Self-reported cognitive functioning in postmenopausal breast cancer patients before and during endocrine treatment: findings from the neuropsychological TEAM side-study.

OBJECTIVE: This study aimed to evaluate self-reported cognitive functioning of postmenopausal breast cancer patients before and during endocrine treatment compared with healthy female controls, and to investigate associations between self-reported cognitive functioning, cognitive test performance and anxiety/depression, fatigue, and menopausal complaints. METHODS: Self-reported cognitive functioning, anxiety/depression, fatigue, menopausal complaints, and cognitive tests performance were assessed before (T1) and after 1 year (T2) of adjuvant endocrine treatment in postmenopausal chemotherapy-naïve breast cancer patients. Self-reported cognitive functioning was assessed by the cognitive failures questionnaire and interview questions concerning cognitive complaints. Patients participated in the TEAM-trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive breast cancer. Identical information was obtained from healthy postmenopausal volunteers. RESULTS: Two measures for self-reported cognitive functioning provided the distinctive results. At T1 and T2, healthy controls reported a higher frequency of cognitive failures than patients; change over time did not differ between groups. The prevalence of cognitive complaints did not differ between the groups at T1, but change over time regarding attention/concentration complaints differed between groups, due to an increased prevalence in tamoxifen users. Self-reported cognitive functioning showed moderate associations with anxiety/depression, fatigue, and menopausal complaints. Cognitive test performance was not associated with self-reported cognitive functioning, but weakly with anxiety/depression and fatigue. CONCLUSION: Adjuvant therapy with tamoxifen and exemestane did not influence the self-reported frequency of cognitive failures. Increased attention/concentration complaints were observed in tamoxifen users, but not in exemestane users. This latter finding should be confirmed with better validated instruments.

Cognitive functioning of postmenopausal breast cancer patients before adjuvant systemic therapy, and its association with medical and psychological factors.

PURPOSE: This study aimed to identify medical and psychological predictors for cognitive performance of breast cancer (BC) patients before the start of adjuvant systemic treatment and to compare cognitive performance between BC patients and healthy controls adjusting for medical and psychological variables. MATERIAL: 205 postmenopausal BC patients underwent pre-treatment neuropsychological tests and provided medical and psychological data. 124 healthy controls underwent the same assessment. RESULTS: 'Treatment for diabetes mellitus' and/or 'hypertension', 'less hours spent on cognitively stimulating activities', 'fewer days since surgery' and 'more reproductive years' were associated with worse cognitive performance in the BC patients, independent of age and IQ. Cognitive differences between BC patients and healthy controls could partly be explained by the evaluated variables. CONCLUSION: The results stress the need for adjustment for pre-treatment cognitive differences between study groups, and also indicate that further research into pre-treatment cognitive dysfunction is warranted.

[The effect of hormone therapy on cognitive function in patients with breast cancer]. / De invloed van hormonale therapie op het cognitieffunctioneren van patiënten met het mammacarcinoom.

Preclinical and clinical studies suggest that oestrogens have an important role in brain functioning and cognitive ability. Given that hormone therapies for breast cancer reduce oestrogen levels or block oestrogen receptors, it is conceivable that these agents also influence cognitive function. Several small studies have been conducted to address this issue, but many of them are methodologically insufficient. The negative effects of oophorectomy and luteinising hormone-releasing hormone (LHRH) analogues on verbal memory and working memory have been demonstrated the most consistently, albeit only in small studies. Anastrozole and tamoxifen also appear to exert some negative effect on cognition, but well-designed studies are lacking. No data are available on the influence of the aromatase inhibitors exemestane and letrozole on cognitive function. Raloxifene, a drug that has no obvious advantages over tamoxifen and will likely not be developed further for breast cancer treatment, has no negative influence on cognitive functioning. It remains unclear whether the observed effects are transient or permanent, and to what extent age, menopausal status and duration of therapy influence the severity of cognitive effects.

[Severe disciplinary measures in the Millecam case: important precedent for revising the rules of conduct by scientific associations and the KNMG]. / Strenge tuchtrechtelijke maatregelen in de zaak-Millecam: belangrijke jurisprudentie voor het aanscherpen van de gedragsregels door de wetenschappelijke verenigingen en de KNMG.

The popular 45-year-old Dutch actress Sylvia Millecam died in August 2001 from untreated advanced breast cancer. She refused standard medical treatment and sought solace in many alternative healers, including three medical physicians. The Dutch Healthcare Inspection accused the three physicians of malpractice and asked the Medical Disciplinary Tribunal to pass judgment. In April 2006 one physician was struck from the physician register and the other two were suspended for 1 year and 6 months, respectively. These unusually severe measures were based mainly on the fact that they had neglected professional standards as defined by specialty boards, they had presented themselves as professional physicians and they had not tried hard enough to convince Millecam of the need for standard treatment. The Tribunal did not accept the strong desire of the patient to undergo only alternative treatment as a defence. Notably, the judgment of the Tribunal seems to be more severe than the present bylaws of medical-scientific bodies and the Dutch Medical Association (KNMG), which are apparently too lenient regarding the use of alternative treatments by their members.

[Premature and over-simplified publication of mortality differences between hospitals in the media]. / Voortijdige en ongenuanceerde publicatie over sterfteverschillen tussen ziekenhuizen in de media.

Prismant, the major institute for health-care research in the Netherlands, presented differences in mortality data from hospitals in the Netherlands. The data from the Prismant study were front-page news. However, the Prismant study was only published on their own website, and contained only raw data. The author did not consider relevant issues, e.g., the differences in case mix in the various hospitals and demographic factors. The public debate on quality of health care would benefit greatly if research institutes published only data that were peer reviewed and if journalists checked with experts before they published an article on such a specialist medical issue.

[The hidden treasure-chests of the regional cancer registries]. / De verborgen schatkamers van de integrale kankercentra.

For physicians and patients, knowledge of the treatment results of individual hospitals is of great importance as it is known that hospitals with more experience perform better. Oncological characteristics of cancer patients in the Netherlands are collected by the nine Comprehensive Cancer Centres. The data are available from each affiliated hospital but remain anonymous. A plea is made for more transparency by requiring that the Comprehensive Cancer Centers place their data in the public domain.

[The measures proposed by the Dutch Healthcare Inspectorate after the death of Sylvia Millecam and her treatment by practitioners of alternative medicine]. / De voorgestelde maatregelen van de Inspectie voor de Gezondheidszorg naar aanleiding van de dood van Sylvia Millecam en haar behandeling door alternatieve genezers.

As a result of the illness and treatment of the Dutch comedian Sylvia Millecam, who died of the consequences of an untreated mammary carcinoma following a quest for help from a series of practitioners of alternative medicine, the Dutch Healthcare Inspectorate has proposed measures designed to prevent a repetition of such a shortcoming in the delivered care. The measures include the compulsory registration of practitioners of alternative medicine, the restriction of diagnostic procedures to regular physicians, the obligation to co-operate with the best possible treatment for the patient in question, mutual exchange of information between practitioners of regular and alternative medicine, and a compulsory protocol regarding the therapeutic agreement with the patient if the regular route is not followed. How feasible these measures are remains a question. A positive aspect of the report is the attention given to the shortcomings in the care provided by the alternative circuit and the deterrent effect of the present case.

[The opinion on care of patients with cancer undergoing palliative treatment in day care]. / De opinie over de zorgverlening van patiënten met kanker die op de dagbehandeling een palliatieve behandeling ondergaan.

OBJECTIVE: To study the care utilisation and unmet care needs of patients receiving palliative treatment at the day care clinic of the Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital. DESIGN: Descriptive. METHODS: During the periods 1 April-31 July 2000 and 1 April-31 May 2001 adult cancer patients were interviewed regarding their complaints and symptoms as a result of the disease and the treatment and regarding the problems that they had with the provision of care. RESULTS: There were 155 patients who agreed to participate: 56 men and 99 women, with an average age of 57.5 years. On average, they had 3.2 'severe' complaints. According to the patients, 65% of these 'severe' complaints were known by the specialists, 38% by the general practitioners, 24% by the day care nurses and 83% by the next of kin. Again according to the patients, 17% of the reported severe complaints received insufficient attention. About 25% of patients felt that they had received insufficient information about their disease, treatment, side effects and/or complications. CONCLUSION: The day care centre did not seem to be optimally equipped to meet the needs of patients receiving chemotherapy on an outpatient basis. According to the patients, the specialists were relatively the best informed of all the care providers about their complaints and problems.

[Less use of alternative treatments by cancer patients in 2002 than in 1999]. / Minder gebruik van alternatieve behandelingen door kankerpatiënten in 2002 dan in 1999.

OBJECTIVE: To determine the use of alternative diets and other alternative treatments in 2002 compared to 1999. DESIGN: Descriptive, questionnaire. METHOD: During the period 13-26 May 2002 a survey was held among all patients visiting the outpatient clinic of the Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital, Amsterdam, the Netherlands. Patients were asked about their current and past use of alternative therapies, their reasons for using these therapies, the way they were informed about these therapies and the expenses involved. The data were compared with the results of a similar study during the period 15-19 March 1999. RESULTS: Of the 729 patients who fulfilled the inclusion criteria, 66 (9%) declined to participate in the study. Of the remaining 663 patients (average age 58.5 years; 28% male), 131 (20%) used an alternative therapy. Of these, 43 patients (7%) used an alternative diet, mainly the Houtsmuller diet, and 88 patients (13%) used a mixture of alternative therapies such as homeopathy, vitamins and herbs. In 1999, 131 patients (30%) used an alternative form of treatment, 51 (13%) of whom used a diet. Of the 43 users of diets in 2002, 11 (26%) believed that the diet would slow down the disease process; in 1999 this was 53% (27/51). Of the 131 users of alternative therapies in 2002, 55% had been made aware of the possibilities of alternative treatments via family and friends. Internet and TV played a minor role as a source of information. 33 (79%) of the diet users informed their physician or nurse about the use. The diet users spent an average of 170 euro per month on their diets. CONCLUSION: Both the percentage of cancer patients who used an alternative diet and the percentage of diet users who believed that a diet could affect the course of the disease were reduced by half compared to three years earlier.

Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients.

BACKGROUND: Neuropsychological examinations have shown an elevated risk for cognitive impairment 2 years after therapy in breast cancer patients randomized to receive adjuvant high-dose cyclophosphamide, thiotepa, carboplatin (CTC) chemotherapy compared with a non-treated control group of stage I breast cancer patients. Patients randomized to receive standard-dose fluorouracil, epirubicin, cyclophosphamide (FEC) chemotherapy showed no elevated risk compared with controls. However, breast cancer patients treated with conventional cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy showed a higher risk of cognitive impairment. The present study was designed to obtain a greater insight into these long-term neuropsychological sequelae following chemotherapy and their course in time. PATIENTS AND METHODS: At 4 years post-therapy, 22 of the original 34 CTC patients, 23 of 36 FEC patients, 31 of 39 CMF patients and 27 of 34 control patients were re-examined with neuropsychological tests. RESULTS: Improvement in performance was observed in all chemotherapy groups, whereas in the control group there was a slight deterioration in test results. A differential attrition was observed among the groups, with a relatively high percentage of initially cognitively impaired patients from the CTC group dropping out due to factors related to disease progression. CONCLUSIONS: The results suggest that cognitive dysfunction following adjuvant chemotherapy in breast cancer patients may be transient. Additional studies are needed to investigate the differential attrition of patients with cognitive impairment.

Translation and validation of the Amsterdam preoperative anxiety and information scale (APAIS) for use in Japan.

Preoperative anxiety is a very common phenomenon that adversely affects a patient's physical and psychological outcome. To evaluate subjective complaints such as anxiety, use of a validated psychological instrument is essential. In this study, we translated, culturally adapted and validated the Amsterdam preoperative anxiety and information scale (APAIS) for use in Japan. One hundred and twenty-six preoperative patients participated in this cross-sectional study. The psychometric properties of the APAIS evaluated by factor analysis, correlation with the state-trait anxiety inventory (STAI) and Cronbach's alpha were very similar to those of the original Dutch and English versions. Female gender and a high information requirement were associated with high preoperative anxiety. In conclusion, the Japanese version of the APAIS is a valid and reliable instrument for screening Japanese patients for preoperative anxiety and information requirements. Female gender and high information requirement may be associated with high preoperative anxiety.

[Information about cancer treatment and the media]. / Voorlichting over kankerbehandeling en de media.

A 'hopeful' development in cancer treatment (angiostatin) was reported in the Dutch press, which led to considerable disquiet amongst patients. There were no scientific articles that warranted this press publication. It has previously been stated that it is unethical for medical researchers to inform the press about treatments which have not been scrutinized by the medical community. The press on the other hand, should maintain a more responsible attitude toward medical claims and double-check medical information, even when it comes from renowned medical researchers. The main distinction between mainstream medicine and medical quackery is that the former is based on the results of controlled published research. When physicians propagate results in the popular press that have not been critically evaluated by the medical community, the distinction between quackery and mainstream medicine is undermined.

Assessment of pain cognitions in cancer patients with chronic pain.

Although reports suggest that beliefs about pain play an important role in the adjustment and pain experience of non-cancer patients, the impact of cognitions on the pain experience is unknown in cancer patients. This study examined the factor structure, reliability, and validity of the Pain Cognition List-Experimental version, a measure developed to assess patients' self-statements about pain and the extent to which patients are effective in dealing with the pain. The Pain Cognition List-Experimental version was administered to 313 cancer patients during hospitalization. Confirmatory factor analysis was conducted to evaluate the adequacy of fit for the original five factors. Because of a failure to replicate the factors, exploratory factor analysis was conducted, finding the factors Pain Impact, Social Comparison, Acquiescence, and Outcome Efficacy. The internal consistency for the factor Pain Impact was high (r = 0.89), while the other three factors showed low reliability. The factor Catastrophizing, usually an important factor in non-cancer patients, did not emerge. No differences were found across sex. The factors Pain Impact and Acquiescence provided evidence for concurrent validity. Patients with district nursing showed higher scores on the factors Pain Impact and Acquiescence, and higher scores on Pain Impact and Acquiescence were associated with higher pain intensity scores. This study was an attempt to evaluate pain cognitions and beliefs in cancer patients. It is concluded that the Pain Cognition List for non-cancer patients cannot be easily used in cancer pain patients and that evaluation of pain cognitions in cancer patients is useful. Health care providers evaluating pain in cancer patients with chronic pain need to be aware of the impact pain cognitions have on patients' pain experience. Although more research is needed, measuring pain cognitions should be considered.

Chemotherapy-induced chromosomal damage in peripheral blood lymphocytes of cancer patients supplemented with antioxidants or placebo.

A total of 27 patients with various types of cancer were treated with cisplatin-based combination chemotherapy. Out of these, 13 patients were randomized to receive supplementation treatment with a beverage containing the antioxidants vitamins C and E, plus selenium, during chemotherapy. The antioxidant mixture was administered to investigate whether it could reduce the potential genotoxic and nephrotoxic effect of the applied chemotherapy. A placebo group of 14 cancer patients received a beverage without selenium or antioxidants. Micronuclei (MN) in cytochalasin B-blocked binucleate (BN) peripheral blood lymphocytes (PBLs) and hypoxanthine phosphoribosyl transferase (HPRT) mutants in PBLs were studied before, during and after chemotherapy as a measure for chemotherapy-induced genotoxic effects. Before chemotherapy, patients mean frequencies of MN and HPRT mutants did not differ from those in a group of 10 healthy subjects. The mean frequency of MN in patients increased significantly after one cycle of chemotherapy (P=0.002). This frequency was still elevated at 2 months after the completion of chemotherapy (not significantly). There was no significant difference in micronuclei frequency (MNF) between the antioxidant and placebo group of patients. Chemotherapy-induced frequencies of MN after three cycles of chemotherapy correlated significantly with the cumulative dose of cisplatin (r=0.58, P=0.012) and the cisplatin-mediated loss of renal function (r=0.53, P=0.03). No consistent change in HPRT mutant frequency following chemotherapy was observed in the placebo and antioxidant group of patients. In conclusion, cisplatin-combination chemotherapy resulted in a cisplatin dose-related increase of the frequency of chromosomal damage. Supplementation with antioxidants did not prevent or reduce this effect.

Improving the quality of pain treatment by a tailored pain education programme for cancer patients in chronic pain.

Educational interventions, aiming to increase patients' knowledge and attitude regarding pain, can affect pain treatment. The purpose of this study was to evaluate the effects of a Pain Education Programme (PEP), on adequacy of pain treatment, and to describe characteristics predicting change in adequacy. The PEP consists of a multi-method approach in which patients are educated about the basic principles regarding pain, instructed how to report pain in a pain diary, how to communicate about pain, and how to contact healthcare providers. The effects of the PEP were evaluated taking into consideration the lack of well-established outcome measures to evaluate adequacy of pain treatment, the lack of long-term follow-up, and the influence of missing data.A prospective, randomized study was utilized in which 313 chronic cancer patients were followed-up until 8 weeks postdischarge. Adequacy of pain treatment was evaluated by means of the Amsterdam Pain Management Index (APMI), consisting of an integrated score of patients' Present Pain Intensity, Average Pain Intensity, and Worst Pain Intensity, corrected for patients' Tolerable Present Pain, with the analgesics used by the patient. At pretest, 60% of the patients in the hospital were treated inadequately for their pain. Postdischarge, the control group patients were significantly more inadequately treated at 2 weeks after discharge (56% vs 41%), at 4 weeks after discharge (62% vs 42%) and at 8 weeks after discharge (57% vs 51%) than the intervention group patients. While the level of inadequacy in the control groups remained relatively stable at all assessment points, a slight increase in the percentage of patients being treated inadequately was found in the intervention group patients over time. A beneficial effect of the PEP was found for patients both with and without district nursing. Variables predicting an improvement in adequacy of pain treatment consisted of the PEP, the APMI score at baseline, patients' level of physical functioning, patients' level of social functioning, the extent of adherence to pain medication, patients' pain knowledge, and the amount of analgesics used. These findings suggest that quality of pain treatment in cancer patients with chronic pain can be enhanced by educating patients about pain and improving active participation in their own pain treatment. The benefit from the PEP, however, decreases slightly over time, pointing at a need for ongoing education.

The implementation of a Pain Monitoring Programme for nurses in daily clinical practice: results of a follow-up study in five hospitals.

AIMS OF THE STUDY: To study the effects of the implementation of a Pain Monitoring Programme (PMP) for nurses in daily clinical practice. In addition, nurses' and physicians' pain knowledge and attitudes were studied, as well as change in nurses' pain knowledge after implementation of the programme. RATIONALE: The rationale for the study was that many hospitalized patients suffer from pain and treatment of pain is often inadequate. BACKGROUND: Reasons for inadequate treatment of pain are the failure of nurses to assess pain on a daily basis and insufficient knowledge about pain and pain management in both nurses and physicians. The PMP tried to overcome these barriers by implementing daily pain assessment and educating nurses about pain and pain management. RESEARCH METHODS: This follow-up study was conducted in five hospitals. In total, 277 nurses and 115 physicians participated. The implementation and long-term effects of the programme were measured with a pretest-post-test design without a control group. RESULTS: Results showed that nurses carried out daily pain assessment in at least 75% of patients during the first 5 months of the intervention period, but in the remaining 2 months professional compliance gradually decreased. Both nurses and physicians are positive about daily pain assessment and want to continue with it. The level of nurses' and physicians' knowledge about pain and pain management is moderate. The programme increased nurses' knowledge and satisfaction regarding the quality of pain treatment. DISCUSSION: Because professional compliance decreased after 5 months, incentives are needed to motivate nurses to continue with daily pain assessment. Continuous Quality Improvement may be a useful method to guide the implementation process. CONCLUSIONS: Based on these results it can be concluded that it is possible to implement the PMP in daily clinical practice. Moreover, the beneficial effects of our programme on nurses' knowledge and attitudes have been demonstrated. Therefore, participating hospitals were advised to continue and extend the programme and other hospitals are encouraged to implement it.

Neurophysiological evaluation of late effects of adjuvant high-dose chemotherapy on cognitive function.

OBJECTIVES: To evaluate late neurotoxicity of adjuvant high-dose (HD) chemotherapy versus standard-dose (SD) chemotherapy by event-related potentials (ERP) and quantitative electroencephalography (qEEG). PATIENTS AND METHODS: From a randomized study in high-risk breast cancer patients on the efficacy of high-dose versus standard-dose adjuvant chemotherapy, late effects on cognitive functioning were analyzed by neuropsychological tests. Cognitive impairment was found in 32% of the HD group, 17% of the SD group and in 9% of a control group of stage I breast cancer patients not treated with chemotherapy. In 17 consecutive patients in the HD group and 16 consecutive patients in the SD group neurophysiological tests were performed, consisting of P300 and qEEG. Results of patients treated with chemotherapy were compared with results of 14 control patients not treated with chemotherapy. All patients were tested two years after treatment. RESULTS: Asymmetry of the alpha rhythm of > or =0.5 Hz was found in 7 HD patients, 2 SD patients and in none of the control patients (p = 0.01). No differences were found between the groups with regard to frequency of alpha rhythm, alpha blocking and latency of P300. No correlation was found between neurophysiological parameters and neuropsychological performance, except for an overall relation between the P300 latencies and the total number of deviant test scores. CONCLUSION: Although the neurophysiological differences are subtle and the relation with the cognitive functioning in individual patients as measured by the neuropsychological examination is equivocal, the results suggest that there is neurophysiological support for cognitive dysfunction as a late complication of high-dose systemic chemotherapy in breast cancer.

[Definition of 'quack' in the public debate on alternative medicine]. / De definitie van 'kwakzalver' in het publieke debat over alternatieve behandelwijzen.

In May 1999 the Amsterdam Court of Justice decided that a retired internist and propagandist of his own alternative cancer therapy, could rightfully be called a quack by his critics. Recently this judgment was reversed on appeal. The first court used the medical definition of quackery: a treatment of which the supposed benefits are unsubstantiated. The court of appeal, however, took into consideration that to the general public calling someone a quack is an indication that this person is a swindler and practises medicine unlawfully. This definition is supported by the most authoritative Dutch dictionary. Apparently a different semantic interpretation of the term quack has led to these strongly diverging verdicts. The terms quack and quackery are indispensable in the public debate on alternative medicine.