Predictive and Prognostic Impact of TP53 Mutations and MDM2 Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel

Background: TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP) T309G increases MDM2 activity and may reduce wildtype p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy. Experimental Design: Each patient was randomly assigned to treatment with epirubicin 90 mg/m2 (n= 109) or paclitaxel 200 mg/m2 (n = 114) every 3rd week as monotherapy for 4–6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy. Principal Findings: While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/ CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007) but also MDM2 309TG/GG genotype status (p = 0.012) were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039) but not among individuals with TP53 mutated tumors (p.0.5). Conclusion: TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy

Any difference? Use of a CAM provider among cancer patients, coronary heart disease (CHD) patients and individuals with no cancer/CHD

<p>Abstract</p> <p>Background</p> <p>Although use of complementary and alternative medicine (CAM) among cancer patients has been described previously, prevalence of use has not commonly been compared to other disease groups in a true population sample where CAM use or cancer is not the main focus. The aims of the present study are to (1) examine how CAM use in cancer patients differs from people with a previous CHD diagnosis and people with no cancer or CHD diagnosis in an unselected general population and (2), investigate the use of a CAM provider among individuals with a previous cancer diagnosis.</p> <p>Methods</p> <p>A total of 8040 men and women aged 29 to 87 in the city of Tromsø, Norway filled in a questionnaire developed specifically for the Tromsø V study with questions on life style and health issues. Visits to a CAM provider within the last 12 months and information on cancer, heart attack and angina pectoris (heart cramp) were among the questions. 1449 respondents were excluded from the analyses.</p> <p>Results</p> <p>Among the 6591 analysed respondents 331 had a prior cancer diagnosis, of whom 7.9% reported to have seen a CAM provider within the last 12 months. This did not differ significantly from neither the CHD group (6.4%, p = 0.402) nor the no cancer/CHD group (9.5%, p = 0.325).</p> <p>Conclusion</p> <p>According to this study, the proportion of cancer patients seeing a CAM provider was not statistically significantly different from patients with CHD or individuals without cancer or CHD.</p

Contributions of other brain pathologies in dementia with lewy bodies.

The clinical picture with its pathological correlate was analysed in 16 patients fulfilling consensus criteria for dementia with Lewy bodies (DLB). The cases were part of a larger cohort (n = 200) of patients within a prospective longitudinal study of dementing disorders. Six cases exhibited not only Lewy bodies (LBs) but also other brain pathologies such as Alzheimer changes, multiple infarcts or complete and incomplete white matter infarcts. Degeneration of the nucleus basalis of Meynert and substantia nigra was also seen. The 10 cases without LBs all had Alzheimer changes. In 7 cases, these changes were combined with mainly incomplete frontal white matter infarcts. However, the degeneration of brain stem nuclei was less pronounced in these cases. Symptoms such as fluctuations in cognition, falls and episodic confusion appeared in association with arterial hypotension, which developed during the course of dementia in almost all the 16 cases. The majority of the cases were treated with neuroleptics and other potentially hypotensive medication. This study shows that multiple and different pathological features may contribute to a clinical symptom constellation as in DLB. The case study approach reveals the complexity of the clinico-pathological relationships in dementia that might otherwise be lost in the analysis of larger group data. Copyright 2002 S. Karger AG, Base

Synapse density related to cerebral blood flow and symptomatology in frontal lobe degeneration and Alzheimer's disease

In order to evaluate the functional significance of synaptic pathology, synaptic density was quantitated and related to clinical symptomatology and regional cerebral blood flow (rCBF) in 8 patients with frontal lobe degeneration of non-Alzheimer type (FLD) and 19 patients with Alzheimer's disease (AD). Synaptic density was measured in all layers of prefrontal and parietal cortex. The clinical picture of FLD was dominated by a frontal lobe syndrome with changes in personality and behavior, while AD was dominated by temporoparietal symptoms. This parallels the finding of frontal rCBF reductions in FLD patients and temporoparietal reductions in AD patients. Synaptic density was significantly decreased in both FLD and AD, with a regional severity which closely correlated with that of the degeneration, symptomatology and rCBF deficit. The results suggest that synaptic pathology is a likely cause of clinical symptoms and regional metabolic decrement in dementia

Regional cerebral blood flow and EEG in clinically diagnosed dementia with Lewy bodies and Alzheimer's disease.

This study was undertaken in order to compare regional cerebral blood now (rCBF) and EEG findings of patients with clinically diagnosed dementia with Lewy bodies (clinDLB) and Alzheimer’s disease (clinAD). Furthermore, within the clinDLB group to compare cases with and without neuropathologically verified Lewy bodies (LBs). When we studied 200 dementia cases in a prospective longitudinal dementia study, 48 had clinDLB and 45 clinAD in retrospective analyses. EEG information was analysed in 34 clinDLB and 28 clinAD patients and cerebral blood flow, measured with the Xe 133 inhalation method, in 26 clinDLB and 25 clinAD. There were no differences in EEG between the clinDLB and clinAD groups or between the cases with and without LBs. The rCBF patterns in the clinDLB and clinAD groups showed similar reductions in the temporoparietal areas. The rCBF in cases with LBs showed heterogeneous pathology. The imaging results in clinDLB and clinAD were strikingly similar. The EEG and rCBF could not differentiate between cases with or without LB. The study illustrates the lack of specific changes of EEG and rCBF in cases with LB pathology

Changes in the rate of publicly financed knee arthroscopies: An analysis of data from the Norwegian patient registry from 2012 to 2016

Objective: To examine rates of publicly financed knee arthroscopic surgery in Norway between 2012 and 2016. Design: Analysis of anonymised data from the National Patient Registry. Interventions: Beginning in 2012, South-Eastern Norway Regional Health Authority implemented administrative measures to bring down rates of knee arthroscopy. Similar measures were not introduced in the other three Regional Health Authorities. Main outcome measures: We analysed annual national rates of publicly financed knee arthroscopies in 2012 and 2016. We compared the rates in South-Eastern Norway Regional Health Authority with corresponding rates in the rest of the country. Variations by county, public hospital versus publicly reimbursed private hospital, gender and age were also assessed. Results: The overall annual rate of arthroscopic procedures declined by 33% from 2012 to 2016, from 310 to 207 per 100 000 inhabitants, respectively. Hospitals in South-Eastern Norway Regional Health Authority reported a 48% reduction, compared with mean 13% in the other three Regional Health Authorities. In public hospitals, rates decreased nationally by 42%, while rates in publicly reimbursed private hospitals increased by 12%. Rates in publicly reimbursed private hospitals decreased by 30% in South-Eastern Norway Regional Health Authority but increased by 63% in the other Regional Health Authorities. The proportion of patients ≥50 years (excluding meniscal repairs) in Norway was 54% in 2012 and fell to 46% in 2016. Average rates per county varied by a factor of 3:1. Conclusion: We report a marked overall reduction of knee arthroscopic procedures from 2012 to 2016 in publicly funded hospitals. The largest decrease was reported in South-Eastern Norway Regional Health Authority, and this coincides in time with implemented administrative measures. The results suggest that the trend of increasing rates of knee arthroscopies can be reversed through purposeful professional and administrative interventions.publishedVersionSeksjon for idrettsmedisinske fag / Department of Sport Medicin

Changes in the rate of publicly financed knee arthroscopies: An analysis of data from the Norwegian patient registry from 2012 to 2016

Objective: To examine rates of publicly financed knee arthroscopic surgery in Norway between 2012 and 2016. Design: Analysis of anonymised data from the National Patient Registry. Interventions: Beginning in 2012, South-Eastern Norway Regional Health Authority implemented administrative measures to bring down rates of knee arthroscopy. Similar measures were not introduced in the other three Regional Health Authorities. Main outcome measures: We analysed annual national rates of publicly financed knee arthroscopies in 2012 and 2016. We compared the rates in South-Eastern Norway Regional Health Authority with corresponding rates in the rest of the country. Variations by county, public hospital versus publicly reimbursed private hospital, gender and age were also assessed. Results: The overall annual rate of arthroscopic procedures declined by 33% from 2012 to 2016, from 310 to 207 per 100 000 inhabitants, respectively. Hospitals in South-Eastern Norway Regional Health Authority reported a 48% reduction, compared with mean 13% in the other three Regional Health Authorities. In public hospitals, rates decreased nationally by 42%, while rates in publicly reimbursed private hospitals increased by 12%. Rates in publicly reimbursed private hospitals decreased by 30% in South-Eastern Norway Regional Health Authority but increased by 63% in the other Regional Health Authorities. The proportion of patients ≥50 years (excluding meniscal repairs) in Norway was 54% in 2012 and fell to 46% in 2016. Average rates per county varied by a factor of 3:1. Conclusion: We report a marked overall reduction of knee arthroscopic procedures from 2012 to 2016 in publicly funded hospitals. The largest decrease was reported in South-Eastern Norway Regional Health Authority, and this coincides in time with implemented administrative measures. The results suggest that the trend of increasing rates of knee arthroscopies can be reversed through purposeful professional and administrative interventions

Changes in the rate of publicly financed knee arthroscopies: An analysis of data from the Norwegian patient registry from 2012 to 2016

Objective: To examine rates of publicly financed knee arthroscopic surgery in Norway between 2012 and 2016. Design: Analysis of anonymised data from the National Patient Registry. Interventions: Beginning in 2012, South-Eastern Norway Regional Health Authority implemented administrative measures to bring down rates of knee arthroscopy. Similar measures were not introduced in the other three Regional Health Authorities. Main outcome measures: We analysed annual national rates of publicly financed knee arthroscopies in 2012 and 2016. We compared the rates in South-Eastern Norway Regional Health Authority with corresponding rates in the rest of the country. Variations by county, public hospital versus publicly reimbursed private hospital, gender and age were also assessed. Results: The overall annual rate of arthroscopic procedures declined by 33% from 2012 to 2016, from 310 to 207 per 100 000 inhabitants, respectively. Hospitals in South-Eastern Norway Regional Health Authority reported a 48% reduction, compared with mean 13% in the other three Regional Health Authorities. In public hospitals, rates decreased nationally by 42%, while rates in publicly reimbursed private hospitals increased by 12%. Rates in publicly reimbursed private hospitals decreased by 30% in South-Eastern Norway Regional Health Authority but increased by 63% in the other Regional Health Authorities. The proportion of patients ≥50 years (excluding meniscal repairs) in Norway was 54% in 2012 and fell to 46% in 2016. Average rates per county varied by a factor of 3:1. Conclusion: We report a marked overall reduction of knee arthroscopic procedures from 2012 to 2016 in publicly funded hospitals. The largest decrease was reported in South-Eastern Norway Regional Health Authority, and this coincides in time with implemented administrative measures. The results suggest that the trend of increasing rates of knee arthroscopies can be reversed through purposeful professional and administrative interventions