| 1. |
- Endisch, Christian, et al.
(författare)
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Hypoxic-Ischemic Encephalopathy Evaluated by Brain Autopsy and Neuroprognostication after Cardiac Arrest
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:11, s. 1430-1439
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Neuroprognostication studies are potentially susceptible to a self-fulfilling prophecy as investigated prognostic parameters may affect withdrawal of life-sustaining therapy. Objective: To compare the results of prognostic parameters after cardiac arrest (CA) with the histopathologically determined severity of hypoxic-ischemic encephalopathy (HIE) obtained from autopsy results. Design, Setting, and Participants: In a retrospective, 3-center cohort study of all patients who died following cardiac arrest during their intensive care unit stay and underwent autopsy between 2003 and 2015, postmortem brain histopathologic findings were compared with post-CA brain computed tomographic imaging, electroencephalographic (EEG) findings, somatosensory-evoked potentials, and serum neuron-specific enolase levels obtained during the intensive care unit stay. Data analysis was conducted from 2015 to 2020. Main Outcomes and Measures: The severity of HIE was evaluated according to the selective eosinophilic neuronal death (SEND) classification and patients were dichotomized into categories of histopathologically severe and no/mild HIE. Results: Of 187 included patients, 117 were men (63%) and median age was 65 (interquartile range, 58-74) years. Severe HIE was found in 114 patients (61%) and no/mild HIE was identified in 73 patients (39%). Severe HIE was found in all 21 patients with bilaterally absent somatosensory-evoked potentials, all 15 patients with gray-white matter ratio less than 1.10 on brain computed tomographic imaging, all 9 patients with suppressed EEG, 15 of 16 patients with burst-suppression EEG, and all 29 patients with neuron-specific enolase levels greater than 67 μg/L more than 48 hours after CA without confounders. Three of 7 patients with generalized periodic discharges on suppressed background and 1 patient with burst-suppression EEG had a SEND 1 score (<30% dead neurons) in the cerebral cortex, but higher SEND scores (>30% dead neurons) in other oxygen-sensitive brain regions. Conclusions and Relevance: In this study, histopathologic findings suggested severe HIE after cardiac arrest in patients with bilaterally absent cortical somatosensory-evoked potentials, gray-white matter ratio less than 1.10, highly malignant EEG, and serum neuron-specific enolase concentration greater than 67 μg/L.
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| 2. |
- Holgersson, Johan, et al.
(författare)
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Hypothermic versus Normothermic Temperature Control after Cardiac Arrest
- 2022
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Ingår i: NEJM Evidence. - 2766-5526. ; 1:11, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDThe evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics.METHODSAn individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted. The intervention was hypothermia at 33°C and the comparator was normothermia. The primary outcome was all-cause mortality at 6 months. Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months. Predefined subgroups based on the design variables in the original trials were tested for interaction with the intervention as follows: age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence).RESULTSThe primary analyses included 2800 patients, with 1403 assigned to hypothermia and 1397 to normothermia. Death occurred for 691 of 1398 participants (49.4%) in the hypothermia group and 666 of 1391 participants (47.9%) in the normothermia group (relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41). A poor functional outcome occurred for 733 of 1350 participants (54.3%) in the hypothermia group and 718 of 1330 participants (54.0%) in the normothermia group (relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88). Outcomes were consistent in the predefined subgroups.CONCLUSIONSHypothermia at 33°C did not decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest. (Funded by Vetenskapsrådet; ClinicalTrials.gov numbers NCT02908308 and NCT01020916.)
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| 3. |
- Jakobsen, Janus Christian, et al.
(författare)
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Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥37.8°C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
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| 4. |
- Allemani, Claudia, et al.
(författare)
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Breast cancer survival in the US and Europe: a CONCORD high-resolution study
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 132:5, s. 1170-1181
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15-99 years during 1996-98 in 7 US states and 12 European countries. Age-standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70-99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment.
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| 5. |
- Andersson, Kristin, et al.
(författare)
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The interface of population-based cancer registries and biobanks in etiological and clinical research : current and future perspectives
- 2010
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 49:8, s. 1227-1234
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The availability of quality assured, population-based cancer registries and biobanks with high quality samples makes it possible to conduct research on large samples sets with long follow-up within a reasonable time frame. Defined quality for both cancer registries and biobanks is essential for enabling high quality biobank-based research. Recent networking projects have brought these infrastructures together to promote the combined use of cancer registries and biobanks in cancer research.MATERIALS AND METHODS: In this report we review the current status and future perspectives of cancer registries and biobanks and how the interface between them should be developed to optimally further cancer research.RESULTS AND DISCUSSION: Major conclusions for future improvements are that the research exploiting cancer registries and biobanks, and the research that is building and optimising the infrastructure, should evolve together for maximally relevant progress. Population-based and sustainable biobanks that continuously and consecutively store all samples ("Biological registries") under strict quality control are needed. There is also a need for increased education, information and visibility of the interdisciplinary sciences required for optimal exploitation of these resources.
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| 6. |
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| 7. |
- Brasso, Klaus, et al.
(författare)
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Differences in survival from prostate cancer in Denmark, Iceland and Sweden
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 49:8, s. 1984-1992
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Register-based studies have shown large survival differences among prostate cancer patients in the Nordic countries. The aim of this study was to determine the background of such differences in Denmark, Iceland and Sweden. Material and methods: Patients with prostate cancer were identified through population-based cancer registers in the three countries. Clinical findings at diagnosis were retrieved from hospital records. In Sweden, clinical information was gathered from regional population-based prostate cancer registers. Country-specific incidence and excess mortality rates were compared, with adjustment for prognostic factors. Results: The relative survival in the cohorts was comparable to that in previous population-based studies. Significant differences in excess mortality rates were found across countries, which diminished or disappeared after adjustment for patient characteristics, i.e. metastatic status, clinical T stage and prostate-specific antigen level. A difference in the proportion of patients with metastatic disease was the main explanation of the differences in survival among countries, while the incidence rates of metastatic cancer were similar. Discussion: Register-based studies of the relative survival of prostate cancer patients are influenced by national differences in clinical presentation at diagnosis. Differences in the proportion of patients with metastatic spread explained most of the difference in relative survival among patients in Denmark, Iceland and Sweden. Future country comparisons of relative survival should include adjustment for differences in patient characteristics, such as stage, prostate-specific antigen level and screening intensity.
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| 8. |
- Christensen, L. H., et al.
(författare)
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Reduced mortality for women with mammography-detected breast cancer in east Denmark and south Sweden
- 2006
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 42:16, s. 2773-2780
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Tidskriftsartikel (refereegranskat)abstract
- The 5-year relative survival from breast cancer in Denmark is 10 percentage points lower than in Sweden. This difference has been demonstrated previously as being caused partly by more involved lymph nodes and larger tumours in Denmark. Sweden has had nationwide mammography-screening coverage since 1991, whereas this is still in its infancy in Denmark. In the search for an explanation for the remaining survival difference, patient delay was a likely candidate. This study compared patient delay and mammography-detection between two national regions. Data on patient delay and mammography were obtained from hospital records from 1989 and 1994, and analysed using Cox proportional hazard analysis of death within the first 5 years, with the factors age, country, delay/mammography detection and established patho-anatomic variables. A comparison of patient delay and mammography detection in 1989 and 1994 showed more mammography-detected tumours in south Sweden and more women with long delay in east Denmark. Mammography detection, but not long patient delay, had a significant effect on the death hazard when adjusting for patho-anatomic risk factors. The hazard ratio was not eliminated in 1989, but in 1994, the hazard ratio between east Denmark and south Sweden was reduced from 1.3 to 1.1. In conclusion, patient delay did not appear to have any effect on 5-year survival when adjusting for patho-anatomic factors, but tumour detection by mammography affected survival favourably and partly explained the survival difference between east Denmark and south Sweden. (c) 2006 Elsevier Ltd. All rights reserved.
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| 9. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 10. |
- Dankiewicz, Josef, et al.
(författare)
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Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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| 11. |
- Engholm, Gerda, et al.
(författare)
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Colorectal cancer survival in the Nordic countries and the United Kingdom : Excess mortality risk analysis of 5 year relative period survival in the period 1999 to 2000
- 2007
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:5, s. 1115-1122
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Tidskriftsartikel (refereegranskat)abstract
- A deficit in colorectal cancer survival in Denmark and in the UK compared to Sweden, Norway and Finland was found in the EUROCARE studies. We set out to explore if these differences still exist. Patients diagnosed with colorectal cancer as their first invasive cancer at age 15-89 in the period 1994-2000 were identified using data from 11 cancer registries in the UK and from four Nordic countries. Five-year relative period survival using deaths in 1999-2000 following cancers diagnosed in 1994-2000 was analysed with excess mortality risk modelling. Follow-up time since diagnosis with age as an effect-modifier in the first half year was the most important factor with the highest excess risk of death immediately after diagnosis and with higher age and decreasing with length of follow-up. Variations between countries were bigger in the first half year following diagnosis than in the interval 0.5-5 years with about 30% higher risk in UK and Denmark. The differences between countries are still substantial and the order has not changed, even if the five year relative survival has improved since the EUROCARE studies. Patient management, diagnostics, and comorbidity likely explain the excess deaths in UK and Denmark during the first 6 months. The effect of stage and quality of management and treatment should be examined in population based studies with detailed patient information. Use of more detailed age-intervals than conventionally applied in survival studies proved to be important in statistical modelling and is recommended for future studies.
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| 12. |
- Fischer, Hans, et al.
(författare)
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Pathogen specific, IRF3-dependent signaling and innate resistance to human kidney infection.
- 2010
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374 .- 1553-7366. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3(-/-) mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFNβ-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3(-/-) mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response.
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| 13. |
- Folkesson, Joakim, et al.
(författare)
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Rectal cancer survival in the Nordic countries and Scotland
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:10, s. 2406-12
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to present detailed population-based survival estimates for patients with a rectal adenocarcinoma, using cancer register data supplemented with clinical data. Based on cancer register data, differences in rectal cancer survival have been reported between countries in Europe. Variation in the distribution of stage at diagnosis, initial therapy including surgical technique, and comorbidity are possible explanatory factors. Adenocarcinomas in the rectum, diagnosed in 1997 and identified in the national cancer registries in the Nordic countries and Scotland were included. Age standardized 5-year relative survival and multiplicative regression models for the relative excess mortality were calculated. 3888 patients were included in the survival study. Men in Denmark, Finland and Iceland had lower 5-year relative survival and poorer stage distribution compared to Norway, Sweden and Scotland. Danish men had the highest rate of excess deaths in the first six months after diagnosis. Stage adjusted, the elevated relative excess mortality decreased and after six months the excess mortality rates were the same in all countries. The poor 5-year relative survival in Danish men was mainly due to a high excess rate of death during the first six months after diagnosis. The low survival in Finland and Iceland was not in accordance with other periods. For both countries this may be explained by random variation due to small numbers. The study emphasizes the need for high quality and detailed data in order to understand international survival differences, and cautions comparisons between large national samples and those of smaller areas.
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| 14. |
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| 15. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 16. |
- Hill, Deirdre A., et al.
(författare)
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Breast cancer risk following radiotherapy for Hodgkin lymphoma : modification by other risk factors
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 106:10, s. 3358-65
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Tidskriftsartikel (refereegranskat)abstract
- The importance of genetic and other risk factors in the development of breast cancer after radiotherapy (RT) for Hodgkin lymphoma (HL) has not been determined. We analyzed data from a breast cancer case-control study (105 patients, 266 control subjects) conducted among 3 817 survivors of HL diagnosed at age 30 years or younger in 6 population-based cancer registries. Odds ratios (ORs) and excess relative risks (ERRs) were calculated using conditional regression. Women who received RT exposure (> or = 5 Gy radiation dose to the breast) had a 2.7-fold increased breast cancer risk (95% confidence interval (CI) 1.4-5.2), compared with those given less than 5 Gy. RT exposure (> or = 5 Gy) was associated with an OR of 0.8 (95% CI, 0.2-3.4) among women with a first- or second-degree family history of breast or ovarian cancer, and 5.8 (95% CI, 2.1-16.3) among all other women (interaction P = .03). History of a live birth appeared to increase the breast cancer risk associated with RT among women not treated with ovarian-damaging therapies. Breast cancer risk following RT varied little according to other factors. The additional increased relative risk of breast cancer after RT for HL is unlikely to be larger among women with a family history of breast or ovarian cancer than among other women.
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| 17. |
- Hjalgrim, Henrik, et al.
(författare)
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Non-melanoma skin cancer may be a marker of poor prognosis in patients with non-Hodgkin's lymphoma
- 2000
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 85:5, s. 639-642
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Tidskriftsartikel (refereegranskat)abstract
- According to recent results, patients with non-melanoma skin cancers are at increased risk of developing non-Hodgkin's lymphoma (NHL). The prognostic significance of this association is unknown. Two cohorts of patients with a first diagnosis of non-melanoma skin cancer and a subsequent diagnosis of either NHL (n = 170) or colon cancer (n = 435) were established using national cancer registry data in Denmark. Two other cohorts of patients in whom NHL (n = 600) or colon cancer (n = 1,541) was the patients' first known malignancy served as comparison groups. Mortality rates were compared using Cox's regression analysis. Among patients younger than 80 years at NHL diagnosis, a history of non-melanoma skin cancer was associated with significantly increased mortality [relative risk (RR) = 1.54; 95% confidence interval: 1.19-1.99]. This association was present in both men (RR = 1.38; 1.02-1.86) and women (RR = 2.15; 1.31-3.54) and was similar after both major subtypes of non-melanoma skin cancer. Overall, antedating non-melanoma skin cancer had no prognostic significance for colon cancer patients (RR = 1.00; 0.84-1.18). Whatever the underlying mechanism, our observation has potential clinical implications. If substantiated in other settings, NHL patients with prior non-melanoma skin cancer may constitute a subgroup of lymphoma patients in need of particular therapeutic attention.
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| 18. |
- Storm, Christian, et al.
(författare)
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A survey on general and temperature management of post cardiac arrest patients in large teaching and university hospitals in 14 European countries-The SPAME trial results
- 2017
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 116, s. 84-90
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: International guidelines recommend a bundle of care, including targeted temperature management (TTM), in post cardiac arrest survivors. Aside from a few small surveys in different European countries, adherence to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recommendations are unknown. Methods: This international European telephone survey was conducted to provide an overview of current clinical practice of post cardiac arrest management with a main focus on TTM. We targeted large teaching and university hospitals within Europe as leading facilities and key opinion leaders in the field of post cardiac arrest care. Selected national principal investigators conducted the survey, which was based on a predefined questionnaire, between December 2014 and March 2015, before the publication of the ERC Guidelines 2015. Results: The return rate was 94% from 268 participating intensive care units (ICU). The majority had a predefined standard operating procedure (SOP) protocol for post cardiac arrest patients. Altogether, 68% of the ICUs provided TTM at a target temperature of 32-34. °C for 24. h, and 33% had changed the target temperature to 36. °C. The minority provided a written SOP for neurological prognostication, which was generally initiated 72. h after return of spontaneous circulation (ROSC). Electroencephalography and somatosensory evoked potentials were used by most ICUs for early prognostication. Treating more than fifty patients a year was significantly associated with providing written SOPs for TTM and prognostication (p. <. 0.01), as well as the use of a computer feedback device (p = 0.03) for TTM. Conclusion: This international European telephone survey revealed a high rate of implementation of TTM in post cardiac arrest patients in university and teaching hospitals. Most participants also provided a SOP, but only a minority had a SOP for neurological prognostication.
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| 19. |
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| 20. |
- Storm, Martin, et al.
(författare)
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Comparison of real-time PCR and pyrosequencing for typing Bordetella pertussis toxin subunit 1 variants
- 2006
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Ingår i: Journal of Microbiological Methods. - : Elsevier BV. - 0167-7012 .- 1872-8359. ; 65:1, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- We describe two newly developed methods for rapid typing of the pertussis toxin subunit 1 gene (ptxS1). A real-time PCR assay based on hybridization probes and a Pyrosequencing assay were developed and the specificity, sensitivity, cost, hands-on time and post-assay data processing were compared to Sanger sequencing. Both methods enabled discrimination of all four allelic variants, correctly identified all ptxS1 alleles of 143 strains tested and proved suitable for large-scale screening of B. pertussis strains.
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| 21. |
- Storm, Martin, 1975-
(författare)
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Identification and Characterization of Biomarkers in Bacterial Infections
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent years molecular biology has become an integral part of the clinical laboratory. With an ever increasing number of methodologies and applications being presented each year it has increased our knowledge of how bacteria cause disease as well as our ability to predict disease outcome. The main focus of this thesis has been to develop methods for identifying biomarkers and prediction methods for bacterial infectious diseases by taking advantage of the ever increasing possibilities of molecular biology. We applied cutting edge techniques in order to establish novel platforms for identifying and characterizing biomarkers of disease. In paper one we describe a novel approach to measure levels of antibiotic resistance and viability of C. trachomatis, a method that is a clear improvement over existing techniques. In the second paper we describe the development of two assays designed to type pertussis toxin subunit 1 in circulating strains, in order to facilitate multi center studies for vaccine escape surveillance. In paper three we develop a novel microarray application designed to identify a large number of bacterial traits of H. pylori simultaneously with human genetic polymorphisms in order to identify a collection of risk factors that could be used as a prediction tool for gastric cancer risk. In the last paper we define the “antigenome” of H. pylori and identified 14 promising, previously unreported antigens as well as a number of potential biomarkers.The platform technologies described in this collection of papers will hopefully help us identifying novel ways of fighting and predicting bacterial disease in future studies.
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| 22. |
- Taccone, Fabio Silvio, et al.
(författare)
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Death after awakening from post-anoxic coma : The "best CPC" project
- 2019
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In patients who recover consciousness after cardiac arrest (CA), a subsequent death from non-neurological causes may confound the assessment of long-term neurological outcome. We investigated the prevalence and causes of death after awakening (DAA) in a multicenter cohort of CA patients. Methods: Observational multicenter cohort study on patients resuscitated from CA in eight European intensive care units (ICUs) from January 2007 to December 2014. DAA during the hospital stay was extracted retrospectively from patient medical records. Demographics, comorbidities, initial CA characteristics, concomitant therapies, prognostic tests (clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEPs)), and cause of death were identified. Results: From a total 4646 CA patients, 2478 (53%) died in-hospital, of whom 196 (4.2%; ranges 0.6-13.0%) had DAA. DAA was less frequent among out-of-hospital than in-hospital CA (82/2997 [2.7%] vs. 114/1649 [6.9%]; p < 0.001). Median times from CA to awakening and from awakening to death were 2 [1-5] and 9 [3-18] days, respectively. The main causes of DAA were multiple organ failure (n = 61), cardiogenic shock (n = 61), and re-arrest (n = 26). At day 3 from admission, results from EEG (n = 56) and SSEPs (n = 60) did not indicate poor outcome. Conclusions: In this large multicenter cohort, DAA was observed in 4.2% of non-survivors. Information on DAA is crucial since it may influence epidemiology and the design of future CA studies evaluating neuroprognostication and neuroprotection.
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| 23. |
- Travis, Lois B, et al.
(författare)
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Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease
- 2003
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 290:4, s. 465-475
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk.OBJECTIVE: To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD.DESIGN, SETTING, AND SUBJECTS: Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998.MAIN OUTCOME MEASURES: Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents.RESULTS: Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P =.03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P =.003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses.CONCLUSIONS: Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.
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| 24. |
- Travis, Lois B., et al.
(författare)
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Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma
- 2005
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:19, s. 1428-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many women develop breast cancer after treatment for Hodgkin lymphoma (HL) at a young age. We estimated this future risk, taking into account age and calendar year of HL diagnosis, HL treatment information, population breast cancer incidence rates, and competing causes of death. METHODS: Relative risks of breast cancer for categories defined by radiation dose to the chest (0, 20- < 40 Gy, or > or = 40 Gy) and use of alkylating agents (yes or no) were estimated from a case-control study conducted within an international population-based cohort of 3817 female 1-year survivors of HL diagnosed at age 30 years or younger from January 1, 1965, through December 31, 1994. To compute cumulative absolute risks of breast cancer, we used modified standardized incidence ratios to relate cohort breast cancer risks to those in the general population, enabling application of population-based breast cancer rates, and we allowed for competing risks by using population-based mortality rates in female HL survivors. RESULTS: Cumulative absolute risks of breast cancer increased with age at end of follow-up, time since HL diagnosis, and radiation dose. For an HL survivor who was treated at age 25 years with a chest radiation dose of at least 40 Gy without alkylating agents, estimated cumulative absolute risks of breast cancer by age 35, 45, and 55 years were 1.4% (95% confidence interval [CI] = 0.9% to 2.1%), 11.1% (95% CI = 7.4% to 16.3%), and 29.0% (95% CI = 20.2% to 40.1%), respectively. Cumulative absolute risks were lower in women treated with alkylating agents. CONCLUSIONS: Breast cancer projections varied considerably by type of HL therapy, time since HL diagnosis, and age at end of follow-up. These estimates are applicable to HL survivors treated with regimens of the past and can be used to counsel such patients and plan management and preventive strategies. Projections should be used with caution, however, in patients treated with more recent approaches, including limited-field radiotherapy and/or ovary-sparing chemotherapy.
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| 25. |
- Travis, Lois B, et al.
(författare)
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Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease
- 2002
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 94:3, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use.METHODS: Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided.RESULTS: Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1-4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment.CONCLUSIONS: Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco.
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