. The most methodologically adequate cancer study, the COMMIT intervention, had only a moderate degree of success in reducing community smoking rates. Similarly, none of the six studies (25 articles) on cardiovascular disease fulfilled all the criteria. The results for the most methodologically adequate study, the Minnesota Heart Health Program, were disappointing, with strong secular trends preventing adequate assessment of the intervention effect., Conclusions: The finding that none of the reviewed studies met all evaluation criteria was due to several factors, including political considerations, feasibility, and the continued evolution of the science of evaluation in health promotion. Some important questions are posed for researchers by the failure of methodologically superior projects, such as COMMIT, to show major gains in reducing health risk behaviors.

Three hundred sixty-four Australian Regular Army recruits with acute ankle sprains sustained during training were randomized to treatment with either piroxicam or placebo. Compared with the placebo group, subjects treated with piroxicam had less pain, were able to resume training more rapidly, were treated at lower cost, and were found to have increased exercise endurance on resumption of activity. Nausea was the only side effect reported significantly more often in the treatment group than in the placebo group (6.8% versus 0.3%). Interestingly, subjects treated with piroxicam showed some evidence of local abnormalities such as instability and reduced range of movement. We conclude that nonsteroidal antiinflammatory agents should form an integral part of the treatment of acute ankle sprains.

We tested the hypothesis that hyperresponsiveness of the upper airway (UAHR) is present in patients with chronic cough of diverse etiology. We determined the frequency of bronchial hyperresponsiveness (BHR), hyperresponsiveness of the upper airway, sputum eosinophilia, pulmonary aspiration, and psychological symptoms in adults with chronic cough. Consecutive adults (n = 30) presenting to a tertiary referral clinic with chronic cough were compared with a group of 20 asymptomatic adults. Measurements included histamine provocation testing with measurement of flow volume curves to determine inspiratory and expiratory airflow obstruction; hypertonic saline induced sputum for analysis of eosinophils, mast cells and lipid-laden macrophages; and a validated psychological symptom questionnaire. Symptomatic rhinitis and gastroesophageal reflux were common causes of chronic cough. BHR occurred in seven patients (23%) and in no control subjects (p < 0.05). UAHR occurred in 40% of patients with cough and in four (20%) control subjects (p > 0.05). Eosinophils were present in the sputum of more patients with cough than control subjects (50% versus 19%; p < 0.05). High degrees of eosinophilia were present in six patients with cough, including three without BHR. No subject had significant lipid-laden macrophages. There was greater somatization in patients with chronic cough; ten subjects scored in the clinically significant range (p < 0.05). Abnormalities in one or more of these tests were 7.67-fold (95% CI 1.83-34.52) more likely to occur in cough patients than control subjects. We conclude that chronic cough is a nonspecific symptom that is associated with several apparently unrelated mechanisms. These include UAHR, somatization, BHR, and eosinophilic bronchitis. UAHR cannot be implicated as a single unifying mechanism. These findings emphasize the need to systematically evaluate several different causes of cough in patients who present with chronic cough.

We report a simple protocol which has potential to estimate community paediatric blood lead levels using opportunistic testing. Permission to use leftover blood for a lead assay was sought from parents or guardians of 397 children one month to 13 years of age who were admitted to general paediatric wards of John Hunter Hospital, Newcastle, between May and August 1993 and who had blood for a full blood count taken for any reason. Results were reviewed by a medical officer and returned to parents. Where a child's blood lead level was of concern according to National Health and Medical Research Council guidelines, the child was referred to a specialist paediatrician for clinical assessment. Written consent was received from the parents or guardians of 95.5 per cent of eligible children (n = 379); 93.4 per cent of responders (354 of 379) had blood suitable for testing, giving an overall result rate of 89.2 per cent (354 of 397). The mean blood lead level for the whole group was 5.3 micrograms/dL. The highest blood lead level for any age group was 6.4 micrograms/dL in the 36 to < 60 month age group. Stratification by geographical area showed a trend in increasing blood lead with increasing population density and areas where lead polluting industries exist. The approximate cost per result achieved was $40. This opportunistic survey method provides a promising technique for obtaining data on community blood lead levels. It may be a practical and resource-efficient alternative to large-scale community surveys. Further studies are under way to validate the method as a community surveillance tool.

Children are not just small adults. They have unique differences and needs both physiologically and psychosocially. The pediatric perioperative nurse is challenged to meet these needs by incorporating a knowledge of growth and development in all aspects of the plan of care.

Community studies of problems with breathing during sleep suggest that sleep-disordered breathing is a better general term than sleep apnoea. Male sex, increasing age and increasing neck size are the main factors differentiating people with from those without sleep-disordered breathing. The contribution of sleep-disordered breathing to morbidity has not been established. Future research should address the possible cardiovascular associations of sleep-disordered breathing, its impact on sleepiness in the community, and the cost-effectiveness of treatment.

In a birth cohort of 114 normal children, this study examined the hypothesis that a transient absence of salivary IgA in the first year of life was associated with an increased risk of developing atopy, asthma, or bronchial hyperreactivity (BHR) later in life. Episodes of transient absence of IgA in saliva, of less than 1 mo, occurred in 18% of the study population in the first year of life. The children were assessed at age 7.5 to 12 yr for the presence of atopy (skin prick test to inhaled allergens), asthma (wheeze in the previous 12 mo), and BHR (histamine provocation). The transient absence of salivary IgA in the first year of life was associated with an increased risk of BHR (adjusted odds ratio [Adj OR]: 11.6; 95% confidence interval [CI]: 2.2 to 60.9) and a trend toward a lowered risk of atopy to inhaled allergens (raw OR: 0.35; CI: 0.11 to 1.11). There was no relationship between the transient absence of salivary IgA and a clinical diagnosis of asthma (Adj OR: 0.9; CI: 0.2 to 3.6). The inconsistency in the relationships between the transient absence of salivary IgA and atopy, asthma, and BHR supports the concept that atopy, wheeze, and bronchial hyperreactivity are independent clinical outcomes. One possible explanation for the relationships observed in this study is that the transient absence of IgA in saliva in the first year of life identifies a cohort with mucosal hypoimmunity. These subjects are thus less likely to develop atopy and less able to effectively respond to a mucosal infection. Presentation of a mucosal antigen in these subjects may subsequently be associated with an inappropriate inflammatory response, which conditions bronchial hyperreactivity, and which is independent of atopy.

Objective: Chronic middle ear disease is common in Aboriginal children, and may be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of nasal inflammation is unknown. The study reported here was performed to define the role of allergy and infection in causing nasal inflammation in Aboriginal children with chronic middle ear disease., Methodology: Thirty-one Aboriginal children aged between 3 and 7 years underwent clinical assessment, audiometry and allergy skin tests. Nasal swabs for bacterial culture and cytology were performed during the winter and again in spring to identify any seasonal variation. A randomized trial of nasal beclomethasone for 8 weeks was conducted in children with abnormal tympanometry to identify the effect of therapy upon nasal cytology., Results: Twenty-six of the 31 children had abnormal tympanograms. Average hearing levels were reduced in nine children. Pathogenic organisms were isolated from most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%), Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31 children (26%) were atopic. Nasal cytology disclosed a marked neutrophil infiltrate (80% of cells) during the winter, which fell significantly in spring to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no effect of beclomethasone on nasal cytology., Conclusions: Chronic ear disease in Aboriginal children is associated with nasal inflammation, neutrophil infiltration and the presence of bacteria. These features suggest respiratory infection as the main cause of chronic nasal inflammation in Aboriginal children with middle ear disease. There is a seasonal variation in the severity of the nasal infiltrate, consistent with increased infections during winter. Despite a high prevalence of atopy, allergic nasal disease was uncommon.

Objective: To compare the action points in published asthma management plans with those derived from quality-control analysis of peak expiratory flow recordings., Design: Longitudinal observational study., Setting: An ambulatory asthma education and management program in a tertiary care hospital., Patients: 35 adults with asthma and exacerbation of asthma., Measurements: Peak expiratory flow diaries and symptom recordings., Results: Asthma action points from published asthma management guidelines had poor operating characteristics. The success rate was 35% when the action point was a peak expiratory flow rate less than 60% of the patient's best peak flow. The success rate improved to 88% when the action point was a peak expiratory flow rate less than 80% of the patient's best peak flow. Published action points had a high failure rate. Peak flow decreased to below the published action points during a stable period of asthma in 7% to 51% of patients studied. Action points defined using quality-control analysis did significantly better. A peak flow value less than 3 standard deviations below the patient's mean peak flow detected 84% of exacerbations and had a low failure rate (19%). Other quality-control tests had sensitivities of 91% and 71%. Quality-control action points could detect exacerbations up to 4.5 days earlier than conventional methods., Conclusions: Individualized action points can be derived for patients with asthma by applying quality-control analysis to peak flow recordings. These action points are more sensitive in detecting exacerbations of asthma and have fewer false-positive results. Action plans developed in this manner should be more useful for the early detection of deteriorating asthma.

Objective: To compare continuity of care from a midwife team with routine care from a variety of doctors and midwives., Design: A stratified, randomised controlled trial., Participants and Setting: 814 women attending the antenatal clinic of a tertiary referral, university hospital., Intervention: Women were randomly allocated to team care from a team of six midwives, or routine care from a variety of doctors and midwives., Main Outcome Measures: Antenatal, intrapartum and neonatal events; maternal satisfaction; and cost of treatment., Results: 405 women were randomly allocated to team care and 409 to routine care; they delivered 385 and 386 babies, respectively. Team care women were more likely to attend antenatal classes (OR, 1.73; 95% CI, 1.23-2.42); less likely to use pethidine during labour (OR, 0.32; 95% CI, 0.22-0.46); and more likely to labour and deliver without intervention (OR, 1.73; 95% CI, 1.28-2.34). Babies of team care mothers received less neonatal resuscitation (OR, 0.59; 95% CI, 0.41-0.86), although there was no difference in Apgar scores at five minutes (OR, 0.86; 95% CI, 0.29-2.57). The stillbirth and neonatal death rate was the same for both groups of mothers with a singleton pregnancy (three deaths), but there were three deaths (birthweights of 600 g, 660 g, 1340 g) in twin pregnancies in the group receiving team care. Team care was rated better than routine care for all measures of maternal satisfaction. Team care meant a cost reduction of 4.5%., Conclusion: Continuity of care provided by a small team of midwives resulted in a more satisfying birth experience at less cost than routine care and fewer adverse maternal and neonatal outcomes. Although a much larger study would be required to provide adequate power to detect rare outcomes, our study found that continuity of care by a midwife team was as safe as routine care.

Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random sample of the community. They answered a questionnaire and were monitored in their homes for sleep-disordered breathing (SDB). This report concerns the association between observed SDB and arterial hypertension and vascular disease. Hypertension was defined as self-report of a diagnosis of hypertension made by a physician, current treatment for hypertension, or a systolic pressure greater than 150 mm Hg or a diastolic pressure greater than 90 mm Hg. Coronary artery disease was defined by self-report of angina or myocardial infarction of "heart attack." There were few cases of stroke or claudication, and a category of "occlusive vascular disease" was defined by self-report of coronary artery disease or of "blocked arteries" or stroke. Subjects were classified as snorers (n = 289) or nonsnorers (n = 73) by self-report of regular snoring, and as having SDB (n = 79) if more than 15 abnormal respiratory events were recorded per hour of recording. There were significant increases in the prevalence of hypertension, coronary artery disease, and occlusive vascular disease from nonsnorers (26, 7, and 10%, respectively) through snorers (39, 12, and 17%) to subjects with SDB (57, 20, and 28%). The crude odds ratio for SDB versus nonsnorers was 3.8 (95% CI, 1.9 to 7.5) for hypertension, 3.5 (1.2 to 10.0) for coronary artery disease, and 3.7 (1.5 to 9.1) for occlusive vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random sample of the community. The sample was biased in favor of men, snorers, and subjects with subjective sleep complaints. They answered a questionnaire and were monitored in their homes for sleep-disordered breathing (SDB). This report concerns the presence of symptoms associated with the obstructive sleep apnea (OSA) syndrome in the subjects with SDB detected in this community sample. Most of the symptoms commonly recognized as occurring in OSA were associated with SDB in our sample: snoring that disturbed the sleep of other persons, reports of apnea, reports of gasping or choking sounds during sleep, and finding the bedclothes in disarray in the mornings had significant univariate associations with SDB. Nocturnal choking and morning headache were negatively associated with SDB. Excessive daytime somnolence (EDS) was reported by 41% of those with SDB, but it was also reported by 37% of snorers without SDB and by 37% of nonsnorers. We conclude that the symptoms seen in clinic patients with OSA also occur in subjects with SDB who have not presented for medical attention. Enumeration of these symptoms by questionnaire, however, is a poor test for OSA in the community. EDS was reported by a higher than expected proportion of subjects not affected by SDB, suggesting that causes of self-reported EDS other than SDB may be common.

We conducted a study of the prevalence of sleep-disordered breathing in subjects derived from a random sample of the population. A total of 2,202 subjects 35 to 69 yr of age were approached. Four hundred forty-one answered a questionnaire concerning their sleep symptoms, general health, and habits such as alcohol consumption, and they were monitored for sleep-disordered breathing (SDB). The sample was biased in favor of snorers and those with other subjective sleep complaints. Fifty-six percent of the subjects were men. Of the 441 subjects 79 (17.9%) had SDB (more than 15 episodes of apnea or hypopnea per hour: respiratory distress index [RDI] > or = 15), 289 were snorers but had RDI < 15, and 73 were nonsnorers. The prevalence of SDB in this sample was therefore at least 3.6% (79 of 2,204). The minimum prevalence in men was 5.7%, and in women it was 1.2%. Logistic regression identified only male sex as an independent predictor of snoring without SDB (adjusted odds ratio [OR], 3.24; 95% CI, 1.33 to 7.82), body mass index (adjusted OR for an increase of 5 kg/m2, 0.95; 95% CI, 0.85 to 1.05), and alcohol consumption (adjusted OR for an increase of 10 g/day, 1.05; 95% CI, 0.84 to 1.37) were not significant predictors of snoring. The independent predictors of SDB among snorers were age (adjusted OR for an increase of 5 yr, 1.26; 95% CI, 1.08 to 1.47) and neck circumference (adjusted OR for an increase of 2 cm, 1.53; 95% CI, 1.16 to 2.00).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To compare the efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home., Design: A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination., Setting: Fourteen Wisconsin nursing homes., Participants: Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy., Interventions: Participants received, by intramuscular injection, 0.5 mL of a trivalent influenza vaccine containing 15 micrograms each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mL of an influenza vaccine containing the same antigens conjugated to diphtheria toxoid (HA-D)., Measurements: Blood was obtained pre- and 1 month post-vaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained., Results: 204 participants received HA and 204 received HA-D. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022)., Conclusions: HA-D was more immunogenic in institutionalized elderly recipients and produced greater protection from influenza infection. Superior protection may be due to HA-D's ability to stimulate and recruit antigen-presenting cells, thus enabling the recipient to achieve and maintain functional antibody titers.

Objective: To audit the assessment and treatment of acute asthma and the subsequent application of the Australian Asthma Management Plan., Design: Prospective audit of case notes with follow-up telephone questionnaire and clinical assessment at 8-12 weeks after discharge., Setting: Tertiary-level teaching hospital., Main Outcome Measures: Comparison with published guidelines for acute and ongoing asthma management., Results: Asthma severity was objectively assessed in the Primary and Emergency Care Department, with lung function performed in 95% of acute presentations. Clinical history and examination were documented completely in 28% of presentations. Corticosteroids were underused and there was inappropriate use of ipratropium bromide. At 8-12 weeks follow-up most patients were symptomatic with limited activity due to asthma (46%) and impaired lung function (66%). One-third of patients were undertreated. Asthma management skills were seriously inadequate: only 20% of patients were performing peak flow monitoring, and only 21% recalled receiving specific instructions for the management of future exacerbations. Inhaler technique was inadequate in one-third of patients and asthma knowledge was poor. These deficits were more frequent in patients not admitted to hospital., Conclusion: This audit identified suboptimal assessment and treatment of acute asthma, and deficits in the implementation of the Australian Asthma Management Plan following discharge. Patients in this audit were undertreated and not provided with the skills to manage future attacks of asthma.

Clonidine-displacing substance (CDS) from brain is biologically active in the kidney and stomach and on platelets. To determine whether CDS is contained in these and other peripheral tissues, homogenates of fresh brain, eight other organs and serum from rat were ultrafiltered (less than 10,000 mol. wt only), dried and extracted with methanol. Evaluation by radioimmunoassay (RIA) using antibodies to p-aminoclonidine showed that adrenal gland and gastric fundus (GF) contained significantly greater amounts of CDS-like radioimmunoactivity than brain; intermediate-to-low activity was present in heart, small intestine, serum, kidney and liver; lung and skeletal muscle values were near-background. RIA-positive extracts elicited well-correlated contractile activity in a GF smooth muscle bioassay; contractions persisted in the presence of antagonists of various transmitters and modulators, but were abolished by low concentrations of the calcium channel blocker verapamil. Serum levels of CDS were profoundly reduced following removal of the adrenal glands. We conclude that a CDS-like substance is present not only in brain as previously reported, but also in peripheral organs and in the circulation.

Objective: To examine the prevalence and management of asthma in adults and children in a population sample in eastern Australia., Setting: A random sample of children from 33 primary schools in Sydney, Melbourne, Brisbane, and the Upper Hunter Valley (New South Wales), and their parents., Design: A cross-sectional analytic survey of 8753 primary school children aged between 5 and 12 years, and their parents (n = 13,945 adults). Asthma prevalence and management practices were determined by parental responses to a questionnaire, and spirometry was performed in children with "probable asthma"., Results: Of 8753 children whose parents responded, the prevalence of current wheeze was 19.5% and diagnosed asthma was 17.1%. Of the children with "probable asthma", 30% had their lung function measured in the previous year, and 6% possessed both a peak flow meter and an action plan for their asthma. Undertreatment was likely, as preventive asthma medications (inhaled corticosteroids or sodium cromoglycate) were used regularly by only 25.5% of these children and by 44.3% of children who had asthma symptoms more than twice per week. Children with the diagnosis of asthma reported higher rates of preventive medication use and ventilatory function measurement than children with frequent symptoms without the diagnosis. In the 13,945 adults, the reported prevalence of asthma was 7%, of whom 39% were using preventive medications, 34% had their ventilatory function assessed in the previous year, and 7% had both a peak flow meter and an asthma action plan., Conclusions: The study illustrated the gap between the current level of asthma management in the community and the standards set by the Thoracic Society of Australia and New Zealand. Undertreatment and suboptimal management of asthma remain important problems in Australia.

Night-to-night variability of breathing and oxygenation during sleep was examined with portable monitoring equipment in 30 residents of a retirement village. Subjects had a variety of health problems as might be expected in the elderly, but all were living independently in self-contained units. None had clinical features to suggest obstructive sleep apnea. Two pairs of consecutive nights were studied, separated by 4-6 months. Satisfactory recordings on all four nights were obtained in 15 subjects, and in these subjects variability of measurements was examined across nights 1-4 using the kappa (K) statistic. There was low but significant agreement in estimated total sleep time (K = 0.23, p less than 0.01) and estimated wakefulness after sleep onset (K = 0.18, p less than 0.05) as assessed with a wrist actigraph. Good agreement was found among measures of disturbed breathing during sleep whether expressed in terms of numbers of events [respiratory disturbance index (RDI), K = 0.62, p less than 0.0001], their duration (event minutes, K = 0.53, p less than 0.0001), or associated disturbance of oxygenation (% cumulative time less than 90% SaO2, K = 0.50, p less than 0.001, n = 9). Twenty-eight subjects had at least two nights' satisfactory recordings. Although some of these individuals showed considerable variation in RDI, this had little overall effect on classification of them into normal (RDI less than or equal to 15) and abnormal groups. The accuracy of the first night's recording in predicting classification derived from recording on three or four nights was 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

IgM responses to a deoxycholate-split influenza vaccine containing the surface antigens of the H3N2 virus A/Philippines/2/82 were studied in five volunteers, three of whom were seronegative by haemagglutination inhibition (HI) tests. Responses were measured by a sucrose-gradient centrifugation technique, in which IgM-specific HI activity was computed as a proportion of total IgM and IgG-specific HI activity, and by a membrane filtration-enzyme immunoassay (MF-EIA). Responses could be detected in all volunteers when measured by sucrose-gradient centrifugation within 1-2 weeks, and the IgM induced was 5-40% of total HI-specific activity. The response was also observed in the presence of low levels of pre-existing antibody. Levels of IgM antibody, when measured by MF-EIA, could be easily detected in two of the volunteers, while those of two others were very low and there was no response in a fifth. No biphasic virus-specific response to vaccination, involving first IgM and then IgG, could be measured by either technique. From these studies, the sucrose-gradient fractionation technique appears to be the more sensitive procedure.

To assess longitudinally the effect of living in the vicinity of coal-fired power stations on children with asthma, 99 schoolchildren with a history of wheezing in the previous 12 months were studied for 1 year, using daily diaries and measurements of air quality. The children had been identified in a cross-sectional survey of two coastal areas: Lake Munmorah (LM), within 5 km of two power stations, and Nelson Bay (NB), free from major industry. Daily air quality [sulphur dioxide (SO2) and nitrogen oxides (NOx)], respiratory symptoms, and treatment for asthma were recorded throughout the year. Measurements of SO2 and NOx at LM were well within recommended guidelines although they were several times higher than at NB: maximum daily levels in SO2 (micrograms/m3) were 26 at LM, 11 at NB (standard, 365); yearly average SO2 was 2 at LM, 0.3 at NB (standard, 60); yearly average NOx (micrograms/m3) was 2 at LM, 0.4 at NB (standard, 94). Marked weekly fluctuations occurred in the prevalence of cough, wheezing, and breathlessness, without any substantial differences between LM and NB. Overall, the prevalence of symptoms was low (10% for wheezing, 20% for any symptom). Whether the daily SO2 and NOx levels affected the occurrence of respiratory symptoms was investigated in children at LM using a logistic regression (Korn and Whittemore technique). For these children as a group, air quality measurements were not associated with the occurrence of symptoms.

The new International Union Against Tuberculosis (IUAT) bronchial symptoms questionnaire was completed by 827 subjects participating in a prospective study of respiratory symptoms and lung function in aluminum smelter workers. A modified Medical Research Council (MRC) questionnaire was also administered. Bronchial reactivity (BR) was measured in 809 subjects by methacholine challenge using a rapid method. Factor analysis demonstrated sensible clustering of responses to items unique to the new questionnaire such as nocturnal, spontaneous, and postexertional dyspnea, dust-induced dyspnea and tightness, and breathing difficulty. Responses to IUAT questions concerning past asthma, wheeze, chest tightness, morning cough and sputum, and asthma medication agreed well with corresponding items from the MRC questionnaire. Questions concerning asthma, medication, dust-induced, nocturnal, and spontaneous dyspnea, chest tightness, wheeze, nocturnal cough, postexertional dyspnea and breathing difficulty also had high validity against the criterion of concurrently measured bronchial reactivity. It is concluded that the IUAT questionnaire is a valid asthma questionnaire.

Respiratory symptoms, atopy, and bronchial reactivity were measured in primary school children living in Lake Munmorah (LM), a coastal town near two power stations, and in Nelson Bay (NB), a coastal town free from any possible major sources of outdoor air pollution. A prevalence survey and longitudinal follow-up study were performed 1 year apart. In both studies, the prevalence of ever wheezed, current wheezing, breathlessness, wheezing with exercise, diagnosed asthma, and use of drugs for asthma at LM were all approximately double the prevalence at NB (all P values less than 0.01). The prevalence of bronchial reactivity was significantly greater at LM than NB (P less than 0.01) at the first but not the second survey. By contrast, no significant differences were found between the two areas for skin test atopy or for parental history of allergic disease. Multivariate analysis supported the conclusion from the univariate analysis that there was more wheezing at LM compared to NB at both studies, when adjusted for atopy, smoking in the home, age, and sex. As expected, a positive skin test reaction to house dust mite was the predominant explanatory variable. Asthma was more common in the community near power stations (LM) than in the NB area. The absence of significant differences in skin test atopy and parental history of allergic disease argued against major genetic differences between the two groups. By contrast, the more common reporting of siblings' chest disease and asthma in Lake Munmorah supported an environmental cause.

As the use of Epoetin alfa to treat the anemia of chronic renal failure expands, attention is beginning to focus on the dietary changes that may occur subsequent to therapy. The anemia-related pattern of poor appetite, lethargy, and decreased mental and physical status can often be reversed as anemia is corrected. Changes in nutritional status increase the importance of monitoring serum chemistries and providing timely interventions. Potentially serious side effects associated with changes in serum chemistries can be minimized or prevented by a teamwork approach involving the physician, nurse, and renal dietitian.