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Jimenez Tejero E, Lopez-Alcalde J, Correa-Pérez A, Stallings E, Gaetano Gil A, Del Campo Albendea L, Mateos-Haro M, Fernandez-Felix BM, Stallings R, Alvarez-Diaz N, García Laredo E, Solier A, Fernández-Martínez E, Morillo Guerrero R, de Miguel M, Perez R, Antequera A, Muriel A, Jimenez D, Zamora J. Sex as a prognostic factor for mortality in adults with acute symptomatic pulmonary embolism. Cochrane Database Syst Rev 2025; 3:CD013835. [PMID: 40110896 PMCID: PMC12043200 DOI: 10.1002/14651858.cd013835.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
BACKGROUND Pulmonary embolism (PE) is relatively common worldwide. It is a serious condition that can be life-threatening. Studies on the relationship between adverse outcomes of this condition and whether a patient is male or female have yielded inconsistent results. Determining whether there is an association between sex and short-term mortality in patients with acute PE is important as this information may help guide different approaches to PE monitoring and treatment. OBJECTIVES To determine whether sex (i.e. being a male or a female patient) is an independent prognostic factor for predicting mortality in adults with acute symptomatic pulmonary embolism. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register up to 17 February 2023. We scanned conference abstracts and reference lists of included studies and systematic reviews. We also contacted experts to identify additional studies. There were no restrictions with respect to language or date of publication. SELECTION CRITERIA We included phase 2-confirmatory prognostic studies, that is, any longitudinal study (prospective or retrospective) evaluating the independent association between sex (male or female) and mortality in adults with acute PE. DATA COLLECTION AND ANALYSIS We followed the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) and the Cochrane Prognosis Methods Group template for prognosis reviews. Two review authors independently screened the studies, extracted data, assessed the risk of bias according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). Meta-analyses were performed by pooling adjusted estimates. When meta-analysis was not possible, we reported the main results narratively. MAIN RESULTS We included seven studies (726,293 participants), all of which were retrospective cohort studies with participants recruited and managed in hospitals between 2000 and 2018. Studies took place in the USA, Spain, and Japan. Most studies were multicentre. None were conducted in low- or middle-income countries. The participants' mean age ranged from 62 to 69 years, and the proportion of females was higher in six of the seven studies, ranging from 46% to 60%. Sex and gender terms were used inconsistently. Participants received different PE treatments: reperfusion, inferior vena cava filter, anticoagulation, and haemodynamic/respiratory support. The prognostication time (the point from which the outcome was predicted) was frequently omitted. The included studies provided data for three of our outcomes of interest. We did not consider any of the studies to be at an overall low risk of bias for any of the outcomes analysed. We judged the certainty of the evidence as moderate to low due to imprecision and risk of bias. We found moderate-certainty evidence (due to imprecision) that for female patients there is likely a small but clinically important reduction in all-cause mortality at 30 days (odds ratio (OR) 0.81, 95% confidence interval (CI) 0.72 to 0.92; I2 = 0%; absolute risk difference (ARD) 24 fewer deaths in women per 1000 participants, 95% CI 35 to 10 fewer; 2 studies, 17,627 participants). However, the remaining review outcomes do not indicate lower mortality in female patients. There is low-certainty evidence (due to serious risk of bias and imprecision) indicating that for females with PE, there may be a small but clinically important increase in all-cause hospital mortality (OR 1.11, 95% CI 1.00 to 1.22; I2 = 21.7%; 95% prediction interval (PI) 0.76 to 1.61; ARD 13 more deaths in women per 1000 participants, 95% CI 0 to 26 more; 3 studies, 611,210 participants). There is also low-certainty evidence (due to very serious imprecision) indicating that there may be little to no difference between males and females in PE-related mortality at 30 days (OR 1.08, 95% CI 0.55 to 2.12; I2 = 0%; ARD 4 more deaths in women per 1000 participants, 95% CI 22 fewer to 50 more; 2 studies, 3524 participants). No study data was found for the other outcomes, including sex-specific mortality data at one year. Moreover, due to insufficient studies, many of our planned methods were not implemented. In particular, we were unable to conduct assessments of heterogeneity or publication bias or subgroup and sensitivity analyses. AUTHORS' CONCLUSIONS The evidence is uncertain about sex (being male or female) as an independent prognostic factor for predicting mortality in adults with PE. We found that, for female patients with PE, there is likely a small but clinically important reduction in all-cause mortality at 30 days relative to male patients. However, this result should be interpreted cautiously, as the remaining review outcomes do not point to an association between being female and having a lower risk of death. In fact, the evidence in the review also suggested that, in female patients, there may be a small but clinically important increase in all-cause hospital mortality. It also showed that there may be little to no difference in PE-related mortality at 30 days between male and female patients. There is currently no study evidence from longitudinal studies for our other review outcomes. Although the available evidence is conflicting and therefore cannot support a recommendation for or against routinely considering sex to quantify prognosis or to guide personalised therapeutic approaches for patients with PE, this Cochrane review offers information to guide future primary research and systematic reviews.
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Affiliation(s)
- Elena Jimenez Tejero
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
- Faculty of Medicine, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain
- Cochrane Associate Centre of Madrid, Madrid, Spain
| | - Jesús Lopez-Alcalde
- Faculty of Medicine, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain
- Cochrane Associate Centre of Madrid, Madrid, Spain
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS); CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Institute for Complementary and Integrative Medicine, University Hospital Zurich; University of Zurich, Zurich, Switzerland
| | - Andrea Correa-Pérez
- Hospital Pharmacy and Medical Devices Department, Hospital Central de la Defensa "Gomez Ulla", Madrid, Spain
| | - Elena Stallings
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS); CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Andrea Gaetano Gil
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
| | - Laura Del Campo Albendea
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS); CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Miriam Mateos-Haro
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
| | - Borja Manuel Fernandez-Felix
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS); CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Raymond Stallings
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
| | | | - Eduardo García Laredo
- Faculty of Health Sciences, Universidad Internacional de La Rioja (UNIR), Logroño, Spain
- Comet Global Innovation SL, Barcelona, Spain
| | - Aurora Solier
- Respiratory Department, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
| | | | - Raquel Morillo Guerrero
- Department of Pneumology, Hospital Universitario Ramón y Cajal (IRYCIS); CIBER Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Marcos de Miguel
- Department of Anesthesiology and Intensive Care, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Raquel Perez
- Respiratory Department, Hospital Universitario 12 de Octubre, Universidad Complutense Madrid, Madrid, Spain
| | - Alba Antequera
- International Health Department, ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
| | - Alfonso Muriel
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS); CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Department of Nursing and Physiotherapy, Universidad de Alcalá, Alcalá De Henares, Spain
| | - David Jimenez
- Respiratory Department, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
- Medicine Department, Universidad de Alcalá (IRYCIS), Madrid, Spain
- CIBER Enfermedades Respiratorias, CIBERES, Madrid, Spain
| | - Javier Zamora
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS); CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
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Liu B, Liu Z, Gui Q, Lin Y, Huang G, Lyu J, Weng N, Tang X. Definition and assessment of adherence to oral nutritional supplements in patients with neoplasms: a scoping review. BMC Cancer 2024; 24:1483. [PMID: 39623358 PMCID: PMC11610086 DOI: 10.1186/s12885-024-13237-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 11/25/2024] [Indexed: 12/06/2024] Open
Abstract
INTRODUCTION Cancer remains a leading cause of death globally, with patients frequently experiencing malnutrition due to both the disease and its treatment, which negatively affects their quality of life and treatment outcomes. Oral nutritional supplements (ONS) provide a noninvasive solution to improve nutritional status, but poor patient adherence limits their effectiveness. Studies on ONS adherence vary in their definitions and assessment tools, creating inconsistencies. A scoping review is essential to synthesize these studies and establish a foundation for future research and clinical practice. METHOD We systematically searched six databases, including Web of Science, PubMed, and Scopus, up to August 2024. Our criteria focused on oncology patients, ONS interventions, and outcomes related to adherence definitions, assessment methods, and adherence rates. RESULTS 37 studies from 2005 to 2024 met the inclusion criteria. Definitions of ONS adherence and assessment methods vary widely, with the most common definition being the ratio of actual intake to the recommended amount. The assessment tools included self-reported ONS diaries, and MMAS scores, among others. Adherence rates also vary significantly, with some studies reporting a decline in adherence over time. CONCLUSION The lack of standardized definitions and assessment methods for ONS adherence across studies hinders comparability. Future research should focus on developing standardized, comprehensive adherence assessment tools that incorporate both quantitative and qualitative data. This would allow for a better understanding of adherence factors and enable more targeted interventions to improve long-term adherence in cancer patients.
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Affiliation(s)
- Beijia Liu
- School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Zhengzheng Liu
- School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Qian Gui
- School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Ying Lin
- School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Guiyu Huang
- School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
- Department of Radiation Oncology, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Jianxia Lyu
- Department of Head and Neck Radiation Oncology, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Niannian Weng
- School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
- Department of Vascular and Interventional Medicine, Chongqing Cancer Hospital, Affiliated Cancer Hospital of Chongqing University, Chongqing, China
| | - Xiaoli Tang
- School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
- Comprehensive Department, Sichuan Cancer Hospital, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
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Krähmer D, Schächtele L, Schneck A. Care to share? Experimental evidence on code sharing behavior in the social sciences. PLoS One 2023; 18:e0289380. [PMID: 37549146 PMCID: PMC10406284 DOI: 10.1371/journal.pone.0289380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 07/18/2023] [Indexed: 08/09/2023] Open
Abstract
Transparency and peer control are cornerstones of good scientific practice and entail the replication and reproduction of findings. The feasibility of replications, however, hinges on the premise that original researchers make their data and research code publicly available. This applies in particular to large-N observational studies, where analysis code is complex and may involve several ambiguous analytical decisions. To investigate which specific factors influence researchers' code sharing behavior upon request, we emailed code requests to 1,206 authors who published research articles based on data from the European Social Survey between 2015 and 2020. In this preregistered multifactorial field experiment, we randomly varied three aspects of our code request's wording in a 2x4x2 factorial design: the overall framing of our request (enhancement of social science research, response to replication crisis), the appeal why researchers should share their code (FAIR principles, academic altruism, prospect of citation, no information), and the perceived effort associated with code sharing (no code cleaning required, no information). Overall, 37.5% of successfully contacted authors supplied their analysis code. Of our experimental treatments, only framing affected researchers' code sharing behavior, though in the opposite direction we expected: Scientists who received the negative wording alluding to the replication crisis were more likely to share their research code. Taken together, our results highlight that the availability of research code will hardly be enhanced by small-scale individual interventions but instead requires large-scale institutional norms.
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Affiliation(s)
- Daniel Krähmer
- Department of Sociology, University of Munich (LMU), Munich, Germany
| | - Laura Schächtele
- Department of Sociology, University of Munich (LMU), Munich, Germany
| | - Andreas Schneck
- Department of Sociology, University of Munich (LMU), Munich, Germany
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Mathur MB, Fox MP. Toward Open and Reproducible Epidemiology. Am J Epidemiol 2023; 192:658-664. [PMID: 36627249 PMCID: PMC10089067 DOI: 10.1093/aje/kwad007] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 12/08/2022] [Accepted: 01/09/2023] [Indexed: 01/12/2023] Open
Abstract
Starting in the 2010s, researchers in the experimental social sciences rapidly began to adopt increasingly open and reproducible scientific practices. These practices include publicly sharing deidentified data when possible, sharing analytical code, and preregistering study protocols. Empirical evidence from the social sciences suggests such practices are feasible, can improve analytical reproducibility, and can reduce selective reporting. In academic epidemiology, adoption of open-science practices has been slower than in the social sciences (with some notable exceptions, such as registering clinical trials). Epidemiologic studies are often large, complex, conceived after data have already been collected, and difficult to replicate directly by collecting new data. These characteristics make it especially important to ensure their integrity and analytical reproducibility. Open-science practices can also pay immediate dividends to researchers' own work by clarifying scientific reasoning and encouraging well-documented, organized workflows. We consider how established epidemiologists and early-career researchers alike can help midwife a culture of open science in epidemiology through their research practices, mentorship, and editorial activities.
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Affiliation(s)
- Maya B Mathur
- Correspondence to Dr. Maya B. Mathur, Quantitative Sciences Unit, 3180 Porter Drive, Palo Alto, CA 94304 (e-mail: )
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Zhang DD, Ou YN, Fu Y, Wang ZB, Huang LY, Tan L, Yu JT. Risk of Dementia in Cancer Survivors: A Meta-Analysis of Population-Based Cohort Studies. J Alzheimers Dis 2022; 89:367-380. [PMID: 35871349 DOI: 10.3233/jad-220436] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: A negative association between cancer and Alzheimer’s disease (AD) was revealed. Objective: We aimed to further explore the dementia risk among cancer survivors and then among cancer survivors who received cancer treatment in subsequent subgroup analyses. Methods: Databases of PubMed, Embase, and Cochrane Library were systematically searched from inception to April 1, 2021, following PRISMA and MOOSE guidelines. Relative risks (RR) of dementia were pooled by a random-effects model stratifying the data by potential confounding factors to explore the heterogeneity. This study is registered with PROSPERO, number CRD42021250654. Results: A total of 36 studies were included in this meta-analysis, of which 16 studies were about the risk of dementia in cancer survivors, and 20 studies were about the risk of dementia in survivors who accepted cancer treatment. The pooled RR reached 0.89 ([95% CI = 0.82–0.97], I2 = 97.9%) for dementia and 0.89 ([0.83–0.95], I2 = 92.6%) for AD in cancer survivors compared with non-cancer controls. Notably, both dementia risk and AD risk significantly decreased in survivors of colon, leukemia, small intestine, and thyroid cancers (RR ranged from 0.64 to 0.92). Furthermore, prostate cancer patients treated with androgen deprivation therapy exhibited a significantly increased risk of dementia (RR:1.18 [1.09–1.27], I2 = 89.5%) and AD (RR:1.17 [1.08–1.25], I2 = 81.3%), with evidence of between-study heterogeneity. Conclusion: Currently, available evidence suggests that the risk of dementia among cancer survivors is decreased. However, large-scale prospective cohort studies are warranted to further prove the association.
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Affiliation(s)
- Dan-Dan Zhang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Ya-Nan Ou
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Yan Fu
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Zhi-Bo Wang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Liang-Yu Huang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Lan Tan
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jin-Tai Yu
- Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China
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Sauerbrei W, Haeussler T, Balmford J, Huebner M. Structured reporting to improve transparency of analyses in prognostic marker studies. BMC Med 2022; 20:184. [PMID: 35546237 PMCID: PMC9095054 DOI: 10.1186/s12916-022-02304-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 02/17/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Factors contributing to the lack of understanding of research studies include poor reporting practices, such as selective reporting of statistically significant findings or insufficient methodological details. Systematic reviews have shown that prognostic factor studies continue to be poorly reported, even for important aspects, such as the effective sample size. The REMARK reporting guidelines support researchers in reporting key aspects of tumor marker prognostic studies. The REMARK profile was proposed to augment these guidelines to aid in structured reporting with an emphasis on including all aspects of analyses conducted. METHODS A systematic search of prognostic factor studies was conducted, and fifteen studies published in 2015 were selected, three from each of five oncology journals. A paper was eligible for selection if it included survival outcomes and multivariable models were used in the statistical analyses. For each study, we summarized the key information in a REMARK profile consisting of details about the patient population with available variables and follow-up data, and a list of all analyses conducted. RESULTS Structured profiles allow an easy assessment if reporting of a study only has weaknesses or if it is poor because many relevant details are missing. Studies had incomplete reporting of exclusion of patients, missing information about the number of events, or lacked details about statistical analyses, e.g., subgroup analyses in small populations without any information about the number of events. Profiles exhibit severe weaknesses in the reporting of more than 50% of the studies. The quality of analyses was not assessed, but some profiles exhibit several deficits at a glance. CONCLUSIONS A substantial part of prognostic factor studies is poorly reported and analyzed, with severe consequences for related systematic reviews and meta-analyses. We consider inadequate reporting of single studies as one of the most important reasons that the clinical relevance of most markers is still unclear after years of research and dozens of publications. We conclude that structured reporting is an important step to improve the quality of prognostic marker research and discuss its role in the context of selective reporting, meta-analysis, study registration, predefined statistical analysis plans, and improvement of marker research.
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Affiliation(s)
- Willi Sauerbrei
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
| | - Tim Haeussler
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - James Balmford
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Marianne Huebner
- Department of Statistics and Probability, Michigan State University, East Lansing, MI, USA
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Abstract
Mayookha Mitra-Majumdar and Aaron Kesselheim reflect on steps taken to combat reporting bias in clinical trials over the last two decades.
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Affiliation(s)
- Mayookha Mitra-Majumdar
- Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Aaron S Kesselheim
- Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
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Raymond J, Naggara O, Guilbert F, Darsaut TE. Douglas Altman's 2009 Grand Lecture: Can we trust our literature? Neurochirurgie 2021; 68:202-205. [PMID: 34186030 DOI: 10.1016/j.neuchi.2021.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 06/19/2021] [Indexed: 11/18/2022]
Abstract
Recent studies of the medical literature have revealed numerous and serious problems. Errors in the design, methods and interpretation of studies can frequently be identified. A huge hidden problem is publication bias, the tendency for positive articles to be published, while negative articles are either not written or submitted. This can systematically lead to an overestimation of the value of treatments, of diagnostic or prognostic studies. Even more worrisome is selective reporting: only a subset of a wide array of tested hypotheses are presented (the ones that turned out to be positive with significance testing). This is particularly true for secondary endpoints and subgroup findings, but even the primary endpoints of trials have been modified when publications are compared to protocols. The peer-review process is fallible. Even if it were strengthened, reviewers cannot examine what is not reported. Hence many problems can only be mitigated with better reporting. Numerous initiatives have proposed guidelines to promote transparent reporting, but progress is slow.
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Affiliation(s)
- J Raymond
- Department of Radiology, Neuroradiology service, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.
| | - O Naggara
- Department of Neuroradiology, Université Paris-Descartes, INSERM UMR 894, Centre hospitalier Sainte-Anne, Paris, Ile de France, France
| | - F Guilbert
- Department of Radiology, Neuroradiology service, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
| | - T E Darsaut
- Division of Neurosurgery, Department of Surgery, University of Alberta hospital, Mackenzie Health Sciences Centre, 8440 112St NW, Edmonton, Alberta, Canada
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Chen ML, Wotiz SB, Banks SM, Connors SA, Shi Y. Dose-Response Association of Tai Chi and Cognition among Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:3179. [PMID: 33808633 PMCID: PMC8003349 DOI: 10.3390/ijerph18063179] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/16/2021] [Accepted: 03/15/2021] [Indexed: 12/16/2022]
Abstract
Previous studies indicated that Tai Chi might be an effective way to improve or prevent cognitive impairments in older populations. However, existing research does not provide clear recommendations about the optimal dose of Tai Chi practice, which is the most effective in improving cognitive function in older adults. The purpose of this systematic review and meta-analysis was to investigate the dose-response relationship between Tai Chi and cognition in community-dwelling older adults. A total of 16 studies with 1121 subjects were included in this study. Meta-regression analyses of Tai Chi duration (Tai Chi session duration, Tai Chi practice duration per week, study duration, and Tai Chi practice duration for the entire study) on the study effect size (ES) were performed to examine the dose-response association of Tai Chi and cognition. The results showed that there was a positive effect of Tai Chi on cognitive function, but there were no statistically significant dose duration effects on cognition. The findings suggest that Tai Chi has beneficial effects on cognitive function, but a longer duration was not associated with larger effects. In order to establish evidence-based clinical interventions using Tai Chi, future research should clearly demonstrate intervention protocol, particularly the style and intensity of Tai Chi.
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Affiliation(s)
- Mei-Lan Chen
- Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, GA 30303, USA; (S.B.W.); (S.M.B.); (S.A.C.)
- Gerontology Institute, Georgia State University, Atlanta, GA 30303, USA
| | - Stephanie B. Wotiz
- Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, GA 30303, USA; (S.B.W.); (S.M.B.); (S.A.C.)
| | - Starr M. Banks
- Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, GA 30303, USA; (S.B.W.); (S.M.B.); (S.A.C.)
| | - Sabine A. Connors
- Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, GA 30303, USA; (S.B.W.); (S.M.B.); (S.A.C.)
| | - Yuyin Shi
- Department of Mathematics, University of Maryland, College Park, MD 20742, USA;
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Use of antibiotics in traumatic mandibular fractures: a systematic review and meta-analysis. Br J Oral Maxillofac Surg 2021; 59:1140-1147. [PMID: 34711441 DOI: 10.1016/j.bjoms.2021.01.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 01/30/2021] [Indexed: 12/25/2022]
Abstract
The treatment of traumatic mandibular fractures constitutes a significant part of the oral and maxillofacial trauma service's workload. There are potential variations in how they are managed. Patients are often admitted and given intravenous antibiotics prior to their definitive treatment. The evidence behind this is inconclusive. We performed a systematic review as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance/ PROSPERO Registered (CRD:42020201398) on the use of antibiotics in the management of mandibular fractures. We identified studies using a search algorithm within the OVID Gateway (including MEDLINE, PubMed, and Cochrane Collaborative). Studies analysing the possible impact of prophylactic antibiotics on traumatic mandibular fractures were eligible. The primary outcome was surgical site infection requiring any treatment beyond the normal postoperative protocol. Secondary outcomes included any complication requiring further intervention. From the 16 studies identified (3,285 patients), seven were randomised controlled clinical trials (RCTs) and nine were retrospective observational studies. We have identified significant between-study variation in choice of antibiotic regimen (timing, dosage, duration) and in reporting both primary and secondary outcomes. There was significant between-study heterogeneity (p = 0.02, I2 = 69%) and none of the assessed interventions was found to be superior. The evidence behind the use of prophylactic antibiotics in mandibular fractures is weak. A properly designed and powered RCT is needed, in order to standardise practice for the benefit of patients and healthcare systems.
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Routila J, Leivo I, Minn H, Westermarck J, Ventelä S. Evaluation of prognostic biomarkers in a population-validated Finnish HNSCC patient cohort. Eur Arch Otorhinolaryngol 2021; 278:4575-4585. [PMID: 33582846 PMCID: PMC8486716 DOI: 10.1007/s00405-021-06650-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/27/2021] [Indexed: 12/31/2022]
Abstract
Introduction Prognostic biomarkers and novel therapeutic approaches have been slow to emerge in the treatment of head and neck squamous cell carcinoma (HNSCC). In this study, an HNSCC patient cohort is created and performance of putative prognostic biomarkers investigated in a population-validated setting. The overall goal is to develop a novel way to combine biomarker analyses with population-level clinical data on HNSCC patients and thus to improve the carryover of biomarkers into clinical practice. Materials and methods To avoid selection biases in retrospective study design, all HNSCC patients were identified and corresponding clinical data were collected from the Southwest Finland geographical area. A particular emphasis was laid on avoiding potential biases in sample selection for immunohistochemical staining analyses. Staining results were evaluated for potential prognostic resolution. Results After comprehensive evaluation, the patient cohort was found to be representative of the background population in terms of clinical characteristics such as patient age and TNM stage distribution. A negligible drop-out of 1.3% (6/476) was observed during the first follow-up year. By immunohistochemical analysis, the role of previously implicated HNSCC biomarkers (p53, EGFR, p16, CIP2A, Oct4, MET, and NDFIP1) was investigated. Discussion Our exceptionally representative patient material supports the use of population validation to improve the applicability of results to real-life situations. The failure of the putative prognostic biomarkers emphasizes the need for controlling bias in retrospective studies, especially in the heterogenous tumor environment of HNSCC. The resolution of simple prognostic examination is unlikely to be sufficient to identify biomarkers for clinical practice of HNSCC. Supplementary Information The online version contains supplementary material available at 10.1007/s00405-021-06650-7.
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Affiliation(s)
- J Routila
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.,Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland
| | - I Leivo
- Biomedical Institute, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland
| | - H Minn
- FICAN West Cancer Centre, Turku, Finland.,Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, Finland
| | - J Westermarck
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.,Biomedical Institute, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.,FICAN West Cancer Centre, Turku, Finland
| | - Sami Ventelä
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland. .,Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland. .,FICAN West Cancer Centre, Turku, Finland.
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12
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Merriel SWD, Ingle SM, May MT, Martin RM. Retrospective cohort study evaluating clinical, biochemical and pharmacological prognostic factors for prostate cancer progression using primary care data. BMJ Open 2021; 11:e044420. [PMID: 33579772 PMCID: PMC7883851 DOI: 10.1136/bmjopen-2020-044420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES To confirm the association of previously reported prognostic factors with future progression of localised prostate cancer using primary care data and identify new potential prognostic factors for further assessment in prognostic model development and validation. DESIGN Retrospective cohort study, employing Cox proportional hazards regression controlling for age, prostate specific antigen (PSA), and Gleason score, was stratified by diagnostic stage. SETTING Primary care in England. PARTICIPANTS Males with localised prostate cancer diagnosedbetween 01/01/1987 and 31/12/2016 within the Clinical Practice ResearchDatalink database, with linked data from the National Cancer Registration andAnalysis Service and Office for National Statistics. PRIMARY AND SECONDARY OUTCOMES Primary outcome measure was prostate cancer mortality. Secondary outcome measures were all-cause mortality and commencing systemic therapy. Up-staging after diagnosis was not used as a secondary outcome owing to significant missing data. RESULTS 10 901 men (mean age 74.38±9.03 years) with localised prostate cancer were followed up for a mean of 14.12 (±6.36) years. 2331 (21.38%) men underwent systemic therapy and 3450 (31.65%) died, including 1250 (11.47%) from prostate cancer. Factors associated with an increased risk of prostate cancer mortality included age; high PSA; current or ex-smoker; ischaemic heart disease; high C reactive protein; high ferritin; low haemoglobin; high blood glucose and low albumin. CONCLUSIONS This study identified several new potential prognostic factors for prostate cancer progression, as well as confirming some known prognostic factors, in an independent primary care data set. Further research is needed to develop and validate a prognostic model for prostate cancer progression.
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Affiliation(s)
| | - Suzanne Marie Ingle
- Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK
| | - Margaret T May
- Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK
- National Institute for Health Research (NIHR) Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK
| | - Richard M Martin
- Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK
- National Institute for Health Research (NIHR) Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK
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13
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Sauerbrei W, Bland M, Evans SJW, Riley RD, Royston P, Schumacher M, Collins GS. Doug Altman: Driving critical appraisal and improvements in the quality of methodological and medical research. Biom J 2021; 63:226-246. [PMID: 32639065 DOI: 10.1002/bimj.202000053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 05/20/2020] [Accepted: 06/03/2020] [Indexed: 12/12/2022]
Abstract
Doug Altman was a visionary leader and one of the most influential medical statisticians of the last 40 years. Based on a presentation in the "Invited session in memory of Doug Altman" at the 40th Annual Conference of the International Society for Clinical Biostatistics (ISCB) in Leuven, Belgium and our long-standing collaborations with Doug, we discuss his contributions to regression modeling, reporting, prognosis research, as well as some more general issues while acknowledging that we cannot cover the whole spectrum of Doug's considerable methodological output. His statement "To maximize the benefit to society, you need to not just do research but do it well" should be a driver for all researchers. To improve current and future research, we aim to summarize Doug's messages for these three topics.
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Affiliation(s)
- Willi Sauerbrei
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Martin Bland
- Department of Health Sciences, University of York, York, UK
| | - Stephen J W Evans
- Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, UK
| | - Richard D Riley
- Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Staffordshire, UK
| | - Patrick Royston
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Martin Schumacher
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Gary S Collins
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK
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14
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Lokuhetty MDS, Wijesinghe HD, Damen JAAG, Lee T, White VA, Cree IA, Indave BI. Prognostic value of the androgen receptor in addition to the established hormone receptors and HER2 status for predicting survival in women with early breast cancer. Hippokratia 2020. [DOI: 10.1002/14651858.cd013784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Menaka Dilani S Lokuhetty
- WHO Classification of Tumours Group, Section of Evidence Synthesis and Classification; International Agency for Research on Cancer/World Health Organization (IARC/WHO); Lyon France
- Department of Pathology, Faculty of Medicine; University of Colombo; Colombo Sri Lanka
| | - Harshima D Wijesinghe
- Department of Pathology, Faculty of Medicine; University of Colombo; Colombo Sri Lanka
| | - Johanna AAG Damen
- Cochrane Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University; Utrecht Netherlands
| | - Teresa Lee
- Communications Group; International Agency for Research on Cancer (IARC), World Health Organization; Lyon France
| | - Valerie A White
- WHO Classification of Tumours Group, Section of Evidence Synthesis and Classification; International Agency for Research on Cancer/World Health Organization (IARC/WHO); Lyon France
| | - Ian A Cree
- WHO Classification of Tumours Group, Section of Evidence Synthesis and Classification; International Agency for Research on Cancer/World Health Organization (IARC/WHO); Lyon France
| | - Blanca Iciar Indave
- WHO Classification of Tumours Group, Section of Evidence Synthesis and Classification; International Agency for Research on Cancer/World Health Organization (IARC/WHO); Lyon France
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15
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Fratelli C, Siqueira J, Silva C, Ferreira E, Silva I. 5HTTLPR Genetic Variant and Major Depressive Disorder: A Review. Genes (Basel) 2020; 11:E1260. [PMID: 33114535 PMCID: PMC7692865 DOI: 10.3390/genes11111260] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/02/2020] [Accepted: 10/16/2020] [Indexed: 02/06/2023] Open
Abstract
Major Depressive Disorder (MDD) is a disease that involves biological, psychological, and social interactions. Studies have shown the importance of genetics contribution to MDD development. The SCL6A4 protein (5HTTLPR) functions transporting serotonin, a neurotransmitter linked to mood and emotion, to the synaptic cleft. Hence, this study seeks, through a literature review, a better comprehension of the 5HTTLPR genetic variant association with MDD. For this purpose, a search was performed on the Virtual Health Library Portal for articles that related 5HTTLPR to MDD. Most of the articles found were conducted in the American continent, with one (1) study implemented in Brazil. 5HTTLPR associations were found regarding changes in the nervous system, pharmacology, and risk factors seen in MDD patients. When verifying the allelic distribution, the S allele had a higher frequency in most of the studies analyzed. Despite not finding a commonality in the different studies, the tremendous genetic variation found demonstrates the MDD complexity. For this reason, further studies in diverse populations should be conducted to assist in the understanding and treatment of the disease.
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Affiliation(s)
- Caroline Fratelli
- Postgraduate Program in Health Sciences and Technologies, Campus Faculty of Ceilandia, University of Brasilia, Brasilia 72220-275, Brazil;
| | - Jhon Siqueira
- Department of Pharmacy, Campus Faculty of Ceilandia, University of Brasilia, Brasilia 72220-275, Brazil; (J.S.); (C.S.); (E.F.)
| | - Calliandra Silva
- Department of Pharmacy, Campus Faculty of Ceilandia, University of Brasilia, Brasilia 72220-275, Brazil; (J.S.); (C.S.); (E.F.)
| | - Eduardo Ferreira
- Department of Pharmacy, Campus Faculty of Ceilandia, University of Brasilia, Brasilia 72220-275, Brazil; (J.S.); (C.S.); (E.F.)
| | - Izabel Silva
- Department of Pharmacy, Campus Faculty of Ceilandia, University of Brasilia, Brasilia 72220-275, Brazil; (J.S.); (C.S.); (E.F.)
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Kyzas P. Management of the cN0 neck in early oral cancer: time to revise the guidance? Br J Oral Maxillofac Surg 2020; 59:387-388. [PMID: 33386181 DOI: 10.1016/j.bjoms.2020.10.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 10/13/2020] [Indexed: 11/30/2022]
Affiliation(s)
- P Kyzas
- Royal Blackburn Teaching Hospital, East Lancashire Hospitals Trust.
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17
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Prognostic Value of Microvessel Density in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis. DISEASE MARKERS 2020; 2020:8842795. [PMID: 33062071 PMCID: PMC7539077 DOI: 10.1155/2020/8842795] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 08/14/2020] [Accepted: 09/02/2020] [Indexed: 02/05/2023]
Abstract
The prognostic value of microvessel density (MVD) in head and neck squamous cell carcinoma (HNSCC) remains disputable. The purpose of this study was to comprehensively determine the prognostic value of MVD in HNSCC. Relevant literatures were identified using PubMed, Embase, and Cochrane Library. A meta-analysis was performed to clarify the prognostic role of MVD in HNSCC patients and different subgroups. A total of 14 eligible articles were included in this meta-analysis. The combined hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival (OS) of 11 studies was 1.663 (1.236-2.237, P = 0.001), and the pooled HR and 95% CI for progression-free survival (PFS) of 7 studies was 2.069 (1.281-3.343, P = 0.003). Subgroup analyses were also performed on different issues, such as regional distribution of patients, age, tumor location, antibody, and treatment strategy. To conclude, high MVD is associated with worse OS and PFS in patients with HNSCC.
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18
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Kyzas P. Editorial: Postoperative risk stratification in oral squamous cell carcinoma. Br J Oral Maxillofac Surg 2020; 58:506-507. [DOI: 10.1016/j.bjoms.2020.01.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 01/06/2020] [Indexed: 11/15/2022]
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Aldin A, Umlauff L, Estcourt LJ, Collins G, Moons KG, Engert A, Kobe C, von Tresckow B, Haque M, Foroutan F, Kreuzberger N, Trivella M, Skoetz N. Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies. Cochrane Database Syst Rev 2020; 1:CD012643. [PMID: 31930780 PMCID: PMC6984446 DOI: 10.1002/14651858.cd012643.pub3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of individuals. Positron emission tomography (PET) is an imaging tool used to monitor a tumour's metabolic activity, stage and progression. Interim PET during chemotherapy has been posited as a prognostic factor in individuals with HL to distinguish between those with a poor prognosis and those with a better prognosis. This distinction is important to inform decision-making on the clinical pathway of individuals with HL. OBJECTIVES To determine whether in previously untreated adults with HL receiving first-line therapy, interim PET scan results can distinguish between those with a poor prognosis and those with a better prognosis, and thereby predict survival outcomes in each group. SEARCH METHODS We searched MEDLINE, Embase, CENTRAL and conference proceedings up until April 2019. We also searched one trial registry (ClinicalTrials.gov). SELECTION CRITERIA We included retrospective and prospective studies evaluating interim PET scans in a minimum of 10 individuals with HL (all stages) undergoing first-line therapy. Interim PET was defined as conducted during therapy (after one, two, three or four treatment cycles). The minimum follow-up period was at least 12 months. We excluded studies if the trial design allowed treatment modification based on the interim PET scan results. DATA COLLECTION AND ANALYSIS We developed a data extraction form according to the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Two teams of two review authors independently screened the studies, extracted data on overall survival (OS), progression-free survival (PFS) and PET-associated adverse events (AEs), assessed risk of bias (per outcome) according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). We contacted investigators to obtain missing information and data. MAIN RESULTS Our literature search yielded 11,277 results. In total, we included 23 studies (99 references) with 7335 newly-diagnosed individuals with classic HL (all stages). Participants in 16 studies underwent (interim) PET combined with computed tomography (PET-CT), compared to PET only in the remaining seven studies. The standard chemotherapy regimen included ABVD (16) studies, compared to BEACOPP or other regimens (seven studies). Most studies (N = 21) conducted interim PET scans after two cycles (PET2) of chemotherapy, although PET1, PET3 and PET4 were also reported in some studies. In the meta-analyses, we used PET2 data if available as we wanted to ensure homogeneity between studies. In most studies interim PET scan results were evaluated according to the Deauville 5-point scale (N = 12). Eight studies were not included in meta-analyses due to missing information and/or data; results were reported narratively. For the remaining studies, we pooled the unadjusted hazard ratio (HR). The timing of the outcome measurement was after two or three years (the median follow-up time ranged from 22 to 65 months) in the pooled studies. Eight studies explored the independent prognostic ability of interim PET by adjusting for other established prognostic factors (e.g. disease stage, B symptoms). We did not pool the results because the multivariable analyses adjusted for a different set of factors in each study. Overall survival Twelve (out of 23) studies reported OS. Six of these were assessed as low risk of bias in all of the first four domains of QUIPS (study participation, study attrition, prognostic factor measurement and outcome measurement). The other six studies were assessed as unclear, moderate or high risk of bias in at least one of these four domains. Four studies were assessed as low risk, and eight studies as high risk of bias for the domain other prognostic factors (covariates). Nine studies were assessed as low risk, and three studies as high risk of bias for the domain 'statistical analysis and reporting'. We pooled nine studies with 1802 participants. Participants with HL who have a negative interim PET scan result probably have a large advantage in OS compared to those with a positive interim PET scan result (unadjusted HR 5.09, 95% confidence interval (CI) 2.64 to 9.81, I² = 44%, moderate-certainty evidence). In absolute values, this means that 900 out of 1000 participants with a negative interim PET scan result will probably survive longer than three years compared to 585 (95% CI 356 to 757) out of 1000 participants with a positive result. Adjusted results from two studies also indicate an independent prognostic value of interim PET scan results (moderate-certainty evidence). Progression-free survival Twenty-one studies reported PFS. Eleven out of 21 were assessed as low risk of bias in the first four domains. The remaining were assessed as unclear, moderate or high risk of bias in at least one of the four domains. Eleven studies were assessed as low risk, and ten studies as high risk of bias for the domain other prognostic factors (covariates). Eight studies were assessed as high risk, thirteen as low risk of bias for statistical analysis and reporting. We pooled 14 studies with 2079 participants. Participants who have a negative interim PET scan result may have an advantage in PFS compared to those with a positive interim PET scan result, but the evidence is very uncertain (unadjusted HR 4.90, 95% CI 3.47 to 6.90, I² = 45%, very low-certainty evidence). This means that 850 out of 1000 participants with a negative interim PET scan result may be progression-free longer than three years compared to 451 (95% CI 326 to 569) out of 1000 participants with a positive result. Adjusted results (not pooled) from eight studies also indicate that there may be an independent prognostic value of interim PET scan results (low-certainty evidence). PET-associated adverse events No study measured PET-associated AEs. AUTHORS' CONCLUSIONS This review provides moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict progression-free survival in treated individuals with HL. This evidence is primarily based on unadjusted data. More studies are needed to test the adjusted prognostic ability of interim PET against established prognostic factors.
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Affiliation(s)
- Angela Aldin
- Faculty of Medicine and University Hospital Cologne, University of Cologne, Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Kerpener Str. 62, Cologne, Germany, 50937
| | - Lisa Umlauff
- Faculty of Medicine and University Hospital Cologne, University of Cologne, Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Kerpener Str. 62, Cologne, Germany, 50937
| | - Lise J Estcourt
- NHS Blood and Transplant, Haematology/Transfusion Medicine, Level 2, John Radcliffe Hospital, Headington, Oxford, UK, OX3 9BQ
| | - Gary Collins
- University of Oxford, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Windmill Road, Oxford, UK, OX3 7LD
| | - Karel Gm Moons
- University Medical Center Utrecht, Utrecht University, Julius Center for Health Sciences and Primary Care, PO Box 85500, Utrecht, Netherlands, 3508 GA
| | - Andreas Engert
- Faculty of Medicine and University Hospital Cologne, University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Kerpener Str. 62, Cologne, Germany, 50924
| | - Carsten Kobe
- Faculty of Medicine and University Hospital Cologne, Department for Nuclear Medicine, University of Cologne, Cologne, Germany
| | - Bastian von Tresckow
- Faculty of Medicine and University Hospital Cologne, University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Kerpener Str. 62, Cologne, Germany, 50924
| | - Madhuri Haque
- Faculty of Medicine and University Hospital Cologne, University of Cologne, Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Kerpener Str. 62, Cologne, Germany, 50937
| | - Farid Foroutan
- McMaster University, Department of Health Research Methods, Evidence, and Impact, 1280 Main St W, Hamilton, Ontario, Canada, L8S 4L8
| | - Nina Kreuzberger
- Faculty of Medicine and University Hospital Cologne, University of Cologne, Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Kerpener Str. 62, Cologne, Germany, 50937
| | - Marialena Trivella
- University of Oxford, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Windmill Road, Oxford, UK, OX3 7LD
| | - Nicole Skoetz
- Faculty of Medicine and University Hospital Cologne, University of Cologne, Cochrane Cancer, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Kerpener Str. 62, Cologne, Germany, 50937
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Iafolla MAJ, Picardo S, Aung K, Hansen AR. Systematic review and REMARK scoring of renal cell carcinoma prognostic circulating biomarker manuscripts. PLoS One 2019; 14:e0222359. [PMID: 31639128 PMCID: PMC6804962 DOI: 10.1371/journal.pone.0222359] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 08/27/2019] [Indexed: 12/19/2022] Open
Abstract
Background No validated molecular biomarkers exist to help guide prognosis of renal cell carcinoma (RCC) patients. We seek to evaluate the quality of published prognostic circulating RCC biomarker manuscripts using the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) guidelines. Methods The phrase “(renal cell carcinoma OR renal cancer OR kidney cancer OR kidney carcinoma) AND circulating AND (biomarkers OR cell free DNA OR tumor DNA OR methylated cell free DNA OR methylated tumor DNA)” was searched in Embase, Medline and PubMed March 2018. Relevant manuscripts were scored using 48 REMARK sub-criteria for a maximal score of 20 points. Results The search identified 535 publications: 33 were manuscripts of primary research and were analyzed. The mean REMARK score was 10.6 (range 6.42–14.2). All manuscripts stated their biomarker, study objectives and method of case selection. The lowest scoring criteria: time lapse between storage of blood/serum and marker assay (n = 2) and lack of flow diagram (n = 2). REMARK scores were significantly higher in publications stating adherence to REMARK guidelines (p = 0.0307) and reporting statistically significant results (p = 0.0318). Conclusions Most RCC prognostic biomarker manuscripts poorly adhere to the REMARK guidelines. Better designed studies and appropriate reporting are required to address this urgent unmet need.
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Affiliation(s)
- Marco A. J. Iafolla
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Sarah Picardo
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Kyaw Aung
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- Livestrong Cancer Institute and Dell Medical School, University of Texas at Austin, Austin, Texas, United States of America
| | - Aaron R. Hansen
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- * E-mail:
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Aldin A, Umlauff L, Estcourt LJ, Collins G, Moons KGM, Engert A, Kobe C, von Tresckow B, Haque M, Foroutan F, Kreuzberger N, Trivella M, Skoetz N. Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies. Cochrane Database Syst Rev 2019; 9:CD012643. [PMID: 31525824 PMCID: PMC6746624 DOI: 10.1002/14651858.cd012643.pub2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of individuals. Positron emission tomography (PET) is an imaging tool used to monitor a tumour's metabolic activity, stage and progression. Interim PET during chemotherapy has been posited as a prognostic factor in individuals with HL to distinguish between those with a poor prognosis and those with a better prognosis. This distinction is important to inform decision-making on the clinical pathway of individuals with HL. OBJECTIVES To determine whether in previously untreated adults with HL receiving first-line therapy, interim PET scan results can distinguish between those with a poor prognosis and those with a better prognosis, and thereby predict survival outcomes in each group. SEARCH METHODS We searched MEDLINE, Embase, CENTRAL and conference proceedings up until April 2019. We also searched one trial registry (ClinicalTrials.gov). SELECTION CRITERIA We included retrospective and prospective studies evaluating interim PET scans in a minimum of 10 individuals with HL (all stages) undergoing first-line therapy. Interim PET was defined as conducted during therapy (after one, two, three or four treatment cycles). The minimum follow-up period was at least 12 months. We excluded studies if the trial design allowed treatment modification based on the interim PET scan results. DATA COLLECTION AND ANALYSIS We developed a data extraction form according to the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Two teams of two review authors independently screened the studies, extracted data on overall survival (OS), progression-free survival (PFS) and PET-associated adverse events (AEs), assessed risk of bias (per outcome) according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). We contacted investigators to obtain missing information and data. MAIN RESULTS Our literature search yielded 11,277 results. In total, we included 23 studies (99 references) with 7335 newly-diagnosed individuals with classic HL (all stages).Participants in 16 studies underwent (interim) PET combined with computed tomography (PET-CT), compared to PET only in the remaining seven studies. The standard chemotherapy regimen included ABVD (16) studies, compared to BEACOPP or other regimens (seven studies). Most studies (N = 21) conducted interim PET scans after two cycles (PET2) of chemotherapy, although PET1, PET3 and PET4 were also reported in some studies. In the meta-analyses, we used PET2 data if available as we wanted to ensure homogeneity between studies. In most studies interim PET scan results were evaluated according to the Deauville 5-point scale (N = 12).Eight studies were not included in meta-analyses due to missing information and/or data; results were reported narratively. For the remaining studies, we pooled the unadjusted hazard ratio (HR). The timing of the outcome measurement was after two or three years (the median follow-up time ranged from 22 to 65 months) in the pooled studies.Eight studies explored the independent prognostic ability of interim PET by adjusting for other established prognostic factors (e.g. disease stage, B symptoms). We did not pool the results because the multivariable analyses adjusted for a different set of factors in each study.Overall survivalTwelve (out of 23) studies reported OS. Six of these were assessed as low risk of bias in all of the first four domains of QUIPS (study participation, study attrition, prognostic factor measurement and outcome measurement). The other six studies were assessed as unclear, moderate or high risk of bias in at least one of these four domains. Nine studies were assessed as high risk, and three studies as moderate risk of bias for the domain study confounding. Eight studies were assessed as low risk, and four studies as high risk of bias for the domain statistical analysis and reporting.We pooled nine studies with 1802 participants. Participants with HL who have a negative interim PET scan result probably have a large advantage in OS compared to those with a positive interim PET scan result (unadjusted HR 5.09, 95% confidence interval (CI) 2.64 to 9.81, I² = 44%, moderate-certainty evidence). In absolute values, this means that 900 out of 1000 participants with a negative interim PET scan result will probably survive longer than three years compared to 585 (95% CI 356 to 757) out of 1000 participants with a positive result.Adjusted results from two studies also indicate an independent prognostic value of interim PET scan results (moderate-certainty evidence).Progression-free survival Twenty-one studies reported PFS. Eleven out of 21 were assessed as low risk of bias in the first four domains. The remaining were assessed as unclear, moderate or high risk of bias in at least one of the four domains. Eleven studies were assessed as high risk, nine studies as moderate risk and one study as low risk of bias for study confounding. Eight studies were assessed as high risk, three as moderate risk and nine as low risk of bias for statistical analysis and reporting.We pooled 14 studies with 2079 participants. Participants who have a negative interim PET scan result may have an advantage in PFS compared to those with a positive interim PET scan result, but the evidence is very uncertain (unadjusted HR 4.90, 95% CI 3.47 to 6.90, I² = 45%, very low-certainty evidence). This means that 850 out of 1000 participants with a negative interim PET scan result may be progression-free longer than three years compared to 451 (95% CI 326 to 569) out of 1000 participants with a positive result.Adjusted results (not pooled) from eight studies also indicate that there may be an independent prognostic value of interim PET scan results (low-certainty evidence).PET-associated adverse eventsNo study measured PET-associated AEs. AUTHORS' CONCLUSIONS This review provides moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict progression-free survival in treated individuals with HL. This evidence is primarily based on unadjusted data. More studies are needed to test the adjusted prognostic ability of interim PET against established prognostic factors.
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Affiliation(s)
- Angela Aldin
- Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cochrane Haematological MalignanciesUniversity of CologneKerpener Str. 62CologneGermany50937
| | - Lisa Umlauff
- Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cochrane Haematological MalignanciesUniversity of CologneKerpener Str. 62CologneGermany50937
| | - Lise J Estcourt
- NHS Blood and TransplantHaematology/Transfusion MedicineLevel 2, John Radcliffe HospitalHeadingtonOxfordUKOX3 9BQ
| | - Gary Collins
- University of OxfordCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesWindmill RoadOxfordUKOX3 7LD
| | - Karel GM Moons
- University Medical Center Utrecht, Utrecht UniversityJulius Center for Health Sciences and Primary CarePO Box 85500UtrechtNetherlands3508 GA
| | - Andreas Engert
- Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne DuesseldorfUniversity of CologneKerpener Str. 62CologneGermany50924
| | - Carsten Kobe
- Faculty of Medicine and University Hospital Cologne, Department for Nuclear MedicineUniversity of CologneCologneGermany
| | - Bastian von Tresckow
- Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne DuesseldorfUniversity of CologneKerpener Str. 62CologneGermany50924
| | - Madhuri Haque
- Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cochrane Haematological MalignanciesUniversity of CologneKerpener Str. 62CologneGermany50937
| | - Farid Foroutan
- McMaster UniversityDepartment of Health Research Methods, Evidence, and Impact1280 Main St WHamiltonCanadaL8S 4L8
| | - Nina Kreuzberger
- Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cochrane Haematological MalignanciesUniversity of CologneKerpener Str. 62CologneGermany50937
| | - Marialena Trivella
- University of OxfordCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesWindmill RoadOxfordUKOX3 7LD
| | - Nicole Skoetz
- Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cochrane CancerUniversity of CologneKerpener Str. 62CologneGermany50937
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Wass MN, Ray L, Michaelis M. Understanding of researcher behavior is required to improve data reliability. Gigascience 2019; 8:giz017. [PMID: 30715291 PMCID: PMC6528747 DOI: 10.1093/gigascience/giz017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Revised: 01/20/2019] [Accepted: 01/25/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND A lack of data reproducibility ("reproducibility crisis") has been extensively debated across many academic disciplines. RESULTS Although a reproducibility crisis is widely perceived, conclusive data on the scale of the problem and the underlying reasons are largely lacking. The debate is primarily focused on methodological issues. However, examples such as the use of misidentified cell lines illustrate that the availability of reliable methods does not guarantee good practice. Moreover, research is often characterized by a lack of established methods. Despite the crucial importance of researcher conduct, research and conclusive data on the determinants of researcher behavior are widely missing. CONCLUSION Meta-research that establishes an understanding of the factors that determine researcher behavior is urgently needed. This knowledge can then be used to implement and iteratively improve measures that incentivize researchers to apply the highest standards, resulting in high-quality data.
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Affiliation(s)
- Mark N Wass
- Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK
| | - Larry Ray
- School of Social Policy, Sociology and Social Research, University of Kent, Canterbury, CT2 7NJ, UK
| | - Martin Michaelis
- Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK
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23
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Riley RD, Moons KGM, Snell KIE, Ensor J, Hooft L, Altman DG, Hayden J, Collins GS, Debray TPA. A guide to systematic review and meta-analysis of prognostic factor studies. BMJ 2019; 364:k4597. [PMID: 30700442 DOI: 10.1136/bmj.k4597] [Citation(s) in RCA: 413] [Impact Index Per Article: 68.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Richard D Riley
- Centre for Prognosis Research, Research Institute for Primary Care and Health Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK
- Contributed equally
| | - Karel G M Moons
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Cochrane Netherlands, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Contributed equally
| | - Kym I E Snell
- Centre for Prognosis Research, Research Institute for Primary Care and Health Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK
| | - Joie Ensor
- Centre for Prognosis Research, Research Institute for Primary Care and Health Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK
| | - Lotty Hooft
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Cochrane Netherlands, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Douglas G Altman
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Jill Hayden
- Centre for Clinical Research, Halifax, Nova Scotia, Canada
| | - Gary S Collins
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Thomas P A Debray
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Cochrane Netherlands, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
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24
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Wu H, Yu DH, Wu MH, Huang T. Long non-coding RNA LOC541471: A novel prognostic biomarker for head and neck squamous cell carcinoma. Oncol Lett 2018; 17:2457-2464. [PMID: 30675311 DOI: 10.3892/ol.2018.9831] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 09/14/2018] [Indexed: 12/26/2022] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer. Early detection and management of HNSCC may prevent progression of the disease. Long non-coding RNAs (lncRNAs) may serve as prognostic biomarkers for various cancer types. The current study downloaded an RNA-Seq dataset containing 43 tumor-normal pairs. An independent t-test identified that the expression level of lncRNA LOC541471 was significantly increased in tumor tissues compared with healthy tissues. Additionally, the current study demonstrated that high lncRNA LOC541471 expression was significantly associated with increasing lymph node metastasis classification and perineural invasion. A multivariate Cox regression analysis revealed that high lncRNA LOC541471 expression levels were an independent predictor for reduced overall survival (n=487) and relapse-free survival (n=355). According to the anatomic neoplasm subdivision, HNSCC samples were classified as oropharyngeal carcinoma (n=297), oral carcinoma (n=80), laryngeal carcinoma and hypopharyngeal carcinoma (n=123). A negative association was revealed between lncRNA LOC541471 expression and overall survival in all subtypes of HNSCC. Therefore, lncRNA LOC541471 is significantly negatively associated with overall survival and relapse-free survival of patients with HNSCC and may be considered a potential prognostic factor for HNSCC.
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Affiliation(s)
- Hua Wu
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
| | - Da Hai Yu
- Department of Radiation Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China.,Department of Radiation Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
| | - Mian Hua Wu
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
| | - Teng Huang
- Department of Radiation Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China.,Department of Radiation Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
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25
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Kempf E, de Beyer JA, Cook J, Holmes J, Mohammed S, Nguyên TL, Simera I, Trivella M, Altman DG, Hopewell S, Moons KGM, Porcher R, Reitsma JB, Sauerbrei W, Collins GS. Overinterpretation and misreporting of prognostic factor studies in oncology: a systematic review. Br J Cancer 2018; 119:1288-1296. [PMID: 30353050 PMCID: PMC6251031 DOI: 10.1038/s41416-018-0305-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 09/21/2018] [Accepted: 09/24/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Cancer prognostic biomarkers have shown disappointing clinical applicability. The objective of this study was to classify and estimate how study results are overinterpreted and misreported in prognostic factor studies in oncology. METHODS This systematic review focused on 17 oncology journals with an impact factor above 7. PubMed was searched for primary clinical studies published in 2015, evaluating prognostic factors. We developed a classification system, focusing on three domains: misleading reporting (selective, incomplete reporting, misreporting), misleading interpretation (unreliable statistical analysis, spin) and misleading extrapolation of the results (claiming irrelevant clinical applicability, ignoring uncertainty). RESULTS Our search identified 10,844 articles. The 98 studies included investigated a median of two prognostic factors (Q1-Q3, 1-7). The prognostic factors' effects were selectively and incompletely reported in 35/98 and 24/98 full texts, respectively. Twenty-nine articles used linguistic spin in the form of strong statements. Linguistic spin rejecting non-significant results was found in 34 full-text results and 15 abstract results sections. One in five articles had discussion and/or abstract conclusions that were inconsistent with the study findings. Sixteen reports had discrepancies between their full-text and abstract conclusions. CONCLUSIONS Our study provides evidence of frequent overinterpretation of findings of prognostic factor assessment in high-impact medical oncology journals.
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Affiliation(s)
- Emmanuelle Kempf
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
- Department of Medical Oncology, Henri Mondor and Albert Chenevier Teaching Hospital, APHP, Créteil, France
| | - Jennifer A de Beyer
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Jonathan Cook
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Jane Holmes
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Seid Mohammed
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Tri-Long Nguyên
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
- Laboratory UPRES EA2415, Biostatistics, Epidemiology, Clinical Research and Health Economics, University of Montpellier, Montpellier, France
| | - Iveta Simera
- Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
| | - Marialena Trivella
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Douglas G Altman
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Sally Hopewell
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Karel G M Moons
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Cochrane Netherlands, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Raphael Porcher
- Department of Epidemiology, Hôtel Dieu Teaching Hospital, APHP, Paris, France
| | - Johannes B Reitsma
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Cochrane Netherlands, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Willi Sauerbrei
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Gary S Collins
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
- NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
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26
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Extraction of unadjusted estimates of prognostic association for meta-analysis: simulation methods as good alternatives to trend and direct method estimation. J Clin Epidemiol 2018; 99:153-163. [DOI: 10.1016/j.jclinepi.2017.12.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 12/04/2017] [Accepted: 12/20/2017] [Indexed: 11/24/2022]
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27
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Nieto T, Tomlinson CL, Dretzke J, Bayliss S, Price MJ, Dilworth M, Beggs AD, Tucker O. A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma. BMJ Open 2018; 8:e020427. [PMID: 29961009 PMCID: PMC6042533 DOI: 10.1136/bmjopen-2017-020427] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 04/16/2018] [Accepted: 05/03/2018] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett's oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC. An epigenetic biomarker could predict patients who are at high risk of progression from BO to OADC which could facilitate earlier diagnosis and spare those unlikely to develop cancer from regular invasive surveillance endoscopy. SETTING A systematic search was conducted of the following databases: MEDLINE, MEDLINE in Process, EMBASE, Cochrane Central, ISI Conference Proceedings Citation Index and the British Library's ZETOC. Studies were conducted in secondary and tertiary care settings. PARTICIPANTS All studies measuring epigenetic change in patients over 18 years old who progressed from non-dysplastic BO to OADC were included. Genetic, in vitro and studies which did not measure progression in the same patient cohort were excluded. Study inclusion and risk of bias of individual eligible studies were assessed in duplicate by two reviewers using a modified Quality in Prognostic Studies tool. RESULTS 14 studies met the inclusion criteria. 42 epigenetic markers were identified, and 5 studies developed models aiming to predict progression to OADC. CONCLUSIONS The evidence from this systematic review is suggestive of a role for p16 as an epigenetic biomarker for the progression of BO to OADC. PROSPERO NUMBER CRD42016038654.
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Affiliation(s)
- Tom Nieto
- Department of Surgery, University of Birmingham, Birmingham, UK
| | - Claire L Tomlinson
- Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Janine Dretzke
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Susan Bayliss
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Malcolm James Price
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Mark Dilworth
- Department of Surgery, Heart of England Foundation Trust and Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Andrew D Beggs
- Department of Surgery, University of Birmingham, Birmingham, UK
| | - Olga Tucker
- Department of Surgery, University of Birmingham, Birmingham, UK
- Department of Surgery, Heart of England Foundation Trust and Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
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28
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Sauerbrei W, Haeussler T. Comment on 'BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses'. Br J Cancer 2018. [PMID: 29540774 PMCID: PMC5931108 DOI: 10.1038/s41416-018-0023-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Affiliation(s)
- Willi Sauerbrei
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
| | - Tim Haeussler
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
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29
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Pang CL, Pilkington N, Wei Y, Peters J, Roobottom C, Hyde C. A methodology review on the incremental prognostic value of computed tomography biomarkers in addition to Framingham risk score in predicting cardiovascular disease: the use of association, discrimination and reclassification. BMC Cardiovasc Disord 2018; 18:39. [PMID: 29466951 PMCID: PMC5822603 DOI: 10.1186/s12872-018-0777-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 02/14/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Computed tomography (CT) biomarkers claim to improve cardiovascular risk stratification. This review focuses on significant differences in incremental measures between adequate and inadequate reporting practise. METHODS Studies included were those that used Framingham Risk Score as a baseline and described the incremental value of adding calcium score or CT coronary angiogram in predicting cardiovascular risk. Searches of MEDLINE, EMBASE, Web of Science and Cochrane Central were performed with no language restriction. RESULTS Thirty five studies consisting of 206,663 patients (men = 118,114, 55.1%) were included. The baseline Framingham Risk Score included the 1998, 2002 and 2008 iterations. Selective reporting, inconsistent reference groupings and thresholds were found. Twelve studies (34.3%) had major and 23 (65.7%) had minor alterations and the respective Δ AUC were significantly different (p = 0.015). When the baseline model performed well, the Δ AUC was relatively lower with the addition of a CT biomarker (Spearman coefficient = - 0.46, p < 0.0001; n = 33; 76 pairs of data). Other factors that influenced AUC performance included exploration of data analysis, calibration, validation, multivariable and AUC documentation (all p < 0.05). Most studies (68.7%) that reported categorical NRI (n = 16; 46 pairs of data) subjectively drew strong conclusions along with other poor reporting practices. However, no significant difference in values of NRI was found between adequate and inadequate reporting. CONCLUSIONS The widespread practice of poor reporting particularly association, discrimination, reclassification, calibration and validation undermines the claimed incremental value of CT biomarkers over the Framingham Risk Score alone. Inadequate reporting of discrimination inflates effect estimate, however, that is not necessarily the case for reclassification.
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Affiliation(s)
- Chun Lap Pang
- University of Plymouth, Plymouth University Peninsula Schools of Medicine and Dentistry, John Bull Building, Tamar Science Park, Research Way, Plymouth, PL6 8BU UK
- Plymouth Hospitals NHS Trust, Derriford Hospital, Imaging Department, Derriford Rd, Plymouth, PL6 8DH UK
- Primary Care Plymouth, Room N9, ITTC Building, Davy Road, Plymouth Science Park, Derriford, Plymouth, Devon PL6 8BX UK
| | - Nicola Pilkington
- Plymouth Hospitals NHS Trust, Derriford Hospital, Department of Anaesthetics, Derriford Rd, Plymouth, PL6 8DH UK
| | - Yinghui Wei
- University of Plymouth, School of Computing, Electronics and Mathematics, Plymouth, PL4 8AA UK
| | - Jaime Peters
- University of Exeter, South Cloisters, St Luke’s Campus, Exeter, EX1 2LU UK
| | - Carl Roobottom
- University of Plymouth, Plymouth University Peninsula Schools of Medicine and Dentistry, John Bull Building, Tamar Science Park, Research Way, Plymouth, PL6 8BU UK
- Plymouth Hospitals NHS Trust, Derriford Hospital, Imaging Department, Derriford Rd, Plymouth, PL6 8DH UK
| | - Chris Hyde
- University of Exeter, South Cloisters, St Luke’s Campus, Exeter, EX1 2LU UK
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Morelli KM, Brown LB, Warren GL. Effect of NSAIDs on Recovery From Acute Skeletal Muscle Injury: A Systematic Review and Meta-analysis. Am J Sports Med 2018; 46:224-233. [PMID: 28355084 DOI: 10.1177/0363546517697957] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND There is debate as to whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is beneficial after acute skeletal muscle injury. Some studies have suggested that NSAID use may be detrimental to injured muscle. PURPOSE To determine whether NSAID use affects recovery from skeletal muscle injury as assessed by strength loss, soreness, and/or blood creatine kinase level. STUDY DESIGN Systematic review and meta-analysis. METHODS An extensive systematic review was completed searching 16 databases (eg, PubMed, Cochrane Library, EMBASE). Inclusion criteria were (1) acute injury to skeletal muscle, (2) use of a control condition, (3) certainty of the NSAID dose administered, and (4) use of 1 or more of the 3 desired outcome measures. A total of 5343 study reports were screened, of which 41 studies were deemed suitable for inclusion. The standardized mean difference was used as the effect size (ES) and was calculated such that a positive ES indicated NSAID efficacy. Meta-analyses were run using a random-effects model. RESULTS For all studies, time points after injury, and injury markers combined, NSAID use was found to elicit a small to medium, significant decrease in the markers of injury (overall ES = +0.34; P = .0001). Because heterogeneity in study ES was apparent (ie, Q- df = 52.4, P = .000005; I2 = 57%), subgroup meta-analyses and meta-regressions were run in an attempt to explain the heterogeneity. In human studies, study ESs were higher when lower body muscles were injured ( P = .045). In animal studies, study ESs were lower with longer NSAID administration durations ( P = .023) and at longer follow-up times after injury ( P = .010). CONCLUSION Overall, our analysis supports NSAID use for reducing strength loss, soreness, and blood creatine kinase level after an acute muscle injury, at least for humans and in the short term. Additional research is required to determine why NSAID use appears to be more effective when lower-body muscles in humans are injured. It would also be important to determine why NSAID use appears detrimental at later times after injury in animals but not humans.
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Affiliation(s)
- Kimberly M Morelli
- Department of Physical Therapy, Georgia State University, Atlanta, Georgia, USA
| | - Laura B Brown
- Department of Physical Therapy, Georgia State University, Atlanta, Georgia, USA
| | - Gordon L Warren
- Department of Physical Therapy, Georgia State University, Atlanta, Georgia, USA
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Wang SM, Han C, Lee SJ, Jun TY, Patkar AA, Masand PS, Pae CU. Efficacy of antidepressants: bias in randomized clinical trials and related issues. Expert Rev Clin Pharmacol 2017; 11:15-25. [PMID: 28893095 DOI: 10.1080/17512433.2017.1377070] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Countless antidepressant randomized trials were conducted and showed statistically significant benefits of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) over placebo. Meanwhile, critics are increasing regarding the efficacy of antidepressants in the treatment of MDD because at least a proportion of clinical trials could be hampered by various biases. In contrast, number of failed trials is increasing in the recent years which have made developing psychiatric medications progressively more time-consuming and expensive. Areas covered: Biases and related issues in clinical trials for antidepressants can be identified as an important common contributing factor to the two paradoxical phenomenon. This review identifies possible biases that can occur before, during, and after clinical trials of antidepressant. Expert commentary: Recent studies not only may over-estimate efficacy of antidepressants, but also may exaggerate placebo response because of various biases. Sponsorship and publication biases have been one of the targets of the criticism and ethical debate. Thus, initiating new trend of research by re-organizing academic-industry partnership will be the most important task in the next five years.
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Affiliation(s)
- Sheng-Min Wang
- a Department of Psychiatry , The Catholic University of Korea College of Medicine , Seoul , Republic of Korea.,b International Health Care Center, Seoul St. Mary's Hospital, College of Medicine , The Catholic University of Korea , Seoul , Republic of Korea
| | - Changsu Han
- c Department of Psychiatry , Korea University, College of Medicine , Seoul , Republic of Korea
| | - Soo-Jung Lee
- a Department of Psychiatry , The Catholic University of Korea College of Medicine , Seoul , Republic of Korea
| | - Tae-Youn Jun
- a Department of Psychiatry , The Catholic University of Korea College of Medicine , Seoul , Republic of Korea
| | - Ashwin A Patkar
- d Department of Psychiatry and Behavioral Sciences , Duke University Medical Center , Durham , NC , USA
| | | | - Chi-Un Pae
- a Department of Psychiatry , The Catholic University of Korea College of Medicine , Seoul , Republic of Korea.,d Department of Psychiatry and Behavioral Sciences , Duke University Medical Center , Durham , NC , USA
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Aitken SJ, Blyth FM, Naganathan V. Incidence, prognostic factors and impact of postoperative delirium after major vascular surgery: A meta-analysis and systematic review. Vasc Med 2017; 22:387-397. [DOI: 10.1177/1358863x17721639] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Although postoperative delirium is a common complication and increases patient care needs, little is known about the predictors and outcomes of delirium in patients having vascular surgery. This review aimed to determine the incidence, prognostic factors and impact of postoperative delirium in vascular surgical patients. MEDLINE and EMBASE were systematically searched for articles published between January 2000 and January 2016 on delirium after vascular surgery. The primary outcome was the incidence of delirium. Secondary outcomes were contributing prognostic factors and impact of delirium. Study quality and risk of bias was assessed using the QUIPS tool for systematic reviews of prognostic studies, and MOOSE guidelines for reviews of observational studies. Quantitative analyses of extracted data were conducted using meta-analysis where possible to determine incidence of delirium and prognostic factors. A qualitative review of outcomes was performed. Fifteen articles were eligible for inclusion. Delirium incidence ranged between 5% and 39%. Meta-analysis found that patients with delirium were older than those without delirium (OR 3.6, p<0.001). Prognostic factors predicting delirium included increased age (OR 1.04, p<0.001), pre-existing cognitive impairment (OR 9.8, p=0.01), hypertension, pre-existing depression and open aortic surgery. Delirious patients remained in hospital 6 days longer ( p<0.001) and had more complications than patients without delirium. Data were limited on the impact of procedure complexity, endovascular compared to open surgery or type of anaesthetic. Postoperative delirium occurs frequently, resulting in major morbidity for vascular patients. Improved quality of prognostic studies may identify modifiable peri-operative factors to improve quality of care for vascular surgical patients.
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Affiliation(s)
- Sarah Joy Aitken
- University of Sydney, Concord Clinical School, Sydney, NSW, Australia
- Concord Institute of Academic Surgery, Department of Vascular Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Fiona M Blyth
- University of Sydney, Concord Clinical School, Sydney, NSW, Australia
- Centre for Education and Research in Ageing, Concord, Sydney, NSW, Australia
- Ageing and Alzheimers Institute, Concord, Sydney, NSW, Australia
| | - Vasi Naganathan
- University of Sydney, Concord Clinical School, Sydney, NSW, Australia
- Centre for Education and Research in Ageing, Concord, Sydney, NSW, Australia
- Ageing and Alzheimers Institute, Concord, Sydney, NSW, Australia
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Ioannidis JPA, Bossuyt PMM. Waste, Leaks, and Failures in the Biomarker Pipeline. Clin Chem 2017; 63:963-972. [DOI: 10.1373/clinchem.2016.254649] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 11/30/2016] [Indexed: 01/05/2023]
Abstract
Abstract
BACKGROUND
The large, expanding literature on biomarkers is characterized by almost ubiquitous significant results, with claims about the potential importance, but few of these discovered biomarkers are used in routine clinical care.
CONTENT
The pipeline of biomarker development includes several specific stages: discovery, validation, clinical translation, evaluation, implementation (and, in the case of nonutility, deimplementation). Each of these stages can be plagued by problems that cause failures of the overall pipeline. Some problems are nonspecific challenges for all biomedical investigation, while others are specific to the peculiarities of biomarker research. Discovery suffers from poor methods and incomplete and selective reporting. External independent validation is limited. Selection for clinical translation is often shaped by nonrational choices. Evaluation is sparse and the clinical utility of many biomarkers remains unknown. The regulatory environment for biomarkers remains weak and guidelines can reach biased or divergent recommendations. Removing inefficient or even harmful biomarkers that have been entrenched in clinical care can meet with major resistance.
SUMMARY
The current biomarker pipeline is too prone to failures. Consideration of clinical needs should become a starting point for the development of biomarkers. Improvements can include the use of more stringent methodology, better reporting, larger collaborative studies, careful external independent validation, preregistration, rigorous systematic reviews and umbrella reviews, pivotal randomized trials, and implementation and deimplementation studies. Incentives should be aligned toward delivering useful biomarkers.
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Affiliation(s)
- John P A Ioannidis
- Departments of Medicine, Health Research and Policy, and Statistics, and the Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA
| | - Patrick M M Bossuyt
- Department of Clinical Epidemiology, Biostatistics & Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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Skoetz N, Collins G, Moons K, Estcourt LJ, Engert A, Kobe C, von Tresckow B, Trivella M. Interim PET for prognosis in adults with Hodgkin lymphoma: a prognostic factor exemplar review. Hippokratia 2017. [DOI: 10.1002/14651858.cd012643] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Nicole Skoetz
- University Hospital of Cologne; Cochrane Haematological Malignancies Group, Department I of Internal Medicine; Kerpener Str. 62 Cologne Germany 50937
| | - Gary Collins
- University of Oxford; Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences; Windmill Road Oxford UK OX3 7LD
| | - Karel Moons
- University Medical Center Utrecht; Julius Center for Health Sciences and Primary Care; PO Box 85500 Utrecht Netherlands 3508 GA
| | - Lise J Estcourt
- NHS Blood and Transplant; Haematology/Transfusion Medicine; Level 2, John Radcliffe Hospital Headington Oxford UK OX3 9BQ
| | - Andreas Engert
- University Hospital of Cologne; Department I of Internal Medicine; Kerpener Str. 62 Cologne Germany 50924
| | - Carsten Kobe
- University Hospital of Cologne; Department for Nuclear Medicine; Cologne Germany
| | - Bastian von Tresckow
- University Hospital of Cologne; Department I of Internal Medicine; Kerpener Str. 62 Cologne Germany 50924
| | - Marialena Trivella
- University of Oxford; Centre for Statistics in Medicine; Botnar Research Centre Windmill Road Oxford UK OX3 7LD
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Catalá-López F, Hutton B, Driver JA, Page MJ, Ridao M, Valderas JM, Alonso-Arroyo A, Forés-Martos J, Martínez S, Gènova-Maleras R, Macías-Saint-Gerons D, Crespo-Facorro B, Vieta E, Valencia A, Tabarés-Seisdedos R. Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies. Syst Rev 2017; 6:69. [PMID: 28376926 PMCID: PMC5379758 DOI: 10.1186/s13643-017-0466-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Accepted: 03/23/2017] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. METHODS/DESIGN We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. DISCUSSION Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016052762.
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Affiliation(s)
- Ferrán Catalá-López
- Department of Medicine, University of Valencia/INCLIVA Health Research Institute and CIBERSAM, Valencia, Spain. .,Fundación Instituto de Investigación en Servicios de Salud, Valencia, Spain. .,Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
| | - Brian Hutton
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Jane A Driver
- Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA, USA.,Division of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Matthew J Page
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.,School of Social and Community Medicine, University of Bristol, Bristol, UK
| | - Manuel Ridao
- Instituto Aragonés de Ciencias de la Salud, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Zaragoza, Spain.,Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO-Salud Pública), Valencia, Spain
| | - José M Valderas
- Health Services and Policy Research Group, Exeter Collaboration for Academic Primary Care, University of Exeter Medical School, University of Exeter, Exeter, UK
| | - Adolfo Alonso-Arroyo
- Department of History of Science and Documentation, University of Valencia, Valencia, Spain.,Unidad de Información e Investigación Social y Sanitaria-UISYS, University of Valencia-Spanish National Research Council (CSIC), Valencia, Spain
| | - Jaume Forés-Martos
- Department of Medicine, University of Valencia/INCLIVA Health Research Institute and CIBERSAM, Valencia, Spain
| | - Salvador Martínez
- Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Spanish National Research Council (UMH-CSIC), San Juan de Alicante, Spain
| | | | - Diego Macías-Saint-Gerons
- Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Medicines and Healthcare Products Agency (AEMPS), Madrid, Spain.,Department of Health Systems and Services, Unit of Medicines and Health Technologies, Pan American Health Organization (PAHO), Washington, DC, USA
| | - Benedicto Crespo-Facorro
- Department of Psychiatry, Hospital Marqués de Valdecilla, University of Cantabria/IDIVAL and CIBERSAM, Santander, Spain
| | - Eduard Vieta
- Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and CIBERSAM, Barcelona, Spain
| | - Alfonso Valencia
- Structural Biology and Biocumputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.,Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain
| | - Rafael Tabarés-Seisdedos
- Department of Medicine, University of Valencia/INCLIVA Health Research Institute and CIBERSAM, Valencia, Spain.
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Hemingway H, Feder GS, Fitzpatrick NK, Denaxas S, Shah AD, Timmis AD. Using nationwide ‘big data’ from linked electronic health records to help improve outcomes in cardiovascular diseases: 33 studies using methods from epidemiology, informatics, economics and social science in the ClinicAl disease research using LInked Bespoke studies and Electronic health Records (CALIBER) programme. PROGRAMME GRANTS FOR APPLIED RESEARCH 2017. [DOI: 10.3310/pgfar05040] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BackgroundElectronic health records (EHRs), when linked across primary and secondary care and curated for research use, have the potential to improve our understanding of care quality and outcomes.ObjectiveTo evaluate new opportunities arising from linked EHRs for improving quality of care and outcomes for patients at risk of or with coronary disease across the patient journey.DesignEpidemiological cohort, health informatics, health economics and ethnographic approaches were used.Setting230 NHS hospitals and 226 general practices in England and Wales.ParticipantsUp to 2 million initially healthy adults, 100,000 people with stable coronary artery disease (SCAD) and up to 300,000 patients with acute coronary syndrome.Main outcome measuresQuality of care, fatal and non-fatal cardiovascular disease (CVD) events.Data platform and methodsWe created a novel research platform [ClinicAl disease research using LInked Bespoke studies and Electronic health Records (CALIBER)] based on linkage of four major sources of EHR data in primary care and national registries. We carried out 33 complementary studies within the CALIBER framework. We developed a web-based clinical decision support system (CDSS) in hospital chest pain clinics. We established a novel consented prognostic clinical cohort of SCAD patients.ResultsCALIBER was successfully established as a valid research platform based on linked EHR data in nearly 2 million adults with > 600 EHR phenotypes implemented on the web portal (seehttps://caliberresearch.org/portal). Despite national guidance, key opportunities for investigation and treatment were missed across the patient journey, resulting in a worse prognosis for patients in the UK compared with patients in health systems in other countries. Our novel, contemporary, high-resolution studies showed heterogeneous associations for CVD risk factors across CVDs. The CDSS did not alter the decision-making behaviour of clinicians in chest pain clinics. Prognostic models using real-world data validly discriminated risk of death and events, and were used in cost-effectiveness decision models.ConclusionsEmerging ‘big data’ opportunities arising from the linkage of records at different stages of a patient’s journey are vital to the generation of actionable insights into the diagnosis, risk stratification and cost-effective treatment of people at risk of, or with, CVD.Future workThe vast majority of NHS data remain inaccessible to research and this hampers efforts to improve efficiency and quality of care and to drive innovation. We propose three priority directions for further research. First, there is an urgent need to ‘unlock’ more detailed data within hospitals for the scale of the UK’s 65 million population. Second, there is a need for scaled approaches to using EHRs to design and carry out trials, and interpret the implementation of trial results. Third, large-scale, disease agnostic genetic and biological collections linked to such EHRs are required in order to deliver precision medicine and to innovate discovery.Study registrationCALIBER studies are registered as follows: study 2 – NCT01569139, study 4 – NCT02176174 and NCT01164371, study 5 – NCT01163513, studies 6 and 7 – NCT01804439, study 8 – NCT02285322, and studies 26–29 – NCT01162187. Optimising the Management of Angina is registered as Current Controlled Trials ISRCTN54381840.FundingThe National Institute for Health Research (NIHR) Programme Grants for Applied Research programme (RP-PG-0407-10314) (all 33 studies) and additional funding from the Wellcome Trust (study 1), Medical Research Council Partnership grant (study 3), Servier (study 16), NIHR Research Methods Fellowship funding (study 19) and NIHR Research for Patient Benefit (study 33).
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Affiliation(s)
- Harry Hemingway
- Institute of Health Informatics, University College London, London, UK
- Farr Institute of Health Informatics Research, University College London, London, UK
| | - Gene S Feder
- Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Bristol, UK
| | - Natalie K Fitzpatrick
- Institute of Health Informatics, University College London, London, UK
- Farr Institute of Health Informatics Research, University College London, London, UK
| | - Spiros Denaxas
- Institute of Health Informatics, University College London, London, UK
- Farr Institute of Health Informatics Research, University College London, London, UK
| | - Anoop D Shah
- Institute of Health Informatics, University College London, London, UK
- Farr Institute of Health Informatics Research, University College London, London, UK
| | - Adam D Timmis
- Farr Institute of Health Informatics Research, University College London, London, UK
- Barts Health NHS Trust, London, UK
- Farr Institute of Health Informatics Research, Queen Mary University of London, London, UK
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Abstract
One of the most important of the nutrient intake values (NIVs) is the average nutrient requirement (ANR). The ANR is defined as an intake value that will be adequate for half of the individuals in a group of people with similar characteristics. It is used to estimate the prevalence of adequacy, and it serves as the basis for the individual nutrient level (INLx). The determination of adequacy is a complex process, with the resulting value of the ANR dependent on the criterion or functional outcome chosen to define nutrient adequacy. Because nutrients have multiple sites of action in human metabolism, it is possible to demonstrate abnormal function in one parameter measured or observed as a result of inadequate intake of a nutrient, while other parameters requiring the same nutrient appear normal or within normal ranges. Thus, depending on the criterion of adequacy selected, the requirement for a given nutrient may be at a lower or a higher intake amount. In harmonizing development of NIVs, it is important to clearly identify the criterion of adequacy selected and the rationale for its selection. Rarely are available data sufficient to provide dose—response information from which to select a level of intake at which half of the individuals demonstrate adequacy and half appear to demonstrate inadequacy. Three levels of intake, of which at least one level of intake is below the requirement for most of the individuals in the sample, and one level of intake is above their requirement, are useful for establishing a level at which half of the group might be considered to demonstrate adequacy. Types of human nutrient studies that may be used to obtain data are discussed, as well as characteristics of the sample size needed to demonstrate adequacy. The variation in requirements is also an important aspect in predicting levels of intake that will have defined probabilities of adequacy for groups (to develop the INLx, where x is the defined probability chosen). An analysis of the origins of different types of variability is presented. When estimating energy requirements, a special case of NIVs, important issues must be considered. Additionally, an example of evaluating data used to establish an ANR for vitamin A, and the effect of variability in requirements for vitamin A, is provided.
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Affiliation(s)
- Allison A Yates
- Beltsville Human Nutrition Research Center, USDA/ARS, 110300 Baltimore Ave., Beltsville, MD 20705, USA.
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Markozannes G, Tzoulaki I, Karli D, Evangelou E, Ntzani E, Gunter MJ, Norat T, Ioannidis JP, Tsilidis KK. Diet, body size, physical activity and risk of prostate cancer: An umbrella review of the evidence. Eur J Cancer 2016; 69:61-69. [PMID: 27816833 DOI: 10.1016/j.ejca.2016.09.026] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 09/15/2016] [Accepted: 09/20/2016] [Indexed: 11/22/2022]
Abstract
The existing literature on the relationship between diet, body size, physical activity and prostate cancer risk was summarised by the World Cancer Research Fund Continuous Update Project (CUP). An evaluation of the robustness of this evidence is required to help inform public health policy. The robustness of this evidence was evaluated using several criteria addressing evidence strength and validity, including the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, number of prostate cancer cases, between-study heterogeneity, 95% prediction intervals, small-study effects bias, excess significance bias and sensitivity analyses with credibility ceilings. A total of 248 meta-analyses were extracted from the CUP, which studied associations of 23 foods, 31 nutrients, eight indices of body size and three indices of physical activity with risk of total prostate cancer development, mortality or cancer development by stage and grade. Of the 176 meta-analyses using a continuous scale to measure the exposures, no association presented strong evidence by satisfying all the aforementioned criteria. Only the association of height with total prostate cancer incidence and mortality presented highly suggestive evidence with a 4% higher risk per 5 cm greater height (95% confidence interval, 1.03, 1.05). Associations for body mass index, weight, height, dietary calcium and spirits intake were supported by suggestive evidence. Overall, the association of diet, body size, physical activity and prostate cancer has been extensively studied, but no association was graded with strong evidence.
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Affiliation(s)
- Georgios Markozannes
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece
| | - Ioanna Tzoulaki
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK
| | - Dimitra Karli
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece
| | - Evangelos Evangelou
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK
| | - Evangelia Ntzani
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece; Center for Evidence-Based Medicine, Department of Health Services, Policy and Practice, School of Public Health, Brown University, 121 South Main Street, Providence, RI, 02903, USA
| | - Marc J Gunter
- International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Teresa Norat
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK
| | - John P Ioannidis
- Department of Medicine, Stanford Prevention Research Center, Stanford School of Medicine, Stanford, CA, 94305, USA; Department of Health Research and Policy, Stanford School of Medicine, Stanford, CA, 94305, USA; Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, 94305, USA
| | - Konstantinos K Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Av., University Campus, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK.
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Ojerholm E, Smith A, Hwang WT, Baumann BC, Tucker KN, Lerner SP, Mamtani R, Boursi B, Christodouleas JP. Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: Assessing prognostic and predictive value in SWOG 8710. Cancer 2016; 123:794-801. [PMID: 27787873 DOI: 10.1002/cncr.30422] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 09/12/2016] [Accepted: 10/03/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Multiple studies have reported the neutrophil-to-lymphocyte ratio (NLR) as a promising candidate; however, these analyses have methodological limitations. Therefore, the authors performed a category B biomarker study to test whether NLR is prognostic for overall survival (OS) after curative treatment or is predictive for the survival benefit from neoadjuvant chemotherapy (NAC). METHODS This study is an unplanned secondary analysis of SWOG 8710, a randomized phase 3 trial that assessed cystectomy with or without NAC in 317 patients with muscle-invasive BC. NLR was calculated from prospectively collected complete blood counts. For the prognostic analysis, 230 patients were identified; for the predictive analysis, 263 were identified. NLR was evaluated with proportional hazards models including prespecified factors (age, sex, T-stage, lymphovascular invasion, and treatment arm). RESULTS With a median follow-up of 18.6 years, there were 172 and 205 deaths in the prognostic and predictive cohorts, respectively. In a multivariable analysis, NLR was not prognostic for OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.98-1.11; P = .24). Furthermore, NLR did not predict for the OS benefit from NAC (HR, 1.01; 95% CI, 0.90-1.14; P = .86). Factors associated with worse OS were older age (HR, 1.05; 95% CI, 1.04-1.07; P < .001) and surgery without NAC (HR, 1.39; 95% CI, 1.03-1.88; P = .03). CONCLUSIONS This is the first analysis of NLR in BC to use prospectively collected clinical trial data. In contrast to previous studies, it suggests that NLR is neither a prognostic nor predictive biomarker for OS in muscle-invasive BC. Cancer 2017;123:794-801. © 2016 American Cancer Society.
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Affiliation(s)
- Eric Ojerholm
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Andrew Smith
- Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Wei-Ting Hwang
- Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Brian C Baumann
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kai N Tucker
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Ronac Mamtani
- Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ben Boursi
- Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - John P Christodouleas
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
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Sekula P, Pressler JB, Sauerbrei W, Goebell PJ, Schmitz-Dräger BJ. Assessment of the extent of unpublished studies in prognostic factor research: a systematic review of p53 immunohistochemistry in bladder cancer as an example. BMJ Open 2016; 6:e009972. [PMID: 27531721 PMCID: PMC5013379 DOI: 10.1136/bmjopen-2015-009972] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 06/20/2016] [Accepted: 07/05/2016] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES When study groups fail to publish their results, a subsequent systematic review may come to incorrect conclusions when combining information only from published studies. p53 expression measured by immunohistochemistry is a potential prognostic factor in bladder cancer. Although numerous studies have been conducted, its role is still under debate. The assumption that unpublished studies too harbour evidence on this research topic leads to the question about the attributable effect when adding this information and comparing it with published data. Thus, the aim was to identify published and unpublished studies and to explore their differences potentially affecting the conclusion on its function as a prognostic biomarker. DESIGN Systematic review of published and unpublished studies assessing p53 in bladder cancer in Germany between 1993 and 2007. RESULTS The systematic search revealed 16 studies of which 11 (69%) have been published and 5 (31%) have not. Key reason for not publishing the results was a loss of interest of the investigators. There were no obviously larger differences between published and unpublished studies. However, a meaningful meta-analysis was not possible mainly due to the poor (ie, incomplete) reporting of study results. CONCLUSIONS Within this well-defined population of studies, we could provide empirical evidence for the failure of study groups to publish their results that was mainly caused by loss of interest. This fact may be coresponsible for the role of p53 as a prognostic factor still being unclear. We consider p53 and the restriction to studies in Germany as a specific example, but the critical issues are probably similar for other prognostic factors and other countries.
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Affiliation(s)
- Peggy Sekula
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center – University of Freiburg,Freiburg, Germany
| | - Julia B Pressler
- Department of Urology, Schön-Klinik Nürnberg Fürth, Fürth, Germany
- KUNO University Children's Hospital, Regensburg, Germany
| | - Willi Sauerbrei
- Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center – University of Freiburg,Freiburg, Germany
| | - Peter J Goebell
- Department of Urology, University Clinic of Erlangen, Waldkrankenhaus St. Marien, Erlangen, Germany
| | - Bernd J Schmitz-Dräger
- Department of Urology, Schön-Klinik Nürnberg Fürth, Fürth, Germany
- Department of Urology, University Clinic of Erlangen, Waldkrankenhaus St. Marien, Erlangen, Germany
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Perera R, McFadden E, McLellan J, Lung T, Clarke P, Pérez T, Fanshawe T, Dalton A, Farmer A, Glasziou P, Takahashi O, Stevens J, Irwig L, Hirst J, Stevens S, Leslie A, Ohde S, Deshpande G, Urayama K, Shine B, Stevens R. Optimal strategies for monitoring lipid levels in patients at risk or with cardiovascular disease: a systematic review with statistical and cost-effectiveness modelling. Health Technol Assess 2016; 19:1-401, vii-viii. [PMID: 26680162 DOI: 10.3310/hta191000] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation. OBJECTIVE To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD. DATA SOURCES We searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke's Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature. METHODS In two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year. RESULTS A total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high (I(2) = 98%); similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention. LIMITATION Heterogeneity in meta-analyses. CONCLUSIONS While acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence. STUDY REGISTRATION This study is registered as PROSPERO CRD42013003727. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Rafael Perera
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Emily McFadden
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Julie McLellan
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Tom Lung
- Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | - Philip Clarke
- Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | - Teresa Pérez
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Thomas Fanshawe
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Andrew Dalton
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Andrew Farmer
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | | | - Osamu Takahashi
- St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan
| | | | - Les Irwig
- Sydney School of Public Health, University of Sydney, Sydney, Australia
| | - Jennifer Hirst
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Sarah Stevens
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Asuka Leslie
- St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan
| | - Sachiko Ohde
- St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan
| | - Gautam Deshpande
- St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan
| | - Kevin Urayama
- St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan
| | - Brian Shine
- Oxford University Hospitals Trust, Oxford, UK
| | - Richard Stevens
- National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
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Kelley GA, Kelley KS. Exercise reduces depressive symptoms in adults with arthritis: Evidential value. World J Rheumatol 2016; 6:23-29. [PMID: 27489782 PMCID: PMC4968945 DOI: 10.5499/wjr.v6.i2.23] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 09/13/2015] [Accepted: 03/09/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether evidential value exists that exercise reduces depression in adults with arthritis and other rheumatic conditions. METHODS Utilizing data derived from a prior meta-analysis of 29 randomized controlled trials comprising 2449 participants (1470 exercise, 979 control) with fibromyalgia, osteoarthritis, rheumatoid arthritis or systemic lupus erythematosus, a new method, P-curve, was utilized to assess for evidentiary worth as well as dismiss the possibility of discriminating reporting of statistically significant results regarding exercise and depression in adults with arthritis and other rheumatic conditions. Using the method of Stouffer, Z-scores were calculated to examine selective-reporting bias. An alpha (P) value < 0.05 was deemed statistically significant. In addition, average power of the tests included in P-curve, adjusted for publication bias, was calculated. RESULTS Fifteen of 29 studies (51.7%) with exercise and depression results were statistically significant (P < 0.05) while none of the results were statistically significant with respect to exercise increasing depression in adults with arthritis and other rheumatic conditions. Right-skew to dismiss selective reporting was identified (Z = -5.28, P < 0.0001). In addition, the included studies did not lack evidential value (Z = 2.39, P = 0.99), nor did they lack evidential value and were P-hacked (Z = 5.28, P > 0.99). The relative frequencies of P-values were 66.7% at 0.01, 6.7% each at 0.02 and 0.03, 13.3% at 0.04 and 6.7% at 0.05. The average power of the tests included in P-curve, corrected for publication bias, was 69%. Diagnostic plot results revealed that the observed power estimate was a better fit than the alternatives. CONCLUSION Evidential value results provide additional support that exercise reduces depression in adults with arthritis and other rheumatic conditions.
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Abstract
Background The published clinical research literature may be distorted by the pursuit of statistically significant results. Purpose We aimed to develop a test to explore biases stemming from the pursuit of nominal statistical significance. Methods The exploratory test evaluates whether there is a relative excess of formally significant findings in the published literature due to any reason (e.g., publication bias, selective analyses and outcome reporting, or fabricated data). The number of expected studies with statistically significant results is estimated and compared against the number of observed significant studies. The main application uses α = 0.05, but a range of α thresholds is also examined. Different values or prior distributions of the effect size are assumed. Given the typically low power (few studies per research question), the test may be best applied across domains of many meta-analyses that share common characteristics (interventions, outcomes, study populations, research environment). Results We evaluated illustratively eight meta-analyses of clinical trials with >50 studies each and 10 meta-analyses of clinical efficacy for neuroleptic agents in schizophrenia; the 10 meta-analyses were also examined as a composite domain. Different results were obtained against commonly used tests of publication bias. We demonstrated a clear or possible excess of significant studies in 6 of 8 large meta-analyses and in the wide domain of neuroleptic treatments. Limitations The proposed test is exploratory, may depend on prior assumptions, and should be applied cautiously. Conclusions An excess of significant findings may be documented in some clinical research fields. Clinical Trials 2007; 4: 245—253; http://ctj.sagepub.com
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Affiliation(s)
- John P A Ioannidis
- Clinical Trials and Evidence Based Medicine Unit and Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
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Serghiou S, Kyriakopoulou A, Ioannidis JPA. Long noncoding RNAs as novel predictors of survival in human cancer: a systematic review and meta-analysis. Mol Cancer 2016; 15:50. [PMID: 27352941 PMCID: PMC4924330 DOI: 10.1186/s12943-016-0535-1] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 06/14/2016] [Indexed: 12/23/2022] Open
Abstract
Background Expression of various long noncoding RNAs (lncRNAs) may affect cancer prognosis. Here, we aim to gather and examine all evidence on the potential role of lncRNAs as novel predictors of survival in human cancer. Methods We systematically searched through PubMed, to identify all published studies reporting on the association between any individual lncRNA or group of lncRNAs with prognosis in human cancer (death or other clinical outcomes). Where appropriate, we then performed quantitative synthesis of those results using meta-analytic methods to identify the true effect size of lncRNAs on cancer prognosis. The reliability of those results was then examined using measures of heterogeneity and testing for selective reporting biases. Results Three hundred ninety-two studies were screened to eventually identify 111 eligible studies on 127 datasets. In total, these represented 16,754 independent participants pertaining to 53 individual and 6 grouped lncRNAs within a total of 19 cancer sites. Overall, 83 % of the studies we identified addressed overall survival and 32 % of the studies addressed recurrence-free survival. For overall survival, 96 % (88/92) of studies identified a statistically significant association of lncRNA expression to prognosis. Meta-analysis of 6 out of 7 lncRNAs for which three or more studies were available, identified statistically significant associations with overall survival. The lncRNA HOTAIR was by far the most broadly studied lncRNA (n = 29; of 111 studies) and featured a summary hazard ratio (HR) of 2.22 (95 % confidence interval (CI), 1.86–2.65) with modest heterogeneity (I2 = 49 %; 95 % CI, 14–79 %). Prominent excess significance was demonstrated across all meta-analyses (p-value = 0.0003), raising the possibility of substantial selective reporting biases. Conclusions Multiple lncRNAs have been shown to be strongly associated with prognosis in diverse cancers, but substantial bias cannot be excluded in this field and larger studies are needed to understand whether these prognostic information may eventually be useful. Electronic supplementary material The online version of this article (doi:10.1186/s12943-016-0535-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Stylianos Serghiou
- St. John's Hospital, Livingston, EH54 6PP, UK.,College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
| | | | - John P A Ioannidis
- Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine Stanford, Stanford, CA, 94305, USA. .,Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, 94305, USA. .,Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, 94305, USA. .,Meta-Research Innovation Center at Stanford (METRICS), Stanford University, 1265 Welch Rd, MSOB X306, Stanford, CA, 94305, USA.
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The Activation of ERK1/2 and JNK MAPK Signaling by Insulin/IGF-1 Is Responsible for the Development of Colon Cancer with Type 2 Diabetes Mellitus. PLoS One 2016; 11:e0149822. [PMID: 26901856 PMCID: PMC4763097 DOI: 10.1371/journal.pone.0149822] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 02/04/2016] [Indexed: 12/13/2022] Open
Abstract
Previous studies showed that type 2 diabetes mellitus (T2DM) is linked to increased risk of developing colon cancer. Insulin and insulin-like growth factor 1 (IGF-1) are increased in patients with T2DM. The increased insulin and IGF-1 may be responsible for the developing of colon cancer. In this study, we investigated the effects and mechanisms of insulin and IGF-1 in colon cancer development in vitro and in vivo. Insulin and IGF-1 alone or together elevated proliferation and reduced apoptosis in colon cancer MC38 cells. Meanwhile, insulin and IGF-1 promoted the phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Treatment with ERK1/2 or JNK inhibitor in the presence of insulin and IGF-1 significantly decreased B-cell lymphoma 2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) expression and finally increased apoptosis and inhibited the proliferation. Accelerative colon tumor growth was found in a mouse model of T2DM with db/db mice which got high level of endogenous insulin and IGF-1. Furthermore, the inhibition of ERK1/2 or JNK suppressed the development of colon tumor in vivo. These results suggest that the activation of ERK1/2 and JNK signaling by insulin and IGF-1, at least in part, is responsible for the development of colon cancer with T2DM.
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Dretzke J, Riley RD, Lordkipanidzé M, Jowett S, O'Donnell J, Ensor J, Moloney E, Price M, Raichand S, Hodgkinson J, Bayliss S, Fitzmaurice D, Moore D. The prognostic utility of tests of platelet function for the detection of 'aspirin resistance' in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation. Health Technol Assess 2016; 19:1-366. [PMID: 25984731 DOI: 10.3310/hta19370] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The use of aspirin is well established for secondary prevention of cardiovascular disease. However, a proportion of patients suffer repeat cardiovascular events despite being prescribed aspirin treatment. It is uncertain whether or not this is due to an inherent inability of aspirin to sufficiently modify platelet activity. This report aims to investigate whether or not insufficient platelet function inhibition by aspirin ('aspirin resistance'), as defined using platelet function tests (PFTs), is linked to the occurrence of adverse clinical outcomes, and further, whether or not patients at risk of future adverse clinical events can be identified through PFTs. OBJECTIVES To review systematically the clinical effectiveness and cost-effectiveness evidence regarding the association between PFT designation of 'aspirin resistance' and the risk of adverse clinical outcome(s) in patients prescribed aspirin therapy. To undertake exploratory model-based cost-effectiveness analysis on the use of PFTs. DATA SOURCES Bibliographic databases (e.g. MEDLINE from inception and EMBASE from 1980), conference proceedings and ongoing trial registries up to April 2012. METHODS Standard systematic review methods were used for identifying clinical and cost studies. A risk-of-bias assessment tool was adapted from checklists for prognostic and diagnostic studies. (Un)adjusted odds and hazard ratios for the association between 'aspirin resistance', for different PFTs, and clinical outcomes are presented; however, heterogeneity between studies precluded pooling of results. A speculative economic model of a PFT and change of therapy strategy was developed. RESULTS One hundred and eight relevant studies using a variety of PFTs, 58 in patients on aspirin monotherapy, were analysed in detail. Results indicated that some PFTs may have some prognostic utility, i.e. a trend for more clinical events to be associated with groups classified as 'aspirin resistant'. Methodological and clinical heterogeneity prevented a quantitative summary of prognostic effect. Study-level effect sizes were generally small and absolute outcome risk was not substantially different between 'aspirin resistant' and 'aspirin sensitive' designations. No studies on the cost-effectiveness of PFTs for 'aspirin resistance' were identified. Based on assumptions of PFTs being able to accurately identify patients at high risk of clinical events and such patients benefiting from treatment modification, the economic model found that a test-treat strategy was likely to be cost-effective. However, neither assumption is currently evidence based. LIMITATIONS Poor or incomplete reporting of studies suggests a potentially large volume of inaccessible data. Analyses were confined to studies on patients prescribed aspirin as sole antiplatelet therapy at the time of PFT. Clinical and methodological heterogeneity across studies precluded meta-analysis. Given the lack of robust data the economic modelling was speculative. CONCLUSIONS Although evidence indicates that some PFTs may have some prognostic value, methodological and clinical heterogeneity between studies and different approaches to analyses create confusion and inconsistency in prognostic results, and prevented a quantitative summary of their prognostic effect. Protocol-driven and adequately powered primary studies are needed, using standardised methods of measurements to evaluate the prognostic ability of each test in the same population(s), and ideally presenting individual patient data. For any PFT to inform individual risk prediction, it will likely need to be considered in combination with other prognostic factors, within a prognostic model. STUDY REGISTRATION This study is registered as PROSPERO 2012:CRD42012002151. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Janine Dretzke
- Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - Richard D Riley
- Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, UK
| | | | - Susan Jowett
- Health Economics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - Jennifer O'Donnell
- Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - Joie Ensor
- Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, UK
| | - Eoin Moloney
- Institute of Health and Society, Newcastle University, Newcastle, UK
| | - Malcolm Price
- Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - Smriti Raichand
- Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - James Hodgkinson
- Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - Susan Bayliss
- Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - David Fitzmaurice
- Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
| | - David Moore
- Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK
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Llewellyn A, Simmonds M, Owen CG, Woolacott N. Childhood obesity as a predictor of morbidity in adulthood: a systematic review and meta-analysis. Obes Rev 2016; 17:56-67. [PMID: 26440472 DOI: 10.1111/obr.12316] [Citation(s) in RCA: 539] [Impact Index Per Article: 59.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 07/31/2015] [Accepted: 07/31/2015] [Indexed: 11/28/2022]
Abstract
Obese children are at higher risk of being obese as adults, and adult obesity is associated with an increased risk of morbidity. This systematic review and meta-analysis investigates the ability of childhood body mass index (BMI) to predict obesity-related morbidities in adulthood. Thirty-seven studies were included. High childhood BMI was associated with an increased incidence of adult diabetes (OR 1.70; 95% CI 1.30-2.22), coronary heart disease (CHD) (OR 1.20; 95% CI 1.10-1.31) and a range of cancers, but not stroke or breast cancer. The accuracy of childhood BMI when predicting any adult morbidity was low. Only 31% of future diabetes and 22% of future hypertension and CHD occurred in children aged 12 or over classified as being overweight or obese. Only 20% of all adult cancers occurred in children classified as being overweight or obese. Childhood obesity is associated with moderately increased risks of adult obesity-related morbidity, but the increase in risk is not large enough for childhood BMI to be a good predictor of the incidence of adult morbidities. This is because the majority of adult obesity-related morbidity occurs in adults who were of healthy weight in childhood. Therefore, targeting obesity reduction solely at obese or overweight children may not substantially reduce the overall burden of obesity-related disease in adulthood.
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Affiliation(s)
- A Llewellyn
- Centre for Reviews and Dissemination, University of York, York, UK
| | - M Simmonds
- Centre for Reviews and Dissemination, University of York, York, UK
| | - C G Owen
- Population Health Research Institute, St George's, University of London, London, UK
| | - N Woolacott
- Centre for Reviews and Dissemination, University of York, York, UK
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Kunath F, Spek A, Jensen K, Zengerling F, Schmidt S. Prognostic factors for tumor recurrence in patients with clinical stage I seminoma undergoing surveillance--protocol for a systematic review. Syst Rev 2015; 4:182. [PMID: 26684760 PMCID: PMC4683799 DOI: 10.1186/s13643-015-0167-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Accepted: 12/07/2015] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Testicular cancer is primarily treated with the surgical removal of the affected testis. About 50% of testicular cancer patients present with a stage I seminoma. If no chemo- or radiotherapy as adjuvant treatment is initiated after orchiectomy, 15-20% of these patients will develop metastases. Although adjuvant treatment is effective in reducing the relapse risk, there is rising concern about overtreatment of these patients. Prognostic factors at primary diagnosis might have the potential to identify patients at higher risk of tumor relapse, allowing to guide individual therapy and to avoid overtreatment. Therefore, we aim to synthesize the available evidence on tumor or patient characteristics as possible prognostic factors for cancer recurrence in patients with clinical stage I seminoma. METHODS/DESIGN We will conduct a broad systematic review to analyze what prognostic factors predict cancer recurrence in patients with a first time diagnosis of clinical stage I seminoma, who received no adjuvant chemo- or radiotherapy after orchiectomy. The literature search will comprise MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the conference proceedings of the American Society of Clinical Oncology (ASCO), American Urologic Association (AUA), and European Urologic Association (EAU) Annual Meetings. Prospective and retrospective longitudinal studies reporting on prognostic factors for cancer recurrence will be considered. We will consider the wealth of any candidate clinical or pathological prognostic factor reported in the literature. Our outcome of interest will be tumor recurrence at a minimum of 2 years follow-up. Study screening, data extraction, and quality assessment will be done by two reviewers independently. Hazard ratios will be used to measure the relationship between the potential prognostic factor and tumor recurrence. Meta-analyses will be conducted with sufficiently homogeneous studies and separately with respect to study design, by using the random-effects generic inverse variance model. DISCUSSION Limitations and strengths will be discussed in our review, and the results will be put into context with other studies in this field. Our results will help to guide evidence-based decision-making on patients with clinical stage I seminoma, allowing a better adjustment of therapies with regard to the individual patient's risk. Our findings will furthermore help to formulate recommendations for future research. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42014009434.
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Affiliation(s)
- Frank Kunath
- Department of Urology, University Hospital of Erlangen, Erlangen, Germany.
- UroEvidence@Deutsche Gesellschaft für Urologie, Berlin, Germany.
| | - Annabel Spek
- Department of Urology, University Hospital of Munich, Munich, Germany.
- UroEvidence@Deutsche Gesellschaft für Urologie, Berlin, Germany.
| | - Katrin Jensen
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
| | - Friedemann Zengerling
- Department of Urology, University Hospital of Ulm, Ulm, Germany.
- UroEvidence@Deutsche Gesellschaft für Urologie, Berlin, Germany.
| | - Stefanie Schmidt
- UroEvidence@Deutsche Gesellschaft für Urologie, Berlin, Germany.
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Evidential Value That Exercise Improves BMI z-Score in Overweight and Obese Children and Adolescents. BIOMED RESEARCH INTERNATIONAL 2015; 2015:151985. [PMID: 26509145 PMCID: PMC4609764 DOI: 10.1155/2015/151985] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Accepted: 09/15/2015] [Indexed: 11/22/2022]
Abstract
Background. Given the cardiovascular disease (CVD) related importance of understanding the true effects of exercise on adiposity in overweight and obese children and adolescents, this study examined whether there is evidential value to rule out excessive and inappropriate reporting of statistically significant results, a major problem in the published literature, with respect to exercise-induced improvements in BMI z-score among overweight and obese children and adolescents. Methods. Using data from a previous meta-analysis of 10 published studies that included 835 overweight and obese children and adolescents, a novel, recently developed approach (p-curve) was used to test for evidential value and rule out selective reporting of findings. Chi-squared tests (χ2) were used to test for statistical significance with alpha (p) values <0.05 considered statistically significant. Results. Six of 10 findings (60%) were statistically significant. Statistically significant right-skew to rule out selective reporting was found (χ2 = 38.8, p = 0.0001). Conversely, studies neither lacked evidential value (χ2 = 6.8, p = 0.87) nor lacked evidential value and were intensely p-hacked (χ2 = 4.3, p = 0.98). Conclusion. Evidential value results confirm that exercise reduces BMI z-score in overweight and obese children and adolescents, an important therapeutic strategy for treating and preventing CVD.
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Little J, Wilson B, Carter R, Walker K, Santaguida P, Tomiak E, Beyene J, Usman Ali M, Raina P. Multigene panels in prostate cancer risk assessment: a systematic review. Genet Med 2015; 18:535-44. [PMID: 26426883 DOI: 10.1038/gim.2015.125] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 07/27/2015] [Indexed: 12/18/2022] Open
Abstract
PURPOSE Single-nucleotide polymorphism (SNP) panel tests have been proposed for use in the detection of, and prediction of risk for, prostate cancer and as prognostic indicator in affected men. A systematic review was undertaken to address three research questions to evaluate the analytic validity, clinical validity, clinical utility, and prognostic validity of SNP-based panels. METHODS Data sources comprised MEDLINE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and EMBASE; these were searched from inception to April 2013. The gray-literature searches included contact with manufacturers. Eligible studies included English-language studies evaluating commercially available SNP panels. Study selection and risk of bias assessment were undertaken by two independent reviewers. RESULTS Twenty-one studies met eligibility criteria. All focused on clinical validity and evaluated 18 individual panels with 2 to 35 SNPs. All had poor discriminative ability (overall area under receiver-operator characteristic curves, 58-74%; incremental gain resulting from inclusion of SNP data, 2.5-11%) for predicting risk of prostate cancer and/or distinguishing between aggressive and asymptomatic/latent disease. The risk of bias of the studies, as assessed by the Newcastle Ottawa Scale (NOS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools, was moderate. CONCLUSION The evidence on currently available SNP panels is insufficient to assess analytic validity, and at best the panels assessed would add a small and clinically unimportant improvement to factors such as age and family history in risk stratification (clinical validity). No evidence on the clinical utility of current panels is available.Genet Med 18 6, 535-544.
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Affiliation(s)
- Julian Little
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Brenda Wilson
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Ron Carter
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Kate Walker
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
| | - Pasqualina Santaguida
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
| | - Eva Tomiak
- The Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
| | - Joseph Beyene
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
| | - Muhammad Usman Ali
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
| | - Parminder Raina
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
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