Reliability and validity of the instrument for scoring clinical outcomes of research for epidermolysis bullosa (iscorEB).

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare and currently incurable genetic blistering disorders. As more pathogenic-driven therapies are being developed, there is an important need for EB-specific validated outcomes measures designed for use in clinical trials. OBJECTIVES: To test the reliability and construct validity of an instrument for scoring clinical outcomes of research for EB (iscorEB), a new combined clinician- and patient-reported outcomes tool. METHODS: We conducted an observational study consisting of independent 1-day assessments (six assessors) at two academic hospitals. The assessments consisted of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity (BEBS) and global severity assessment for physicians; and iscorEB patient (iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's Dermatology Life Quality Index for patients. Construct validity and intraclass correlation coefficients (ICCs) for interobserver, intraobserver and test-retest reliability were calculated. RESULTS: Overall, 31 patients with a mean age of 19·5 years (1·8-45·2) were included. Disease severity was mild in 42% of cases, moderate in 29% and severe in 29%. The interobserver ICC was 0·96 for both the clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver reliability was 0·91 and 0·70 for the skin and mucosal domains of iscorEB-c, respectively. Cronbach's alpha for iscorEB-c was 0·89. The test-retest reliability of iscorEB-p was 0·97 and Cronbach's alpha was 0·84. The clinical score differentiated between subjects with mild, moderate and severe disease, and both clinical and patient subscores discriminated between recessive dystrophic EB and other EB subtypes. CONCLUSIONS: iscorEB has robust reliability and construct validity, including strong ability to distinguish EB types and severities. Further studies are planned to test its responsiveness to change.

Diets of reef-dwelling labrids (Choerodon species) vary with body size, season and habitat: influence of foraging ability, specialization and opportunism.

Contemporary multivariate statistics were used to test the hypotheses that the dietary compositions of three populations of labrids on the west Australian coast are related to body size and undergo seasonal changes and to elucidate the relative extents and basis for any dietary differences within and between those populations. Gut content analyses determined the dietary compositions of Choerodon rubescens in marine waters of the outer reefs in the World Heritage Area of Shark Bay (26° S; 114° E) and of Choerodon schoenleinii in inner protected reefs of that large embayment. The dietary compositions of C. rubescens and C. schoenleinii differed significantly among length classes, progressed serially with increasing body size, both overall and almost invariably in each season and were more closely related to body size than season, whose effect was at best minimal. The size-related dietary change in C. rubescens involved, in particular, a shift from crustaceans and non-mytilid bivalves to mytilid bivalves and echinoid echinoderms. Although the diet of C. schoenleinii followed similar size-related changes, it contained a greater volume of gastropods when the fish were small and mytilids when large and only a small volume of echinoids. The dietary composition of C. rubescens in the Abrolhos Islands, 300 km to the south of Shark Bay, was related both to length class and season and differed from that of this labrid in Shark Bay with the ingestion of lesser volumes of mytilids and greater volumes of echinoids. The size-related changes in diet imply that these species shift from foraging over soft substrata to over reefs as their very well-developed jaws become sufficiently strong to remove attached and larger prey. The dietary compositions of C. rubescens and C. schoenleinii in Shark Bay and of C. rubescens at the Abrolhos Islands were related far more to habitat-locational differences than to length class and season. The above intraspecific and interspecific differences in diet are consistent with qualitative accounts of the relative abundances of the main prey in their respective environments, supporting the view that, despite specializations in their feeding apparatus, these labrids can feed opportunistically to a certain extent and could thus potentially respond to moderate changes in the composition of their prey caused by climate change and other anthropogenic effects.

Real-time PCR validation of visually identified snapper Chrysophrys auratus (Sparidae) eggs.

In this study, a total of 212 eggs were visually identified as snapper Chrysophrys auratus. Real-time PCR confirmed visual identification in 69% of cases but corroboration varied widely among plankton samples. The use of molecular tools to support visual identification prior to adopting daily egg production stock assessment methods should be considered.

Do the maximum sizes, ages and patterns of growth of three reef-dwelling labrid species at two latitudes differ in a manner conforming to the metabolic theory of ecology?

The size and age data and patterns of growth of three abundant, reef-dwelling and protogynous labrid species (Coris auricularis, Notolabrus parilus and Ophthalmolepis lineolata) in waters off Perth at c. 32° S and in the warmer waters of the Jurien Bay Marine Park (JBMP) at c. 30° S on the lower west coast of Australia are compared. Using data for the top 10% of values and a randomization procedure, the maximum total length (L(T) ) and mass of each species and the maximum age of the first two species were estimated to be significantly greater off Perth than in the JBMP (all P < 0.001) and the maximum ages of O. lineolata in the two localities did not differ significantly (P > 0.05). These latitudinal trends, thus, typically conform to those frequently exhibited by fish species and the predictions of the metabolic theory of ecology (MTE). While, in terms of mass, the instantaneous growth rates of each species were similar at both latitudes during early life, they were greater at the higher latitude throughout the remainder and thus much of life, which is broadly consistent with the MTE. When expressed in terms of L(T), however, instantaneous growth rates did not exhibit consistent latitudinal trends across all three species. The above trends with mass, together with those for reproductive variables, demonstrate that a greater amount of energy is directed into somatic growth and gonadal development by each of these species at the higher latitude. The consistency of the direction of the latitudinal trends for maximum body size and age and pattern of growth across all three species implies that each species is responding in a similar manner to differences between the environmental characteristics, such as temperature, at those two latitudes. The individual maximum L(T), mass and age and pattern of growth of O. lineolata at a higher and thus cooler latitude on the eastern Australian coast are consistent with the latitudinal trends exhibited by those characteristics for this species in the two western Australian localities. The implications of using mass rather than length as the indicator variable when comparing the maximum sizes of the three species and the trends exhibited by the instantaneous growth rates of those species at different latitudes are explored. Although growth curves fitted to both the L(T) and masses at age for the males of each species lay above those for their females, this would not have influenced the conclusions drawn from common curves for both sexes.

Implications of the divergent use of a suite of estuaries by two exploited marine fish species.

Biological characteristics of the marine species King George whiting Sillaginodes punctatus and Australian herring Arripis georgianus in three seasonally open estuaries (Broke, Irwin and Wilson Inlets), one permanently open estuary (Oyster Harbour) and one normally closed estuary (Wellstead Estuary) on the south coast of Western Australia have been determined and compared. Sillaginodes punctatus enters the seasonally and permanently open estuaries early in life and reaches total lengths (L(T)) >280 mm at which it can be legally retained and thus contributes to commercial and recreational fisheries in these systems. This sillaginid almost invariably emigrates from these estuaries before reaching its typical size at maturity (L(T50)) and does not return after spawning in marine waters. In contrast, virtually all female A. georgianus (≥ 98%) in the three seasonally open estuaries and the majority in the normally closed (89·5%) and permanently open estuaries (83%) exceeded the L(T50) of this species at maturity, reflecting the fact that the nursery areas of this species are predominantly located much further to the east. Although adult females of A. georgianus in seasonally open and normally closed estuaries had developed mature ovaries by autumn, at which time they were prevented from migrating to the sea by closure of the estuary mouths, this species did not spawn in those estuaries. The oocytes in their ovaries were undergoing extensive atresia, a process that had been incipient prior to oocyte maturation. As the adult females of A. georgianus in the permanently open Oyster Harbour at this time all possessed resting gonads, i.e. their oocytes were all previtellogenic, the adults that were present in that estuary earlier and were destined to spawn in autumn must have emigrated from that permanently open estuary to their marine spawning areas prior to the onset of gonadal recrudescence. The body masses at length of A. georgianus, which were almost invariably higher in summer and autumn than in winter and spring, were greater in the very productive environments of the seasonally open and normally closed estuaries than in the less productive and essentially marine environment of Oyster Harbour and coastal marine waters. In general, the same pattern of differences between water bodies was exhibited by the growth of A. georgianus and by the more restricted data for body mass at L(T) and growth of S. punctatus. Despite an increase in anthropogenic activities in Wilson Inlet over the last two decades, the growth of both species was very similar to that recorded 20 years earlier. The fisheries implications of the results for the two species are discussed.

To what extent are the dietary compositions of three abundant, co-occurring labrid species different and related to latitude, habitat, body size and season?

This study demonstrated that the dietary composition of each of three abundant reef-associated labrid species in temperate Western Australia differed significantly with latitude and changed with increasing body size and almost invariably differed among those species when they co-occurred. These results were derived from comparisons and multivariate analyses of volumetric dietary data, obtained from the foregut contents of Coris auricularis, Notolabrus parilus and Ophthalmolepis lineolatus from the Jurien Bay Marine Park (JBMP) and waters off Perth, 250 km to the south. Latitudinal differences in the dietary compositions of each species in exposed reefs typically reflected greater contributions by large crustaceans, bivalve molluscs, echinoids and annelids to the diets in the waters off Perth than in the JBMP, whereas the reverse was true for gastropods and small crustaceans. The diet of each species exhibited similar, but not identical, quantitative changes with increasing body size, with the contributions of small crustaceans declining and those of large crustaceans and echinoids increasing, while that of gastropods underwent little change. Within the JBMP, the dietary compositions of both C. auricularis and N. parilus were similar in exposed and sheltered reefs and the same was true for N. parilus in the sheltered reefs and interspersed areas of seagrass. The latter similarity demonstrated that, in both of those divergent habitat types, N. parilus feeds on prey associated with either the sand or the macrophytes that cover and lie between the reefs. Although the main dietary components of each species were the same, i.e. gastropods, small crustaceans (mainly amphipods and isopods), large crustaceans (particularly penaeids and brachyuran crabs) and echinoids, their contributions varied among those species, which accounts for the significant interspecific differences in diet. Coris auricularis had the most distinct diet, due mainly to an ingestion of greater volumes of small crustaceans, e.g. amphipods and isopods, and lesser volumes of large crustaceans, e.g. brachyuran crabs, which was associated with a relatively narrower mouth and smaller teeth and the absence of prominent canines at the rear of the jaw. The above intra and interspecific differences in dietary composition would reduce, on the south-west coast of Australia, the potential for competition for food among and within these three abundant labrids, each of which belongs to different genera within the Julidine clade.

A prospective comparison of neuropsychologic performance of children surviving leukemia who received 18-Gy, 24-Gy, or no cranial irradiation.

To compare the late neuropsychologic toxicities of CNS prophylaxis for childhood acute lymphoblastic leukemia (ALL), longitudinal assessments were performed on three groups of patients: those who received repeated courses of moderate-dose (1 g/m2) intravenous (IV) and intrathecal methotrexate (IT MTX) without cranial irradiation (MTX group, n = 26), those who received IT MTX and 18 Gy cranial irradiation (18-Gy group, n = 23), and those who received IT MTX and 24 Gy cranial irradiation (24-Gy group, n = 28). All patients were free of CNS leukemia at diagnosis and had remained in continuous, complete remission 5 to 11 years (median, 7.4 years) following CNS prophylaxis. An analysis of serial intelligence quotient (IQ), achievement, and neuropsychologic studies revealed no significant influence of either age at CNS prophylaxis or CNS prophylaxis group on any neuropsychologic outcome measure. After adjusting for changes in IQ test versions that were necessitated by advancing patient age, no statistically significant declines in Verbal, Performance, or Full Scale IQs were noted for the three CNS treatment groups. However, comparisons of group means masked declines in individual children; 22% to 30% of children exhibited a clinically significant deterioration (greater than or equal to 15 points) in uncorrected IQ values over the study period. Female sex was associated with an increased risk of deterioration in Verbal IQ, but we were unable to identify risk factors associated with other declines in intellect and achievement. The inability to reliably predict individual patients at risk for clinically significant neuropsychologic toxicities on the basis of age at diagnosis or specific method of CNS prophylaxis suggests that other etiologic factors must be explored as the basis for these changes, such as ecologic factors and chemotherapy during the continuation phase of treatment.

Memory function in disease-free survivors of childhood acute lymphocytic leukemia given CNS prophylaxis with or without 1,800 cGy cranial irradiation.

Previous studies have found that CNS prophylaxis of children with leukemia, especially young children receiving cranial irradiation, causes neuropsychologic deficits. In the present study, 40 children in continuous complete remission from acute lymphocytic leukemia (ALL) were given a battery of tests to assess memory functioning 5 years after CNS prophylaxis. All children were free of CNS disease at diagnosis and had been randomly assigned to receive CNS prophylaxis with either 1,800 cGy cranial irradiation (CRT) plus intrathecal (IT) methotrexate (MTX) or IT MTX plus intravenous (IV) high-dose MTX (HDMTX). No treatment- or age-related differences were seen on 16 standardized memory measures. However, scores of the combined sample were significantly lower than age-corrected norms on a test of visual-spatial memory and on four scales of verbal memory. Differences in methods or intensity of CNS prophylaxis and study group selection criteria are proposed to explain our findings and to resolve discrepancies with previous reports. The long-term neuropsychological sequelae in these survivors of ALL may be attributable to some common factor, such as the disease itself or systemic and IT chemotherapy.

Physician desire for euthanasia and assisted suicide: would physicians practice what they preach?

PURPOSE: Euthanasia is a pressing public issue. We sought to assess how frequently physicians could perceive of a desire for euthanasia themselves and whether they would be willing to provide patients the same interventions. METHODS: We interviewed 355 randomly selected oncologists from the United States and interviewed them about their attitudes and practices related to euthanasia and assisted suicide. RESULTS: Of the 355 oncologists, 48.1% could imagine a situation in which they might desire euthanasia or assisted suicide for themselves. Oncologists who were Catholic and more religious were significantly less likely to desire these interventions for themselves. Of those oncologists who could imagine a situation in which they might desire euthanasia or assisted suicide for themselves, 85.8% found euthanasia and/or assisted suicide acceptable for their patients. Of the oncologists who could not imagine a situation in which they might desire euthanasia or assisted suicide for themselves, 41.7% still found these interventions ethical for their patients. Only 6.8% of oncologists could imagine a situation in which they might desire euthanasia or assisted suicide for themselves but found these interventions unacceptable for their patients. CONCLUSION: Almost half of surveyed oncologists could imagine a situation in which they would desire euthanasia or assisted suicide. However, in many cases, this was for nonterminal illness which would be prohibited by proposed laws. When physicians desire euthanasia or assisted suicide for themselves, they are willing to provide these interventions for their patients; therefore, most physicians would practice what they preach. Indeed, when they deviate, oncologists overwhelmingly respect patient autonomy rather than impose their own views on patients.

Patient preferences concerning the trade-off between the risks and benefits of routine radiation therapy after conservative surgery for early-stage breast cancer.

PURPOSE: To assess patients' preferences regarding the trade-off between risks and benefits of radiation therapy after conservative surgery for early-stage breast cancer. PATIENTS AND METHODS: Utilities (measures of preference) of 97 early-stage breast cancer patients treated with conservative surgery and radiation therapy and 20 medical oncology nurses were assessed for five health states using standard gambles. RESULTS: Patients had the highest mean utility for treatment with conservative surgery and radiation therapy without a local recurrence (0.92), intermediate utilities for treatment with conservative surgery alone followed either by no local recurrence or by a local recurrence salvaged by conservative surgery and radiation therapy (0.88 and 0.87, respectively), and the lowest utilities for treatment with or without radiation therapy followed by a local recurrence salvaged by mastectomy and reconstructive surgery (0.82 and 0.81, respectively). All differences between health states' utilities were significant (P < .0001), except between the two intermediate and two lowest rated health states. None of the clinical or sociodemographic factors examined explained more than 5% of the variability in the patients' utilities or their differences. Nurses' utilities were similar to those of the patients. CONCLUSIONS: These results strongly suggest that fear of a local recurrence and an actual local recurrence leading to mastectomy have such a negative impact on quality of life that patients are willing to accept the risks and inconvenience of radiation therapy to avoid them. There is also considerable interpatient variability that was not explained by the clinical or sociodemographic factors examined.

Attitudes of 47 mothers of pediatric oncology patients toward genetic testing for cancer predisposition.

PURPOSE: To assess attitudes toward testing for cancer susceptibility genes, we interviewed mothers of pediatric oncology patients about their cancer causation theories, interest in hypothetical predisposition testing for themselves and their healthy children, and anticipated impact of testing. PATIENTS AND METHODS: The subjects were 47 mothers of two or more living children, one of whom was 6 to 24 months postdiagnosis of cancer. Potential risks and benefits of hypothetical genetic predisposition testing for cancer susceptibility were described. A semistructured interview assessed the following: (1) recall of discussions with the pediatric oncologist about the possible role of heredity in causing the child's cancer; (2) mothers' personal theories of the etiology of their child's cancer; (3) family cancer history; (4) interest in genetic predisposition testing for themselves and unaffected (cancer-free) children; and (5) expected sequelae of testing. RESULTS: If genetic cancer predisposition tests were available, 51% of mothers would test themselves and 42% would test healthy children, even with no medical benefit. With established medical benefit, an additional 36% of mothers would seek testing for themselves and another 49% would test their healthy children. Interest in cancer predisposition testing among mothers extended far beyond those with significant family histories of cancer. Most mothers would consider minor children's wishes in the decision about testing and would tell children under age 18 their test results. CONCLUSION: As increasing numbers of cancer susceptibility genes are identified, parents of pediatric oncology patients may be receptive to opportunities to test themselves and their healthy children. Counseling will be important to aid in decisions about testing. Research is essential to evaluate the long-term impact of predisposition testing.

Non-Hodgkin's lymphomas of childhood: an analysis of the histology, staging, and response to treatment of 338 cases at a single institution.

Between 1962 and 1986, a total of 338 consecutive newly diagnosed children and adolescents with non-Hodgkin's lymphomas (NHLs) were evaluated and treated at St Jude Children's Research Hospital (SJCRH). Median follow-up is 6.6 years (range, 1.8 to 23 years). The patients ranged in age from 7 months to 21 years (median, 10 years), and 71% were males. All cases were staged (I to IV) by a clinical staging system. Eighteen percent were stage I, 21% stage II, 43% stage III, and 18% stage IV. Cases frankly leukemic at diagnosis (ie, greater than 25% marrow blasts) were excluded from the analysis. Pathologic material from all cases was reviewed and classified according to the Working Formulation. The histologic distribution of cases was as follows: 38.8% diffuse small non-cleaved cell (undifferentiated, Burkitt's and non-Burkitt's); 26.3% diffuse large-cell, mainly immunoblastic; 28.1% lymphoblastic; and 6.8% other. Treatment policy evolved over time to a stage- and histology-specific strategy for treatment assignment, and overall results significantly improved by era from 37% (+/- 5%) 2-year event-free survival (EFS) for patients treated before 1975 to 77% (+/- 4%) since 1978. By univariate and multivariate Cox regression analyses, the era of treatment (hence, the protocol-specific treatment itself), the stage, and the log of the initial serum lactic dehydrogenase (LDH) emerged as the most powerful prognostic indicators, while histology per se was not significantly related to outcome. For the 154 patients treated since 1978, the 2-year EFS by stage was 97% (+/- 3%) for stage I, 86% (+/- 6%) for stage II, 73% (+/- 6%) for stage III, and 47% (+/- 11%) for stage IV (P less than .0001). Compared with our previous experience, we conclude that the cure rate of childhood NHL has doubled in the last decade with modern management.

Intellectual and academic achievement status after CNS relapse: a retrospective analysis of 40 children treated for acute lymphoblastic leukemia.

We determined the intellectual and academic status of 40 children with acute lymphoblastic leukemia who had experienced a primary isolated relapse in the CNS by analyzing the results of psychoeducational tests administered a median of 6.1 years after the relapse. Mean scores for full-scale IQ (87.5), verbal IQ (86.7), performance IQ (90.3), as well as academic achievement in reading (89.8), spelling (83.9), and mathematics (83.5) were significantly below normal expectations for age. Twenty percent of the group were mentally retarded and were receiving special educational assistance. The best clinical predictors of full-scale IQ were the number of radiation therapy courses, age, and the presence or absence of cerebral pathology as measured by computed tomography (CT). Children who were younger at the time of treatment, who received two courses of radiation therapy, and who had clinical seizures and structural abnormalities of the brain as detected by CT had the poorest psychological outcome. Although the psychoeducational consequences of CNS relapse and its attendant treatment are significant, these must be balanced by consideration of the relatively low probability of long-term survival without aggressive therapy. Recognition of this type of delayed morbidity with systematic surveillance and prompt attempts at rehabilitation may decrease or at least minimize these sequelae.

Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.

Long-term survivors of leukemia treated in infancy: factors associated with neuropsychologic status.

PURPOSE: Because of concerns about late toxicities of treatment among infants diagnosed with acute lymphoblastic leukemia (ALL), and especially the effects of cranial radiation therapy (CRT), we compared the functional and neuropsychologic status of 26 long-term survivors of ALL who were diagnosed in the first 24 months of life versus 26 children who were treated previously for Wilms' tumor. PATIENTS AND METHODS: Of the children with ALL, CNS prophylaxis included no CRT in six, 18 Gy CRT in five, 20 Gy CRT in seven, and 24 Gy CRT in five. Three additional children experienced CNS relapse and received total CRT doses of 24, 40, and 44 Gy. All children received neuropsychologic testing; children with ALL also participated in diagnostic imaging studies. RESULTS: As a group, the children who were treated for ALL did not differ significantly from those who were treated for Wilms' tumor on objective measures of global functional status. However, children treated for ALL had a significantly lower mean intelligence quotient (IQ) (87 v 96), poorer performance on four of six measures of visual and auditory memory, lower achievement with regard to arithmetic skills, and a greater frequency of special educational intervention than those who were treated for Wilms' tumor. IQ and auditory memory performance in the ALL group was correlated inversely with time since the completion of therapy and total CRT dose. CONCLUSIONS: These results reinforce the contemporary trend of prophylactic CRT omission in very young children except for those who are at risk for CNS relapse. For infants and very young children who require CRT, evidence is presented that supports the approach for the delay of CRT until the child is older.

Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial.

PURPOSE: Treatment with cisplatin-based chemotherapy provides a modest survival advantage over supportive care alone in advanced non-small-cell lung cancer (NSCLC). To determine whether a new agent, paclitaxel, would further improve survival in NSCLC, the Eastern Cooperative Oncology Group conducted a randomized trial comparing paclitaxel plus cisplatin to a standard chemotherapy regimen consisting of cisplatin and etoposide. PATIENTS AND METHODS: The study was carried out by a multi-institutional cooperative group in chemotherapy-naive stage IIIB to IV NSCLC patients randomized to receive paclitaxel plus cisplatin or etoposide plus cisplatin. Paclitaxel was administered at two different dose levels (135 mg/m(2) and 250 mg/m(2)), and etoposide was given at a dose of 100 mg/m(2) daily on days 1 to 3. Each regimen was repeated every 21 days and each included cisplatin (75 mg/m(2)). RESULTS: The characteristics of the 599 patients were well-balanced across the three treatment groups. Superior survival was observed with the combined paclitaxel regimens (median survival time, 9.9 months; 1-year survival rate, 38.9%) compared with etoposide plus cisplatin (median survival time, 7.6 months; 1-year survival rate, 31.8%; P =. 048). Comparing survival for the two dose levels of paclitaxel revealed no significant difference. The median survival duration for the stage IIIB subgroup was 7.9 months for etoposide plus cisplatin patients versus 13.1 months for all paclitaxel patients (P =.152). For the stage IV subgroup, the median survival time for etoposide plus cisplatin was 7.6 months compared with 8.9 months for paclitaxel (P =.246). With the exceptions of increased granulocytopenia on the low-dose paclitaxel regimen and increased myalgias, neurotoxicity, and, possibly, increased treatment-related cardiac events with high-dose paclitaxel, toxicity was similar across all three arms. Quality of life (QOL) declined significantly over the 6 months. However, QOL scores were not significantly different among the regimens. CONCLUSION: As a result of these observations, paclitaxel (135 mg/m(2)) combined with cisplatin has replaced etoposide plus cisplatin as the reference regimen in our recently completed phase III trial.

Stability of attitudes regarding physician-assisted suicide and euthanasia among oncology patients, physicians, and the general public.

PURPOSE: Attitudes regarding the ethics of physician-assisted suicide (PAS) and euthanasia have been examined in many cross-sectional studies. Stability of these attitudes has not been studied, and this is important in informing the dialog on PAS in this country. We evaluated the stability of attitudes regarding euthanasia and PAS among three cohorts. METHODS: Subjects included 593 respondents: 111 oncology patients, 324 oncologists, and 158 members of the general public. We conducted initial and follow-up interviews separated by 6 to 12 months by telephone, regarding acceptance of PAS and euthanasia in four different clinical vignettes. RESULTS: The proportion of respondents with stable responses to vignettes ranged from 69.2% to 94.8%. In comparison to patients and the general public, physicians had less stable responses concerning the PAS pain vignette (69.1% v 80.8%; P =.001) and more stable responses for all euthanasia vignettes (P <.001) except for pain. Over time, physicians were significantly more likely to change toward opposing PAS and euthanasia in all vignettes (P <.05). Characteristics previously associated with attitudes regarding PAS and euthanasia, such as Roman Catholic religion, were not predictive of stability. CONCLUSION: Up to one third of participants changed their attitudes regarding the ethical acceptability of PAS and euthanasia in their follow-up interview. This lack of consistency mandates careful interpretation of referendums and requests for physician-assisted suicide. Furthermore, in this study, we found that physicians are becoming increasingly opposed to PAS and euthanasia. The growing disparity between physicians and patients regarding the role of these practices is large enough to suggest possible conflicts in the delivery of end-of-life care.

Attitudes and practices among pediatric oncologists regarding end-of-life care: results of the 1998 American Society of Clinical Oncology survey.

PURPOSE: In 1998, the American Society of Clinical Oncology (ASCO) surveyed its membership to assess the attitudes, practices, and challenges associated with end-of-life care of patients with cancer. In this report, we summarize the responses of pediatric oncologists and the implications for care of children dying from cancer. METHODS: The survey consisted of 118 questions, covering eight categories. All ASCO members in the United States, Canada, and the United Kingdom were mailed a survey, which was completed by 228 pediatric oncologists. Predictors of particular attitudes and practices were identified using stepwise logistic regression analysis. Potential predictors were age, sex, religious affiliation, importance of religious beliefs, recent death of a relative, specialty, type of practice (rural or urban, academic or nonacademic), amount of time spent in patient care, number of new patients in the past 6 months, and number of patients who died in the past year. RESULTS: Pediatric oncologists reported a lack of formal courses in pediatric palliative care, a strikingly high reliance on trial and error in learning to care for dying children, and a need for strong role models in this area. The lack of an accessible palliative care team or pain service was often identified as a barrier to good care. Communication difficulties exist between parents and oncologists, especially regarding the shift to end-of-life care and adequate pain control. CONCLUSION: Pediatric oncologists are working to integrate symptom control, psychosocial support, and palliative care into the routine care of the seriously ill child, although barriers exist that make such comprehensive care a challenge.

Recovery after stem-cell transplantation for hematologic diseases.

PURPOSE: Although the number of autologous and allogeneic stem-cell transplantations (SCT) is increasing, relatively little information about recovery after transplantation is available. Quantitative information appropriate for patient counseling is difficult to discern from the literature. We sought to suggest reasonable expectations for recovery and symptoms after SCT for hematologic malignancies and other disorders using the following measures: (1) objective measures of health status, such as frequency of clinic visits, need for rehospitalization, medication usage, work status, and overall and event-free survival; (2) qualitative assessment of quality of life, such as returning to a normal life, resumption of normal activities, satisfaction with appearance, and whether recovery has occurred; and (3) quantification of specific bothersome symptoms. PATIENTS AND METHODS: Autologous and allogeneic SCT recipients at a tertiary-care transplant center participated in the prospective, longitudinal questionnaire study. RESULTS: Three hundred twenty patients were studied. Questionnaire response rates at 6, 12, and 24 months range from 85% to 88% among survivors. Although autologous patients had better event-free and overall survival, fewer symptoms, and more complete recovery at 6 months, these advantages had largely equalized by 12 months. Specific bothersome symptoms were reported by less than 24% of patients after transplantation, except for fatigue and financial and sexual difficulties, which were more prevalent. CONCLUSION: These findings may help counsel patients considering transplantation and educate them about reasonable expectations for recovery. Overall, the low level of bothersome symptoms and continued recovery through the first year after transplantation are encouraging.