Methodological considerations in injury burden of disease studies across Europe: a systematic literature review

Background: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. Methods: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. Results: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. Conclusions: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond. © 2022, The Author(s)

a review of methodological design choices

Publisher Copyright: © 2023 Cambridge University Press. All rights reserved.This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the Disability-Adjusted Life Years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3,053 studies of which 2,948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.publishersversionepub_ahead_of_prin

Burden of disease attributable to risk factors in European countries: a scoping literature review

Objectives: Within the framework of the burden of disease (BoD) approach, disease, and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe, and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites, and targeted public health agencies' websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year, or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors since they might significantly influence the quantification of the attributable burden. From our analysis, we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis, and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, and avoid misinterpretations thus improving comparability among estimates.info:eu-repo/semantics/publishedVersio

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results

Uzunlamasına Verilerde Zamana Bağlı ROC Eğrilerinin Tanısal Performansını Etkileyen Faktörler

In medicine, ROC Curve Analysis is frequently used to determine the diagnostic performances of biomarkers. However, time-dependent ROC Curve is utilized in assessing the diagnostic accuracies of longitudinal biomarkers. One of the objectives of this thesis is to evaluate and to compare the diagnostic values of serial biomarker measurements taken from adults in predicting death in Intensive Care Units (ICU) at the end of follow-up period. Time-dependent Area Under Curve (AUC) values, which are calculated by performing joint modeling approach are used for this aim. The other objective is to compare the diagnostic performances of single measurement taken at baseline (t=0) and serial biomarker measurements taken within the follow-up period to determine whether a single value is sufficient to predict the event of interest. Furthermore, time-dependent diagnostic accuracies of these biomarkers are evaluated throughout the follow-up to identify which biomarker should be used at which time-point. Moreover, for each biomarker, cut-off values are determined with the help of Monte-Carlo simulation procedure. Also time-dependent cut-off values are obtained for discriminating subjects at risk and without risk of death on the first three days after the last biomarker measurement for each gender group. Besides, different joint model combinations are constructed for each biomarker to find out the best combination that provides the optimal diagnostic accuracy. In application part, diagnostic performances of serial C-Reactive Protein (CRP) and serial Procalcitonin (PCT) values in predicting death at ICU are investigated and determined that serial CRP values have higher diagnostic accuracy than serial PCT values in predicting death at the end of follow-up. Furthermore, the highest diagnostic accuracy is observed when single measurement of PCT is taken. PCT values are found to have higher diagnostic accuracy than CRP at especially later time-points within the follow-up period. Cut-off value of CRP is proposed to distinguish the groups since it has smaller Coefficient of Quartile Variation and smaller Robust Coefficient of Variation values compared to PCT. The first three days after the last biomarker measurement, cut-off values for PCT are found to be in decreasing trend for men and women, while constant cut-off values in the first two days; then decreasing trend for CRP are observed for both genders. Standard joint model gives the optimal diagnostic accuracy for both CRP and PCT. In conclusion, a comprehensive study has been carried out to assess the factors affecting the diagnostic performance of longitudinal biomarkers via a real-life data application. Coefficient of Quartile Variation measure and Robust Coefficient of Variation are suggested in the decision of choosing the relevant cut-off value. Taking serial biomarker values are suggested to better evaluate the longitudinal profiles of the subjects when needed.TABLE OF CONTENTS CONTENTS Page APPROVAL PAGE iii YAYINLAMA VE FİKRİ MÜLKİYET HAKLARI BEYANI iv ETHICAL DECLARATION v TEŞEKKÜR vii ABSTRACT viiii ÖZET viii LIST OF ABBREVATIONS xii LIST OF FIGURES xiiiii LIST OF TABLES xv 1. INTRODUCTION 1 2. GENERAL INFORMATION 4 2.1. Classical ROC Curve Method 4 2.2. Time-Dependent ROC Curve 6 2.3. Time-Dependent ROC Curves for Longitudinal Data 8 2.4. Literature Review for Diagnostic Performance of Longitudinal Data 11 2.5. Model Types 16 2.5.1. Two-Stage Modeling 17 2.5.2. Time-Dependent Cox Regression Analysis 17 2.5.3. Joint Modeling Approach 18 2.6. Linear Mixed Effects Model 18 2.6.1. Parameter Estimation in Linear Mixed Effects Model 19 2.7. Cox Proportional Hazard Regression Model 21 2.7.1. Parameter Estimation in Cox Proportional Hazard Regression Model 22 2.8. Joint Modeling Approach 23 2.8.1. Assumptions of Joint Modelling Approach 24 2.8.2. Estimation Methods in Joint Modeling Approach 25 2.9. Missing Data Structures in Longitudinal Data 27 2.9.1. Modeling the Missing Data 28 2.9.1.1. Shared Parameter Models 28 2.10. Parameterization Types in Joint Modeling Approach 29 2.10.1. Time-Dependent Slopes Parameterization 30 2.10.2. Current Value and Time-Dependent Slope Parameterization 30 2.10.3. Cumulative Effects Parameterization 31 2.11. Survival Distribution Types 31 2.11.1. Piecewise-Constant Distribution 31 2.12. Diagnostic Performance in Joint Modeling Approach 32 3. MATERIAL AND METHOD 36 4. RESULTS 40 4.1. Evaluating Diagnostic Performances of Serial CRP and PCT Values 49 4.2. Comparison of Single vs. Serial Biomarker Measurements in Predicting Time-to-Event Outcome 50 4.3. Assessing the Diagnostic Performance Throughout the Follow-up Period 56 4.4. Obtaining the Optimum Cut-Off Value 62 4.5. Investigating Factors Affecting the Diagnostic Performance of Serial CRP and PCT Measurements 72 4.6. Evaluating Cut – Off Values for Longitudinal Data 79 4.6.1. Diagnostic Accuracy of CRP Biomarker 83 4.6.2. Diagnostic Accuracy of PCT Biomarker 85 4.7. Time-Dependent Diagnostic Accuracy Metrics 86 4.8. Evaluating the Diagnostic Performance throughout the Follow – up Period 87 4.8.1. Diagnostic Accuracy of CRP Biomarker in terms of Genders 88 4.8.2. Diagnostic Accuracy of PCT Biomarker in terms of Genders 93 5. DISCUSSION 98 6. CONCLUSION 103 7. REFERENCES 106 8. APPENDICES 111 I - ETHICAL APPROVAL FORM OF HACETTEPE UNIVERSITY II - PART OF CRP DATASET III - PART OF PCT DATASET IV - PARAMETER ESTIMATES OF JOINT MODEL COMBINATIONS V - R CODES 9. CURRICULUM VITAE 179Tıpta, belirteçlerin tanısal performanslarının belirlenmesinde ROC Eğrisi sıklıkla kullanılmaktadır. İzlem süresi içinde tekrarlı ölçümleri alınan belirteçlerin tanısal doğruluğunun belirlenmesinde ise zamana bağlı ROC Eğrisi’nden yararlanılmaktadır. Bu tez çalışmasının amaçlarından ilki, Erişkin Yoğun Bakım’da yatan hastalara ait tekrarlı ölçümleri alınan belirteçlerin izlem süresi sonundaki tanısal performansını değerlendirmektir. Bu amaç için birleşik modelleme yaklaşımı yardımı ile elde edilebilen Zamana Bağlı Eğri Altında Kalan Alan (EAA) değerlerinden yararlanılmıştır. Bir diğer amaç, izlemin başında (t=0) alınan belirteç değeri ile izlem süresince alınan tekrarlı belirteç ölçümlerinin tanısal doğruluklarını karşılaştırmaktır. Bununla birlikte, tekrarlı ölçümleri alınan belirteçlerin zamana bağlı tanısal performansları, izlem süresi boyunca değerlendirilmiş ve yoğun bakımda ölümü kestirmede hangi zaman noktalarında hangi belirtecin kullanılması gerektiği belirlenmiştir. Her bir belirteç için izlem sonunda yoğun bakımda ölecek ve sağkalacak bireyleri ayrımsamada kullanılacak kesim noktaları, Monte-Carlo simülasyonu ile elde edilmiştir. Farklı birleşik modeller kurularak belirteçler için en yüksek tanısal doğruluğu veren kombinasyon saptanmıştır. Her bir belirteç için alınan son ölçümden sonraki ilk üç gün boyunca cinsiyet gruplarına göre zamana-bağlı kesim noktaları belirlenmiştir. Uygulamada, erişkin yoğun bakımda yatan hastalardan elde edilen C-Reaktif Protein (CRP) ve Prokalsitonin (PCT) belirteçlerinin yoğun bakımda ölümü kestirmedeki tanısal performansları değerlendirilmiş, izlem süresi sonunda ölümü kestirmede CRP’nin tanısal performansının, PCT’den daha yüksek olduğu belirlenmiştir. Bununla birlikte en yüksek tanısal doğruluğun, izlem başında alınan tek bir PCT ölçümü ile elde edildiği saptanmıştır. İzlem süresi içinde özellikle izlem sonuna yakın zaman noktalarında PCT’nin tanısal doğruluğunun, CRP’ye göre daha yüksek olduğu belirlenmiştir. Çeyrekler (Kartil) Değişim Katsayısı ile Dayanıklı Değişim Katsayısının daha küçük bulunmasından dolayı, CRP’ye ait kesim noktasının kullanılması önerilmiştir. Her bir belirteç için, son ölçümden sonra, hem erkek hem de kadınlarda PCT’nin kesim noktalarının giderek düştüğü, CRP için her iki cinsiyet grubunda da kesim noktalarının izlem sonundaki ilk iki gün sabit kalıp üçüncü günde düştüğü gözlenmiştir. Optimum tanısal doğruluğun elde edilmesinde, her iki belirteç için de standart birleşik modelin kullanılması gerektiği belirlenmiştir. Sonuç olarak, tekrarlı belirteç ölçümlerinin tanısal performansının belirlenebilmesi amacıyla gerçek veri seti üzerinde kapsamlı bir çalışma gerçekleştirilmiştir. Uygun kesim noktasının seçiminde çeyrekler (kartil) değişim katsayısı ile dayanıklı değişim katsayısının kullanılması ve bireylerin uzunlamasına profillerinin daha iyi incelenebilmesi için gerektiğinde belirteçlerden tekrarlı ölçümler alınması önerilmiştir

Status and trends of personalized medicine research from 2000 to 2020: a bibliometric analysis

Background: Personalized medicine (PM), as a rapidly growing research area, provides treatments, practices, and interventions being adapted to an individual patient based on his own risk of disease. This study aims to analyze the productivity of countries, institutions, and authors in this field, to determine the existing research trends worldwide, and to forecast future research activity for specific countries. Methods: Documents published between 2000 and 2020 were retrieved from the Web of Science (WoS) database. Bibliometric analysis was performed to assess the outputs, correlation analysis was applied to analyze the relationship between Gross Domestic Product per capita (GDP-PP) and the number of publications, and an extrapolation method was used for predicting the future productivity trends for certain countries. Results: A total of 7,772 documents were published globally on PM between 2000 and 2020. The most productive country, journal, and institution are the USA, Personalized Medicine, and Harvard Medical School, respectively. The USA is also first in line in terms of total citations. Netherlands, Denmark, and the USA are listed at the top in terms of the total number of papers and citations, after adjusting for GDP-PP and population size. Also, as predictions suggest, the USA will maintain its predominant role in the PM field in the next 5 years. Conclusions: Owing to its both interdisciplinary and multidisciplinary nature, PM bestows researchers’ numerous sources to benefit and enables them a field that they can be productive of for the future. Therefore, this field is expected to progress and be the lead area in medicine in the upcoming years. © 2022 Informa UK Limited, trading as Taylor & Francis Group

Evaluation of satisfaction levels of expatriate patients presenting to emergency department

People who emigrated from Turkey to European countries for work are called expatriate. It was aimed to analyze demographic characteristics of expatriate patients who presented to the emergency department, to compare satisfaction levels of emergency departments between their country of residence and Turkey, and to identify the factors that affect patient satisfaction. This descriptive study was conducted with questionnaires filled by face-to-face interviews in 150 expatriate patients who were living abroad, came to Turkey for vacation/annual permit and applied to the emergency department with any complaint. We found a statistically significant difference when we evaluated expatriate patients' monthly average number of emergency department applies and their views on priority to apply to emergency departments for health problems, the cleanliness of emergency departments, attitude of doctors, security and receptionist/nursing staff towards patients in Turkey and in their country of residence. It has been found that expatriates prefer the emergency department more in our country and they are more satisfied in their country of residence in terms of the cleanliness of emergency department, attitude of doctors, security and receptionist/nursing staff

Methodological considerations in injury burden of disease studies across Europe: a systematic literature review

Background: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in the burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. Methods: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, Web of Science, and the grey literature supplemented by hand-searching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early 1990 and mid-2021. Results: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. Conclusions: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of a life table for YLL calculations. The development and use of guidelines for performing and reporting of injury BoD studies are crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.info:eu-repo/semantics/publishedVersio

Methodological considerations in injury burden of disease studies across Europe: a systematic literature review.

BACKGROUND Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. METHODS We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. RESULTS We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. CONCLUSIONS Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond

Burden of non-communicable disease studies in Europe : a systematic review of data sources and methodological choices

Background Assessment of disability-adjusted life years (DALYs) resulting from non-communicable diseases (NCDs) requires specific calculation methods and input data. The aims of this study were to (i) identify existing NCD burden of disease (BoD) activities in Europe; (ii) collate information on data sources for mortality and morbidity; and (iii) provide an overview of NCD-specific methods for calculating NCD DALYs. Methods NCD BoD studies were systematically searched in international electronic literature databases and in grey literature. We included all BoD studies that used the DALY metric to quantify the health impact of one or more NCDs in countries belonging to the European Region. Results A total of 163 BoD studies were retained: 96 (59%) were single-country or sub-national studies and 67 (41%) considered more than one country. Of the single-country studies, 29 (30%) consisted of secondary analyses using existing Global Burden of Disease (GBD) results. Mortality data were mainly derived (49%) from vital statistics. Morbidity data were frequently (40%) drawn from routine administrative and survey datasets, including disease registries and hospital discharge databases. The majority (60%) of national BoD studies reported mortality corrections. Multimorbidity adjustments were performed in 18% of national BoD studies. Conclusion The number of national NCD BoD assessments across Europe increased over time, driven by an increase in BoD studies that consisted of secondary data analysis of GBD study findings. Ambiguity in reporting the use of NCD-specific BoD methods underlines the need for reporting guidelines of BoD studies to enhance the transparency of NCD BoD estimates across Europe