Albiges L.,Institute Gustave Roussy |
Choueiri T.,Dana-Farber Cancer Institute |
Escudier B.,Institute Gustave Roussy |
Galsky M.,Mount Sinai School of Medicine |
And 10 more authors.
European Urology | Year: 2015
Context The introduction of novel molecular-targeted agents has revolutionised the management of patients with metastatic renal cell carcinoma (mRCC). However, uncertainties remain over sequential or simultaneous combination therapies. Objective To systematically review relevant literature comparing the clinical effectiveness and harms of different sequencing and combinations of systemic targeted therapies for mRCC. Evidence acquisition Relevant databases (including Medline, Cochrane Library, trial registries, and conference proceedings) were searched (January 2000 to September 2013) including only randomised controlled trials (RCTs). Risk of bias assessment was performed. A qualitative and quantitative synthesis of the evidence was presented. Evidence synthesis The literature search identified 5149 articles. A total of 24 studies reporting on 9589 patients were eligible for inclusion; data from four studies were included for meta-analysis. There were generally low risks of bias across studies; however, clinical and methodological heterogeneity prevented pooling of data for most studies. Overall, the data showed several targeted therapies were associated with an improvement in progression-free survival in patients with mRCC. There were limited data from RCTs regarding the issue of sequencing; studies on combination therapies have been hampered by difficulties with tolerability and safety. Conclusions Although the role of vascular endothelial growth factor/vascular endothelial growth factor receptor targeting therapies and mammalian target of rapamycin inhibition in the management of mRCC is now established, limited reliable data are available regarding sequencing and combination therapies. Although data from retrospective cohort studies suggest a potential benefit for sequencing systemic therapies, significant uncertainties remain. Presently, mRCC systemic treatment should follow international guidelines (such as the European Society for Medical Oncology, National Comprehensive Cancer Network, and European Association of Urology) for patients fit to receive several lines of systemic therapies. Patient summary We thoroughly examined the literature on the benefits and harms of combining drugs for the treatment of kidney cancer that has spread and on the sequence in which the drugs should be given. © 2014 European Association of Urology.
Werneke U.,Umeå University |
Werneke U.,Sunderby Hospital |
Taylor D.,King's College London |
Sanders T.A.B.,King's College London
Current Psychiatry Reports | Year: 2013
Weight gain remains a well recognized yet difficult to treat adverse effect of many anti-psychotic drugs including agents of the first and second generation. The weight gain liabilities of antipsychotic drugs are partly associated with their ability to increase appetite.Most behavioral interventions for weight control remain of limited efficacy, possibly because they do not specifically target the neuroendocrine factors regulating appetite. Identifying new weight management interventions directly acting on the biochemical and neuroendocrine mechanisms of anti-psychotic induced weight gain may help to improve the efficacy of behavioral weight management programs. Such potentially specific strategies include (1) using diets which do not increase appetite despite calorie restriction; (2) countering thirst as an anticholinergic sideeffect; (3) discouraging cannabis use and (4) adding metforminto a behavioral intervention. In view of our currentlyrather limited treatment repertoire it seems timely systematically to explore such novel options © The Author(s) 2013.
Werneke U.,Umeå University |
Ott M.,Sunderby Hospital |
Renberg E.S.,Umeå University |
Taylor D.,King's College London |
Stegmayr B.,Umeå University
Acta Psychiatrica Scandinavica | Year: 2012
Objective: To establish whether lithium or anticonvulsant should be used for maintenance treatment for bipolar affective disorder (BPAD) if the risks of suicide and relapse were traded off against the risk of end-stage renal disease (ESRD). Method: Decision analysis based on a systematic literature review with two main decisions: (1) use of lithium or at treatment initiation and (2) the potential discontinuation of lithium in patients with chronic kidney disease (CKD) after 20years of lithium treatment. The final endpoint was 30years of treatment with five outcomes to consider: death from suicide, alive with stable or unstable BPAD, alive with or without ESRD. Results: At the start of treatment, the model identified lithium as the treatment of choice. The risks of developing CKD or ESRD were not relevant at the starting point. Twenty years into treatment, lithium still remained treatment of choice. If CKD had occurred at this point, stopping lithium would only be an option if the likelihood of progression to ESRD exceeded 41.3% or if anticonvulsants always outperformed lithium regarding relapse prevention. Conclusion: At the current state of knowledge, lithium initiation and continuation even in the presence of long-term adverse renal effects should be recommended in most cases. © 2012 John Wiley & Sons A/S.
Frobert O.,Örebro University |
Lagerqvist B.,Uppsala University |
Olivecrona G.K.,Lund University |
Omerovic E.,Sahlgrenska University Hospital |
And 18 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: The clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. METHODS: We conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. RESULTS: No patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P = 0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P = 0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P = 0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P = 0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. CONCLUSIONS: Routine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. Copyright © 2013 Massachusetts Medical Society.
Olsson M.,Lulea University of Technology |
Stafstrom L.,Sunderby Hospital |
Soderberg S.,Lulea University of Technology
Qualitative Health Research | Year: 2013
The existing knowledge of women's experiences of living with Parkinson's disease and fatigue is limited. To gain first-hand knowledge, we interviewed 11 women using a phenomenological hermeneutic interpretation. The results indicate that the familiar daily routines of women with Parkinson's disease had changed in the sense that their bodily attachment to the world had been altered. The body no longer provided smooth access to the surrounding world; rather, the body served as a barrier to daily living. In practice, understanding this barrier can be significant in recognizing how to create positive conditions that support the women's experiences and how to formulate their care in congruence with their needs. © The Author(s) 2013.
Ljungberg B.,Umeå University |
Bensalah K.,University of Rennes 1 |
Canfield S.,University of Houston |
Dabestani S.,Skåne University Hospital |
And 11 more authors.
European Urology | Year: 2015
Context The European Association of Urology Guideline Panel for Renal Cell Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for RCC management. Objectives To provide an update of the 2010 RCC guideline based on a standardised methodology that is robust, transparent, reproducible, and reliable. Evidence acquisition For the 2014 update, the panel prioritised the following topics: percutaneous biopsy of renal masses, treatment of localised RCC (including surgical and nonsurgical management), lymph node dissection, management of venous thrombus, systemic therapy, and local treatment of metastases, for which evidence synthesis was undertaken based on systematic reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Relevant databases (Medline, Cochrane Library, trial registries, conference proceedings) were searched (January 2000 to November 2013) including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm. Risk of bias (RoB) assessment and qualitative and quantitative synthesis of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Evidence synthesis All chapters of the RCC guideline were updated. For the various systematic reviews, the search identified a total of 10 862 articles. A total of 151 studies reporting on 78 792 patients were eligible for inclusion; where applicable, data from RCTs were included and meta-analyses were performed. For RCTs, there was low RoB across studies; however, clinical and methodological heterogeneity prevented data pooling for most studies. The majority of studies included were retrospective with matched or unmatched cohorts based on single or multi-institutional data or national registries. The exception was for systemic treatment of metastatic RCC, in which several RCTs have been performed, resulting in recommendations based on higher levels of evidence. Conclusions The 2014 guideline has been updated by a multidisciplinary panel using the highest methodological standards, and provides the best and most reliable contemporary evidence base for RCC management. Patient summary The European Association of Urology Guideline Panel for Renal Cell Carcinoma has thoroughly evaluated available research data on kidney cancer to establish international standards for the care of kidney cancer patients. © 2015 European Association of Urology.
Dabestani S.,Skåne University Hospital |
Marconi L.,University of Coimbra |
Hofmann F.,Sunderby Hospital |
Stewart F.,University of Aberdeen |
And 6 more authors.
The Lancet Oncology | Year: 2014
Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research. © 2014 Elsevier Ltd.
Niklasson A.,Pitea Hospital |
Tano K.,Sunderby Hospital
Laryngoscope | Year: 2011
Aim: To examine if a Gelfoam® plug in combination with surgical removal of the perforation edges could be an alternative to the widely accepted fat plug treatment for smaller ear drum perforations. Materials and Methods: A prospective study of 17 consecutive patients with persistent small ear drum perforations considered for myringoplasty. The perforations were central perforations 2 to 4 mm in diameter. Patient ages ranged from 6 to 83 years, and the operation was performed under general anesthesia with mask ventilation in children and under topical local anesthesia in adults. A Gelfoam® plug was inserted into the perforation after surgical removal of the perforation edges. The follow-up time was more than 3 months. Results: The closure rate of the ear drum was 83% (15/18). Pure tone average (PTA) was 19 dB preoperatively and 16 dB postoperatively. Conclusions: We show for the first time in humans that a Gelfoam® plug in combination with surgical removal of the perforation edges seems to result in about the same closure rate as the fat plug technique in persistent small ear drum perforations. Moreover, the method using Gelfoam® is simpler and faster than the fat plug technique. We suggest that randomized studies comparing the Gelfoam® plug technique with the fat plug technique should be performed. © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
Eriksson M.,Statistics Sweden |
Eriksson M.,Umeå University |
Carlberg B.,Umeå University |
Eliasson M.,Umeå University |
Eliasson M.,Sunderby Hospital
Cerebrovascular Diseases | Year: 2012
Background: Diabetes is an established risk factor for stroke. Compared to nondiabetic patients, diabetic patients also have an increased risk of new vascular events and death after stroke. We analyzed how differences in long-term survival between diabetic and nondiabetic stroke patients have changed over time, and if differences varied with respect to sex and age. Methods: This population-based study included 12,375 first-ever stroke patients, 25-74 years old, who were registered in the Northern Sweden MONICA Stroke Registry 1985-2005. Uniform diagnostic criteria for stroke case ascertainment were used throughout the study period. The diagnosis of diabetes was based on medical records or diabetes diagnosed during the acute stroke event. Patients were separated into four cohorts according to year of stroke and followed for survival until August 30, 2008. Results: The diabetes prevalence at stroke onset was 21%, similar in men and women, and remained stable throughout the study period. The diabetic patients were an average of 2 years older, more often nonsmokers and more likely to have antihypertensive treatment, antithrombotics, atrial fibrillation, and a history of myocardial infarction or transient ischemic attack than the nondiabetic patients. The total follow-up time was 86,086 patient-years during which a total of 1,930 (75.7%) of the diabetic patients and 5,744 (58.5%) of the nondiabetic patients died (p < 0.001). Median survival was 60 months (95% CI: 57-64) in diabetic patients and 117 months (113-120) in the nondiabetic patients. Survival improved significantly in both groups (p < 0.001). A Cox regression, adjusting for possible confounders (age, sex, antihypertensive medication, antithrombotics or other thrombolytic agents, history of myocardial infarction, type of stroke, diabetes, cohort and the diabetes-by-sex, diabetes-by-age and diabetes-by-cohort interactions), showed a hazard ratio of 1.67 (1.58-1.76) comparing survival in diabetic versus nondiabetic patients. The reduced survival in diabetic stroke patients was more pronounced in women (p = 0.02) and younger patients (p < 0.001). There was a tendency that the difference in survival decreased between the earlier cohorts and the 2000-2005 cohort, but the test for interaction did not reach statistical significance (p = 0.08). Conclusion: Long-term survival after a first stroke has improved in both diabetic and nondiabetic patients. Survival is markedly lower in diabetics, especially in women and younger patients, and the disparity persisted over 24 years. Decreasing the disparity in stroke survival is a challenge for stroke and diabetes care. New treatment methods in combination with intense secondary prevention in diabetic patients, especially in younger women, are needed. © 2012 S. Karger AG, Basel.
Werneke U.,Sunderby Hospital
NeuroQuantology | Year: 2011
Current concepts of delusion rely on the assumption that one single objective external reality exists as a benchmark for our internal experiences. With the advent of quantum theory this assumption has become untenable. Accepting the Copenhagen interpretation that there is no reality beyond what is revealed by the act of measurement or observation implies that there is no objective reality. One alternative interpretation of quantum theory is the "many worlds" interpretation which finds its philosophical correlate in the "plurality of worlds" theory. However, the idea of all possible worlds being not just possible but real is even more counter-intuitive. Virtual reality is a way to systematically alter the usual relationship between external reality and the user's experience of it. Although virtual reality is not the same as parallel reality and both are separate strands in the "fabric of reality" they are related. With the advance of virtual reality there is already developing an increasing sense that the real and digital worlds seem to converge. But even if we believed in only one single objective external reality we could still never experience this reality directly. Our experience of reality is essentially one of virtual reality as generated by our brain. The "many worlds" interpretation implies that other copies of our brain rendering other experiences exist. Thus, in view of the uncertain nature of reality it is necessary to rethink our accepted concept of psychosis. Currently, meticulous history taking and accurate clinical observation remains our best option trying to understand psychotic symptoms.