Treatment of acute myocardial infarction in the sub-arctic region of Norway. Do we offer an equal quality of care?

Patients, relatives, healthcare workers and administrators are concerned about the quality of care offered. We aimed to explore the treatment of acute myocatrdial infarction (AMI) in Northern Norway, compare it with the national figures, and document whether there is an equal quality of care or not. The retrospective study included data on patients' treatment for AMI. The following sources were employed. The Norwegian Patient Registry, National Quality of Care Database, Norwegian Myocardial Infarction Registry and data from the National Air Ambulance Services of Norway. The period 2012-2014/15 was studied and the variables were: incidence of AMI, gender and age adjusted rates of AMI and revascularization (PCI, CABG) based on patient's place of living (according to hospital catchment area) and 30-day survival rate. The annual incidence of AMI was 9% higher in the northern region. Significant incidence variations (2.7-5.9 AMI/1000 inhabitants) between the hospitals' catchment areas were revealed. The 30-day survival rate varied between 85.1-92.1% between hospitals. The variation in revascularization/AMI rate was 0.72-1.54. Air amublance services' availability varied through the day. In conclusion, significant variations in the AMI rate and an unequal service within the region was revealed.

Lessons learned from the intrinsic subtypes of breast cancer in the quest for precision therapy.

BACKGROUND: Wide variability in breast cancer, between patients and within each individual neoplasm, adds confounding complexity to the treatment of the disease. In clinical practice, hormone receptor status has been used to classify breast tumours and to guide treatment. Modern classification systems should take the wide tumour heterogeneity into account to improve patient outcome. METHODS: This article reviews the identification of the intrinsic molecular subtypes of breast cancer, their prognostic and therapeutic implications, and the impact of tumour heterogeneity on cancer progression and treatment. The possibility of functionally addressing tumour-specific characteristics in in vivo models to inform decisions for precision therapies is also discussed. RESULTS: Despite the robust breast tumour classification system provided by gene expression profiling, heterogeneity is also evident within these molecular portraits. A complicating factor in breast cancer classification is the process of selective clonality within developing neoplasms. Phenotypically and functionally distinct clones representing the intratumour heterogeneity might confuse molecular classification. Molecular portraits of the heterogeneous primary tumour might not necessarily reflect the subclone of cancer cells that causes the disease to relapse. Studies of reciprocal relationships between cancer cell subpopulations within developing tumours are therefore needed, and are possible only in genetically engineered mouse models or patient-derived xenograft models, in which the treatment-induced selection pressure on individual cell clones can be mimicked. CONCLUSION: In the future, more refined classifications, based on integration of information at several molecular levels, are required to improve treatment guidelines. Large-scale translational research efforts paved the way for identification of the intrinsic subtypes, and are still fundamental for ensuring future progress in cancer care.

Sunitinib, sorafenib, temsirolimus or bevacizumab in the treatment of metastatic renal cell carcinoma: a review of health economic evaluations.

Renal cell carcinoma (RCC) is the most prevalent kidney cancer and the 5-year overall survival figure in metastatic disease (mRCC) is about 10%. New targeted drugs (sunitinib, sorafenib, bevacizumab, temsirolimus) have shown activity in the treatment of mRCC, but they are all associated with a significant burden of cost. To support decision makers in their allocation of resources, costeffectiveness models are constructed to compare the costs and outcomes of anticancer therapy. This survey focuses on studies since 2003 exploring health economics in the treatment of metastatic and/or advanced RCC employing these new drugs. This paper summarizes the results, focuses on the level of evidence of these studies, compares the calculated cost-effectiveness ratios and makes suggestions for future studies. This review reveals costs per life years gained (LYG) or quality-adjusted life years (QALY) in the range of euro 22,648 to euro203,692, depending on whether the setting is first-line or second-line and drug used. When compared to the other agents, sunitinib has the best cost-effectiveness figure. Second-line therapy does not offer valid incremental cost-effectiveness ratios.

Prediction of very short survival in patients with brain metastases from breast cancer.

AIMS: Current prognostic models are not accurate enough to identify brain metastases patients with very short survival, i.e. <2 months, who are unlikely to derive major benefit from whole brain radiotherapy. Our aim was to develop a more reliable model. MATERIALS AND METHODS: This was a retrospective analysis of a German database, which was used to develop a score, and an additional database from Norway, which was used for validation purposes. RESULTS: The groups included 67 and 32 patients, respectively. An analysis of prognostic factors resulted in a risk score based on performance status, extra-cranial metastases, the interval from breast cancer to brain metastases and a need for corticosteroid treatment, which classified 63 of 67 test patients correctly. However, the validation failed and unfortunately the risk score that performed best in the Norwegian patients (31 of 32 correctly predicted) was not applicable to the German patients. CONCLUSIONS: The prediction of short survival is associated with several caveats and seems to result in an unacceptable risk of withholding radiotherapy in patients who actually survive for longer than 2 months.

Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness analysis.

Trastuzumab has shown activity in early breast cancer patients that overexpress HER2. Significant resources have to be allocated to finance this therapy, underlining the need for cost-effectiveness analysis. A model was set up, societal costs were calculated and the discount rate was 3%. Life expectancy data were based on the literature and prolonged according to qualified guess (10% and 20% absolute improvement in overall survival (OS)). The comparator was the FEC(100) regimen. The median additional health care cost per patient treated was 33,597 euros. The yielding cost per life year gained (LYG) was 15,341 euros with a 20% improved OS and 35,947 euros with 10% improved OS. The corresponding net health care cost per quality adjusted life year (QALY) was 19,176 euros and 44,934 euros. Including all resource use the figures were 8148 euros and 30,290 euros per LYG. Sensitivity analyses documented survival gain, price of trastuzumab, production gain and discount rate to be the major factors influencing cost-effectiveness ratio. Trastuzumab is indicated cost effective in Norway.

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis.

Cetuximab (Erbitux) has shown activity in patients with metastatic colorectal cancer (mCRC). To evaluate the cost-effectiveness of this drug combined with irinotecan in mCRC, a model-based cost-effectiveness analysis (CEA) was performed. Data on cetuximab obtained from Medline in December 2004 and from the 2004 ASCO-meeting were analyzed for life years gained (LYG) with regard to the use of this monoclonal antibody (MAb). Norwegian prices as of January 2005 were employed. The LYG ranged between 1.7 and 2.0 years. The median cost per patient treated was calculated to 34,256 Euro to 45,764 Euro yielding a cost per LYG in the range between 205,536 Euro and 323,040 Euro. Sensitivity analysis documented price of cetuximab and survival gain to be the major factors influencing the cost-effectiveness ratio. In conclusion, the analysis indicates cetuximab to be a promising, but very expensive antibody.

A monoclonal antibody against HER-2 (trastuzumab) for metastatic breast cancer: a model-based cost-effectiveness analysis.

BACKGROUND: The aim of this study was to evaluate the cost-effectiveness of trastuzumab in patients with metastatic breast cancer (MBC) in a model-based cost-effectiveness analysis (CEA). Trastuzumab has shown considerable activity in patients with MBC that overexpress HER2. However, significant resources have been allocated to finance this new therapy. Due to ever increasing pressures on health care budgets, economic evaluations are requested in order to compare health effects with costs. METHODS: All available data on trastuzumab in MBC presented at the San Antonio breast cancer conference in late 2003 and all data on Medline in December 2003 were analysed for life years (LY) gained and quality of life (QoL) with regard to the use of this new monoclonal antibody. Randomised studies comparing standard chemotherapy, with or without trastuzumab, were focused. The costs were calculated according to Norwegian prices as of January 2003. RESULTS: The LY gained ranged between 0.3 and 0.7 years. The median cost per patient treated was 44 196 yielding costs per life year saved in the range 63 137-162 417 depending on survival gain and discount rate employed. A sensitivity analysis documented the price of trastuzumab and the survival benefit the two major factors influencing the cost-effectiveness ratio. CONCLUSION: The economic evaluation indicates that trastuzumab is not cost effective in metastatic breast cancer. Reduced drug costs and/or improved survival may alter the conclusion.

A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer.

The purpose of this phase II trial was to compare the efficacy, safety and pharmacokinetics of four irinotecan schedules for the treatment of metastatic colorectal cancer. In total, 174 5-fluorouracil pretreated patients were randomised to: arm A (n=41), 350 mg m(-2) irinotecan as a 90-min i.v. infusion q3 weeks; arm B (n=38), 125 mg m(-2) irinotecan as a 90-min i.v. infusion weekly x 4 weeks q6 weeks; arm C (n=46), 250 mg m(-2) irinotecan as a 90-min i.v. infusion q2 weeks; or arm D (n=49), 10 mg m(-2) day(-1) irinotecan as a 14-day continuous infusion q3 weeks. No significant differences in efficacy across the four arms were observed, although a shorter time to treatment failure was noted for arm D (1.7 months; P=0.02). Overall response rates were in the range 5-11%. Secondary end points included median survival (6.4-9.4 months), and time to progression (2.7-3.8 months) and treatment failure (1.7-3.2 months). Similarly, there were no significant differences in the incidence of grade 3-4 toxicities, although the toxicity profile between arms A, B, and C and D did differ. Generally, significantly less haematologic toxicity, alopecia and cholinergic syndrome were observed in arm D; however, there was a trend for increased gastrointestinal toxicity. Irinotecan is an effective and safe second-line treatment for colorectal cancer. The schedules examined yielded equivalent results, indicating that there is no advantage of the prolonged vs short infusion schedules.

A mobile telemedicine unit for emergency and screening purposes: experience from north-west Russia.

A mobile telemedicine unit (MTU) was constructed for emergency and screening purposes in north-west Russia. The MTU included facilities for endoscopy, electrocardiography and digital photography. Data transmission was by ordinary telephone line. Between July and December 1999, the MTU was used in 48 incidents, involving 44 patients. The MTU was used to conduct 22 teleradiology examinations and 20 electrocardiograms were transmitted; in 10 cases still images of patients were transmitted and three consultations included tele-electroencephalography. Despite poor-quality analogue telephone lines, the MTU may prove useful in north-west Russia. Following the pilot study, the local Russian health administration stated that the MTU should always be included on emergency trips to the districts.

Injuries and diseases among commercial fishermen in the Northeast Atlantic and Barents Sea. Data from the Royal Norwegian Coast Guard.

OBJECTIVES: The working conditions in the Northeast Atlantic may be hazardous, and accidents are frequent. The objective of this study was to clarify the situation as viewed by the Royal Norwegian Coast Guard (RNCG). METHODS: Consecutive reports on medical assistance given by the three major RNCG vessels from October 1995 and March 2001 were analysed. RESULTS: There were 117 reports. Men constituted 96%, and 54% were Norwegians. The median age was 38 years. Seriousness was classified as low (46 cases), moderate (43 cases), serious (22 cases) and life threatening [five cases (two died)]. Infection caused 27 visits. Fifty-five cases were due to trauma, and hand injuries constituted 19 cases. Fishermen over 40 years of age were more severely injured ( P<0.04). In 52 cases, the RNCG personnel requested further medical advice. Sixty-one patients were hospitalised and 48 transported by helicopter. CONCLUSIONS: The RNCG offers an important medical service, but there is frequently a need for consulting medical advisors. Telemedicine should be investigated in this setting.

Ralitrexed (Tomudex) or Nordic-FLv regimen in metastatic colorectal cancer: a randomized phase II study focusing on quality of life, patients' preferences and health economics.

Raltitrexed (Tomudex) is proven effective in metastatic colorectal cancer. Between 1998-2000, 25 patients were included in a randomized phase II study comparing raltitrexed (13 patients) and the Nordic FLv regimen (12 patients). 23 patients were evaluable for response. The overall response rate was 2/12 (1 CR, 1 PR) in the raltitrexed arm and 1/11 (1 CR) in the Nordic FLv arm, respectively. There was no difference in overall survival (raltitrexed--14.7 months, Nordic FLv--15.4 months). 23 patients were evaluable for Quality of Life (QoL) analysis. 23/25 and 17/21 questionnaires (EORTC QLQ C-30) were returned at baseline and first evaluation. Raltitrexed tended to be the most toxic regimen, when looking at nausea and vomiting, appetite loss, diarrhea and global QoL. However, most patients (65%) recommended the raltitrexed treatment schedule. The total treatment cost was equal in both arms (about 6,800 EURO/patient) and the hospital/hospital hotel stay costs accounted for more than half of it.

Goserelin (Zoladex) or orchiectomy in metastatic prostate cancer? A quality of life and cost-effectiveness analysis.

BACKGROUND: We have today two treatment alternatives (orchiectomy or LHRH-analogue) in metastatic prostate cancer offering the same expectations of survival. This study documents the quality of life (QoL) and cost-effectiveness of these alternatives. PATIENTS AND METHODS: 65 consecutive patients treated at the University Hospital of Tromsø (UHT), Norway, between 1994 and 1999 were registered. At evaluation, 45 patients (LHRH-analogue--15 patients, orchiectomy--30 patients) were alive and included in the QoL-study (EORTC QLQ C-30, QoL 15D). 45 patients were followed-up at the UHT and included in the cost-analysis. Costs were calculated for a 36-month interval and converted to British pounds (1 Pound = 13 NOK). A 5% d.r. was employed. RESULTS: The mean QoL (15D) was 76.4 (orchiectomy) and 72 (LHRH) (0-100 scale). Constipation, urinating problems, fatigue, pain and loss of sexual functioning were the dominant symptoms. The treatment costs per patient treated were 8,895 Pounds (orchiectomy) and 10,937 Pounds (LHRH-analogue). The crossover in cost was located at 25 months. A sensitivity analysis varying discount rate (0-10%), drug charges (25-50% off) and treatment time (12-18 months) did not alter the conclusion. CONCLUSION: Orchiectomy is the treatment of choice when life expectancy is more than two years.

Molecular cloning of a mammalian nuclear phosphoprotein NUCKS, which serves as a substrate for Cdk1 in vivo.

We have isolated and characterized a cDNA encoding a mammalian nuclear phosphoprotein NUCKS, previously designated P1. Molecular analyses of several overlapping and full-length cDNAs from HeLa cells and rat brain revealed a protein with an apparent molecular mass of 27 kDa in both species. The deduced amino-acid sequences are highly conserved between human and rodents, but show no homology with primary structures in protein databases or with translated sequences of cDNAs in cDNA databanks. Although the protein has some features in common with the high mobility group proteins HMGI/Y, attempts to find a putative protein family by database query using both sequence alignment methods and amino-acid composition have failed. Northern blot analyses revealed that human and rat tissues contain three NUCKS transcripts varying in size from 1.5 to 6.5 kb. All human and rat tissues express the gene, but the level of transcripts varies among different tissues. Circular dichroism analysis and secondary structure predictions based on the amino-acid sequence indicate a low level of alpha helical content and substantial amounts of beta turn structures. The protein is phosphorylated in all phases of the cell cycle and exhibits mitosis-specific phosphorylation of threonine residues. Phosphopeptide mapping and back-phosphorylation experiments employing NUCKS from HeLa interphase and metaphase cells show that the protein is phosphorylated by Cdk1 during mitosis of the cell cycle.

Should cancer patients receive a copy of the medical record when visiting an out-patient clinic?

The aim of this study was to clarify the benefit and inconvenience to cancer patients of receiving a copy of the medical record following a visit to the out-patient clinic of the Department of Oncology, University Hospital of Tromsø, Norway. Between January and December 1998, after their attendance at the clinic a printout of the record made after the consultation was mailed to each of 199 patients seen by the same medical oncologist. A 15-item questionnaire was later mailed to 178 survivors in March 1999. The questionnaire had items on the use made of the copy report, side effects it might have occasioned, such as anxiety, worries and fear, and patients' general opinion of this procedure. There were 119 responders (67%), and 93 acknowledged receipt of the record. Most (96%) replied that the report had been beneficial; 78% had shown it to family members or friends; and 27% had shown it to other doctors. Only 9% had taken it with them when travelling. Such side effects as anxiety and worries were mentioned by only a few patients. Some 20% (mostly men) stated that medical terms had caused difficulties. Most patients in the study group (93%) recommended that the study practice should be introduced as standard procedure. Patients who considered receipt of the copy report of little value experienced the highest level of anxiety. In conclusion, cancer patients should be offered a copy of the medical record following an out-patient visit.

Evaluation of Norwegian cancer hospitals web sites and explorative survey among cancer patients on their use of the internet.

BACKGROUND: Hospital homepages should provide comprehensive information on the hospital's services, such as departments and treatments available, prices, waiting time, leisure facilities, and other information important for patients and their relatives. Norway, with its population of approximately 4.3 million, ranks among the top countries globally for its ability to absorb and use technology. It is unclear to what degree Norwegian hospitals and patients use the Internet for information about health services. OBJECTIVES: This study was undertaken to evaluate the quality of the biggest Norwegian cancer hospitals Web sites and to gather some preliminary data on patients use of the Internet. METHODS: In January 2001, we analyzed Web sites of 5 of the 7 biggest Norwegian hospitals treating cancer patients using a scoring system. The scoring instrument was based on recommendations developed by the Norwegian Central Information Service for Web sites and reflects the scope and depth of service information offered on hospital Web pages. In addition, 31 cancer patients visiting one hospital-based medical oncologist were surveyed about their use of the Internet. RESULTS: Of the 7 hospitals, 5 had a Web site. The Web sites differed markedly in quality. Types of information included - and number of Web sites that included each type of information - were, for example: search option, 1; interpreter service, 2; date of last update, 2; postal address, phone number, and e-mail service, 3; information in English, 2. None of the Web sites included information on waiting time or prices. Of the 31 patients surveyed, 12 had personal experience using the Internet and 4 had searched for medical information. The Internet users were significantly younger (mean age 47.8 years, range 28.4-66.8 years) than the nonusers (mean age 61.8 years, range 33.1-90.0 years) (P = 0.007). CONCLUSIONS: The hospitals Web sites offer cancer patients and relatives useful information, but the Web sites were not impressive.

Screening for metastatic disease in newly diagnosed breast cancer patients. What is cost-effective?

BACKGROUND: Significant health care resources are today spent on diagnosing and treatment of early breast cancer. MATERIALS AND METHODS: 98 consecutive patients referred to our oncological unit between January 1997 and June 1998 underwent an evaluation programme including thoracic X-ray, liver and bone scan and blood test. When findings suspected for metastatic disease were revealed, further examinations (CT-scan, MRI) were performed. RESULTS: Whereas the screening programme disclosed four cases (4%) of distant metastasis, several patients had to suffer the psychological distress of false positive results. One in three suspicious thoracic X-rays, two in two liver scans and 18 out of 21 suspected bone scans were concluded false positive in terms of metastatic disease. A screening programme including blood test and thoracic X-ray alone, would have mis-classified one out of 98 patients. CONCLUSION: This study indicated thoracic X-ray and blood test as being sufficient and 110 Pounds per patient screened could be saved.

Health, life and disability insurance and hereditary risk for breast or colorectal cancer.

Fear of insurance discrimination affecting the insurance-seeker and family has been reported as the singlemost important reason why individuals choose not to undergo genetic testing. The eleven health insurers operating on the Norwegian market were mailed a questionnaire asking them to list their insurance products and evaluate two individuals' requests for insurance. The requests were constructed in order to illustrate a high genetic risk for (a) colorectal (HNPCC) and (b) breast cancer (BRCAI/BRCA2), respectively. Nine out of 11 insurers responded. While no restriction was documented concerning risk of BRCA1/BRCA2 and life insurance or disability pension, the premium paid by persons with susceptibility to HNPCC varied between the different insurers from standard to raised premiums. The product 'critical disease' insurance was refused or obtained at normal or raised premiums in both cases, depending on the insurer in question. On examining personal indemnity insurance, we found that the BRCA1/BRCA2-risk individual was offered insurance at the standard premium, whereas HNPCC-risk individuals were offered a standard or raised premium. Only the major Norwegian insurer is in fact diverging in its policies.

Faith among patients with advanced cancer. A pilot study on patients offered "no more than" palliation.

Spiritual wellbeing is an important topic in cancer care. Being religious is reported by patients facing dilemmas concerning the quality and meaning of life to be potentially helpful. However, the fear of death may be close to the surface and easily stimulated. The aim of this study was to clarify patients' attitudes to faith. Between February 1998 and February 1999, 20 patients aged 37-74 years and suffering from ten different incurable cancers were enrolled in the study. An interview technique focusing on the topic by way of an open question about faith was employed. The topic was only continued if the patient signalled a clear wish for this. Half the patients had a close relative present during the conversation, and an oncology nurse was present in all cases. Most patients (18, or 90%) intimated that the topic was of interest: 85% responded by saying they believed in God, and 75% reported that they prayed. A quarter (25%) mentioned that they had visited their local Lutheran pastor before their admission to hospital. One patient reported being a Jehovah's Witness and one, a member of the Norwegian Humanistically Ethical Association (HEA). Following the conversation, 4 patients requested a visit from the hospital chaplain, 1 asked for contact with the Salvation Army to be arranged, and 1 wanted to talk to the local leader of HEA. Following the conversation all patients were observed by a nurse, and no raised level of anxiety was reported. Sixteen of the patients died within a median of 18 (1-180) days after the conversation. In conclusion, most patients responded positively to a question about faith. The topic should be addressed in the treatment of patients with advanced disease. However, care must be taken to avoid frightening the patients. Patients' attitudes with regard to what death brings deserve respect.

Oxaliplatin in colorectal cancer patients living in an arctic or subarctic area: significant cold-triggered dysesthesias and laryngeal reactions.

Oxaliplatin combined with 5-fluorouracil (5-FU) and folinic acid (FA) has been proven effective in colorectal cancer. However, side effects such as cold-triggered dysesthesia and laryngo-pharyngeal spasm have been reported. To clarify the side effects of oxaliplatin in a subarctic or arctic setting, a phase II study was performed. In October and November 1999, 8 patients with colorectal cancer were enrolled and treated with oxaliplatin (130 mg/m2 - day 1) and the FLv - Nordic regimen (5-FU 500 mg/m2 and leucovorin 100 mg for 2 days) every 3rd week as second- (6 pts) or third-line (2 pts) therapy. At evaluation in March 2000, 7 patients were alive and 6 PD, 1 SD and 1 PR were obtained. Acute laryngeal reaction was reported by 3 out of 8 patients and cold-triggered dysesthesia by all patients. Six available patients were interviewed by phone. Half of the interviewed patients recommend the therapy to be offered to other patients. In conclusion, oxaliplatin (130 mg/m2) therapy in arctic or subarctic areas during the winter introduces significant cold-triggered symptoms.