Increased prevalence of risk factors for cardiovascular disease in long-term survivors of acute lymphoblastic leukemia and Wilms tumor treated with radiotherapy.

BACKGROUND: Only a few studies have assessed cardiovascular risk factors (CRFs) in childhood cancer survivors. We determined the prevalence of CRFs in long-term survivors of acute lymphoblastic leukemia (ALL) and Wilms tumor. PROCEDURE: Adult survivors of ALL and Wilms tumor treated with radiotherapy and chemotherapy (RT + CT) or treated with chemotherapy alone (CT) were compared with sibling controls. CRFs (hypertension, diabetes mellitus, hypercholesterolemia, obesity, renal insufficiency) and hormonal deficiencies were assessed in each participant. Multivariate logistic regression analysis was used to evaluate the association between CRFs and treatment. RESULTS: Seventy-nine ALL, 62 Wilms tumor survivors, and 69 control subjects (mean ages 24.5, 25.9, and 26 years, respectively) were enrolled. Mean follow-up time since cancer treatment was 20.8 years. In the Wilms RT + CT group significantly more survivors had hypertension (21.6% vs. 1.4%, P < 0.001) and renal insufficiency (8.1% vs. 0%, P = 0.016) compared to controls. There were also more patients with multiple CRFs in the Wilms RT + CT group (16.2% vs. 2.9% in controls, P = 0.019). Almost 15% of ALL RT + CT survivors had growth hormone deficiency. Hypogonadism was seen in 18.9% of survivors in the Wilms RT + CT group. We observed no significant differences between CT-treated survivors of both malignancies and controls. The adjusted odds ratio for the occurrence of at least one CRF was 2.6 increased for survivors following abdominal radiotherapy. Treatment with CT alone was not associated with the occurrence of multiple CRFs. CONCLUSIONS: Long-term survivors of ALL and Wilms tumor have unfavorable CRFs due to previous RT not CT.

Proclets in healthcare.

Healthcare processes can be characterized as weakly-connected interacting light-weight workflows coping with different levels of granularity. Classical workflow notations fall short in supporting these kind of processes. Although these notations are able to describe the life-cycle of individual cases and allow for hierarchical decomposition, they primarily support monolithic processes. However, they are less suitable for healthcare processes. The Proclets framework is one formalism that provides a solution to this problem. Based on a large case study, describing the diagnostic process of the gynecological oncology care process at the Academic Medical Center (AMC), we identify the limitations of "monolithic workflows". Moreover, by using the same case study, we investigate whether healthcare processes can be described effectively using Proclets. In this way, we provide a comparison between the Proclet framework and existing workflow languages and identify research challenges.

Models as instruments for optimizing hospital processes: a systematic review.

PURPOSE: The purpose of this article is to find decision-making models for the design and control of processes regarding patient flows, considering various problem types, and to find out how usable these models are for managerial decision making. DESIGN/METHODOLOGY/APPROACH: A systematic review of the literature was carried out. Relevant literature from three databases was selected based on inclusion and exclusion criteria and the results were analyzed. FINDINGS: A total of 68 articles were selected. Of these, 31 contained computer simulation models, ten contained descriptive models, and 27 contained analytical models. The review showed that descriptive models are only applied to process design problems, and that analytical and computer simulation models are applied to all types of problems to approximately the same extent. Only a few models have been validated in practice, and it seems that most models are not used for their intended purpose: to support management in decision making. RESEARCH LIMITATIONS/IMPLICATIONS: The comparability of the relevant databases appears to be limited and there is an insufficient number of suitable keywords and MeSH headings, which makes searching systematically within the broad field of health care management relatively hard to accomplish. PRACTICAL IMPLICATIONS: The findings give managers insight into the characteristics of various types of decision-support models and into the kinds of situations in which they are used. ORIGINALITY/VALUE: This is the first time literature on various kinds of models for supporting managerial decision making in hospitals has been systematically collected and assessed.

Simulation to analyse planning difficulties at the preoperative assessment clinic.

BACKGROUND: Little research has been performed on designing appointment systems for the preoperative assessment clinic (PAC). We aimed to investigate how two organizational planning difficulties, (i) long access times and (ii) long waiting times, could be analysed systematically. METHODS: Two simulation models were used to test different scenarios to reduce access time and waiting times. First, we determined the number of appointments needed to reduce the access time from 5 weeks to 10 working days for 95% of all patients. Subsequently, we determined how long the consultation time should be, taking patients' American Society Anesthesiologists (ASA) physical status into account, to reduce the maximum waiting time to 10 min for 95% of all patients. RESULTS: Although we found the actual capacity, that is, consultations per day, to be enough to meet demand, a backlog existed, as the access time for the PAC was 5 weeks. A temporary extra capacity is needed to eliminate this backlog. When the reserved consultation time is 18 min for patients with ASA class I or II and 30 min for patients with ASA class III or IV, the maximum waiting times decrease to 10 min for 95% of all patients. CONCLUSIONS: This study shows that a simulation model is a helpful tool to determine the capacity needed to achieve and to maintain a proposed service level for access times and waiting times. In addition, waiting times at the PAC can be reduced by making the reserved consultation time dependent on patients' ASA physical status.

Electromagnetic interference from radio frequency identification inducing potentially hazardous incidents in critical care medical equipment.

CONTEXT: Health care applications of autoidentification technologies, such as radio frequency identification (RFID), have been proposed to improve patient safety and also the tracking and tracing of medical equipment. However, electromagnetic interference (EMI) by RFID on medical devices has never been reported. OBJECTIVE: To assess and classify incidents of EMI by RFID on critical care equipment. DESIGN AND SETTING: Without a patient being connected, EMI by 2 RFID systems (active 125 kHz and passive 868 MHz) was assessed under controlled conditions during May 2006, in the proximity of 41 medical devices (in 17 categories, 22 different manufacturers) at the Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Assessment took place according to an international test protocol. Incidents of EMI were classified according to a critical care adverse events scale as hazardous, significant, or light. RESULTS: In 123 EMI tests (3 per medical device), RFID induced 34 EMI incidents: 22 were classified as hazardous, 2 as significant, and 10 as light. The passive 868-MHz RFID signal induced a higher number of incidents (26 incidents in 41 EMI tests; 63%) compared with the active 125-kHz RFID signal (8 incidents in 41 EMI tests; 20%); difference 44% (95% confidence interval, 27%-53%; P < .001). The passive 868-MHz RFID signal induced EMI in 26 medical devices, including 8 that were also affected by the active 125-kHz RFID signal (26 in 41 devices; 63%). The median distance between the RFID reader and the medical device in all EMI incidents was 30 cm (range, 0.1-600 cm). CONCLUSIONS: In a controlled nonclinical setting, RFID induced potentially hazardous incidents in medical devices. Implementation of RFID in the critical care environment should require on-site EMI tests and updates of international standards.

Risk of second malignancies in long-term survivors of childhood cancer.

INTRODUCTION: Childhood cancer survivors are known to be at increased risk for second malignancies. PATIENTS AND METHODS: The risk of second malignancies was assessed in 1368 5-year survivors of childhood cancer treated in the Emma Children's Hospital AMC in Amsterdam. The median follow-up time was 16.8 years. RESULTS: Sixty two malignancies were observed against 5.4 expected, yielding a standardised incidence ratio (SIR) of 11.2 (95% confidence interval: 8.53-14.4; absolute excess risk: 3.2 per 1000 person-years). New observations were the strongly increased risks of meningiomas (SIR=40) and basal cell carcinomas (SIR=9). Patients whose treatment involved radiotherapy had a 2-fold increased second cancer risk compared to patients with chemotherapy alone. DISCUSSION: The relative risk of second malignancies does not decrease till at least 30 years of follow-up. With aging of the survivor cohort this results in a strong increase of the AER, due to the rising background risk of cancer with age.

Development of a national protocol to screen Dutch cancer survivors on late cancer treatment effects.

PURPOSES: The development of a national protocol to formalize the screening of Dutch cancer survivors on potential late cancer treatment effects and the medical terminology used in describing the patient follow up procedures. METHODS: A combined evidence-based and qualitative approach, the Glaser's State of the Art Strategy, was used to reach consensus on how to screen Dutch cancer survivors on late cancer treatment effects. A core working group set up a first proposal of a screening protocol and a handbook of medical term definitions by incorporating available research evidence (1980-2003), clinical expertise and definitions from Dutch medical dictionaries and textbooks. External experts reviewed this proposal in a cycle of two postal and two discussion rounds. The follow-up procedures and medical term definitions described in the draft screening protocol were to be accepted if consensus among external experts was > or =50%. RESULTS: A protocol for screening cancer survivors on late cancer treatment effects was developed describing the follow-up procedures for cancer survivors according to previous therapeutic exposures. Four hundred and twenty one medical terms were used in describing these follow-up procedures. One hundred and fifteen of these terms were classified as multi-interpretable and 101 of these terms were defined. No definitions could be found for the remaining 14 medical terms. CONCLUSIONS: We succeeded in reaching consensus throughout The Netherlands on a protocol to screen cancer survivors on late cancer treatment effects. This protocol is now in use by all Dutch outpatient clinics and warrants that the screening of cancer survivors is consistent across The Netherlands. The screening protocol specifies in detail how screening of cancer survivors should take place and can therefore be used by clinicians who were not involved in the consensus study.

Evidence-based re-engineering: re-engineering the evidence--a systematic review of the literature on business process redesign (BPR) in hospital care.

PURPOSE: Business process redesign (BPR) is used to implement organizational transformations towards more customer-focused and cost-effective care. Ideally, these innovations should be carefully described and evaluated so that "best practices" can be re-applied. To investigate this, available evidence was collected on patient care redesign projects. DESIGN/METHODOLOGY/APPROACH: The Ebsco Business Source Premier, Embase and Medline databases were searched. Studies on innovations related to re-engineering patient care that used before-after design as minimum prerequisites were selected. General characteristics, logistic parameters and other outcome measures to determine the objectives and results and interventions used were looked at. FINDINGS: A total of 86 studies that conformed to the criteria were found: a minority mentioned measurable parameters in their objectives. In the majority of studies, multiple interventions were combined within single studies, making it impossible to compare the effects of individual interventions. Only three randomized controlled trials were found. Furthermore, inconsistencies were noted between the study objectives and the reported results. Many more issues were reported in the results than were mentioned in the study aims. It would appear that publications were hard to find owing to a lack of specific MeSH headings. Nearly 7,500 abstracts were scanned and from these it was concluded that clear and univocal research methods, terms and reporting guidelines are advisable and must be developed in order to learn and benefit from BPR innovations in health care organizations. ORIGINALITY/VALUE: This appears to be the first time available evidence about redesign projects in hospitals has been systematically collected and assessed.

Hyperthermia enhances tumor uptake and antitumor efficacy of thermostable liposomal daunorubicin in a rat solid tumor.

The combination of local hyperthermia (HT) with thermostable liposomal daunorubicin (DaunoXome, DX) was investigated to assess targeted drug delivery to experimental tumors. Female Wag/Rij rats bearing solid R-1 rhabdomyosarcomas received i.v. injections of 10 or 15 mg/kg of DX or free-Daunorubicin (f-Dau). After a 1-h interval, HT (60 min at 43 degrees C) was applied. Pharmacokinetics were studied in relation to tumor growth time (TGT), i.e., the time for tumors to reach their original volumes. Pharmacokinetic studies revealed that DX accumulation in tumor tissue was similar to f-Dau. A 5.4-fold increase (P = 0.0084) in tumor drug delivery was observed when DX was combined with HT, whereas liposomes remained stable. For f-Dau, HT had an additional effect on TGT at both drug doses tested (9.6 and 6.2 days, respectively, for 10 mg/kg, P = 0.0092; 17.7 and 13.7, respectively, for 15 mg/kg, P = 0.0431). For DX, HT significantly enhanced TGT of DX in the lower dose (17.1 and 6.4 days, respectively, P = 0.0005), whereas tumors did not regrow at day 25 after DX + HT in the higher dose. Unfortunately, after this time interval, the animals died of late toxicity, probably not related to HT. These results indicate that HT promotes extravasation of DX into tumor tissue and enhances its effectiveness. The finding that HT-induced drug release from the liposomes was not responsible for enhanced antitumor activity provides a rationale for further investigation of thermostable liposomes in conjunction with HT.

Palliative chemotherapy or watchful waiting? A vignettes study among oncologists.

PURPOSE: To determine the preferences of oncologists for palliative chemotherapy or watchful waiting and the factors considered important to that preference. METHODS: Sixteen vignettes (paper case descriptions), varying on eight patient and treatment characteristics, were designed to assess the oncologists' preferences. Their strength of preference was rated on a 7-point scale. An orthogonal main effects design provided a subset of all possible combinations of the characteristics, allowing estimations of the relative weights of the presented characteristics. A written questionnaire was sent to a random sample of oncologists (N = 1,235). RESULTS: The response rate was 67%, and 697 questionnaires were available for analysis. Eighty-one percent of the respondents were male. The mean age was 46 years. We found considerable variation among the oncologists. No major associations between physician characteristics and preferences were found. Of the patient and treatment characteristics affecting treatment preference, age was the strongest predictor, followed by the patient's wish to be treated and the expected survival gain. Other patient and treatment characteristics had a limited effect on preferences, except for psychologic distress, which had no independent impact. CONCLUSION: Patients will encounter different decisions depending on their oncologists' preferences and their own personal background. Therefore, to ensure adequate information for decision-making processes, decision aids are proposed.

Imaging of estrogen receptors in primary and metastatic breast cancer patients with iodine-123-labeled Z-MIVE.

PURPOSE: To evaluate the feasibility of noninvasive imaging of estrogen receptors (ERs) in primary and metastatic breast cancer with the iodine-123-labeled ER-specific ligand cis-11beta-methoxy-17alpha-iodovinylestradiol-17beta (Z-[123I]MIVE) using conventional nuclear medicine techniques. PATIENTS AND METHODS: Z-[123I]MIVE planar scintigraphy and single-photon emission computed tomography (SPECT) were performed in 12 patients with proven primary breast cancer and 13 patients with proven or from other imaging modalities evident bone, liver, lung, pleura and/or lymph node metastases. The results were compared with those of ER immunohistochemistry (IHC). Blocking studies with the antiestrogen tamoxifen were performed to test whether Z-[123I]MIVE tumor uptake was ER-mediated. RESULTS: Planar imaging showed uptake in 11 of 12 primary carcinomas. ER IHC performed for nine of these was positive. For the planar scintigraphy-negative patient, SPECT was faintly positive, but ER IHC negative (agreement, 90%). In nine of 13 metastatic patients, planar scintigraphy was positive. The agreement between the results of ER IHC on the original primary tumor and of Z-[123I]MIVE scintigraphy was 82%. Specificity of tumor Z-[123I]MIVE uptake was established by complete blockade of uptake by tamoxifen, except in two patients who showed progressive disease. Z-[123I]MIVE scintigraphy also enabled discriminating metastases from confounding nonmalignant abnormalities of the bone scan. CONCLUSION: Z-[123I]MIVE scintigraphy shows high sensitivity and specificity for the detection of ER-positive breast cancer. This may have impact on diagnostic possibilities and therapeutic management. Since ER imaging shows the functional status, addressing known intratumoral and intertumoral ER heterogeneity, it may improve the characterization of disease and the selection of patients who may benefit from hormonal therapy.

Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre.

PURPOSE: To investigate the pharmacokinetics and pharmacodynamics of paclitaxel (P) and carboplatin (C) in a sequence-finding and dose-escalating study in untreated non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Fifty-five chemotherapy-naive patients with NSCLC were entered onto the pharmacokinetic part of a large phase I trial in which P was administered as a 3-hour infusion at dosages of 100 to 250 mg/m2, and C over 30 minutes at dosages of 300 to 400 mg/m2. Patients were randomized for the sequence of administration, first C followed by P or vice versa. Each patient received the alternate sequence during the second and subsequent courses. RESULTS: The most important hematologic toxicity encountered-was neutropenia. Hematologic toxicity was not dependent on the sequence in which P and C were administered, but there was cumulative neutropenia. Nonhematologic toxicities consisted mainly of vomiting, myalgia, and arthralgia. No sequence-dependent pharmacokinetic interactions for the P area under the concentration-time curve (P-AUC), maximal plasma concentration (P-Cmax), or time above a threshold concentration of 0.1 mumol/L (P-T > or = 0.1 mumol/L) were observed. However, there was a significant difference for the metabolite 6 alpha-hydroxypaclitaxel AUC (6OHP-AUC). Higher 6OHP-AUCs were observed when C was administered before P. The mean plasma ultrafiltrate AUC of C (CpUF-AUC) at the dosage of 300 mg/m2 for the sequence C-->P was 3.52 mg/mL.min (range, 1.94 to 5.83) and 3.62 mg/mL.min for the sequence P-->C (range, 1.91 to 5.01), which is not significantly different (P = .55). Of 45 assessable patients, there were five major responders (three complete responders and two partial responders). Four of five responses occurred at dosages above dose level 4 (P 175 mg/m2 + C 300 mg/m2). The median survival duration was best correlated with the P dose (4.8 months for doses < 175 mg/m2 v 7.9 months for doses > or = 175 mg/m2, P = .07; P-T > or = 0.1 mumol/L, 4.8 months for < 15 hours v 8.2 months for > or = 15 hours, P = .06). CONCLUSION: There was no pharmacokinetic-sequence interaction between C and P in this study. A clear dose-response relation with respect to response rate and survival was observed. The pharmacokinetic parameter P-T > or = 0.1 mumol/L was related to improved survival in this study.

Lack of activity of zidovudine in AIDS-associated Kaposi's sarcoma.

The efficacy of zidovudine (AZT) for treatment of patients with Kaposi's sarcoma as the initial manifestation of AIDS was determined in a non-randomized, phase-II clinical trial. Twenty-two patients were treated with zidovudine (300 mg 4 times daily for 8 weeks). In patients with stable disease or showing a response, treatment was continued. After 12 weeks the total daily dose was changed to 1000 mg. Only two of all 22 evaluable patients achieved a response (one complete and one partial response), of only brief duration (2 and 4 months, respectively). There was no such association between antiretroviral activity, increase in CD4+ cells and tumour response, as was reported during treatment with human recombinant interferon alpha (IFN-alpha). These findings do not support the use of zidovudine as a first-line treatment for patients with AIDS-associated Kaposi's sarcoma.

Temporary increase in serum beta 2-microglobulin during treatment with interferon-alpha for AIDS-associated Kaposi's sarcoma.

Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment. However, the increase of serum beta 2-M levels in responders appeared to be more pronounced than in those with progressive disease, but this difference was not significant. The increase was only found during the initial 8 weeks; thereafter, beta 2-M levels declined in patients with continuing clinical improvement during ongoing treatment with IFN alpha. This may have been related to IFN alpha dose modification at 8 weeks for all patients. The initial rise in serum beta 2-M might be related to the immunomodulation properties of IFN alpha. Because serum beta 2-M levels were also enhanced in non-responders, this rise does not demonstrate that immunomodulation by IFN alpha is a mechanism of anti-tumour activity in AIDS-associated Kaposi's sarcoma.

Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans.

Cytokines, such as tumor necrosis factor-alpha and interleukin-1 beta (IL-1 beta), alter thyroid hormone metabolism, and may be involved in the pathogenesis of the euthyroid sick syndrome. Both cytokines also induce the production of IL-6. To assess whether IL-6 itself modulates thyroid hormone metabolism, we studied the acute and chronic effects of recombinant human IL-6 (rhIL-6) on thyroid hormone concentrations in patients with renal cell cancer. In the first study protocol, plasma thyroid hormone concentrations were measured during a 4-h infusion of rhIL-6 (150 micrograms) or, on another day, during infusion of saline (control; n = 8). There were no effects of rhIL-6 infusion on T4, free T4, or thyroid hormone-binding index. However, rhIL-6 induced a significant decrease in the plasma concentrations of TSH (P < 0.001) and T3 (P < 0.001) compared with those in the control study, associated with an increase in rT3 concentrations (P < 0.001). In the second study, a dose of 150 micrograms rhIL-6 was administered sc for 42 consecutive days (n = 8). Weekly assessment of thyroid hormone and TSH concentrations showed a decrease in the T3 concentration (P < 0.001) and a transient increase in rT3 (P < 0.01) and free T4 concentrations (P < 0.01). There were no changes in T4 concentrations during chronic administration of rhIL-6. It is concluded that IL-6 induces major changes in thyroid hormone metabolism and may be another pathogenetic factor in the euthyroid sick syndrome.

Application of a DNA double labelling method for the flow cytometric analysis of recruitment of non-cycling cells in a mixed population of P and Q cells.

In this paper we describe the application of a non-radioactive DNA double labelling and staining method to an analysis of cell proliferation kinetics by flow cytometry, aimed at the direct measurement of recruitment rates in cell cultures. The method is based on the application of two halogenated deoxyuridines: iododeoxyuridine (IdUrd) and chlorodeoxyuridine (CldUrd) which are incorporated into DNA synthesizing cells. By applying two commercially available monoclonal antibodies both deoxyuridines can be detected separately. To measure recruitment all proliferating cells in a plateau phase culture were labelled first with IdUrd applied during a time interval approximately equal to the cell cycle time. Subsequently, recruitment induced by a medium change was analysed by flow cytometric assessment of incorporation of CldUrd in cells which had not taken up IdUrd. Experiments designed to determine the toxicity of continuous labelling with IdUrd in different concentrations and of pulse labelling with CldUrd showed that there was no effect on the progression of cells through the cell cycle. The aim of this study is to test the sensitivity of the procedure to detect changes in proliferation kinetics, in particular the entrance of resting cells into the S phase. Although the cell culture model used is very simple, the results demonstrate clearly that a low rate of recruitment can be detected. It is suggested that the procedure described here is specific and sensitive enough to quantify changes in cell proliferation in tumours induced by various treatments and has advantages over other methods, which measure recruitment indirectly, or directly by using two radioactive thymidines.

Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma.

The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25 years (median 16 years) after therapy. The radiation dose to the whole cranium and spinal axis was 35 +/- 2.6 Gray (mean +/- standard deviation) with a boost to the posterior fossa of 18 +/- 3.7 Gray. 13 subjects had received additional chemotherapy. In 15 of 20 (75%) subjects, endocrine abnormalities were observed. In 14 (70%), growth hormone (GH) secretion was impaired; 7 (35%) subjects had an absolute GH deficiency, while 7 (35%) showed subnormal responses to insulin-induced hypoglycaemia. In contrast, only 20% (4) of these subjects showed impairment of the hypothalamus-pituitary-thyroid (HPT) axis, while 15% (3) showed central impairment of hypothalamus-pituitary-gonadal (HPG) function. Central impairment of the HPG axis was associated with impaired GH secretion in all cases. Central adrenal insufficiency was not observed. Basal levels of prolactin were normal in all subjects. Young age at treatment was a determinant of GH deficiency in adulthood (P = 0.014). Neither post-treatment interval, nor the use of chemotherapy were determinants of central endocrine impairment in adulthood. In long-term survivors of medulloblastoma, GH deficiency has a high prevalence. In contrast, impairment of the HPG and HPT axis is less common, while central adrenal insufficiency was not observed.

A dose-escalation study of recombinant interferon-alpha in patients with a metastatic carcinoid tumour.

The efficacy of interferon alpha-2b in doses up to 12 x 10(6) IU three times weekly was studied in 21 patients with a metastatic carcinoid tumour. Of these 21 patients, 19 were evaluable for response. Patients were treated with escalating dosages of interferon alpha-2b: 3 x 10(6) IU, 6 x 10(6) IU and 12 x 10(6) IU. The escalation was performed every 8 weeks when no objective tumour regression was observed. Patients were also evaluated for biochemical response and symptomatic improvement. One objective tumour regression was observed. Of the 15 patients with elevated 5-hydroxyindole acetic acid (5-HIAA) excretion, 5 (33%) had a more than 50% decrease in 5-HIAA excretion. Relief of symptoms occurred in 11 patients (58%). This improvement was already apparent during the initial 8 weeks of treatment. Increasing the dose to 6 or 12 x 10(6) IU interferon alpha-2b did not result in further symptomatic improvement. In contrast toxicity was considerable with the higher dosages of interferon alpha-2b. It is concluded that low dose interferon alpha-2b (3 x 10(6) IU) three times weekly is as effective as higher dosages of interferon alpha-2b at ameliorating symptoms of the carcinoid syndrome.

The content and amount of information given by medical oncologists when telling patients with advanced cancer what their treatment options are. palliative chemotherapy and watchful-waiting.

This study aimed to determine the content and the amount of information given by medical oncologists when proposing palliative chemotherapy and whether this information given is influenced by patient or physician background characteristics. In a prospective study, 95 patients with incurable cancer were interviewed before they consulted their medical oncologist. Their first consultation was audiotaped, and their eventual decision scored. A coding scheme comprised six categories of information given during the consultation. Medical oncologists mentioned or explained the disease course (53%), symptoms (35%) and prognosis (39%). Most patients were told about the absence of cure (84%). Watchful-waiting was mentioned to only half of the patients, either in one sentence (23%) or explained more extensively (27%). Multilevel analysis revealed that the patients' age, patient's marital status, and consulting in an academic hospital explained 38% of the amount of information given. Most of the physicians' attention is spent on the 'active' treatment option. Older patients, married patients and patients in academic hospitals receive more information.

Cumulative incidence and risk factors of mitoxantrone-induced cardiotoxicity in children: a systematic review.

Mitoxantrone is believed to maintain anthracycline antitumour activity but be associated with a reduced cardiotoxicity. The aim of this study was to evaluate the evidence for the cumulative incidence of and risk factors for mitoxantrone-induced cardiotoxicity (M-CT) in children treated for childhood cancers. After an extensive literature search, 17 studies were included. The cumulative incidence varied between 0 and 6.7% in the 16 studies evaluating symptomatic M-CT and between 0 and 80% in the 11 studies evaluating asymptomatic M-CT. Risk factors for developing M-CT remain unclear. All studies had serious methodological limitations. In conclusion, children treated with mitoxantrone are at risk of developing M-CT, but due to the low quality of the current evidence, the exact cumulative incidence and risk factors for M-CT remain unclear. It is too early to conclude that in children mitoxantrone is less cardiotoxic than anthracyclines. More well-designed studies are needed to reliably evaluate the incidence of M-CT and its associated risk factors.