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  • 1. Aleksandrova, Krasimira
    et al.
    Pischon, Tobias
    Jenab, Mazda
    Bueno-de-Mesquita, H Bas
    Fedirko, Veronika
    Norat, Teresa
    Romaguera, Dora
    Knüppel, Sven
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Dartois, Laureen
    Kaaks, Rudolf
    Li, Kuanrong
    Tjønneland, Anne
    Overvad, Kim
    Quirós, José Ramón
    Buckland, Genevieve
    Sánchez, María José
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Bradbury, Kathryn E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Siersema, Peter D
    Peeters, Petra HM
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Ericson, Ulrika
    Ohlsson, Bodil
    Weiderpass, Elisabete
    Skeie, Guri
    Borch, Kristin
    Rinaldi, Sabina
    Romieu, Isabelle
    Kong, Joyce
    Gunter, Marc J
    Ward, Heather A
    Riboli, Elio
    Boeing, Heiner
    Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study2014Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, nr 1, s. 168-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

  • 2.
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa ; Institute of Applied Health Sciences, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
    The global burden of liver disease: a challenge for methods and for public health2014Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, s. 159-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    New Global Burden of Disease estimates for liver cirrhosis, published in BMC Medicine, suggest that cirrhosis caused over a million deaths in 2010, with a further million due to liver cancer and acute hepatitis. Cause-specific mortality data were very sparse for some regions, particularly in Africa, with no relevant mortality data for 58/187 countries. Liver disease involves infectious, malignant and chronic aetiologies with overlapping symptoms. Where available mortality data come from verbal autopsies, separating different types of liver disease is challenging. Cirrhosis is a disease of rich and poor alike; key public health risk factors such as alcohol consumption play an important role. Risk-reduction strategies such as controlling the price of alcohol are being widely discussed. Since these estimates used alcohol consumption as a covariate, they cannot be used to explore relationships between alcohol consumption and cirrhosis mortality. There is hope: coming generations of adults will have been vaccinated against hepatitis B, and this is envisaged to reduce the burden of fatal liver disease. But more complete civil registration globally is needed to fully understand the burden of liver disease.

  • 3.
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. WHO Collaborating Centre for Verbal Autopsy, Umeå Centre for Global Health Research, Umeå University and School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
    Usefulness of the Population Health Metrics Research Consortium gold standard verbal autopsy data for general verbal autopsy methods2014Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, nr 1, s. 23-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Verbal Autopsy (VA) is widely viewed as the only immediate strategy for registering cause of death in much of Africa and Asia, where routine physician certification of deaths is not widely practiced. VA involves a lay interview with family or friends after a death, to record essential details of the circumstances. These data can then be processed automatically to arrive at standardized cause of death information.

    METHODS: The Population Health Metrics Research Consortium (PHMRC) undertook a study at six tertiary hospitals in low- and middle-income countries which documented over 12,000 deaths clinically and subsequently undertook VA interviews. This dataset, now in the public domain, was compared with the WHO 2012 VA standard and the InterVA-4 interpretative model.

    RESULTS: The PHMRC data covered 70% of the WHO 2012 VA input indicators, and categorized cause of death according to PHMRC definitions. After eliminating some problematic or incomplete records, 11,984 VAs were compared. Some of the PHMRC cause definitions, such as 'preterm delivery', differed substantially from the International Classification of Diseases, version 10 equivalent. There were some appreciable inconsistencies between the hospital and VA data, including 20% of the hospital maternal deaths being described as non-pregnant in the VA data. A high proportion of VA cases (66%) reported respiratory symptoms, but only 18% of assigned hospital causes were respiratory-related. Despite these issues, the concordance correlation coefficient between hospital and InterVA-4 cause of death categories was 0.61.

    CONCLUSIONS: The PHMRC dataset is a valuable reference source for VA methods, but has to be interpreted with care. Inherently inconsistent cases should not be included when using these data to build other VA models. Conversely, models built from these data should be independently evaluated. It is important to distinguish between the internal and external validity of VA models. The effects of using tertiary hospital data, rather than the more usual application of VA to all-community deaths, are hard to evaluate. However, it would still be of value for VA method development to have further studies of population-based post-mortem examinations.

  • 4.
    Byass, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa. Institute of Applied Health Sciences, University of Aberdeen, Scotland, UK; Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa.
    Hussain-Alkhateeb, Laith
    D'Ambruoso, Lucia
    Clark, Samuel
    Davies, Justine
    Fottrell, Edward
    Bird, Jon
    Kabudula, Chodziwadziwa
    Tollman, Stephen M.
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa. Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa; INDEPTH Network, Accra, Ghana.
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa. Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa; INDEPTH Network, Accra, Ghana.
    Schiöler, Linus
    Petzold, Max
    An integrated approach to processing WHO-2016 verbal autopsy data: the InterVA-5 model2019Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 17, artikel-id 102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Verbal autopsy is an increasingly important methodology for assigning causes to otherwise uncertified deaths, which amount to around 50% of global mortality and cause much uncertainty for health planning. The World Health Organization sets international standards for the structure of verbal autopsy interviews and for cause categories that can reasonably be derived from verbal autopsy data. In addition, computer models are needed to efficiently process large quantities of verbal autopsy interviews to assign causes of death in a standardised manner. Here, we present the InterVA-5 model, developed to align with the WHO-2016 verbal autopsy standard. This is a harmonising model that can process input data from WHO-2016, as well as earlier WHO-2012 and Tariff-2 formats, to generate standardised cause-specific mortality profiles for diverse contexts.

    The software development involved building on the earlier InterVA-4 model, and the expanded knowledge base required for InterVA-5 was informed by analyses from a training dataset drawn from the Population Health Metrics Research Collaboration verbal autopsy reference dataset, as well as expert input.

    Results: The new model was evaluated against a test dataset of 6130 cases from the Population Health Metrics Research Collaboration and 4009 cases from the Afghanistan National Mortality Survey dataset. Both of these sources contained around three quarters of the input items from the WHO-2016, WHO-2012 and Tariff-2 formats. Cause-specific mortality fractions across all applicable WHO cause categories were compared between causes assigned in participating tertiary hospitals and InterVA-5 in the test dataset, with concordance correlation coefficients of 0.92 for children and 0.86 for adults.

    The InterVA-5 model’s capacity to handle different input formats was evaluated in the Afghanistan dataset, with concordance correlation coefficients of 0.97 and 0.96 between the WHO-2016 and the WHO-2012 format for children and adults respectively, and 0.92 and 0.87 between the WHO-2016 and the Tariff-2 format respectively.

    Conclusions: Despite the inherent difficulties of determining “truth” in assigning cause of death, these findings suggest that the InterVA-5 model performs well and succeeds in harmonising across a range of input formats. As more primary data collected under WHO-2016 become available, it is likely that InterVA-5 will undergo minor re-versioning in the light of practical experience. The model is an important resource for measuring and evaluating cause-specific mortality globally.

  • 5. Desai, Nikita
    et al.
    Aleksandrowicz, Lukasz
    Miasnikof, Pierre
    Lu, Ying
    Leitao, Jordana
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. WHO Collaborating Centre for Verbal Autopsy, Umeå Centre for Global Health Research, Umeå University, Umeå.
    Tollman, Stephen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa and International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) Network, Accra, Ghana.
    Mee, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
    Alam, Dewan
    Rathi, Suresh Kumar
    Singh, Abhishek
    Kumar, Rajesh
    Ram, Faujdar
    Jha, Prabhat
    Performance of four computer-coded verbal autopsy methods for cause of death assignment compared with physician coding on 24,000 deaths in low- and middle-income countries2014Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, nr 1, s. 20-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Physician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (CODs) in countries where medical certification of death is uncommon. Computer-coded verbal autopsy (CCVA) methods have been proposed as a faster and cheaper alternative to PCVA, though they have not been widely compared to PCVA or to each other.

    METHODS: We compared the performance of open-source random forest, open-source tariff method, InterVA-4, and the King-Lu method to PCVA on five datasets comprising over 24,000 verbal autopsies from low- and middle-income countries. Metrics to assess performance were positive predictive value and partial chance-corrected concordance at the individual level, and cause-specific mortality fraction accuracy and cause-specific mortality fraction error at the population level.

    RESULTS: The positive predictive value for the most probable COD predicted by the four CCVA methods averaged about 43% to 44% across the datasets. The average positive predictive value improved for the top three most probable CODs, with greater improvements for open-source random forest (69%) and open-source tariff method (68%) than for InterVA-4 (62%). The average partial chance-corrected concordance for the most probable COD predicted by the open-source random forest, open-source tariff method and InterVA-4 were 41%, 40% and 41%, respectively, with better results for the top three most probable CODs. Performance generally improved with larger datasets. At the population level, the King-Lu method had the highest average cause-specific mortality fraction accuracy across all five datasets (91%), followed by InterVA-4 (72% across three datasets), open-source random forest (71%) and open-source tariff method (54%).

    CONCLUSIONS: On an individual level, no single method was able to replicate the physician assignment of COD more than about half the time. At the population level, the King-Lu method was the best method to estimate cause-specific mortality fractions, though it does not assign individual CODs. Future testing should focus on combining different computer-coded verbal autopsy tools, paired with PCVA strengths. This includes using open-source tools applied to larger and varied datasets (especially those including a random sample of deaths drawn from the population), so as to establish the performance for age- and sex-specific CODs.

  • 6. Disney-Hogg, Linden
    et al.
    Cornish, Alex J.
    Sud, Amit
    Law, Philip J.
    Kinnersley, Ben
    Jacobs, Daniel I.
    Ostrom, Quinn T.
    Labreche, Karim
    Eckel-Passow, Jeanette E.
    Armstrong, Georgina N.
    Claus, Elizabeth B.
    Il'yasova, Dora
    Schildkraut, Joellen
    Barnholtz-Sloan, Jill S.
    Olson, Sara H.
    Bernstein, Jonine L.
    Lai, Rose K.
    Schoemaker, Minouk J.
    Simon, Matthias
    Hoffmann, Per
    Noethen, Markus M.
    Joeckel, Karl-Heinz
    Chanock, Stephen
    Rajaraman, Preetha
    Johansen, Christoffer
    Jenkins, Robert B.
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wrensch, Margaret R.
    Sanson, Marc
    Bondy, Melissa L.
    Houlston, Richard S.
    Impact of atopy on risk of glioma: a Mendelian randomisation study2018Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, artikel-id 42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.

    Methods: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.

    Results: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).

    Conclusions: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.

  • 7. European Delirium Association,
    et al.
    American Delirium Society,
    The DSM-5 criteria, level of arousal and delirium diagnosis: inclusiveness is safer2014Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, nr 1, artikel-id 141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Delirium is a common and serious problem among acutely unwell persons. Although linked to higher rates of mortality, institutionalisation and dementia, it remains underdiagnosed. Careful consideration of its phenomenology is warranted to improve detection and therefore mitigate some of its clinical impact. The publication of the fifth edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-5) provides an opportunity to examine the constructs underlying delirium as a clinical entity.

    DISCUSSION: Altered consciousness has been regarded as a core feature of delirium; the fact that consciousness itself should be physiologically disrupted due to acute illness attests to its clinical urgency. DSM-5 now operationalises 'consciousness' as 'changes in attention'. It should be recognised that attention relates to content of consciousness, but arousal corresponds to level of consciousness. Reduced arousal is also associated with adverse outcomes. Attention and arousal are hierarchically related; level of arousal must be sufficient before attention can be reasonably tested.

    SUMMARY: Our conceptualisation of delirium must extend beyond what can be assessed through cognitive testing (attention) and accept that altered arousal is fundamental. Understanding the DSM-5 criteria explicitly in this way offers the most inclusive and clinically safe interpretation.

  • 8. Fedirko, Veronika
    et al.
    Tran, Hao Quang
    Gewirtz, Andrew T
    Stepien, Magdalena
    Trichopoulou, Antonia
    Aleksandrova, Krasimira
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Carbonnel, Franck
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Kühn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Bamia, Christina
    Lagiou, Pagona
    Grioni, Sara
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Naccarati, Alessio
    Peeters, Petra H
    Bueno-de-Mesquita, H B
    Weiderpass, Elisabete
    Castaño, José María Huerta
    Barricarte, Aurelio
    Sánchez, María-José
    Dorronsoro, Miren
    Quirós, J Ramón
    Agudo, Antonio
    Sjöberg, Klas
    Ohlsson, Bodil
    Hemmingsson, Oskar
    Department of Surgical and Perioperative Sciences, Kirurgcentrum, Norrlands Universitetssjukhus, Umeå, Sweden.
    Werner, Mårten
    Department of Medicine Sections for Hepatology and Gastroenterology, Umeå University Hospital, SE-90185 Umeå, Sweden.
    Bradbury, Kathryn E
    Khaw, Kay-Tee
    Wareham, Nick
    Tsilidis, Konstantinos K
    Aune, Dagfinn
    Scalbert, Augustin
    Romieu, Isabelle
    Riboli, Elio
    Jenab, Mazda
    Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study2017Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 72, nr 15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.

    METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.

    RESULTS:  = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.

    CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

  • 9.
    Franks, Paul W
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ling, Charlotte
    Epigenetics and obesity: the devil is in the details2010Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 8, s. 88-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity is a complex disease with multiple well-defined risk factors. Nevertheless, susceptibility to obesity and its sequelae within obesogenic environments varies greatly from one person to the next, suggesting a role for gene × environment interactions in the etiology of the disorder. Epigenetic regulation of the human genome provides a putative mechanism by which specific environmental exposures convey risk for obesity and other human diseases and is one possible mechanism that underlies the gene × environment/treatment interactions observed in epidemiological studies and clinical trials. A study published in BMC Medicine this month by Wang et al. reports on an examination of DNA methylation in peripheral blood leukocytes of lean and obese adolescents, comparing methylation patterns between the two groups. The authors identified two genes that were differentially methylated, both of which have roles in immune function. Here we overview the findings from this study in the context of those emerging from other recent genetic and epigenetic studies, discuss the strengths and weaknesses of the study and speculate on the future of epigenetics in chronic disease research.

  • 10. Gnanapragasam, V. J.
    et al.
    Bratt, O.
    Muir, K.
    Lees, L. S.
    Huang, H. H.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Lophatananon, A.
    The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study2018Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, artikel-id 31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.

    Methods: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.

    Results: The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n =3D 20,586), C-index 0.77 vs. 074; radiotherapy (n =3D 11,872), C-index 0.73 vs. 0.69; and conservative management (n =3D 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).

    Conclusions: This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

  • 11. Leitao, Jordana
    et al.
    Desai, Nikita
    Aleksandrowicz, Lukasz
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå Centre for Global Health Research, Umeå University.
    Miasnikof, Pierre
    Tollman, Stephen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå Centre for Global Health Research, Umeå University, University of the Witwatersrand, Johannesburg, South Africa and International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) Network, Accra, Ghana.
    Alam, Dewan
    Lu, Ying
    Rathi, Suresh Kumar
    Singh, Abhishek
    Suraweera, Wilson
    Ram, Faujdar
    Jha, Prabhat
    Comparison of physician-certified verbal autopsy with computer-coded verbal autopsy for cause of death assignment in hospitalized patients in low- and middle-income countries: systematic review2014Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, nr 1, s. 22-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Computer-coded verbal autopsy (CCVA) methods to assign causes of death (CODs) for medically unattended deaths have been proposed as an alternative to physician-certified verbal autopsy (PCVA). We conducted a systematic review of 19 published comparison studies (from 684 evaluated), most of which used hospital-based deaths as the reference standard. We assessed the performance of PCVA and five CCVA methods: Random Forest, Tariff, InterVA, King-Lu, and Simplified Symptom Pattern.

    METHODS: The reviewed studies assessed methods' performance through various metrics: sensitivity, specificity, and chance-corrected concordance for coding individual deaths, and cause-specific mortality fraction (CSMF) error and CSMF accuracy at the population level. These results were summarized into means, medians, and ranges.

    RESULTS: The 19 studies ranged from 200 to 50,000 deaths per study (total over 116,000 deaths). Sensitivity of PCVA versus hospital-assigned COD varied widely by cause, but showed consistently high specificity. PCVA and CCVA methods had an overall chance-corrected concordance of about 50% or lower, across all ages and CODs. At the population level, the relative CSMF error between PCVA and hospital-based deaths indicated good performance for most CODs. Random Forest had the best CSMF accuracy performance, followed closely by PCVA and the other CCVA methods, but with lower values for InterVA-3.

    CONCLUSIONS: There is no single best-performing coding method for verbal autopsies across various studies and metrics. There is little current justification for CCVA to replace PCVA, particularly as physician diagnosis remains the worldwide standard for clinical diagnosis on live patients. Further assessments and large accessible datasets on which to train and test combinations of methods are required, particularly for rural deaths without medical attention.

  • 12. Merritt, Melissa A
    et al.
    Riboli, Elio
    Murphy, Neil
    Kadi, Mai
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Dossus, Laure
    Dartois, Laureen
    Clavel-Chapelon, Françoise
    Fortner, Renée T
    Katzke, Verena A
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H
    Lund, Eiliv
    Nakamura, Aurelie
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Molina-Montes, Esther
    Larrañaga, Nerea
    Dorronsoro, Miren
    Cirera, Lluís
    Barricarte, Aurelio
    Olsson, Åsa
    Butt, Salma
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wareham, Nicholas J
    Key, Timothy J
    Brennan, Paul
    Ferrari, Pietro
    Wark, Petra A
    Norat, Teresa
    Cross, Amanda J
    Gunter, Marc J
    Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition: a cohort study2015Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, artikel-id 252Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. Methods: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled > 500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. Results: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (>= 15 years versus < 12; 0.90; 0.85-0.96; P for trend = 0.038). Conclusions: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.

  • 13. Muller, David C.
    et al.
    Murphy, Neil
    Johansson, Mattias
    Ferrari, Pietro
    Tsilidis, Konstantinos K.
    Boutron-Ruault, Marie-Christine
    Clavel, Francoise
    Dartois, Laureen
    Li, Kuanrong
    Kaaks, Rudolf
    Weikert, Cornelia
    Bergmann, Manuela
    Boeing, Heiner
    Tjonneland, Anne
    Overvad, Kim
    Luisa Redondo, M.
    Agudo, Antonio
    Molina-Portillo, Elena
    Altzibar, Jone M.
    Cirera, Lluis
    Ardanaz, Eva
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Key, Timothy J.
    Travis, Ruth C.
    Bamia, Christina
    Orfanos, Philippos
    Trichopoulou, Antonia
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Vineis, Paolo
    Panico, Salvatore
    Bueno-de-Mesquita, H. Bas
    Verschuren, W. M. Monique
    Struijk, Ellen A.
    Peeters, Petra H.
    Engstrom, Gunnar
    Melander, Olle
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Weiderpass, Elisabete
    Skeie, Guri
    Lund, Eiliv
    Norat, Teresa
    Gunter, Marc
    Riboli, Elio
    Brennan, Paul
    Modifiable causes of premature death in middle-age in Western Europe: results from the EPIC cohort study2016Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 14, artikel-id 87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. Methods: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models. Results: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31-32 %) and 14 % (95 % CI, 12-16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8-12 %) and high blood pressure (9 %; 95 % CI, 7-11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55-59 %), being 35 % (95 % CI, 32-37 %) among never smokers and 74 % (95 % CI, 73-75 %) among current smokers. Conclusions: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.

  • 14. Mutie, Pascal M.
    et al.
    Giordano, Giuseppe N.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund Univ, Skane Univ Hosp, Dept Clin Sci, Harvard Sch Publ Hlth, Univ Oxford, Radcliff Dept Med.
    Lifestyle precision medicine: the next generation in type 2 diabetes prevention?2017Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, artikel-id 171Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The driving force behind the current global type 2 diabetes epidemic is insulin resistance in overweight and obese individuals. Dietary factors, physical inactivity, and sedentary behaviors are the major modifiable risk factors for obesity. Nevertheless, many overweight/obese people do not develop diabetes and lifestyle interventions focused on weight loss and diabetes prevention are often ineffective. Traditionally, chronically elevated blood glucose concentrations have been the hallmark of diabetes; however, many individuals will either remain 'prediabetic' or regress to normoglycemia. Thus, there is a growing need for innovative strategies to tackle diabetes at scale. The emergence of biomarker technologies has allowed more targeted therapeutic strategies for diabetes prevention (precision medicine), though largely confined to pharmacotherapy. Unlike most drugs, lifestyle interventions often have systemic health-enhancing effects. Thus, the pursuance of lifestyle precision medicine in diabetes seems rational. Herein, we review the literature on lifestyle interventions and diabetes prevention, describing the biological systems that can be characterized at scale in human populations, linking them to lifestyle in diabetes, and consider some of the challenges impeding the clinical translation of lifestyle precision medicine.

  • 15. Ndila, Carolyne
    et al.
    Bauni, Evasius
    Nyirongo, Vysaul
    Mochamah, George
    Makazi, Alex
    Kosgei, Patrick
    Nyutu, Gideon
    Macharia, Alex
    Kapesa, Sailoki
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Williams, Thomas N.
    Verbal autopsy as a tool for identifying children dying of sickle cell disease: a validation study conducted in Kilifi district, Kenya2014Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, s. 65-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Sickle cell disease (SCD) is common in many parts of sub-Saharan Africa (SSA), where it is associated with high early mortality. In the absence of newborn screening, most deaths among children with SCD go unrecognized and unrecorded. As a result, SCD does not receive the attention it deserves as a leading cause of death among children in SSA. In the current study, we explored the potential utility of verbal autopsy (VA) as a tool for attributing underlying cause of death (COD) in children to SCD. Methods: We used the 2007 WHO Sample Vital Registration with Verbal Autopsy (SAWY) VA tool to determine COD among child residents of the Kilifi Health and Demographic Surveillance System (KHDSS), Kenya, who died between January 2008 and April 2011. VAs were coded both by physician review (physician coded verbal autopsy, PCVA) using COD categories based on the WHO International Classification of Diseases 10(th) Edition (ICD-10) and by using the InterVA-4 probabilistic model after extracting data according to the 2012 WHO VA standard. Both of these methods were validated against one of two gold standards: hospital ICD-10 physician-assigned COD for children who died in Kilifi District Hospital (KDH) and, where available, laboratory confirmed SCD status for those who died in the community. Results: Overall, 6% and 5% of deaths were attributed to SCD on the basis of PCVA and the InterVA-4 model, respectively. Of the total deaths, 22% occurred in hospital, where the agreement coefficient (AC(1)) for SCD between PCVA and hospital physician diagnosis was 95.5%, and agreement between InterVA-4 and hospital physician diagnosis was 96.9%. Confirmatory laboratory evidence of SCD status was available for 15% of deaths, in which the AC(1) against PCVA was 87.5%. Conclusions: Other recent studies and provisional data from this study, outlining the importance of SCD as a cause of death in children in many parts of the developing world, contributed to the inclusion of specific SCD questions in the 2012 version of the WHO VA instruments, and a specific code for SCD has now been included in the WHO and InterVA-4 COD listings. With these modifications, VA may provide a useful approach to quantifying the contribution of SCD to childhood mortality in rural African communities. Further studies will be needed to evaluate the generalizability of our findings beyond our local context.

  • 16. Ordóñez-Mena, José Manuel
    et al.
    Schöttker, Ben
    Mons, Ute
    Jenab, Mazda
    Freisling, Heinz
    Bueno-de-Mesquita, Bas
    O'Doherty, Mark G.
    Scott, Angela
    Kee, Frank
    Stricker, Bruno H.
    Hofman, Albert
    de Keyser, Catherine E.
    Ruiter, Rikje
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Jousilahti, Pekka
    Kuulasmaa, Kari
    Freedman, Neal D.
    Wilsgaard, Tom
    de Groot, Lisette C. P. G. M.
    Kampman, Ellen
    Håkansson, Niclas
    Orsini, Nicola
    Wolk, Alicja
    Nilsson, Lena Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Tjønneland, Anne
    Pająk, Andrzej
    Malyutina, Sofia
    Kubínová, Růžena
    Tamosiunas, Abdonas
    Bobak, Martin
    Katsoulis, Michail
    Orfanos, Philippos
    Boffetta, Paolo
    Trichopoulou, Antonia
    Brenner, Hermann
    Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium2016Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 14, artikel-id 62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.

    Methods: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.

    Results: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.

    Conclusions: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

  • 17. O'Reilly, Kathleen M.
    et al.
    Lowe, Rachel
    Edmunds, W. John
    Mayaud, Philippe
    Kucharski, Adam
    Eggo, Rosalind M.
    Funk, Sebastian
    Bhatia, Deepit
    Khan, Kamran
    Kraemer, Moritz U. G.
    Wilder-Smith, Annelies
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK; Institute of Public Health, University of Heidelberg, Heidelberg, Germany.
    Rodrigues, Laura C.
    Brasil, Patricia
    Massad, Eduardo
    Jaenisch, Thomas
    Cauchemez, Simon
    Brady, Oliver J.
    Yakob, Laith
    Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis2018Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, artikel-id 180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC) region in 2013, with serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and the lack of a comprehensive collation of data from affected countries.

    Methods: Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 90 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.

    Results: There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 would present within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p < 0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.

    Conclusions: The findings suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.

  • 18. Perez-Cornago, Aurora
    et al.
    Appleby, Paul N.
    Pischon, Tobias
    Tsilidis, Konstantinos K.
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Kaaks, Rudolf
    Kuehn, Tilman
    Boeing, Heiner
    Steffen, Annika
    Trichopoulou, Antonia
    Lagiou, Pagona
    Kritikou, Maria
    Krogh, Vittorio
    Palli, Domenico
    Sacerdote, Carlotta
    Tumino, Rosario
    Bueno-de-Mesquita, H. Bas
    Agudo, Antonio
    Larranaga, Nerea
    Molina-Portillo, Elena
    Barricarte, Aurelio
    Chirlaque, Maria-Dolores
    Ramon Quiros, J.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University.
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University.
    Wareham, Nick
    Khaw, Kay-Tee
    Schmidt, Julie A.
    Gunter, Marc
    Freisling, Heinz
    Aune, Dagfinn
    Ward, Heather
    Riboli, Elio
    Key, Timothy J.
    Travis, Ruth C.
    Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study2017Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, artikel-id 115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. Results: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P-heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P-heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P-heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96). Conclusions: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

  • 19.
    Risberg, Gunilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Hamberg, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Johansson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Gender perspective in medicine: a vital part of medical scientific rationality. A useful model for comprehending structures and hierarchies within medical science.2006Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, nr 4, s. 20-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: During the past few decades, research has reported gender bias in various areas of clinical and academic medicine. To prevent such bias, a gender perspective in medicine has been requested, but difficulties and resistance have been reported from implementation attempts. Our study aimed at analysing this resistance in relation to what is considered good medical research.

    METHOD: We used a theoretical model, based on scientific competition, to understand the structures of scientific medicine and how they might influence the resistance to a gender perspective in medicine. The model was originally introduced to discuss how pluralism improves rationality in the social sciences.

    RESULTS: The model provided a way to conceptualise different fields of research in medicine: basic research, applied research, medical philosophy, and 'empowering' research. It clarified how various research approaches within medicine relate to each other, and how they differ and compete. It also indicated why there might be conflicts between them: basic and applied research performed within the biomedical framework have higher status than gender research and other research approaches that are performed within divergent research paradigms.

    CONCLUSION: This hierarchy within medical research contributes to the resistance to a gender perspective, causing gender bias and making medical scientific rationality suboptimal. We recommend that the theoretical model can be applied in a wider medical context when different and hierarchically arranged research traditions are in conflict. In this way, the model might contribute to shape a medical community where scientific pluralism is acknowledged to enlarge, not to disturb, the scientific rationality of medicine.

  • 20. Rohrmann, Sabine
    et al.
    Overvad, Kim
    Bueno-de-Mesquita, H Bas
    Jakobsen, Marianne U
    Egeberg, Rikke
    Tjonneland, Anne
    Nailler, Laura
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Krogh, Vittorio
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Bergmann, Manuela M
    Boeing, Heiner
    Li, Kuanrong
    Kaaks, Rudolf
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Crowe, Francesca L
    Key, Timothy J
    Naska, Androniki
    Trichopoulou, Antonia
    Trichopoulos, Dimitirios
    Leenders, Max
    Peeters, Petra HM
    Engeset, Dagrun
    Parr, Christine L
    Skeie, Guri
    Jakszyn, Paula
    Sanchez, Maria-Jose
    Huerta, Jose M
    Luisa Redondo, M
    Barricarte, Aurelio
    Amiano, Pilar
    Drake, Isabel
    Sonestedt, Emily
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Fedirko, Veronika
    Romieux, Isabelle
    Ferrari, Pietro
    Norat, Teresa
    Vergnaud, Anne C
    Riboli, Elio
    Linseisen, Jakob
    Meat consumption and mortality: results from the European Prospective Investigation into Cancer and Nutrition2013Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 11, s. 63-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality.

    Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality.

    Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

  • 21. Romaguera, Dora
    et al.
    Ward, Heather
    Wark, Petra A
    Vergnaud, Anne-Claire
    Peeters, Petra H
    van Gils, Carla H
    Ferrari, Pietro
    Fedirko, Veronika
    Jenab, Mazda
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Dartois, Laureen
    Hansen, Camilla Plambeck
    Dahm, Christina Catherine
    Buckland, Genevieve
    Sánchez, María José
    Dorronsoro, Miren
    Navarro, Carmen
    Barricarte, Aurelio
    Key, Timothy J
    Trichopoulou, Antonia
    Tsironis, Christos
    Lagiou, Pagona
    Masala, Giovanna
    Pala, Valeria
    Tumino, Rosario
    Vineis, Paolo
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Ohlsson, Bodil
    Jirström, Karin
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Weiderpass, Elisabete
    Kühn, Tilman
    Katzke, Verena
    Khaw, Kay-Tee
    Wareham, Nick J
    Tjønneland, Anne
    Boeing, Heiner
    Quirós, José R
    Gunter, Marc J
    Riboli, Elio
    Norat, Teresa
    Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study2015Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, artikel-id 107Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients.

    METHODS: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.

    RESULTS: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models.

    CONCLUSIONS: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.

  • 22.
    Santosa, Ailiana
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Rocklöv, Joacim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Högberg, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Achieving a 25% reduction in premature non-communicable disease mortality: the Swedish population as a cohort study2015Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, nr 65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The 2012 World Health Assembly set a target for Member States to reduce premature non-communicable disease (NCD) mortality by 25% over the period 2010 to 2025. This reflected concerns about increasing NCD mortality burdens among productive adults globally.

    OBJECTIVES: We firstly considered whether the WHO target of a 25% reduction in the unconditional probability of dying between ages of 30 and 70 from NCDs (cardiovascular diseases, cancer, diabetes or chronic respiratory diseases) had already taken place in Sweden during an equivalent 15-year period. Secondly, we assessed which population sub-groups had been more or less successful in contributing to overall changes in premature NCD mortality in Sweden.

    METHODS: A retrospective dynamic cohort database was constructed from Swedish population registers in the Linnaeus database, covering the entire population in the age range 30-69 years for the period 1991 to 2006, which was used directly to measure reductions in premature NCD mortality. Multivariate Poisson regression models were used to assess the contributions of individual background factors to decreases in premature NCD mortality.

    RESULTS: A total of 292,320 deaths occurred in the 30-69 year age group during the period 1991 to 2006, against 70,768,848 person-years registered. The crude all-cause mortality rate declined from 5.03 to 3.72 per 1,000 person-years, a 26% reduction. Within this, the unconditional probability of dying between the ages of 30 and 70 from NCD causes as defined by WHO fell by 30.0%. Age was consistently the strongest determinant of NCD mortality. Background determinants of NCD mortality changed significantly over the four time periods 1991-1994, 1995-1998, 1999-2002 and 2003-2006.

    CONCLUSIONS: Sweden, now at a late stage of epidemiological transition, has already exceeded the 25% premature NCD mortality reduction target during an earlier 15-year period. This should be encouraging news for countries currently implementing premature NCD mortality reduction programmes. Our findings suggest, however, that it may be difficult for Sweden and other late-transition countries to reach the current 25x25 target, particularly where substantial premature mortality reductions have already been achieved.

  • 23.
    Stewart Williams, Jennifer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Research Centre for Gender, Health and Ageing, Faculty of Health, University of Newcastle, Newcastle, Australia.
    Kowal, Paul
    Hestekin, Heather
    O'Driscoll, Tristan
    Peltzer, Karl
    Yawson, Alfred
    Biritwum, Richard
    Maximova, Tamara
    Salinas Rodriguez, Aaron
    Manrique Espinoza, Betty
    Wu, Fan
    Arokiasamy, Perianayagam
    Chatterji, Somnath
    Prevalence, risk factors and disability associated with fall-related injury in older adults in low- and middle-income countries: results from the WHO Study on global AGEing and adult health (SAGE)2015Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, artikel-id 147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In 2010 falls were responsible for approximately 80 % of disability stemming from unintentional injuries excluding traffic accidents in adults 50 years and over. Falls are becoming a major public health problem in low-and middle-income countries (LMICs) where populations are ageing rapidly. Methods: Nationally representative standardized data collected from adults aged 50 years and over participating in the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) Wave 1 in China, Ghana, India, Mexico, the Russian Federation and South Africa are analysed. The aims are to identify the prevalence of, and risk factors for, past-year fall-related injury and to assess associations between fall-related injury and disability. Regression methods are used to identify risk factors and association between fall-related injury and disability. Disability was measured using the WHO Disability Assessment Schedule Version 2.0 (WHODAS 2.0). Results: The prevalence of past-year fall-related injuries ranged from 6.6 % in India to 1.0 % in South Africa and was 4.0 % across the pooled countries. The proportion of all past-year injuries that were fall-related ranged from 73.3 % in the Russian Federation to 44.4 % in Ghana. Across the six countries this was 65.7 %. In the multivariable logistic regression, the odds of past-year fall-related injury were significantly higher for: women (OR: 1.27; 95 % CI: 0.99,1.62); respondents who lived in rural areas (OR: 1.36; 95 % CI: 1.06,1.75); those with depression (OR: 1.43; 95 % CI: 1.01,2.02); respondents who reported severe or extreme problems sleeping (OR: 1.54; 95 % CI: 1.15,2.08); and those who reported two or more (compared with no) chronic conditions (OR: 2.15; 95 % CI: 1.45,3.19). Poor cognition was also a significant risk factor for fall-related injury. The association between fall-related injury and the WHODAS measure of disability was highly significant (P<0.0001) with some attenuation after adjusting for confounders. Reporting two or more chronic conditions (compared with none) was significantly associated with disability (P<0.0001). Conclusions: The findings provide a platform for improving understanding of risk factors for falls in older adults in this group of LMICs. Clinicians and public health professionals in these countries must be made aware of the extent of this problem and the need to implement policies to reduce the risk of falls in older adults.

  • 24. Wilder-Smith, Annelies
    et al.
    Leong, Wei-Yee
    Lopez, Luis Fernandez
    Amaku, Marcos
    Quam, Mikkel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Khan, Kamran
    Massad, Eduardo
    Potential for international spread of wild poliovirus via travelers2015Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, artikel-id 133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The endgame of polio eradication is hampered by the international spread of poliovirus via travelers. In response to ongoing importations of poliovirus into polio-free countries, on 5 May 2014, WHO's Director-General declared the international spread of wild poliovirus a public health emergency of international concern. Our objective was to develop a mathematical model to estimate the international spread of polio infections. Methods: Our model took into account polio endemicity in polio-infected countries, population size, polio immunization coverage rates, infectious period, the asymptomatic-to-symptomatic ratio, and also the probability of a traveler being infectious at the time of travel. We applied our model to three scenarios: (1) number of exportations of both symptomatic and asymptomatic polio infections out of currently polio-infected countries, (2) the risk of spread of poliovirus to Saudi Arabia via Hajj pilgrims, and (3) the importation risk of poliovirus into India. Results: Our model estimated 665 polio exportations (>99 % of which were asymptomatic) from nine polio-infected countries in 2014, of which 78.3 % originated from Pakistan. Our model also estimated 21 importations of poliovirus into Saudi Arabia via Hajj pilgrims and 20 poliovirus infections imported to India in the same year. Conclusion: The extent of importations of asymptomatic and symptomatic polio infections is substantial. For countries that are vulnerable to polio outbreaks due to poor national polio immunization coverage rates, our newly developed model may help guide policy-makers to decide whether imposing an entry requirement in terms of proof of vaccination against polio would be justified.

  • 25.
    Wilder-Smith, Annelies
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Immunization, Vaccines & Biologicals, World Health Organization, Geneva, Switzerland; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
    Vannice, Kirsten
    Durbin, Anna
    Hombach, Joachim
    Thomas, Stephen J.
    Thevarjan, Irani
    Simmons, Cameron P.
    Zika vaccines and therapeutics: landscape analysis and challenges ahead2018Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, artikel-id 84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines.

    DISCUSSION: Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome.

    CONCLUSION: Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.

  • 26. Zheng, Ju-Sheng
    et al.
    Sharp, Stephen J.
    Imamura, Fumiaki
    Koulman, Albert
    Schulze, Matthias B.
    Ye, Zheng
    Griffin, Jules
    Guevara, Marcela
    María Huerta, José
    Kröger, Janine
    Sluijs, Ivonne
    Agudo, Antonio
    Barricarte, Aurelio
    Boeing, Heiner
    Colorado-Yohar, Sandra
    Dow, Courtney
    Dorronsoro, Miren
    Dinesen, Pia T.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University, Malmö, Sweden.
    Feskens, Edith J. M.
    Kühn, Tilman
    Katzke, Verena Andrea
    Key, Timothy J.
    Khaw, Kay-Tee
    de Magistris, Maria Santucci
    Romana Mancini, Francesca
    Molina-Portillo, Elena
    Nilsson, Peter M.
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Ramón Quirós, Jose
    Rolandsson, Olov
    Ricceri, Fulvio
    Spijkerman, Annemieke M. W.
    Slimani, Nadia
    Tagliabue, Giovanna
    Tjonneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Langenberg, Claudia
    Riboli, Elio
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study2017Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, artikel-id 203Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. Methods: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. Results: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. Conclusions: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

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