The impact of a cervical dysplasia diagnosis on individual cancer prevention habits over time: a bicentric case-control study.

PURPOSE: Annual cervical cancer screening is recommended in Germany as a part of the statutory preventive care. Abnormal results can provoke psychological distress and anxiety, compromising women's adherence. Little is known about how a cervical dysplasia impacts adherence follow-up visits and prevention habits over time. To optimize care strategies, this study aims to identify women at risk for nonadherence to follow-up visits after a screening event. METHODS: Between November 2015 and May 2017, participants with an abnormal Pap smear at the Heidelberg and Leipzig University Hospitals received a four-part questionnaire (sociodemographic data, PHQ-D, self-designed fear and prevention habit questions) at the first consultation (T1) and subsequently after 3 (T2) and 6 (T3) months; healthy controls completed the questionnaire at T1. RESULTS: 132 women with an abnormal Pap smear [with conization: S1 (n = 68, 51.5%), without intervention: S2 (n = 64, 48.5%)] and healthy controls (K, n = 101) generally adhered to gynecological checkups, except S1 6 months after the first diagnosis (S1/T3 - 0.47, signed rank p < 0.0005). Knowledge of primary prevention information, i.e., HPV vaccination, was significantly higher among K (K 58%, S1 29%, S2 44%, Chi-squared p = 0.01) as was vaccine uptake (K 39% versus S1/S2 7% and 17%, respectively, Chi-squared p = 0.0004). Fear of upcoming Pap smears rose significantly over time (S1/T1-S1/T2-S1/T3, Wilcoxon signed-rank test p < 0.001) and was higher among those with conization at T2 (Chi-square test, p = 0.01) and partially accompanied by panic disorders at T1 (Chi-square test p = 0.035). Realization of general preventive habits rose significantly among women without an operative procedure (S2) over the study. CONCLUSION: This study advances the understanding of non-participation in follow-up visits after a dysplasia diagnosis, identifying post-conization women as a special risk group for decreased adherence.

Changes of breast and axillary surgery patterns in patients with primary breast cancer during the past decade.

PURPOSE: Breast-conserving therapy (BCT) is the standard procedure for most patients with primary breast cancer (BC). By contrast, axillary management is still under transition to find the right balance between avoiding of morbidity, maintaining oncological safety, and performing a staging procedure. The rising rate of primary systemic therapy creates further challenges for surgical management. METHODS: Patients with primary, non-metastatic BC treated between 01.01.2003 and 31.12.2016 under guideline-adherent conditions were included in this study. For this prospectively followed cohort, breast and axillary surgery patterns are presented in a time-trend analysis as annual rate data (%) for several subgroups. RESULTS: Overall, 6700 patients were included in the analysis. While BCT rates remained high (mean 2003-2016: 70.4%), the proportion of axillary lymph node dissection has declined considerably from 80.1% in 2003 to 16.0% in 2016, while the proportion for sentinel lymph node biopsy (SLND) has increased correspondingly from 10.3 to 76.4%. Among patients with cT1-2, cN0 breast cancer receiving BCT with positive SLND, the rate of axillary completion has decreased from 100% in 2008 to 24.4% in 2016. CONCLUSIONS: In the past decade, SLNB has been established as the standard procedure for axillary staging of clinically node-negative patients. Surgical morbidity has been further reduced by the rapid implementation of new evidence from the ACOSOG Z0011 trial into clinical routine. The results reflect the transition towards more individually tailored, less invasive treatment for selected patient subgroups, especially in regards to axillary lymph node management.

Reconsideration of the scheme of the international classification of functioning, disability and health: incentives from the Netherlands for a global debate.

PURPOSE: The ICF (International Classification of Functioning, Disability and Health) framework (used worldwide to describe 'functioning' and 'disability'), including the ICF scheme (visualization of functioning as result of interaction with health condition and contextual factors), needs reconsideration. The purpose of this article is to discuss alternative ICF schemes. METHOD: Reconsideration of ICF via literature review and discussions with 23 Dutch ICF experts. Twenty-six experts were invited to rank the three resulting alternative schemes. RESULTS: The literature review provided five themes: 1) societal developments; 2) health and research influences; 3) conceptualization of health; 4) models/frameworks of health and disability; and 5) ICF-criticism (e.g. position of 'health condition' at the top and role of 'contextual factors'). Experts concluded that the ICF scheme gives the impression that the medical perspective is dominant instead of the biopsychosocial perspective. Three alternative ICF schemes were ranked by 16 (62%) experts, resulting in one preferred scheme. CONCLUSIONS: There is a need for a new ICF scheme, better reflecting the ICF framework, for further (inter)national consideration. These Dutch schemes should be reviewed on a global scale, to develop a scheme that is more consistent with current and foreseen developments and changing ideas on health. Implications for Rehabilitation We propose policy makers on community, regional and (inter)national level to consider the use of the alternative schemes of the International Classification of Functioning, Disability and Health within their plans to promote functioning and health of their citizens and researchers and teachers to incorporate the alternative schemes into their research and education to emphasize the biopsychosocial paradigm. We propose to set up an international Delphi procedure involving citizens (including patients), experts in healthcare, occupational care, research, education and policy, and planning to get consensus on an alternative scheme of the International Classification of Functioning, Disability and Health. We recommend to discuss the alternatives for the present scheme of the International Classification of Functioning, Disability and Health in the present update and revision process within the World Health Organization as a part of the discussion on the future of the International Classification of Functioning, Disability and Health framework (including ontology, title and relation with the International Classification of Diseases). We recommend to revise the definition of personal factors and to draft a list of personal factors that can be used in policy making, clinical practice, research, and education and to put effort in the revision of the present list of environmental factors to make it more useful in, e.g., occupational health care.

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial.

PURPOSE: The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. PATIENTS AND METHODS: This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously treated ovarian, peritoneal, or fallopian tube cancer. Here, 50mg cyclophosphamide were combined with 400 to 800mg pazopanib daily. RESULTS: Sixteen patients were treated; mean age was 66years. At dose levels (DL) I and II, one instance of dose-limiting toxicity (DLT) was seen in one of 6 patients. At DL III, two of four patients showed a DLT, leading to a maximum tolerated dose (MTD) of 600mg pazopanib daily. Median number of administered cycles was 6 (2-13), with three patients being treated for at least 13months. Median progression-free survival (PFS) and overall survival (OS) were 8.35months and 24.95months, respectively. 155 adverse events (AE) occurred, most frequently elevation of liver enzymes, leukopenia, diarrhea and fatigue. Altogether, five serious adverse events (SAE) developed in four patients. CONCLUSION: Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. TRIAL REGISTRATION: Clin.trial.gov registry no.: NCT01238770.

Hormone Therapy and its Effect on the Prognosis in Breast Cancer Patients.

Introduction: Use of hormone therapy (HT) has declined dramatically in recent years. Some studies have reported that HT use before a diagnosis of breast cancer (BC) may be a prognostic factor in postmenopausal patients. This study aimed to examine the prognostic relevance of HT use before BC diagnosis. Methods: Four BC cohort studies in Germany were pooled, and 4492 postmenopausal patients with HT use data were identified. Patient data and tumor characteristics were compared between users and nonusers, along with overall survival (OS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Cox proportional hazards models were stratified by study center and adjusted for age at diagnosis, tumor stage, grading, nodal status, and hormone receptors. Results: Women with HT use before the diagnosis of BC were more likely to have a lower tumor stage, to be estrogen receptor-negative, and to have a lower grading. With regard to prognosis there were effects seen for OS, DMFS and LRFS, specifically in the subgroup of women with a positive hormone receptor. In these subgroups, BC patients had a better prognosis with previous HT use. Conclusions: HT use before a diagnosis of BC is associated with a more favorable prognosis in women with a positive hormone receptor status. It may be recommended that the prognostic factor HT should be documented and analyzed as a confounder for prognosis in studies of postmenopausal hormone-responsive breast cancers.

Impact of multimorbidity on functioning: evaluating the ICF Core Set approach in an empirical study of people with rheumatic diseases.

OBJECTIVE: Chronic conditions can lead to considerable deterioration in functioning. Several condition-specific Core Sets, selections of categories from the International Classification of Functioning, Disability and Health (ICF), have been developed to facilitate the rehabilitation process. Considering the increase in patients with more than one specific condition, we evaluated the impact of multimorbidity on functioning and the implications for the Core Set approach. DESIGN: Internet survey. SUBJECTS: A total of 127 people with a rheumatic disease and 707 people with rheumatic disease and multimorbidity were included. METHODS: Self-report information on chronic conditions and perceived functioning using the IMPACT-S (ICF Measure of Participitation and Activities Screener) questionnaire, measuring the ICF component activities and participation (32 items). RESULTS: The mean number of reported serious limitations/restrictions was 5.6 (standard deviation (SD) 5.7) for respondents with rheumatic disease and 6.7 (SD 6.8) for respondents with rheumatic disease and multimorbidity (p < 0.05). Seventeen items were relevant (more than 20% of the respondents reported serious limitations/restrictions) for individuals with rheumatic disease and multimorbidity, and 12 items were relevant for individuals with rheumatic disease only. CONCLUSION: Multimorbidity seriously aggravates the already existing functioning problems of people with rheumatic disease. We recommend that in the ICF Core Set approach more emphasis is given to systematic empirical analysis of the impact of multimorbidity on functioning.

Outcome analysis of patients with primary breast cancer initially treated at a certified academic breast unit.

INTRODUCTION: Evaluation of oncological outcome and prognostic factors of patients with primary breast cancer treated at a certified academic breast unit. PATIENTS AND METHODS: We prospectively collected data of 3338 patients, diagnosed with primary breast cancer between 01.01.2003 and 31.12.2010 and treated at the Breast Unit Heidelberg, Germany, in order to analyze outcome in clinical practice. We evaluated local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), observed overall survival (OS) and age-adjusted relative overall survival (ROS). In addition, the impact of known prognostic factors on these outcome variables was examined in univariate and multivariate analyses. RESULTS: Of all patients, 368 (11.0%) had carcinoma in situ (CIS) and 197 (5.9%) had bilateral cancers. For the 2970 patients with invasive cancer, of which 49 patients (1.7%) had metastastic disease at time of diagnosis, DFS, LCR, DDFS, OS and ROS at 5 years were 79.8%, 84.7%, 81.2%, 86.3%, and 89.8%, respectively. In multivariate analysis age, pT category, nodal status, hormone receptor status and grading were identified as independent prognostic factors for OS. CONCLUSION: Compared with recent population-based reports from Germany, more favourable patient characteristics and nominally higher survival was found among this large cohort of patients with primary breast cancer treated at a single certified breast unit.

An empirical exploration of the relations between the health components of the International Classification of Functioning, Disability and Health (ICF).

PURPOSE: The aim of this study was to investigate the relations between the ICF components from a subjective perspective. METHOD: Data on health condition and perceived functioning were collected among 2941 individuals with at least one chronic disease or disorder. Path analysis was used with perceived level of participation as the final denominator. Three models were tested: one with the number of chronic diseases and disorders as an indicator of health condition, one with perceived health as indicator of health condition, and one with perceived health as part of the personal factors. RESULTS: Although all models showed a good fit, the model with the best fit was that with perceived health as an indicator of health condition. CONCLUSIONS: From a patient's perspective, components of the ICF scheme appear to be associated with each other, with perceived health being the best indicator of the health condition.

Status of robotic assistance--a less traumatic and more accurate minimally invasive surgery?

PURPOSE: Robotic assistance is considered one innovation within abdominal surgery over the past decade that has the potential to compensate for the drawbacks of conventional laparoscopy, such as limited degree of freedom, 2D vision, fulcrum, and pivoting effect. Robotic systems provide corresponding solutions as 3D view, intuitive motion and enable additional degrees of freedom. This review provides an overview of the history of medical robotics, experimental studies, clinical state-of-the-art and economic impact. METHODS: The Medline database was searched for the terms "robot, telemanipulat, and laparoscop." A total of 2,573 references were found. All references were considered for information on robotic assistance in advanced laparoscopy. Further references were obtained through cross-referencing the bibliography cited in each work. RESULTS: In experimental studies, current robotic systems showed superior handling and ergonomics compared to conventional laparoscopic techniques. In gynecology especially for hysterectomy and in urology especially for prostatectomy, two procedures formerly performed via an open approach, the robot enables a laparoscopic approach. This results in reduced need for pain medication, less blood loss, and shorter hospital stay. Within abdominal surgery, clinical studies were generally unable to prove a benefit of the robot. While the benefit still remains open to discussion, robotic systems are spreading and are available worldwide in tertiary centers. CONCLUSION: Robotic assistance will remain an intensively discussed subject since clinical benefits for most procedures have not yet been proven. The most promising procedures are those in which the robot enables a laparoscopic approach where open surgery is usually required.

Do patients with invasive lobular breast cancer benefit in terms of adequate change in surgical therapy from a supplementary preoperative breast MRI?

BACKGROUND: Breast magnetic resonance imaging (MRI) has been introduced in the preoperative management of invasive lobular breast cancer (ILC). We analysed if MRI leads to adequate changes in surgical management. PATIENTS AND METHODS: We carried out a single-centre retrospective confirmatory analysis of 92 patients with ILC and a preoperative breast MRI. By applying a blinded tumour board method, we analysed if surgical procedures were altered due to breast MRI. In case of alteration, we analysed whether the change was adequate according to the postoperative pathology findings. We considered an adequate rate of change>5% to be a clinically relevant benefit. RESULTS: A change in surgical therapy due to the MRI findings occurred in 23 of 92 patients (25%). According to the postoperative pathology findings, this change was adequate for 20 of these patients (22%; 95% confidence interval [CI] 14%-31%, P<0.0001). An overtreatment occurred for three patients (3%; 95% CI 0%-6%) who underwent a mastectomy following the results of breast MRI. Patients with larger tumours did likely benefit more from preoperative breast MRI. CONCLUSIONS: Patients with ILC might benefit from a preoperative breast MRI. Possible harm from overtreatment should be minimised by diligent use of preoperative histological clarification.

Urethral catheters: can we reduce use?

BACKGROUND: Indwelling urinary catheters are the main cause of healthcare-associated urinary tract infections. It can be expected that reduction of the use of urinary catheters will lead to decreased numbers of urinary tract infection. METHODS: The efficacy of an intervention programme to improve adherence to recommendations to reduce the use of urethral catheters was studied in a before-after comparison in ten Dutch hospitals. The programme detected barriers and facilitators and each individual facility was supported with developing their own intervention strategy. Outcome was evaluated by the prevalence of catheters, alternatives such as diapers, numbers of urinary tract infections, the percentage of correct indications and the duration of catheterization. The costs of the implementation as well as the catheterization were evaluated. RESULTS: Of a population of 16,495 hospitalized patients 3335 patients of whom 2943 were evaluable for the study, had a urethral catheter. The prevalence of urethral catheters decreased insignificantly in neurology (OR 0.93; 95% CI 0.77 - 1.13) and internal medicine wards (OR 0.97; 95% CI 0.83 - 1.13), decreased significantly in surgical wards (OR 0.84; 95% CI 0.75 - 0.96), but increased significantly in intensive care (IC) and coronary care (CC) units (OR 1.48; 95% CI 1.01 - 2.17). The use of alternatives was limited and remained so after the intervention. Duration of catheterization decreased insignificantly in IC/CC units (ratio after/before 0.95; 95% CI 0.78 - 1.16) and neurology (ratio 0.97; 95% CI 0.80 - 1.18) and significantly in internal medicine (ratio 0.81; 95% CI 0.69 - 0.96) and surgery wards (ratio 0.80; 95% CI 0.71 - 0.90). The percentage of correct indications on the day of inclusion increased from 50 to 67% (p < 0.0001). The prevalence of urinary tract infections in catheterized patients did not change. The mean cost saved per 100 patients was € 537. CONCLUSION: Targeted implementation of recommendations from an existing guideline can lead to better adherence and cost savings. Especially, hospitals which use a lot of urethral catheters or where catheterization is prolonged, can expect important improvements.

[Prospective performance evaluation of first trimester screenings in Germany for risk calculation through http://www.firsttrimester.net]. / Prospektive Testleistungsbewertung des Ersttrimester Screenings in Deutschland bei Risikoberechnung über http://www.firsttrimester.net.

BACKGROUND: In 2008, 2 351 first trimester screenings were calculated by a newly developed internet database ( http:// www.firsttrimester.net ) to evaluate the risk for the presence of Down's syndrome. MATERIAL AND METHODS: All data were evaluated by the conventional first trimester screening according to Nicolaides (FTS), based on the previous JOY Software, and by the advanced first trimester screening (AFS). After receiving the feedback of the karyotype as well as the rates of the correct positives, correct negatives, false positives, false negatives, the sensitivity and specificity were calculated and compared. RESULTS: Overall 255 cases were investigated which were analysed by both methods. These included 2 cases of Down's syndrome and one case of trisomy 18. The FTS and the AFS had a sensitivity of 100%. The specificity was 88.5% for the FTS and 93.0% for the AFS. CONCLUSION: As already shown in former studies, the higher specificity of the AFS is a result of a reduction of the false positive rate (28 to 17 cases). As a consequence of the AFS with a detection rate of 100% the rate of further invasive diagnostics in pregnant women is decreased by having 39% fewer positive tested women.

Phase I study of apoptosis gene modulation with oblimersen within preoperative chemotherapy in patients with primary breast cancer.

Expression of the Bcl-2 protein confers resistance to chemotherapy-mediated apoptotic signals in patients with breast cancer. We investigated effects of Bcl-2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide oblimersen in breast tumor biopsies. Oblimersen targets Bcl-2 messenger RNA (mRNA), down-regulates Bcl-2 protein translation and enhances antitumor effects of subtherapeutic chemotherapy doses. Within a phase I trial, we administered escalating doses of oblimersen (3, 5 or 7 mg/kg/day) as continuous infusion on days 1-7 in combination with standard-dose docetaxel (Taxotere), Adriamycin and cyclophosphamide (TAC) on day 5 as preoperative chemotherapy in 28 patients with T2-4 tumors. Effects of oblimersen were evaluated in tumor biopsies and peripheral blood mononuclear cells (PBMCs) 4 days after start of oblimersen and before TAC treatment by quantitative microfluidic real-time PCR. Read-outs consisted in measurement of Bcl-2 mRNA modulations and of 18 putative predictive markers. Two of 13 patients showed a diminution of Bcl-2 transcripts after 4 days of treatment with oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a surrogate tissue because no qualified RNA could be isolated. Nevertheless, we demonstrated feasibility to process clinical samples and to obtain good quality RNA from tumor biopsies and indicated the potential of oblimersen to lower Bcl-2 mRNA in breast cancer.

[Prehospital obstetrical emergencies in a physician-staffed ground-based emergency service. A retrospective analysis over a 5-year period]. / Prähospitale geburtshilfliche Notfälle in einem bodengebundenen städtischen Notarztsystem. Retrospektive Analyse eines 5-jährigen Zeitraums.

BACKGROUND: In the German emergency medical system (EMS) obstetrical emergencies are rarely encountered, but are highly emotional situations for all concerned and form a special challenge for the emergency physician. The aim of this study was to evaluate the incidence, the course and the performance of rescue missions in a ground-based EMS system. METHODS: In a retrospective study the prehospital emergency charts concerning obstetrical emergencies over a 5-year period (10/2002-09/2007) were analysed. RESULTS: A total of 40 physician-staffed rescue missions with obstetrical emergencies were identified. On average seven rescue missions were performed per year. The majority of cases with 73% of the rescue missions was performed during the night service (16:00-07:00 h). On average the emergency patients (26th-41st week of gestation) were classified by the National Advisory Committee for Aeronautics (NACA) score as NACA III. Of the 40 obstetrical emergencies delivery occurred out of hospital in 18 cases (33rd-41st week of gestation), while the emergency physician was present in only 3 cases during childbirth. In 15 cases prehospital childbirth took place in the domestic environment of the patient, in 2 cases in an ambulance and in 1 case in the medical office of a gynecologist. In 20 cases the pregnant women were transported to hospital while labor had already begun. The emergency physicians on scene applied intravenous access, guided through labor and delivery, and administered tocolysis and in cases of prehospital delivery the emergency physicians also applied oxytocin, cut the umbilical cord and performed primary care of the newborn. CONCLUSIONS: Obstetrical emergencies are rare but recurrent in the ground-based EMS. However, prehospital management of women in labor, supervision of spontaneous prehospital delivery and the initial management of a newborn form a challenge for the emergency physician responsible. Consequently, prehospital management of obstetrical emergencies needs intensive consideration during education and training of emergency medical personnel.

Development and validation of IMPACT-S, an ICF-based questionnaire to measure activities and participation.

OBJECTIVE: IMPACT-S is the screener part of the ICF Measure of Participation and ACTivities questionnaire. IMPACT-S consists of 33 items in 9 scales, reflecting the 9 activity and participation chapters of the International Classification of Functioning, Disability and Health (ICF). The reliability and validity of IMPACT-S as an independent brief measure of activities and participation was examined. DESIGN: Repeated administration of a postal questionnaire. PATIENTS: Road accident victims were recruited through several Dutch hospitals and rehabilitation centres. A total of 276 patients participated and 197 took part in both measurements. METHODS: Examination of test-retest reliability, reproducibility and construct validity. The World Health Organization Disability Assessment Schedule II (WHODAS-II) was included as criterion measure for concurrent validity. RESULTS: Types of main injury were fractures (38%), trauma?tic brain injury (37%), spinal cord injury (13%), whiplash (9%) and other (3%). Mean time after injury was 2.2 years. Internal consistency of IMPACT-S was satisfying for all 9 domains (0.75-0.89) and excellent for the total score (0.96). Test-retest reliability was good at item level (0.44-0.72), domain level (0.72-0.92) and total score (0.94). Strong correlations (0.61-0.88) between IMPACT-S and corresponding WHODAS-II scores were found. CONCLUSION: IMPACT-S is a reliable and valid generic measure of activity limitations and participation restrictions that fits the ICF.

Oblimersen combined with docetaxel, adriamycin and cyclophosphamide as neo-adjuvant systemic treatment in primary breast cancer: final results of a multicentric phase I study.

BACKGROUND: Combining the Bcl-2 down-regulator oblimersen with cytotoxic treatment leads to synergistic antitumor effects in preclinical trials. This multicentric phase I study was carried out to evaluate maximum tolerated dose (MTD), safety and preliminary efficacy of oblimersen in combination with docetaxel, adriamycin and cyclophosphamide as neo-adjuvant systemic treatment (NST) in primary breast cancer (PBC). METHODS: Previously untreated patients with PBC T2-4a-c N0-3 M0 received one cycle of docetaxel 75 mg/m(2), adriamycin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) administered on day 5 combined with escalating doses of oblimersen as a 24-h continuous infusion on days 1-7 followed by five cycles of combination of docetaxel, adriamycin and cyclophosphamide (TAC) without oblimersen every 3 weeks. Prophylactic antibiotic therapy and granulocyte colony-stimulating factor administration were used in all six cycles. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. RESULTS: Twenty-eight patients were enrolled (median age, 50 years; ductal-invasive histology, 68%; tumorsize 2-5 cm, 61%; grade 3, 43%; hormone receptor negative, 36%; Her2 positive 18%) and received oblimersen in a dose of 3 mg/kg/day (cohort I, nine patients), 5 mg/kg/day (cohort II, nine patients) and 7 mg/kg/day (cohort III, 10 patients) respectively. No dose-limiting toxicity occurred. Following oblimersen combined with TAC, the most severe toxicity was neutropenia [National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 1-2/3/4] which developed in 0/0/56% of patients (cohort I), 11/0/56% of patients (cohort II) and 20/20/50% of patients (cohort III). No febrile neutropenia occurred. Most common adverse events (all NCI-CTC grade < or = 2) were fatigue, nausea, alopecia, headache and flue-like symptoms observed in 78% (cohort I), 89% (cohort II) and 90% (cohort III) of patients. With increasing dose of oblimersen, a higher incidence of grade IV leukopenia and neutropenia was noted. At the MTD of 7 mg/kg/day of oblimersen, serious adverse events occurred in 40% of the patients. CONCLUSION: Oblimersen up to a dose of 7 mg/kg/day administered as a 24-h infusion on days 1-7 can be safely administered in combination with standard TAC on day 5 as NST in patients with PBC. The safety and preliminary efficacy warrants further evaluation of oblimersen in combination with every cycle of the TAC regimen in a randomized trial.

c-myc amplifications in primary breast carcinomas and their local recurrences.

OBJECTIVE: To evaluate the role of c-myc oncogene amplifications in the progression of invasive breast carcinomas. METHODS: c-myc gene copy number was evaluated in a series of 49 primary breast carcinomas and the corresponding local recurrences using fluorescence in situ hybridisation. RESULTS: 11 of the primary carcinomas (22%) harboured c-myc amplifications; these tumours typically were hormone receptor negative and occurred in younger patients (43 v 53 years). At the time of relapse, six additional tumours had acquired a c-myc amplification. The mean recurrence-free survival was 24 months; c-myc amplified tumours relapsed significantly earlier than carcinomas without amplification (18 v 27 months). Univariate analysis showed a worse overall survival in these patients. CONCLUSIONS: While c-myc amplifications can be observed in early stage breast cancer, especially in younger patients, they often occur later in tumour development and appear to be associated with disease progression.

Measuring participation according to the International Classification of Functioning, Disability and Health (ICF).

PURPOSE: To report which existing survey instruments assess participation according to the International Classification of Functioning, Disability and Health (ICF). METHOD: A literature search for relevant survey instruments was conducted. Subsequently, survey instruments were evaluated of which the complete questionnaire, published in the English language, was obtained. Items on participation were evaluated according to the ICF, defined as involvement in life situations, including being autonomous to some extent or being able to control your own life. RESULTS AND CONCLUSIONS: Eleven survey instruments were identified, of which nine were evaluated on participation. All of the nine instruments measure participation to some extent. The two instruments closest to solely involve items on participation level are the Perceived Handicap Questionnaire (PHQ) and the London Handicap Scale (LHS). The PHQ is measuring the perception of participation. In the LHS, the items are formulated in terms of participation, while the response categories include all components of the ICF, from problems in body function to participation. Much more discussion is needed to be able to get an unambiguous picture to distinguish between activity and participation.