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Background: The CHANCE-2 study compared 3 weeks of aspirin–ticagrelor to aspirin–clopidogrel in CYP2C19 loss-of-function (LOF) allele carriers following a transient ischemic attack (TIA)/minor stroke and demonstrated a modestly lower risk of stroke recurrence with aspirin–ticagrelor. This stroke protection was largely for minor stroke and came at an increased risk of bleeding. The cost-effectiveness of implementing testing for LOF allele status to personalize antiplatelet regimen for secondary stroke prevention after a TIA/minor stroke in the Canadian health care context is unknown. Methods: Cost-effectiveness analysis using a decision-analytic Markov cohort model with a lifetime horizon was performed to determine the costs and health benefits of testing for LOF allele status compared with no testing (current standard of care). The population of interest was patients living in Canada who suffered a TIA/minor stroke. Outcomes of interest were life-years gained (LYG), quality-adjusted life years (QALY) gained, costs (reported in 2022 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). We adopted the perspective of the Federal, Provincial, and Territorial Ministries of Health and used a 1.5% annual discount rate. Sensitivity analyses were performed to assess uncertainty. Results: Compared to standard of care, LOF allele testing leads to 0.14 LYG (undiscounted), 0.12 QALYs gained (undiscounted), and additional lifetime costs of CAD$432 (discounted) per patient. The ICER of the LOF allele testing strategy is CAD$4310 per QALY gained compared with standard of care. The probabilistic sensitivity analyses demonstrated that LOF allele testing was cost-effective in more than 99.99% of simulations using a willingness-to-pay threshold of CAD$50,000 per QALY. Conclusion: Based on available evidence, testing for LOF allele followed by short duration 3 weeks of aspirin–ticagrelor compared to standard-of-care aspirin–clopidogrel can lead to prolonged life and improved quality of life and can be considered very cost-effective when compared with other well-accepted technologies in health and medicine.

Objectives: Benefit and cost effectiveness of breast cancer screening are still matters of controversy. Risk-adapted strategies are proposed to improve its benefit-harm and cost–benefit relations. Our objective was to perform a systematic review on economic breast cancer models evaluating primary and secondary prevention strategies in the European health care setting, with specific focus on model results, model characteristics, and risk-adapted strategies. Methods: Literature databases were systematically searched for economic breast cancer models evaluating the cost effectiveness of breast cancer screening and prevention strategies in the European health care context. Characteristics, methodological details and results of the identified studies are reported in evidence tables. Economic model outputs are standardized to achieve comparable cost-effectiveness ratios. Results: Thirty-two economic evaluations of breast cancer screening and seven evaluations of primary breast cancer prevention were included. Five screening studies and none of the prevention studies considered risk-adapted strategies. Studies differed in methodologic features. Only about half of the screening studies modeled overdiagnosis-related harms, most often indirectly and without reporting their magnitude. All models predict gains in life expectancy and/or quality-adjusted life expectancy at acceptable costs. However, risk-adapted screening was shown to be more effective and efficient than conventional screening. Conclusions: Economic models suggest that breast cancer screening and prevention are cost effective in the European setting. All screening models predict gains in life expectancy, which has not yet been confirmed by trials. European models evaluating risk-adapted screening strategies are rare, but suggest that risk-adapted screening is more effective and efficient than conventional screening.

Evidence on long-term effectiveness and cost effectiveness of treatment sequences for multiple myeloma (MM) is sparse. We used published data and country-specific data to assess the cost effectiveness of four-line treatment sequences for elderly transplant-ineligible patients with MM in Serbia.We developed a Markov cohort model to compare long-term effectiveness and cost effectiveness of five sequential MM treatment alternatives from the perspective of the national healthcare provider. Effectiveness parameters on progression, mortality and adverse events were extracted from published clinical trials. Costs were based on price lists of the National Health Insurance Fund. We compared life expectancy, costs, and incremental cost-effectiveness ratios among alternative courses of action. The model was analyzed over a lifelong time horizon applying a 3% annual discount rate for effectiveness outcomes and costs. Robustness of the model was tested in multiple deterministic sensitivity analyses.The sequences were defined by the frontline treatment: MPT (melphalan-prednisone-thalidomide), MPV (melphalanprednisone-bortezomib), CTD (cyclophosphamide-thalidomide-dexamethasone), VCD (bortezomib-cyclophosphamidedexamethasone) and BP (bendamustine-prednisone). MPV sequence resulted in the highest remaining life expectancy (4.76 life years). Cost-effectiveness analysis resulted in three non-dominated strategies: MPT, VCD, and MPV sequences, with an incremental cost-effectiveness ratio of EUR 35,300 per life-year gained (LYG) for VCD and EUR 47,200/LYG for MPV relative to MPT.MPV sequence was the most effective in terms of life expectancy for elderly transplant-ineligible MM patients in Serbia. Bortezomib-based strategies would be recommended for the frontline treatment of patients with MM in Serbia if the willingness-to-pay threshold is around EUR 35,000-60,000/LYG.O dolgoročni uspešnosti in stroškovni učinkovitosti zaporedij zdravljenja multiplega mieloma (MM) ni veliko dokazov. Na podlagi objavljenih podatkov in podatkov za posamezne države smo ocenili stroškovno učinkovitost štirih zaporedij zdravljenja starejših bolnikov z MM, ki niso primerni za presaditev, v Srbiji.Za primerjanje dolgoročne uspešnosti in stroškovne učinkovitosti petih alternativ zaporednega zdravljenja MM z vidika nacionalnega izvajalca zdravstvenega varstva smo razvili kohortni model Markova. Parametre uspešnosti glede napredovanja, umrljivosti in neželenih dogodkov smo pridobili iz objavljenih kliničnih preskušanj. Stroški temeljijo na cenikih nacionalnega sklada za zdravstveno zavarovanje. Med različnimi ukrepi smo primerjali pričakovano življenjsko dobo, stroške in mejno razmerje stroškovne učinkovitosti. Model smo analizirali v vseživljenjskem časovnem okviru, pri čemer smo za rezultate uspešnosti in stroške uporabili 3-odstotno letno diskontno stopnjo. Robustnost modela smo preizkusili z več determinističnimi analizami občutljivosti.Zaporedja so bila opredeljena z zdravljenjem v prvi liniji: MPT (melfalan-prednizon-talidomid), MPV (melfalanprednizon-bortezomib), CTD (ciklofosfamid-talidomid-deksametazon), VCD (bortezomib-ciklofosfamid-deksametazon) in BP (bendamustin-prednizon). Pri zaporedju MPV je bila pričakovana preostala življenjska doba najdaljša (4,76 leta življenja). Pri analizi stroškovne učinkovitosti so bile ugotovljene tri neprevladujoče strategije: zaporedja MPT, VCD in MPV z mejnim razmerjem stroškovne učinkovitosti 35.300 EUR na pridobljeno leto življenja (LYG) za VCD in 47.200 EUR/LYG za MPV glede na MPT.Zaporedje MPV je bilo najuspešnejše v smislu pričakovane življenjske dobe starejših bolnikov z MM, ki niso primerni za presaditev, v Srbiji. Strategije, ki temeljijo na bortezomibu, bi bile priporočljive za zdravljenje bolnikov z MM v prvi liniji v Srbiji, če je prag pripravljenosti na plačilo približno 35.000–60.000 EUR/LYG.

FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost effectiveness of screening for familial hypercholesterolemia (FH) and at providing an overview of the main characteristics and methodological approaches of applied decision-analytic models.A systematic literature search was conducted in MEDLINE, EconLit, CRD-databases and the CEA-registry for FH screening starting 2012. Earlier studies were included from a published systematic review. Results were reported in standardized semi-quantitative evidence tables. Costs were converted to current euros. Incremental cost-effectiveness ratios (ICERs) were recalculated according to economic guidelines.Out of our 211 retrieved studies, eight were included in the review in addition to six studies from an earlier review. Studies were conducted in Europe (UK, The Netherlands, Spain, Poland), USA and Australia evaluating cascade (CS), opportunistic (OS), universal screening (UniS), or combinations using genetic testing, clinical criteria or combinations. Studies evaluating only CS identified strategies with an ICER of up to 37,100 EUR/quality-adjusted life-year (QALY) but some strategies were dominated depending on test combinations. UniS of newborns in combination with CS had an ICER≤15,000 EUR/QALY for sequential cholesterol-genetic screening. In other studies, UniS was dominated by OS/CS.Our systematic review demonstrates the values of FH screening and provides an overview of potentially relevant screening strategies to be tested using a decision-analytic model for the respective country or region. Future research is needed on the transferability of results to other countries and modeling spillover effects to newborns.

Background and objective The distribution of the newly developed vaccines presents a great challenge in the ongoing SARS-CoV-2 pandemic. Policy makers must decide which subgroups should be vaccinated first to minimize the negative consequences of the pandemic. These decisions must be made upfront and under uncertainty regarding the amount of vaccine doses available at a given time. The objective of the present work was to develop an iterative optimization algorithm, which provides a prioritization order of predefined subgroups. The results of this algorithm should be optimal but also robust with respect to potentially limited vaccine supply. Methods We present an optimization meta-heuristic which can be used in a classic simulation-optimization setting with a simulation model in a feedback loop. The meta-heuristic can be applied in combination with any epidemiological simulation model capable of depicting the effects of vaccine distribution to the modeled population, accepts a vaccine prioritization plan in a certain notation as input, and generates decision making relevant variables such as COVID-19 caused deaths or hospitalizations as output. We finally demonstrate the mechanics of the algorithm presenting the results of a case study performed with an epidemiological agent-based model. Results We show that the developed method generates a highly robust vaccination prioritization plan which is proven to fulfill an elegant supremacy criterion: the plan is equally optimal for any quantity of vaccine doses available. The algorithm was tested on a case study in the Austrian context and it generated a vaccination plan prioritization favoring individuals age 65+, followed by vulnerable groups, to minimize COVID-19 related burden. Discussion The results of the case study coincide with the international policy recommendations which strengthen the applicability of the approach. We conclude that the path-dependent optimum optimum provided by the algorithm is well suited for real world applications, in which decision makers need to develop strategies upfront under high levels of uncertainty.

The recent rise of populism has generated a resurgence of interest in critical theory, in the wider public debate and in academia—with critical theory being variously accused of paving the way for post-truth politics, hailed as explaining the rise of populism, or criticized for failing to achieve its emancipatory political goals. Failure of the latter kind, many International Relations scholars argue, calls for a fundamental reform of critical theory if it is to address current political developments. Investigating this claim, this article makes three contributions: First, an empirical account shows that, far from failing, critical theory has been politically highly successful. Second, a theoretical reconstruction of critical theory shows that it is precisely this success that leads to the alienation of critical theorists from their own approach. In light of this analysis, third, the article concludes that the task of critical theory in times of Brexit and Trump does not lie in abandoning its core principles but in systematically applying them to a new historical conjuncture.

Background The supply of COVID-19 vaccine was limited when introduced. We aimed to inform decision makers at an early stage about targeted COVID vaccination strategies, accounting for limited capacities and adherence to support vaccination prioritization in Austria. Methods We applied a dynamic agent-based population model to compare different vaccination prioritization strategies targeting the elderly (65 ≥ years), middle aged (45-64 years), younger (15-44 years), vulnerable (risk of severe disease due to comorbidities), and healthcare workers (HCW), to minimize COVID-19-related hospitalizations and deaths. First, outcomes were optimized for an initially available vaccine batch for 200,000 individuals. Second, stepwise optimization was performed, deriving a prioritization sequence for 2.5 million people. We considered sterilizing and non-sterilizing immunity, with different assumptions of effectiveness, over a 6-month period. The project team was advised by a Standing Policy and Expert Panel, consisting of Austrian decision makers, clinical and ethical experts as well as international modeling specialists. Results Maximum reduction of hospitalizations and deaths was achieved by starting vaccinations with the elderly and vulnerable, followed by middle-aged, HCW, and younger individuals. Optimizations for vaccinating 2.5 million individuals yielded the same prioritization and avoided about one third of deaths and hospitalizations. Starting vaccination with HCWs leads to slightly smaller reductions. The negative effects of COVID-19-related HCW absenteeism were not yet considered in our model. Conclusions Our decision-analytic study shows that the elderly and vulnerable should be prioritized for vaccination until further vaccines are available to minimize COVID-19-related hospitalizations and deaths. An important ethical aspect complementing our modeling results is the protection of HCW, maximizing their occupational safety and ensuring risk-compensatory justice. Key messages To minimize COVID-19-related hospitalizations and death the elderly and vulnerable should be prioritized for vaccination until further vaccines are available. Prioritizing health care workers for COVID-19 vaccination is slightly less effective in the simulation but they may be considered for occupational safety and to ensure risk-compensatory justice.

A pandemic poses particular challenges to decision-making because of the need to continuously adapt decisions to rapidly changing evidence and available data. For example, which countermeasures are appropriate at a particular stage of the pandemic? How can the severity of the pandemic be measured? What is the effect of vaccination in the population and which groups should be vaccinated first? The process of decision-making starts with data collection and modeling and continues to the dissemination of results and the subsequent decisions taken. The goal of this paper is to give an overview of this process and to provide recommendations for the different steps from a statistical perspective. In particular, we discuss a range of modeling techniques including mathematical, statistical and decision-analytic models along with their applications in the COVID-19 context. With this overview, we aim to foster the understanding of the goals of these modeling approaches and the specific data requirements that are essential for the interpretation of results and for successful interdisciplinary collaborations. A special focus is on the role played by data in these different models, and we incorporate into the discussion the importance of statistical literacy and of effective dissemination and communication of findings.

Since the end of the Cold War, peacebuilding operations have become an integral part of world politics—despite their continuing failures. This chapter provides an account of peacebuilding operations in practice and identifies cycles of failure and reform, namely the successful integration of peacebuilding into the fabric of the world order despite its continuing failures. It traces these dynamics back to the internal contradictions of liberalism and argues that the main function of peacebuilding operations lies in managing the tensions and contradictions inherent in a liberal world order. Peacebuilding—in one form or another—is therefore likely to persist for the duration of a liberal world order.

Despite repeated announcements of the end of ideology and the demise of religion during the twentieth century, both play a crucial role in world politics today. This disjuncture between theoretical expectations and historical developments has its roots in conventional conceptions of ideology. While the latter grasp the representative nature of ideology as an expression of historical forces and political interests, they miss its constitutive role for modern politics. Based on an analysis of its historical origins and political implications, this article develops a new conception of ideology which accounts for the resilience and historical dynamics of ideological struggle. Like the sorcerer’s apprentice, I show, liberalism has called ideology into being but lost control of its own creation.

This chapter explores the relationship between liberal theory and practice in world politics. It provides an account of classical and contemporary conceptions of liberalism and their role in guiding liberal foreign policies, particularly in the post–Cold War period. The failure of these policies and the subsequent demise of the liberal world order therefore provided a fundamental challenge for liberal theories and motivated the development of new conceptions – often recognising its internal tensions and contradictions. The latter, the chapter argues, suggests that liberalism is not just a product of history or a theory about history but itself a progenitor of history – and must be approached as such in future research.

(1) Background: The Austrian supply of COVID-19 vaccine is limited for now. We aim to provide evidence-based guidance to the authorities in order to minimize COVID-19-related hospitalizations and deaths in Austria. (2) Methods: We used a dynamic agent-based population model to compare different vaccination strategies targeted to the elderly (65 ≥ years), middle aged (45–64 years), younger (15–44 years), vulnerable (risk of severe disease due to comorbidities), and healthcare workers (HCW). First, outcomes were optimized for an initially available vaccine batch for 200,000 individuals. Second, stepwise optimization was performed deriving a prioritization sequence for 2.45 million individuals, maximizing the reduction in total hospitalizations and deaths compared to no vaccination. We considered sterilizing and non-sterilizing immunity, assuming a 70% effectiveness. (3) Results: Maximum reduction of hospitalizations and deaths was achieved by starting vaccination with the elderly and vulnerable followed by middle-aged, HCW, and younger individuals. Optimizations for vaccinating 2.45 million individuals yielded the same prioritization and avoided approximately one third of deaths and hospitalizations. Starting vaccination with HCW leads to slightly smaller reductions but maximizes occupational safety. (4) Conclusion: To minimize COVID-19-related hospitalizations and deaths, our study shows that elderly and vulnerable persons should be prioritized for vaccination until further vaccines are available.

Beate Jahn follows on from Nina Wilén’s chapter: Contrary to the widely held belief that humanitarian intervention is the result of a gradual universalization of moral obligations, Jahn shows that classical authors—Francisco de Vitoria, Edmund Burke, Thomas Paine, and John Stuart Mill—as well as state practice regularly contemplated and often justified the use of force as measures to rescue citizens of other states from excessive violence. The authors dealt with, moreover, show that humanitarian action requires particular political arrangements—making regime change the direct aim of such wars. The meteoric rise of the concept of humanitarian intervention during the 1990s thus did not signify the advent of a new type of war. Instead, it functioned as a ‘doctrinal advance guard’ for a new international political order—which finds itself today in rapid decline.

Background Knowing the number of undetected cases of COVID-19 is important for a better understanding of the spread of the disease. This study analyses the temporal dynamic of detected vs. undetected cases to provide guidance for the interpretation of prevalence studies performed with PCR or antibody tests to estimate the detection rate. Methods We used an agent-based model to evaluate assumptions on the detection probability ranging from 0.1 to 0.9. For each general detection probability, we derived age-dependent detection probabilities and calibrated the model to reproduce the epidemic wave of COVID-19 in Austria from March 2020 to June 2020. We categorized infected individuals into presymptomatic, symptomatic unconfirmed, confirmed and never detected to observe the simulated dynamic of the detected and undetected cases. Results The calculation of the age-dependent detection probability ruled values lower than 0.4 as most likely. Furthermore, the proportion of undetected cases depends strongly on the dynamic of the epidemic wave: during the initial upswing, the undetected cases account for a major part of all infected individuals, whereas their share decreases around the peak of the confirmed cases. Conclusions The results of prevalence studies performed to determine the detection rate of COVID-19 patients should always be interpreted with regard to the current dynamic of the epidemic wave. Applying the method proposed in our analysis, the prevalence study performed in Austria in April 2020 could indicate a detection rate of 0.13, instead of the prevalent ratio of 0.29 between detected and estimated undetected cases at that time.

PURPOSE To assess the effects of three-dimensional image-guided brachytherapy (3D BT) compared to bi-dimensional BT (2D BT) on clinical outcomes in patients with cervical cancer. METHODS AND MATERIALS We searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL, Web of Science, and LILACS for studies assessing the effects of 3D BT versus 2D BT on clinical outcomes. Two reviewers independently screened retrieved citations, extracted data and assessed risk of bias from eligible studies. Hazard ratios (HR) were calculated from Kaplan-Meier curves considering the number of events, their timing and the followup of censored patients. We conducted meta-analyses of HR using the inverse-variance random-effects method. Risk Difference (RD) for toxicities were pooled using the Mantel–Haenszel random-effects method. We used the GRADE system to rate the certainty of evidence. RESULTS Twenty observational studies involving 4287 patients were included. The meta-analyses assessing the effect of 3D BT versus 2D BT on overall survival resulted in a HR of 0.78 (95%CI 0.62–0.98), HR of 0.75 (95%CI 0.62–0.90) for pelvic disease-free survival, HR of 0.93 (95%CI 0.81–1.06) for metastatic disease-free survival, and HR of 0.77 (95%CI 0.59–0.99) for local control. Grade 3–4 global and gastrointestinal toxicities were, respectively, 9% lower (95%CI 6% to 11%) and 5% lower (95%CI 2% to 8%) in patients receiving 3D BT versus 2D BT. Certainty of evidence was very low for all assessed outcomes. CONCLUSIONS Our study may suggest a benefit of 3D BT over conventional 2D BT on important clinical outcomes.

Coronavirus disease 2019 (COVID-19) is caused by the novel betacoronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most people infected with SARS-CoV-2 have mild disease with unspecific symptoms, but about 5% become critically ill with respiratory failure, septic shock and multiple organ failure. An unknown proportion of infected individuals never experience COVID-19 symptoms although they are infectious, that is, they remain asymptomatic. Those who develop the disease, go through a presymptomatic period during which they are infectious. Universal screening for SARS-CoV-2 infections to detect individuals who are infected before they present clinically, could therefore be an important measure to contain the spread of the disease.We conducted a rapid review to assess (1) the effectiveness of universal screening for SARS-CoV-2 infection compared with no screening and (2) the accuracy of universal screening in people who have not presented to clinical care for symptoms of COVID-19.An information specialist searched Ovid MEDLINE and the Centers for Disease Control (CDC) COVID-19 Research Articles Downloadable Database up to 26 May 2020. We searched Embase.com, the CENTRAL, and the Cochrane Covid-19 Study Register on 14 April 2020. We searched LitCovid to 4 April 2020. The World Health Organization (WHO) provided records from daily searches in Chinese databases and in PubMed up to 15 April 2020. We also searched three model repositories (Covid-Analytics, Models of Infectious Disease Agent Study [MIDAS], and Society for Medical Decision Making) on 8 April 2020.Trials, observational studies, or mathematical modelling studies assessing screening effectiveness or screening accuracy among general populations in which the prevalence of SARS-CoV2 is unknown.After pilot testing review forms, one review author screened titles and abstracts. Two review authors independently screened the full text of studies and resolved any disagreements by discussion with a third review author. Abstracts excluded by a first review author were dually reviewed by a second review author prior to exclusion. One review author independently extracted data, which was checked by a second review author for completeness and accuracy. Two review authors independently rated the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for diagnostic accuracy studies and a modified form designed originally for economic evaluations for modelling studies. We resolved differences by consensus. We synthesized the evidence in narrative and tabular formats. We rated the certainty of evidence for days to outbreak, transmission, cases missed and detected, diagnostic accuracy (i.e. true positives, false positives, true negatives, false negatives) using the GRADE approach.We included 22 publications. Two modelling studies reported on effectiveness of universal screening. Twenty studies (17 cohort studies and 3 modelling studies) reported on screening test accuracy. Effectiveness of screening We included two modelling studies. One study suggests that symptom screening at travel hubs, such as airports, may slightly slow but not stop the importation of infected cases (assuming 10 or 100 infected travellers per week reduced the delay in a local outbreak to 8 days or 1 day, respectively). We assessed risk of bias as minor or no concerns, and certainty of evidence was low, downgraded for very serious indirectness. The second modelling study provides very low-certainty evidence that screening of healthcare workers in emergency departments using laboratory tests may reduce transmission to patients and other healthcare workers (assuming a transmission constant of 1.2 new infections per 10,000 people, weekly screening reduced infections by 5.1% within 30 days). The certainty of evidence was very low, downgraded for high risk of bias (major concerns) and indirectness. No modelling studies reported on harms of screening. Screening test accuracy All 17 cohort studies compared an index screening strategy to a reference reverse transcriptase polymerase chain reaction (RT-PCR) test. All but one study reported on the accuracy of single point-in-time screening and varied widely in prevalence of SARS-CoV-2, settings, and methods of measurement. We assessed the overall risk of bias as unclear in 16 out of 17 studies, mainly due to limited information on the index test and reference standard. We rated one study as being at high risk of bias due to the inclusion of two separate populations with likely different prevalences. For several screening strategies, the estimates of sensitivity came from small samples. For single point-in-time strategies, for symptom assessment, the sensitivity from 12 cohorts (524 people) ranged from 0.00 to 0.60 (very low-certainty evidence) and the specificity from 12 cohorts (16,165 people) ranged from 0.66 to 1.00 (low-certainty evidence). For screening using direct temperature measurement (3 cohorts, 822 people), international travel history (2 cohorts, 13,080 people), or exposure to known infected people (3 cohorts, 13,205 people) or suspected infected people (2 cohorts, 954 people), sensitivity ranged from 0.00 to 0.23 (very low- to low-certainty evidence) and specificity ranged from 0.90 to 1.00 (low- to moderate-certainty evidence). For symptom assessment plus direct temperature measurement (2 cohorts, 779 people), sensitivity ranged from 0.12 to 0.69 (very low-certainty evidence) and specificity from 0.90 to 1.00 (low-certainty evidence). For rapid PCR test (1 cohort, 21 people), sensitivity was 0.80 (95% confidence interval (CI) 0.44 to 0.96; very low-certainty evidence) and specificity was 0.73 (95% CI 0.39 to 0.94; very low-certainty evidence). One cohort (76 people) reported on repeated screening with symptom assessment and demonstrates a sensitivity of 0.44 (95% CI 0.29 to 0.59; very low-certainty evidence) and specificity of 0.62 (95% CI 0.42 to 0.79; low-certainty evidence). Three modelling studies evaluated the accuracy of screening at airports. The main outcomes measured were cases missed or detected by entry or exit screening, or both, at airports. One study suggests very low sensitivity at 0.30 (95% CI 0.1 to 0.53), missing 70% of infected travellers. Another study described an unrealistic scenario to achieve a 90% detection rate, requiring 0% asymptomatic infections. The final study provides very uncertain evidence due to low methodological quality.The evidence base for the effectiveness of screening comes from two mathematical modelling studies and is limited by their assumptions. Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases. This review highlights the uncertainty and variation in accuracy of screening strategies. A high proportion of infected individuals may be missed and go on to infect others, and some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals. Further studies need to evaluate the utility of rapid laboratory tests, combined screening, and repeated screening. More research is also needed on reference standards with greater accuracy than RT-PCR. Given the poor sensitivity of existing approaches, our findings point to the need for greater emphasis on other ways that may prevent transmission such as face coverings, physical distancing, quarantine, and adequate personal protective equipment for frontline workers.배경: 코로나 바이러스 질병 2019 (COVID‐19)는 새로운 베타 코로나 바이러스, 중증 급성 호흡기 증후군 코로나 바이러스 ‐2 (SARS‐CoV‐2)에 의해 발생합니다. SARS‐CoV‐2에 감염된 대부분의 사람들은 특이한 증상이없는 경증의 질병을 가지고 있지만 약 5 %는 호흡 부전, 패 혈성 쇼크 및 다발성 장기 부전으로 중병에 걸립니다. 감염된 개인의 알려지지 않은 비율은 감염성이 있지만 증상이없는 상태로 남아 있지만 COVID‐19 증상을 경험하지 않습니다. 질병에 걸린 사람들은 감염되기 전 증상이있는 기간을 거치게됩니다. SARS‐CoV‐2 감염에 대한 보편적 인 스크리닝은 임상 적으로 존재하기 전에 감염된 개인을 탐지하므로 질병의 확산을 억제하는 중요한 수단이 될 수 있습니다. 목적: 우리는 (1) SARS‐CoV‐2 감염에 대한 보편적 검사의 효과와 (2) COVID‐19 증상에 대한 임상 치료를받지 않은 사람들의 보편적 검사의 정확성을 평가하기 위해 신속한 검토를 수행했습니다. . 검색 전략: 정보 전문가가 2020 년 5 월 26 일까지 Ovid MEDLINE과 질병 통제 센터 (CDC) COVID‐19 연구 기사 다운로드 가능한 데이터베이스를 검색했습니다. 2020 년 4 월 14 일에 Embase.com, CENTRAL 및 Cochrane Covid‐19 연구 등록부를 검색했습니다. LitCovid를 2020 년 4 월 4 일까지 검색했습니다. 세계 보건기구 (WHO)는 2020 년 4 월 15 일까지 중국 데이터베이스와 PubMed의 일일 검색 기록을 제공했습니다. 또한 2020 년 4 월 8 일에 3 개의 모델 저장소 (Covid‐Analytics, MIDAS (Infectious Disease Agent Study) 모델, 의료 의사 결정 협회)를 검색했습니다. 선정 기준: SARS‐CoV2의 유병률이 알려지지 않은 일반 인구의 선별 효과 또는 선별 정확도를 평가하는 시험, 관찰 연구 또는 수학적 모델링 연구. 자료 수집 및 분석: 파일럿 테스트 검토 양식 후 한 검토 작성자가 제목과 초록을 선별했습니다. 두 명의 리뷰 저자가 독립적으로 연구의 전체 텍스트를 선별하고 세 번째 리뷰 저자와의 토론을 통해 의견 불일치를 해결했습니다. 첫 번째 리뷰 작성자가 제외시킨 초록은 제외 전에 두 번째 리뷰 작성자가 이중 검토했습니다. 한 리뷰 작성자가 독립적으로 데이터를 추출하여 두 번째 리뷰 작성자가 완전성과 정확성을 확인했습니다. 두 명의 검토 저자가 진단 정확도 연구를위한 진단 정확도 연구의 품질 평가 (QUADAS‐2) 도구와 모델링 연구를위한 경제적 평가를 위해 원래 설계된 수정 된 양식을 사용하여 포함 된 연구의 품질을 독립적으로 평가했습니다. 우리는 합의를 통해 차이를 해결했습니다. 우리는 내러티브 및 표 형식으로 증거를 종합했습니다. 우리는 GRADE 접근법을 사용하여 발병, 전염, 누락 및 감지 된 사례, 진단 정확도 (예: 참 양성, 거짓 양성, 참 음성, 거짓 음성)에 대한 증거의 확실성을 평가했습니다. 주요 결과: 22 개의 출판물을 포함했습니다. 보편적 스크리닝의 효과에 대한 두 가지 모델링 연구가보고되었습니다. 스크리닝 테스트 정확도에 대한 20 건의 연구 (코호트 연구 17 건 및 모델링 연구 3 건)가보고되었습니다. 스크리닝의 효과 두 가지 모델링 연구를 포함했습니다. 한 연구에 따르면 공항과 같은 여행 허브에서 증상 선별 검사가 약간 느려질 수 있지만 감염 사례의 유입을 막지는 못할 수 있습니다 (주당 10 명 또는 100 명의 감염된 여행자가 현지 발병 지연을 각각 8 일 또는 1 일로 줄 였다고 가정). . 우리는 편견의 위험을 사소하거나 전혀 우려하지 않는 것으로 평가했으며 증거의 확실성이 낮았으며 매우 심각한 간접적 인 것으로 인해 하향 조정되었습니다. 두 번째 모델링 연구는 실험실 테스트를 사용하여 응급실의 의료 종사자를 선별하면 환자와 다른 의료 종사자에게 전염이 감소 할 수 있다는 매우 낮은 불확실성 증거를 제공합니다 (1 만 명당 1.2 개의 새로운 감염의 전파 상수를 가정하고 매주 선별을 통해 감염을 5.1 % 감소 시킨다고 가정). 30 일 이내). 근거의 확실성은 매우 낮았으며, 편견 (주요 우려) 및 간접 성 위험이 높기 때문에 하향 조정되었습니다. 스크리닝의 위해에 대해보고 된 모델링 연구는 없습니다. 스크리닝 테스트 정확도 17 개 코호트 연구 모두 인덱스 스크리닝 전략을 참조 역전사 효소 중합 효소 연쇄 반응 (RT‐PCR) 테스트와 비교했습니다. 한 연구를 제외한 모든 연구는 단일 시점 선별 검사의 정확성에 대해보고했으며 SARS‐CoV‐2의 유병률, 설정 및 측정 방법이 매우 다양했습니다. 17 개 연구 중 16 개 연구에서 전반적인 비뚤림 위험을 명확하지 않은 것으로 평가했습니다. 주로 지수 테스트 및 참조 표준에 대한 정보가 제한되어 있기 때문입니다. 우리는 한 연구를 유병률이 다른 두 개의 개별 모집단을 포함하여 비뚤림 위험이 높은 것으로 평가했습니다. 여러 선별 전략에서 민감도 추정치는 작은 샘플에서 나왔습니다. 단일 시점 전략의 경우 증상 평가를 위해 12 개 코호트 (524 명)의 민감도 범위는 0.00 ~ 0.60 (매우 낮은 불확실성 증거)이고 12 개 코호트 (16,165 명)의 특이도 범위는 0.66 ~ 1.00입니다 ( 낮은 불확실성 증거). 직접 체온 측정 (3 개 코호트, 822 명), 해외 여행 이력 (2 개 코호트, 13,080 명) 또는 알려진 감염자 (3 개 코호트, 13,205 명) 또는 의심되는 감염자 (2 개 코호트, 954 명)에 대한 노출을 사용한 스크리닝의 경우, 민감도 범위는 0.00 ~ 0.23 (매우 낮음에서 낮음 증거)이고 특이도 범위는 0.90 ~ 1.00 (낮음에서 중간 정도의 증거)입니다. 증상 평가와 직접 체온 측정 (2 개 코호트, 779 명)의 경우 민감도 범위는 0.12 ~ 0.69 (매우 낮은 확실성 증거), 특이도는 0.90 ~ 1.00 (낮은 확실성 증거)이었습니다. 신속한 PCR 검사 (1 코호트, 21 명)의 경우 민감도는 0.80 (95 % 신뢰 구간 (CI) 0.44 ~ 0.96, 매우 낮은 불확실성 증거)이었고 특이도는 0.73 (95 % CI 0.39 ~ 0.94, 매우 낮은 불확실성 증거)이었습니다. ). 한 코호트 (76 명)는 증상 평가와 함께 반복 스크리닝에 대해보고했으며 민감도는 0.44 (95 % CI 0.29 ~ 0.59, 매우 낮은 확실성 증거) 및 특이도 0.62 (95 % CI 0.42 ~ 0.79, 낮은 확실성 증거)를 보여줍니다. . 세 가지 모델링 연구는 공항에서 스크리닝의 정확성을 평가했습니다. 측정 된 주요 결과는 공항에서 출입국 심사 또는 둘 다에서 누락되거나 감지 된 사례였습니다. 한 연구에 따르면 0.30 (95 % CI 0.1 ~ 0.53)에서 민감도가 매우 낮아 감염된 여행자의 70 %가 누락되었습니다. 또 다른 연구에서는 90 %의 탐지율을 달성하기위한 비현실적인 시나리오에 대해 설명했으며 0 %의 무증상 감염이 필요했습니다. 최종 연구는 낮은 방법 론적 질로 인해 매우 불확실한 증거를 제공합니다. 연구진 결론: 스크리닝의 효과에 대한 근거 기반은 두 가지 수학적 모델링 연구에서 비롯되며 그 가정에 의해 제한됩니다. 낮은 불확실성 증거는 여행 허브에서 선별 검사가 감염된 사례의 수입을 약간 늦출 수 있음을 시사합니다. 이 검토는 스크리닝 전략의 정확성의 불확실성과 변동을 강조합니다. 감염된 개인의 높은 비율은 놓치고 다른 사람을 감염시킬 수 있으며, 일부 건강한 개인은 양성으로 잘못 식별되어 확인 검사가 필요하며 잠재적으로 이러한 개인을 불필요하게 격리시킬 수 있습니다. 추가 연구는 신속한 실험실 테스트, 조합 스크리닝 및 반복 스크리닝의 유용성을 평가해야합니다. RT‐PCR보다 더 정확한 기준 표준에 대한 더 많은 연구가 필요합니다. 기존 접근 방식의 민감도가 낮다는 점을 감안할 때, 우리의 연구 결과는 얼굴 가리개, 물리적 거리 유지, 격리 및 일선 작업자를위한 적절한 개인 보호 장비와 같은 전파를 방지 할 수있는 다른 방법에 더 많은 강조가 필요함을 지적합니다.บทนำ: โรคโคโรนาไวรัส 2019 (COVID‐19) เกิดจากเชื้อเบตาโคโรนาไวรัสสายพันธุ์ใหม่ กลุ่มอาการทางเดินหายใจเฉียบพลันรุนแรง coronavirus‐2 (SARS‐CoV‐2) คนส่วนใหญ่ที่ติดเชื้อ SARS‐CoV‐2 มีอาการไม่รุนแรงโดยมีอาการไม่เฉพาะเจาะจง แต่ประมาณ 5% ป่วยหนักด้วยระบบหายใจล้มเหลว ภาวะช็อกจากติดเชื้อ และอวัยวะล้มเหลว ผู้ติดเชื้อที่ไม่ทราบสัดส่วนไม่เคยพบอาการ COVID‐19 แม้ว่าจะมีการติดเชื้อ กล่าวคือยังคงไม่มีอาการ ผู้ที่เป็นโรค จะต้องผ่านช่วงเวลาที่ไม่มีอาการซึ่งเป็นช่วงที่มีการแพร่เชื้อ การตรวจคัดกรองทั่วไปสำหรับการติดเชื้อ SARS‐CoV‐2 เพื่อตรวจหาบุคคลที่ติดเชื้อก่อนที่จะมีอาการทางคลินิก จึงอาจเป็นมาตรการสำคัญในการควบคุมการแพร่กระจายของโรค วัตถุประสงค์: เราได้ทำการทบทวนวรรณกรรมอย่างรวดเร็วเพื่อประเมิน (1) ประสิทธิผลของการตรวจคัดกรองแบบครอบคลุมสำหรับการติดเชื้อซาร์ส ‐ โควี ‐2 เปรียบเทียบกับการไม่ตรวจคัดกรองและ (2) ความแม่นยำของการตรวจคัดกรองแบบครอบคลุมในผู้ที่ไม่ได้รับการดูแลทางคลินิกสำหรับอาการของ COVID‐19 วิธีการสืบค้น: ผู้เชี่ยวชาญด้านข้อมูลค้นหา Ovid MEDLINE และศูนย์ควบคุมโรค (CDC) COVID‐19 Research Articles Downloadable Database ถึง 26 พฤษภาคม 2020 เราสืบค้น Embase.com, CENTRAL และ Cochrane Covid‐19 Study Register ในวันที่ 14 เมษายน 2020 เราค้นหา LitCovid ถึง 4 เมษายน 2020 องค์การอนามัยโลก (WHO) จัดทำบันทึกจากการค้นหารายวันในฐานข้อมูลภาษาจีนและใน PubMed ถึง 15 เมษายน 2020 นอกจากนี้เรายังสืบค้นที่เก็บโมเดล 3 แห่ง (Covid‐Analytics, Models of Infectious Disease Agent Study [MIDAS] และ Society for Medical Decision Making) ในวันที่ 8 เมษายน 2020 เกณฑ์การคัดเลือก: การทดลอง การศึกษาเชิงสังเกต หรือการศึกษาแบบจำลองทางคณิตศาสตร์เพื่อประเมินประสิทธิผลการคัดกรองหรือความแม่นยำในการคัดกรอง ในกลุ่มประชากรทั่วไปที่ไม่ทราบความชุกของโรค SARS‐CoV2 การรวบรวมและวิเคราะห์ข้อมูล: หลังจากการทดสอบนำร่องแบบฟอร์มการทบทวนวรรณกรรม ผู้เขียนการทบทวนวรรณกรรมคนหนึ่งได้คัดกรองชื่อเรื่องและบทคัดย่อ ผู้ประพันธ์ 2 คนคัดกรองการศึกษาฉบับเต็ม และแก้ไขความเห็นที่ไม่ตรงกันโดยการปรึกษากับผู้ประพันธ์คนที่สาม บทคัดย่อที่ถูกคัดออกโดยผู้เขียนการทบทวนวรรณกรรมคนแรกได้รับการตรวจสอบโดยผู้เขียนคนที่สองก่อนที่จะคัดออก ผู้ประพันธ์การทบทวนวรรณกรรม 1 คน คัดลอกข้อมูลการศึกษาโดยอิสระ ซึ่งตรวจสอบโดยผู้ประพันธ์การทบทวนวรรณกรรมคนที่สอง ผู้เขียนการทบทวนวรรณกรรม 2 คนประเมินคุณภาพของการศึกษาที่รวมไว้อย่างอิสระ โดยใช้เครื่องมือการประเมินคุณภาพของการศึกษาความแม่นยำในการวินิจฉัย (QUADAS‐2) สำหรับการศึกษาความแม่นยำในการวินิจฉัย และรูปแบบที่แก้ไขซึ่งออกแบบมาสำหรับการประเมินทางเศรษฐศาสตร์สำหรับการศึกษาแบบจำลอง เราแก้ไขความแตกต่างโดยฉันทามติ เราสังเคราะห์หลักฐานในรูปแบบบรรยายและตาราง เราประเมินความเชื่อมั่นของหลักฐานสำหรับ จำนวนวันถึงการแพร่ระบาด การแพร่เชื้อ ผู้ป่วยที่วินิจฉัยไม่ได้และได้ ความแม่นยำในการวินิจฉัย (เช่นผลบวกจริง ผลบวกลวง ผลลบจริง ผลลบลวง) โดยใช้วิธี GRADE ผลการวิจัย: เรารวมสิ่งตีพิมพ์ 22 รายการ การศึกษาแบบจำลอง 2 รายการรายงานประสิทธิผลของการคัดกรองแบบครอบคลุม การศึกษา 20 รายการ (17 cohort studies และการศึกษาแบบจำลอง 3 รายการ) รายงานเกี่ยวกับความแม่นยำในการทดสอบการคัดกรอง ประสิทธิผลของการคัดกรอง เราได้รวมการศึกษาการสร้างแบบจำลอง 2 รายการ การศึกษา 1 รายการชี้ให้เห็นว่าการตรวจคัดกรองอาการที่ศูนย์กลางการเดินทาง เช่นสนามบิน อาจทำให้การนำเข้าผู้ติดเชื้อช้าลงเล็กน้อย แต่ไม่ได้หยุด (สมมติว่ามีผู้ติดเชื้อ 10 หรือ 100 คนต่อสัปดาห์จะลดความช้าในการระบาดในพื้นที่เหลือ 8 วันหรือ 1 วันตามลำดับ) เราประเมินความเสี่ยงของการมีอคติว่าเป็นเรื่องเล็กน้อยหรือไม่มีเลย และความเชื่อมั่นของหลักฐานอยู่ในระดับต่ำโดยลดระดับลงสำหรับ very serious indirectness การศึกษาแบบจำลองรายการที่ 2 ให้หลักฐานที่มีความเชื่อมั่นต่ำมากว่า การตรวจคัดกรองบุคลากรสุขภาพในแผนกฉุกเฉินโดยใช้การตรวจทางห้องปฏิบัติการ อาจลดการแพร่เชื้อไปยังผู้ป่วยและบุคลากรสุขภาพอื่น ๆ (สมมติว่ามีการแพร่เชื้อคงที่ 1.2 การติดเชื้อใหม่ต่อ 10,000 คน การตรวจคัดกรองรายสัปดาห์ลดการติดเชื้อลง 5.1% ภายใน 30 วัน) ความเชื่อมั่นของหลักฐานอยู่ในระดับต่ำมาก โดยลดระดับลงเนื่องจากมีความเสี่ยงสูงต่อการเกิดอคติ (ข้อกังวลหลัก) และ indirectness ไม่มีการศึกษาแบบจำลองที่รายงานเกี่ยวกับอันตรายของการตรวจคัดกรอง ความแม่นยำในการทดสอบการคัดกรอง การศึกษาแบบ cohort 17 รายการเปรียบเทียบกลยุทธ์การคัดกรองกับการทดสอบมาตรฐาน ปฏิกิริยาลูกโซ่โพลีเมอเรสแบบย้อนกลับ transcriptase (RT‐PCR) การศึกษาทั้งหมดยกเว้น 1 รายการรายงานเกี่ยวกับความแม่นยำของการตรวจคัดกรองแบบจุดเดียวในเวลาเดียว และมีความแตกต่างกันอย่างมากในความชุกของ SARS‐CoV‐2 บริบทและวิธีการตรวจ เราประเมินความเสี่ยงโดยรวมของอคติว่าไม่มีความชัดเจนในการศึกษา 16 จาก 17 การศึกษาสาเหตุหลักมาจากข้อมูลที่จำกัดของการทดสอบที่ทำและมาตรฐานอ้างอิง เราประเมินการศึกษา 1 รายการว่ามีความเสี่ยงสูงที่จะเกิดอคติเนื่องจากการรวมประชากรสองกลุ่มที่แยกจากกัน ซึ่งมีแนวโน้มที่จะมีความชุกต่างกัน สำหรับกลยุทธ์การคัดกรองหลาย ๆ แบบ การประมาณความไวมาจากกลุ่มตัวอย่างขนาดเล็ก สำหรับกลยุทธ์จุดเดียวในเวลาสำหรับการประเมินอาการความไวจาก 12 cohorts (524 คน) อยู่ระหว่าง 0.00 ถึง 0.60 (หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะจาก 12 cohorts (16,165 คน) อยู่ในช่วง 0.66 ถึง 1.00 ( หลักฐานที่มีความเชื่อมั่นต่ำ) สำหรับการตรวจคัดกรองโดยใช้การวัดอุณหภูมิโดยตรง (3 cohorts, 822 คน) ประวัติการเดินทางระหว่างประเทศ (2 cohorts, 13,080 คน) หรือการสัมผัสผู้ติดเชื้อที่รู้จัก (3 cohorts, 13,205 คน) หรือผู้ที่สงสัยว่าติดเชื้อ (2 cohorts, 954 คน) ความไวอยู่ในช่วง 0.00 ถึง 0.23 (หลักฐานที่มีความเชื่อมั่นต่ำถึงต่ำมาก) และความจำเพาะอยู่ระหว่าง 0.90 ถึง 1.00 (หลักฐานที่มีความเชื่อมั่นต่ำถึงปานกลาง) สำหรับการประเมินอาการร่วมกับการวัดอุณหภูมิโดยตรง (2 cohorts, 779 คน) ความไวอยู่ระหว่าง 0.12 ถึง 0.69 (หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะตั้งแต่ 0.90 ถึง 1.00 (หลักฐานที่มีความเชื่อมั่นต่ำ) สำหรับการทดสอบ PCR อย่างรวดเร็ว (1 cohort, 21 คน) ความไวเท่ากับ 0.80 (ช่วงความเชื่อมั่น 95% (CI) 0.44 ถึง 0.96 หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะเท่ากับ 0.73 (95% CI 0.39 ถึง 0.94 หลักฐานที่มีความเชื่อมั่นต่ำมาก ) การศึกษา 1 cohort (76 คน) รายงานเกี่ยวกับการตรวจคัดกรองซ้ำด้วยการประเมินอาการ แสดงให้เห็นถึงความไว 0.44 (95% CI 0.29 ถึง 0.59 หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะ 0.62 (95% CI 0.42 ถึง 0.79; หลักฐานที่มีความเชื่อมั่นต่ำ) การศึกษาแบบจำลอง 3 รายการประเมินความถูกต้องของการคัดกรองที่สนามบิน ผลลัพธ์หลักที่วัดได้คือกรณีที่พลาดหรือตรวจพบโดยการคัดกรองการเข้าหรือออกหรือทั้งสองอย่างที่สนามบิน การศึกษาชิ้นหนึ่งชี้ให้เห็นความไวต่ำมากที่ 0.30 (95% CI 0.1 ถึง 0.53) ซึ่งพลาด 70% ของผู้เดินทางที่ติดเชื้อ การศึกษาอีก 1 รายการอธิบายถึงสถานการณ์ที่ไม่เป็นจริงเพื่อให้ได้อัตราการตรวจพบ 90% โดยต้องมีการติดเชื้อที่ไม่มีอาการ 0% การศึกษาสุดท้ายให้หลักฐานที่ไม่แน่นอนเนื่องจากคุณภาพของวิธีการต่ำ ข้อสรุปของผู้วิจัย: หลักฐานสำหรับประสิทธิผลของการคัดกรองมาจากการศึกษาแบบจำลองทางคณิตศาสตร์ 2 รายการ และถูกจำกัดโดยสมมติฐาน หลักฐานที่มีความเชื่อมั่นต่ำ ชี้ให้เห็นว่าการตรวจคัดกรองที่ศูนย์กลางการเดินทางอาจทำให้การนำเข้าผู้ติดเชื้อช้าลงเล็กน้อย การทบทวนวรรณกรรมนี้เน้นให้เห็นถึงความไม่แน่นอนและความแตกต่างในความแม่นยำของกลยุทธ์การคัดกรอง ผู้ติดเชื้อในสัดส่วนที่สูงอาจพลาดไปและแพร่เชื้อไปสู่ผู้อื่น และบุคคลที่มีสุขภาพดีบางคนอาจถูกระบุว่าเป็นผลบวกโดยต้องได้รับการทดสอบยืนยันและอาจนำไปสู่การแยกบุคคลเหล่านี้โดยไม่จำเป็น การศึกษาเพิ่มเติมจำเป็นต้องประเมินประโยชน์ของการทดสอบในห้องปฏิบัติการอย่างรวดเร็ว การตรวจคัดกรองแบบรวม และการตรวจคัดกรองซ้ำ จำเป็นต้องมีการวิจัยเพิ่มเติมเกี่ยวกับมาตรฐานอ้างอิงที่มีความแม่นยำมากกว่า RT‐PCR ด้วยความไวที่ไม่ดีของแนวทางที่มีอยู่ การค้นพบของเราชี้ให้เห็นถึงความจำเป็นในการให้ความสำคัญกับวิธีการอื่น ๆ ที่อาจป้องกันการแพร่เชื้อ เช่นการปกปิดใบหน้า ระยะห่างทางกายภาพการกักกัน และอุปกรณ์ป้องกันส่วนบุคคลที่เพียงพอสำหรับพนักงานส่วนหน้า.پیشینه: بیماری کروناویروس 2019 (COVID‐19) توسط بتاکوروناویروس جدید، سندرم حاد تنفسی شدید کروناویروس ‐2 (SARS‐CoV‐2) ایجاد می‌شود. بیشتر افراد آلوده به SARS‐CoV‐2 مبتلا به بیماری خفیف با نشانه‌های غیراختصاصی هستند، اما حدود 5% از آنها به دلیل نارسایی تنفسی، شوک سپتیک و نارسایی چند عضو به شدت بیمار می‌شوند. نسبت نامشخصی از افراد آلوده هرگز دچار نشانه‌های COVID‐19 نمی‌شوند، اگرچه آلوده هستند، یعنی بدون نشانه باقی می‌مانند. افرادی که به این بیماری مبتلا می‌شوند، از یک دوره پیش‌علامت عبور می‌کنند که در طول آن عفونی هستند. غربالگری جهانی برای عفونت‌های SARS‐CoV‐2 به منظور تشخیص افراد آلوده پیش از آنکه از نظر بالینی تظاهر پیدا کنند، می‌تواند اقدامی مهم برای مهار گسترش بیماری باشد. اهداف: ما یک مرور سریع را انجام دادیم تا (1) اثربخشی غربالگری جهانی را برای عفونت SARS‐CoV‐2 در مقایسه با عدم انجام غربالگری و (2) دقت غربالگری جهانی را در افرادی که برای نشانه‌های COVID‐19 تحت مراقبت‌های بالینی قرار نگرفته‌اند، ارزیابی کنیم. روش‌های جست‌وجو: یک متخصص اطلاعات، Ovid MEDLINE و بانک اطلاعاتی مقالات پژوهشی قابل دانلود COVID‐19 را در سایت مراکز کنترل بیماری (CDC) تا 26 می 2020 جست‌وجو کرد. ما Embase.com؛ CENTRAL، و Cochrane Covid‐19 Register Study Register را در تاریخ 14 اپریل 2020 جست‌وجو کردیم. LitCovid تا 4 اپریل 2020 بررسی شد. سازمان بهداشت جهانی (WHO) رکوردها را از جست‌وجوهای روزانه در بانک‌های اطلاعاتی چینی و در PubMed تا 15 اپریل 2020 فراهم کرد. ما همچنین در 8 اپریل 2020، سه مخزن مدل‌سازی (Covid‐Analytics؛ Models of Infectious Disease Agent Study [MIDAS]، و Society for Medical Decision Making) را جست‌وجو کردیم. معیارهای انتخاب: کارآزمایی‌ها، مطالعات مشاهده‌ای، یا مطالعات ریاضی مدل‌سازی که به ارزیابی اثربخشی غربالگری یا دقت غربالگری میان جمعیت‌های عمومی پرداختند که در آنها شیوع SARS‐CoV2 ناشناخته است. گردآوری و تجزیه‌وتحلیل داده‌ها: پس از پایلوت فرم‌های مرور تست، یکی از نویسندگان مطالعه عناوین و خلاصه مقالات را بررسی کرد. دو نویسنده مرور به‌طور مستقل از هم متن کامل مطالعات را غربالگری کرده و هر گونه اختلاف‌نظری، با بحث با نویسنده سوم مرور برطرف شد. خلاصه مقالاتی که توسط نویسنده اول مرور رد شدند، پیش از حذف کامل، توسط نویسنده دوم مجددا بررسی شدند. یکی از نویسندگان مرور مستقلا داده‌ها را استخراج کرد، که توسط نویسنده دوم مرور از نظر کامل بودن و دقت بررسی شدند. دو نویسنده مرور به‌طور مستقل از هم کیفیت مطالعات وارد شده را با استفاده از ابزار ارزیابی کیفیت مطالعات دقت تشخیصی (QUADAS‐2) برای مطالعات دقت تشخیصی و فرم اصلاح شده‌ای از آن که در ابتدا برای ارزیابی‌های اقتصادی برای مطالعات مدل‌سازی طراحی شده بود، رتبه‌بندی کردند. ما تفاوت‌ها را با همفکری و اجماع‌نظر حل کردیم. شواهد را در قالب‌های روایت‌گونه (narrative) و جدولی (tabular) سنتز کردیم. با استفاده از رویکرد GRADE، قطعیت شواهد را برای روزهای شیوع و طغیان، انتقال، موارد از دست رفته و تشخیص داده شده، دقت تشخیصی (یعنی مثبت واقعی، مثبت کاذب، منفی واقعی، منفی کاذب) ارزیابی کردیم. نتایج اصلی: 22 مقاله وارد شدند. دو مطالعه مدل‌سازی، در مورد اثربخشی غربالگری جهانی گزارش دادند. بیست مطالعه (17 مطالعه کوهورت و 3 مطالعه مدل‌سازی) در مورد دقت آزمون غربالگری به ارائه گزارش پرداختند. اثربخشی غربالگری ما دو مطالعه مدل‌سازی را وارد کردیم. یک مطالعه نشان می‌دهد که غربالگری نشانه بیماری در مراکز مسافرتی، مانند فرودگاه‌ها، ممکن است ورود موارد عفونی را اندکی کاهش دهد اما آن را متوقف نمی‌کند (با فرض 10 یا 100 مسافر آلوده در هر هفته، تاخیر را در شیوع محلی به ترتیب، به 8 روز یا 1 روز کاهش داد) . ما خطر سوگیری (bias) را در سطح پائین یا بدون نگرانی ارزیابی کردیم، و قطعیت شواهد پائین بود، که به دلیل غیرمستقیم بودن بسیار جدی، تنزل رتبه پیدا کرد. مطالعه مدل‌سازی دوم شواهدی را با قطعیت بسیار پائین نشان می‌دهد که غربالگری کارکنان بخش مراقبت‌‌های سلامت در بخش‌های اورژانس با استفاده از تست‌های آزمایشگاهی ممکن است انتقال ویروس را به بیماران و دیگر کارکنان بخش مراقبت‌‌های سلامت کاهش دهد (با فرض انتقال ثابت 1.2 مورد عفونت جدید در هر 10,000 نفر، غربالگری هفتگی باعث کاهش عفونت تا 5.1% طی 30 روز شد). قطعیت شواهد بسیار پائین بود، که دلیل کاهش سطح کیفیت آن، خطر بالای سوگیری (نگرانی‌های اساسی) و غیرمستقیم بودن آنها گزارش شد. هیچ یک از مطالعات مدل‌سازی در مورد مضرات غربالگری گزارشی ارائه ندادند. دقت تست غربالگری همه 17 مطالعه کوهورت یک استراتژی غربالگری شاخص را با واکنش زنجیره‌ای پلیمراز ترانس‌کریپتاز معکوس (RT‐PCR) مرجع مقایسه کردند. همه مطالعات به جز یک مورد در مورد دقت انجام یک بار غربالگری گزارش داده و در شیوع SARS‐CoV‐2، شرایط، و روش‌های اندازه‌گیری تفاوت بسیاری داشتند. ما خطر کلی سوگیری را در 16 مطالعه از 17 مورد در سطح نامشخص ارزیابی کردیم، که دلیل اصلی آن، به اطلاعات محدود در مورد تست شاخص و استاندارد مرجع باز می‌گشت. یک مطالعه را به دلیل وارد کردن دو جمعیت جداگانه با احتمال شیوع متفاوت بیماری، در معرض خطر بالایی از سوگیری قرار دادیم. برای چندین استراتژی غربالگری، برآوردها از حساسیت آنها، از نمونه‌های کوچکی به دست آمدند. برای استراتژی‌های تکی که یک بار انجام شدند، به منظور ارزیابی نشانه‌ها، محدوده حساسیت از 12 مطالعه کوهورت (524 نفر) از 0.00 تا 0.60 (شواهد با قطعیت بسیار پائین) و محدوده ویژگی از 12 مطالعه کوهورت (16,165 نفر) از 0.66 تا 1.00 (شواهد با قطعیت پائین) متغیر بودند. برای غربالگری با استفاده از اندازه‌گیری مستقیم دمای بدن (3 مطالعه کوهورت، 822 نفر)، سابقه مسافرت بین‌المللی (2 مطالعه کوهورت، 13,080 نفر)، یا تماس با افراد آلوده شناخته شده (3 مطالعه کوهورت، 13,205 نفر) یا مواجهه با افراد آلوده مشکوک (2 مطالعه کوهورت، 954 نفر)، محدوده حساسیت از 0.00 تا 0.23 (شواهد با قطعیت بسیار پائین تا پائین) و محدوده ویژگی از 0.90 تا 1.00 (شواهد با قطعیت پائین تا متوسط) بود. برای ارزیابی نشانه‌ها به‌علاوه اندازه‌گیری مستقیم درجه حرارت بدن (2 مطالعه کوهورت، 779 نفر)، محدوده حساسیت از 0.12 تا 0.69 (شواهد با قطعیت بسیار پائین) و محدوده ویژگی از 0.90 تا 1.00 (شواهد با قطعیت پائین) قرار داشت. برای تست PCR سریع (1 مطالعه کوهورت، 21 نفر)، حساسیت معادل 0.80 (95% فاصله اطمینان (CI): 0.44 تا 0.96؛ شواهد با قطعیت بسیار پائین) و ویژگی معادل 0.73 (95% CI؛ 0.39 تا 0.94؛ شواهد با قطعیت بسیار پائین) گزارش شد. یک مطالعه کوهورت (76 نفر) در مورد غربالگری مکرر با ارزیابی نشانه‌ها گزارش دادند و حساسیتی را معادل 0.44 (95% CI؛ 0.29 تا 0.59؛ شواهد با قطعیت بسیار پائین) و ویژگی را معادل 0.62 (95% CI؛ 0.42 تا 0.79؛ شواهد با قطعیت پائین) اعلام کردند. سه مطالعه مدل‌سازی دقت غربالگری را در فرودگاه‌ها ارزیابی کردند. پیامدهای اصلی اندازه‌گیری شده عبارت بودند از مواردی که با غربالگری ورود یا خروج، یا هر دو، در فرودگاه‌ها از دست رفتند یا شناسایی شدند. یک مطالعه حساسیت بسیار کمی را معادل 0.30 (95% CI؛ 0.1 تا 0.53) نشان داد، بدان معنی که 70% مسافران آلوده را از دست داد. مطالعه دیگر یک سناریوی غیر‐واقعی را برای دستیابی به نرخ تشخیص معادل 90% توصیف کرد، که نیاز به 0% عفونت بدون علامت دارد. مطالعه نهایی به دلیل کیفیت پائین روش‌شناسی، شواهد بسیار نامطمئنی را ارائه می‌دهد. نتیجه‌گیری‌های نویسندگان: پایه شواهد برای اثربخشی غربالگری از دو مطالعه مدل‌سازی ریاضی به دست آمده و با فرضیات آنها محدود می‌شود. شواهدی با قطعیت پائین نشان می‌دهد که غربالگری در مراکز مسافرتی ممکن است ورود موارد آلوده را اندکی آهسته کند. این مرور عدم قطعیت و تغییر در دقت استراتژی‌های غربالگری را برجسته می‌کند. ممکن است نسبت بالایی از افراد آلوده تشخیص داده نشوند و دیگران را آلوده کنند، و برخی از افراد سالم نیز به اشتباه مثبت شناخته شوند، این امر به آزمایشات تأ‌ییدی نیاز دارد و به‌طور بالقوه منجر به ایزوله کردن غیرضروری این دسته از افراد می‌شود. مطالعات بیشتر نیاز به ارزیابی سودمندی آزمایشات سریع آزمایشگاهی، غربالگری ترکیبی، و غربالگری مکرر دارند. همچنین انجام تحقیقات بیشتری در مورد استانداردهای مرجع، با دقت بیشتری از RT‐PCR لازم است. با توجه به حساسیت ضعیف رویکردهای موجود، یافته‌های ما به لزوم تأکید بیشتر بر راه‌های دیگری که ممکن است از انتقال پیشگیری کنند، از جمله پوشش صورت، فاصله‌گذاری فیزیکی، قرنطینه، و تجهیزات محافظتی شخصی مناسب برای کارکنان خط مقدم، اشاره دارد.La maladie à coronavirus 2019 (COVID‐19) est causée par le nouveau bêtacoronavirus, le coronavirus 2 du syndrome respiratoire aigu sévère (SARS‐CoV‐2). La plupart des personnes infectées par le SARS‐CoV‐2 ont une maladie bénigne avec des symptômes non spécifiques, mais environ 5 % d'entre elles deviennent gravement malades avec une insuffisance respiratoire, un choc septique et une défaillance de plusieurs organes. Une proportion inconnue de personnes infectées ne présentent jamais de symptômes de la COVID‐19 bien qu'elles soient infectieuses, c'est‐à‐dire qu'elles restent asymptomatiques. Celles qui développent la maladie passent par une période présymptomatique pendant laquelle elles sont infectieuses. Le dépistage universel des infections par le SARS‐CoV‐2 pour détecter les personnes infectées avant qu'elles ne se présentent cliniquement, pourrait donc être une mesure importante pour contenir la propagation de la maladie.Nous avons procédé à une revue rapide pour évaluer (1) l'efficacité du dépistage universel de l'infection par le SARS‐CoV‐2 par rapport à l'absence de dépistage et (2) la précision du dépistage universel chez les personnes ne s’étant pas présentées en soins cliniques pour des symptômes de la COVID‐19. STRATÉGIE DE RECHERCHE DOCUMENTAIRE: Un spécialiste de l'information a effectué des recherches sur Ovid MEDLINE et dans la base de données téléchargeable des articles de recherche sur la COVID‐19 des Centres pour le contrôle et la prévention des maladies (Centers for Disease Control (CDC) COVID‐19 Research Articles Downloadable Database) jusqu'au 26 mai 2020. Nous avons effectué des recherches sur Embase.com, CENTRAL et le registre des études sur la Covid‐19 de Cochrane le 14 avril 2020. Nous avons recherché LitCovid jusqu'au 4 avril 2020. L'Organisation mondiale de la santé (OMS) a fourni des enregistrements issus de recherches quotidiennes dans les bases de données chinoises et dans PubMed jusqu'au 15 avril 2020. Nous avons également effectué des recherches dans trois répertoires de modèles (Covid‐Analytics, Models of Infectious Disease Agent Study [MIDAS], et la Société pour la prise de décision médicale) le 8 avril 2020. CRITÈRES DE SÉLECTION: Essais, études observationnelles ou études de modélisation mathématique évaluant l'efficacité ou la précision du dépistage parmi la population générale où la prévalence du SARS‐CoV‐2 est inconnue. RECUEIL ET ANALYSE DES DONNÉES: Après avoir réalisé un test pilote des formulaires d'évaluation, un auteur a passé en revue les titres et les résumés. Deux auteurs ont examiné de manière indépendante le texte intégral des études et ont résolu les éventuels désaccords par une discussion avec un troisième auteur. Les résumés exclus par un premier auteur ont été doublement examinés par un deuxième auteur avant d'être exclus. Un des auteurs de la revue a extrait de manière indépendante les données, dont l'exhaustivité et l'exactitude ont été vérifiées par un deuxième auteur. Deux auteurs de la revue ont évalué de manière indépendante la qualité des études incluses en utilisant l'outil QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies) pour les études de précision diagnostique et un formulaire modifié conçu à l'origine pour les évaluations économiques, pour les études de modélisation. Nous avons résolu les divergences par consensus. Nous avons synthétisé les données probantes sous forme narrative et de tableaux. Nous avons évalué le niveau de confiance dans les données probantes pour les jours précédant l'épidémie, la transmission, les cas manqués et détectés, la précision diagnostique (c'est‐à‐dire les vrais positifs, les faux positifs, les vrais négatifs, les faux négatifs) en utilisant l'approche GRADE. RÉSULTATS PRINCIPAUX: Nous avons inclus 22 publications. Deux études de modélisation ont porté sur l'efficacité du dépistage universel. Vingt études (17 études de cohorte et 3 études de modélisation) ont porté sur la précision des tests de dépistage. Efficacité du dépistage Nous avons inclus deux études de modélisation. Une étude suggère que le dépistage des symptômes dans les terminaux de voyage, tels que les aéroports, pourrait légèrement ralentir mais pas arrêter l'importation de cas infectés (en supposant que 10 ou 100 voyageurs infectés par semaine réduisent le délai d'une épidémie locale à 8 jours ou 1 jour, respectivement). Nous avons évalué le risque de biais comme étant mineur ou ne suscitant pas de préoccupations, et le niveau de confiance dans les données probantes était faible, rétrogradé pour très sérieuses préoccupations quant à leur caractère indirecte. La deuxième étude de modélisation fournit des données probantes d’un niveau de confiance très faible indiquant que le dépistage du personnel de santé travaillant dans les services d'urgence au moyen de tests de laboratoire pourrait réduire la transmission aux patients et aux autres personnels de santé (en supposant une constante de transmission de 1,2 nouvelle infection pour 10 000 personnes, le dépistage hebdomadaire a réduit les infections de 5,1 % dans les 30 jours). Le niveau de confiance dans les données probantes était très faible, rétrogradé en raison du risque élevé de biais (préoccupations majeures) et de leur caractère indirect. Aucune étude de modélisation n'a rapporté les effets néfastes du dépistage. Précision des tests de dépistage Les 17 études de cohorte ont comparé une stratégie de dépistage index à un test de référence de réaction de polymérisation en chaîne par transcription inverse (RT‐PCR). Toutes les études, sauf une, ont fait état de la précision du dépistage à un moment précis et variaient largement en ce qui concerne la prévalence du SARS‐CoV‐2, les milieux de vie et les méthodes de mesure. Nous avons estimé que le risque global de biais n'était pas clair dans 16 études sur 17, principalement en raison du peu d'informations sur le test index et le standard de référence. Nous avons estimé qu'une étude présentait un risque élevé de biais en raison de l'inclusion de deux populations distinctes ayant probablement des prévalences différentes. Pour plusieurs stratégies de dépistage, les estimations de la sensibilité sont issues de petits échantillons. Pour les stratégies à moment précis, pour l'évaluation des symptômes, la sensibilité de 12 cohortes (524 personnes) variait de 0,00 à 0,60 (données probantes d’un niveau de confiance très faible) et la spécificité de 12 cohortes (16 165 personnes) variait de 0,66 à 1,00 (données probantes d’un niveau de confiance faible). Pour le dépistage par mesure directe de la température (3 cohortes, 822 personnes), les antécédents de voyages internationaux (2 cohortes, 13 080 personnes), ou l'exposition à des cas connus de COVID‐19 (3 cohortes, 13 205 personnes) ou des cas suspects (2 cohortes, 954 personnes), la sensibilité variait de 0,00 à 0,23 (données probantes d’un niveau de confiance faible à très faible) et la spécificité variait de 0,90 à 1,00 (données probantes d’un niveau de confiance faible à modéré). Pour l'évaluation des symptômes combinée à la mesure directe de la température (2 cohortes, 779 personnes), la sensibilité allait de 0,12 à 0,69 (données probantes d’un niveau de confiance très faible) et la spécificité de 0,90 à 1,00 (données probantes d’un niveau de confiance faible). Pour le test PCR rapide (1 cohorte, 21 personnes), la sensibilité était de 0,80 (intervalle de confiance (IC) à 95% de 0,44 à 0,96 ; données probantes d’un niveau de confiance très faible) et la spécificité de 0,73 (IC à 95% de 0,39 à 0,94 ; données probantes d’un niveau de confiance très faible). Une cohorte (76 personnes) a fait état d'un dépistage répété avec évaluation des symptômes et présente une sensibilité de 0,44 (IC à 95% 0,29 à 0,59 ; données probantes d’un niveau de confiance très faible) et une spécificité de 0,62 (IC à 95% 0,42 à 0,79 ; données probantes d’un niveau de confiance faible). Trois études de modélisation ont évalué la précision du contrôle dans les aéroports. Les principaux critères de jugement mesurés étaient les cas manqués ou détectés par les contrôles d'entrée ou de sortie, ou les deux, dans les aéroports. Une étude suggère une très faible sensibilité à 0,30 (IC à 95% 0,1 à 0,53), manquant 70% des voyageurs infectés. Une autre étude a décrit un scénario irréaliste pour atteindre un taux de détection de 90%, nécessitant 0% d'infections asymptomatiques. L'étude finale fournit des données probantes très incertaines en raison de la faible qualité méthodologique.Les données probantes sur l'efficacité du dépistage proviennent de deux études de modélisation mathématique et sont limitées par leurs hypothèses. Des données probantes d’un niveau de confiance faible suggèrent que le dépistage dans les terminaux de voyage pourrait légèrement ralentir l'importation de cas infectés. Cette revue met en évidence l'incertitude et la variation de la précision des stratégies de dépistage. Une forte proportion de personnes infectées pourrait passer inaperçue et infecter d'autres personnes, et certaines personnes en bonne santé pourraient être faussement identifiées comme étant positives, ce qui nécessite des tests de confirmation et peut entraîner l'isolement inutile de ces personnes. D'autres études doivent évaluer l'utilité des tests rapides de laboratoire, du dépistage combiné et du dépistage répété. Il faut également poursuivre les recherches sur les standards de référence avec une plus grande précision que la RT‐PCR. Étant donné la faible sensibilité des approches existantes, nos conclusions soulignent la nécessité de mettre davantage l'accent sur d'autres moyens susceptibles de prévenir la transmission, tels que se couvrir le visage, la distanciation physique, la quarantaine et l'utilisation d'équipements de protection individuelle adéquats pour les travailleurs en première ligne.La enfermedad por coronavirus 2019 (covid‐19) está causada por el nuevo betacoronavirus: coronavirus‐2 del síndrome respiratorio agudo grave por coronavirus‐2 (SARS‐CoV‐2, del inglés). La mayoría de las personas contagiadas con el SARS‐CoV‐2 presenta una enfermedad leve con síntomas inespecíficos, pero alrededor del 5% se enferma gravemente con insuficiencia respiratoria, shock séptico e insuficiencia multiorgánica. Un porcentaje desconocido de individuos contagiados nunca experimenta síntomas de covid‐19 aunque son infecciosos, es decir, permanecen asintomáticos. Los que presentan la enfermedad, pasan por un período presintomático durante el cual son infecciosos. Por consiguiente, el cribado universal de las infecciones por SARS‐CoV‐2 para detectar a las personas contagiadas antes de que se presenten clínicamente, podría ser una medida importante para contener la propagación de la enfermedad.Se realizó una revisión rápida para evaluar (1) la efectividad del cribado universal de la infección por SARS‐CoV‐2 en comparación con la ausencia de cribado y (2) la precisión del cribado universal en las personas que no han solicitado atención clínica por síntomas de covid‐19. MÉTODOS DE BÚSQUEDA: Un documentalista buscó en Ovid MEDLINE y en la base de datos COVID‐19 Research Articles Downloadable Database de los Centers for Disease Control (CDC) hasta el 26 de mayo de 2020. Se hicieron búsquedas en Embase.com, CENTRAL y en el Registro Cochrane de estudios de covid‐19 el 14 de abril de 2020. Se buscaron estudios en LitCovid el 4 de abril de 2020. La Organización Mundial de la Salud (OMS) proporcionó entradas de búsquedas diarias en las bases de datos chinas y en PubMed hasta el 15 de abril de 2020. También se buscó en tres repositorios de modelos (Covid‐Analytics, Models of Infectious Disease Agent Study [MIDAS], y Society for Medical Decision Making) el 8 de abril de 2020. CRITERIOS DE SELECCIÓN: Ensayos, estudios observacionales o estudios de modelización matemática que evalúen la efectividad o la exactitud de los cribados en poblaciones generales en las que se desconoce la prevalencia del SARS‐CoV‐2. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Tras realizar pruebas piloto de formularios de revisión, un autor de la revisión examinó los títulos y resúmenes. Dos autores de la revisión identificaron el texto completo los estudios de forma independiente y resolvieron cualquier desacuerdo mediante discusión con un tercer autor de la revisión. Los resúmenes excluidos por un primer autor de revisión fueron revisados por un segundo autor de revisión antes de la exclusión. Un autor de la revisión extrajo de forma independiente datos, que fueron verificados por un segundo autor de la revisión en aras de su completitud y exactitud. Dos autores de la revisión de manera independiente calificaron la calidad de los estudios incluidos mediante la herramienta Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) para estudios de exactitud diagnóstica y un formulario modificado diseñado en origen para evaluaciones económicas de estudios de modelización. Las diferencias se resolvieron mediante consenso. Se resumió la evidencia en formatos narrativo y de tabla. Se evaluó la certeza de la evidencia de los días hasta el brote, la transmisión, los casos no detectados y detectados, la exactitud del diagnóstico (es decir, verdaderos positivos, falsos positivos, verdaderos negativos, falsos negativos) utilizando los criterios GRADE.Se incluyeron 22 publicaciones. Dos estudios de modelización informaron de la efectividad del cribado universal. Veintidós estudios (17 estudios de cohorte y tres de modelización) informaron acerca de la exactitud de las pruebas de detección. Efectividad del cribado Se incluyeron dos estudios de modelización. Un estudio sugiere que la detección de síntomas en los espacios de tránsito de viajeros, como los aeropuertos, puede ralentizar ligeramente pero no detener la importación de casos infectados (suponiendo que 10 o 100 viajeros infectados por semana reduzcan la demora en un brote local a ocho días o un día, respectivamente). Se evaluó el riesgo de sesgo como menor o sin preocupaciones, y la certeza de la evidencia fue baja, reducida por carácter indirecto muy grave. El segundo estudio de modelización proporciona evidencia de muy baja certeza de que el cribado de los trabajadores sanitarios en los servicios de urgencias mediante pruebas de laboratorio podría reducir la transmisión a los pacientes y a otros trabajadores sanitarios (suponiendo una constante de transmisión de 1,2 nuevas infecciones por cada 10 000 personas, el cribado semanal redujo las infecciones en un 5,1% en un plazo de 30 días). La certeza de la evidencia fue muy baja, disminuida debido al riesgo alto de sesgo, (preocupaciones importantes) y al carácter indirecto. Ningún estudio de modelización informó de los efectos perjudiciales del cribado. Exactitud de pruebas de detección Los 17 estudios de cohorte compararon una estrategia de cribado índice con la prueba de referencia de reacción en cadena de la polimerasa con transcriptasa inversa (de sus siglas en inglés, RT‐PCR). Todos los estudios, excepto uno, informaron sobre la exactitud del cribado en un solo punto temporal y variaron ampliamente en cuanto a la prevalencia de SARS‐CoV‐2, los entornos y los métodos de medición. Se evaluó el riesgo general de sesgo como poco claro en 16 de 17 estudios, debido principalmente a la información limitada sobre la prueba del índice y el patrón de referencia. Calificamos un estudio como de alto riesgo de sesgo debido a la inclusión de dos poblaciones separadas con prevalencias probablemente diferentes. En varias estrategias de cribado, las estimaciones de sensibilidad procedían de muestras pequeñas. En el caso de las estrategias de punto temporal único, para la evaluación de los síntomas, la sensibilidad de 12 cohortes (524 personas) osciló entre 0,00 y 0,60 (evidencia de certeza muy baja) y la especificidad de 12 cohortes (16 165 personas) osciló entre 0,66 y 1,00 (evidencia de certeza baja). En el caso del cribado mediante la medición directa de la temperatura (tres cohortes, 822 personas), los antecedentes de viajes internacionales (dos cohortes, 13 080 personas), o la exposición a personas contagiadas conocidas (tres cohortes, 13 205 personas) o sospechosas de estarlo (dos cohortes, 954 personas), la sensibilidad osciló entre 0,00 y 0,23 (evidencia de certeza muy baja a baja) y la especificidad entre 0,90 y 1,00 (evidencia de certeza moderada). Para la evaluación de los síntomas más medición de la temperatura (dos cohortes, 779 personas) la sensibilidad osciló entre 0,12 y 0,69 (evidencia de certeza muy baja) y la especificidad entre 0,90 y 1,00 (evidencia de certeza baja). Para la prueba PCR rápida (una cohorte, 21 personas), la sensibilidad fue de 0,80 (intervalo de confianza [IC] del 95%: 0,44 a 0,96; evidencia de certeza muy baja), y la especificidad fue del 0,73 (IC del 95%: 0,39 a 0,94; evidencia de certeza muy baja). Una cohorte (76 personas) informó de cribados repetidos con evaluación de síntomas y mostró una sensibilidad de 0,44 (IC del 95%: 0,29 a 0,59; evidencia de certeza muy baja) una especificidad de 0,62 (IC del 95%: 0,42 a 0,79; evidencia de certeza baja). Tres estudios de modelización evaluaron la exactitud del cribado en aeropuertos. Los principales desenlaces que se midieron fueron los casos detectados o no detectados por medio de cribados de entrada o salida, o ambos, en los aeropuertos. Un estudio sugiere una sensibilidad muy baja, de 0,30 (IC del 95%: 0,1 a 0,53), y un 70% de viajeros infectados no detectados. Otro estudio describió un escenario poco realista para lograr una tasa de detección del 90%, que requiere un 0% de infecciones asintomáticas. El estudio final proporciona evidencia muy incierta debido a la baja calidad metodológica.La base de la evidencia de la efectividad del cribado proviene de dos estudios de modelización matemática y está limitada por sus supuestos. Evidencia de certeza baja sugiere que el cribado en espacios de tránsito de viajeros podría ralentizar ligeramente la importación de casos infectados. Esta revisión pone de relieve la incertidumbre y la variación en la exactitud de las estrategias de cribado. Es posible que un elevado porcentaje de personas infectadas no se detecte y continúe contagiando a otras, y que algunas personas sanas sean identificadas falsamente como positivas, con la consiguiente realización de pruebas de confirmación y un posible aislamiento innecesario de esas personas. Es necesario realizar más estudios para evaluar la utilidad de las pruebas rápidas de laboratorio, el cribado combinado y el cribado repetido. También es necesario investigar más en patrones de referencia con mayor exactitud que la RT‐PCR. Dada la escasa sensibilidad de las técnicas existentes, estos hallazgos apuntan a la necesidad de hacer mayor hincapié en otras formas de prevención de la transmisión, como cubrirse el rostro, mantener la distancia física, imponer cuarentena y utilizar equipos de protección individual adecuados para los trabajadores de primera línea.

Benefit and cost effectiveness of breast cancer screening are still matters of controversy. Risk-adapted strategies are proposed to improve its benefit-harm and cost-benefit relations. Our objective was to perform a systematic review on economic breast cancer models evaluating primary and secondary prevention strategies in the European health care setting, with specific focus on model results, model characteristics, and risk-adapted strategies.Literature databases were systematically searched for economic breast cancer models evaluating the cost effectiveness of breast cancer screening and prevention strategies in the European health care context. Characteristics, methodological details and results of the identified studies are reported in evidence tables. Economic model outputs are standardized to achieve comparable cost-effectiveness ratios.Thirty-two economic evaluations of breast cancer screening and seven evaluations of primary breast cancer prevention were included. Five screening studies and none of the prevention studies considered risk-adapted strategies. Studies differed in methodologic features. Only about half of the screening studies modeled overdiagnosis-related harms, most often indirectly and without reporting their magnitude. All models predict gains in life expectancy and/or quality-adjusted life expectancy at acceptable costs. However, risk-adapted screening was shown to be more effective and efficient than conventional screening.Economic models suggest that breast cancer screening and prevention are cost effective in the European setting. All screening models predict gains in life expectancy, which has not yet been confirmed by trials. European models evaluating risk-adapted screening strategies are rare, but suggest that risk-adapted screening is more effective and efficient than conventional screening.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goi...

Background: Knowing the number of undetected cases of COVID-19 is important for a better understanding of the spread of the disease. This study analyses the temporal dynamic of detected vs. undetected cases to provide guidance for the interpretation of prevalence and incidence studies performed to estimate the detection rate. Methods: We used an agent-based model to evaluate assumptions on the detection probability ranging from 0·1 to 0·9. For each general detection probability, we derived age-dependent detection probabilities and calibrated the model to reproduce the epidemic wave of COVID-19 in Austria from March 2020 to June 2020. We categorized infected individuals into presymptomatic, symptomatic unconfirmed, confirmed and never detected to observe the simulated dynamic of the detected and undetected cases. Findings: The calculation of the age-dependent detection probability ruled values lower than 0·4 as most likely. Furthermore, the proportion of undetected cases depends strongly on the dynamic of the epidemic wave: during the initial upswing, the undetected cases account for a major part of all infected individuals, whereas their share decreases around the peak of the confirmed cases. Interpretation: The results of prevalence studies performed to determine the detection rate of COVID-19 patients should always be interpreted with regard to the current dynamic of the epidemic wave. Applying the method proposed in our analysis, the prevalence study performed in Austria in April 2020 could indicate a detection rate of 0·13, instead of the prevalent ratio of 0·29 between detected and estimated undetected cases at that time. Funding: This study has been partially funded by The Austrian Research Promotion Agency (FFG) Covid19 Emergency Call, the WWTF-COVID-19 Rapid Response Funding, the Medizinisch-Wissenschaftlicher Fonds des Burgermeisters der Bundeshauptstadt Wien, and the Society for Medical Decision Making (SMDM) Covid-19 Decision Modeling Initiative. Declaration of Interests: The authors declare that they have no competing interests.

Aim: To develop a prognostic score for primary breast cancer patients integrating conventional predictors and the novel biomarker CHAC1 to aid adjuvant chemotherapy decisions. Patients & methods: A prognostic score for overall survival was developed using: conventional predictors from a dataset of 1777 patients and the weight of CHAC1 mRNA expression from an independent dataset of 106 patients using multivariate Cox regression. Results: The new score includes: CHAC1 mRNA expression, age, tumor size, HER2 neu status, lymph node status and degree of malignancy. Using a cut-off value of 11 score points, 10-year survival was 82% in low-risk (n = 34) and 43% in high-risk patients (n = 72). The addition of CHAC1 resulted in 16% reclassification. Conclusion: Including CHAC1 in prognostic prediction may aid (and change) personalized treatment selection.

Background In 2014, Austrian health authorities implemented an organized breast cancer screening program. Until then, there has been a long-standing tradition of opportunistic screening. Objectives To evaluate the cost-effectiveness of organized screening compared with opportunistic screening, as well as to identify factors influencing the clinical and economic outcomes. Methods We developed and validated an individual-level state-transition model and assessed the health outcomes and costs of organized and opportunistic screening for 40-year-old asymptomatic women. The base-case analysis compared a scenario involving organized biennial screening with a scenario reflecting opportunistic screening practice for an average-risk woman aged 45 to 69 years. We applied an annual discount rate of 3% and estimated the incremental cost-effectiveness ratio in terms of the cost (2012 euros) per life-year gained (LYG) from a health care perspective. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. Results Compared with opportunistic screening, an organized program yielded on average additional 0.0118 undiscounted life-years (i.e., 4.3 days) and cost savings of €41 per woman. In the base-case analysis, the incremental cost-effectiveness ratio of organized screening was approximately €20,000 per LYG compared with no screening. Assuming a willingness-to-pay threshold of €50,000 per LYG, there was a 70% probability that organized screening would be considered cost-effective. The attendance rate, but not the test accuracy of mammography, was an influential factor for the cost-effectiveness. Conclusions The decision to adopt organized screening is likely an efficient use of limited health care resources in Austria.

Many Western countries have long-established population-based mammography screening programs. Prior to implementing these programs, decision-analytic modeling was widely used to inform decisions.The aim of this study was to perform a systematic review of cost-effectiveness models in breast cancer screening in the general population to analyze their structural and methodological approaches.A systematic literature search for health economic models was performed in the electronic databases MEDLINE (Ovid), EMBASE, CRD Databases, Cochrane Library, and EconLit in August 2011 with updates in June 2013, April 2015, and November 2016. To assess studies systematically, a standardized form was applied to extract relevant information that was then summarized in evidence tables.Thirty-five studies were included; 27 state-transition models were analyzed using cohort (n = 12) and individual-level simulation (n = 15). Twenty-one studies modeled the natural history of breast cancer and predicted mortality as a function of the early detection modality. The models employed different assumptions regarding ductal carcinoma in situ. Thirteen studies performed cost-utility analyses with different sources for utility values, but assumptions were often made about utility weights. Twenty-two models did not report any validation.State-transition modeling was the most frequently applied analytic approach. Different methods in modeling the progression of ductal carcinoma in situ to invasive cancer were identified because there is currently no agreement on the biological behavior of noninvasive breast cancer. Main weaknesses were the lack of precise utility estimates and insufficient reporting of validation. Sensitivity analyses of assumptions regarding ductal carcinoma in situ and in particular adequate validation are critical to minimize the risk of biased model outcomes.

BackgroundChronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality worldwide. Estimation of incidence, prevalence and disease burden through routine insurance data is challenging because of under-diagnosis and under-treatment, particularly for early stage disease in health care systems where outpatient International Classification of Diseases (ICD) diagnoses are not collected. This poses the question of which criteria are commonly applied to identify COPD patients in claims datasets in the absence of ICD diagnoses, and which information can be used as a substitute. The aim of this systematic review is to summarize previously reported methodological approaches for the identification of COPD patients through routine data and to compile potential criteria for the identification of COPD patients if ICD codes are not available.MethodsA systematic literature review was performed in Medline via PubMed and Google Scholar from January 2000 through October 2018, followed by a manual review of the included studies by at least two independent raters. Study characteristics and all identifying criteria used in the studies were systematically extracted from the publications, categorized, and compiled in evidence tables.ResultsIn total, the systematic search yielded 151 publications. After title and abstract screening, 38 publications were included into the systematic assessment. In these studies, the most frequently used (22/38) criteria set to identify COPD patients included ICD codes, hospitalization, and ambulatory visits. Only four out of 38 studies used methods other than ICD coding. In a significant proportion of studies, the age range of the target population (33/38) and hospitalization (30/38) were provided. Ambulatory data were included in 24, physician claims in 22, and pharmaceutical data in 18 studies. Only five studies used spirometry, two used surgery and one used oxygen therapy.ConclusionsA variety of different criteria is used for the identification of COPD from routine data. The most promising criteria set in data environments where ambulatory diagnosis codes are lacking is the consideration of additional illness-related information with special attention to pharmacotherapy data. Further health services research should focus on the application of more systematic internal and/or external validation approaches.

Background: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. Methods: A decision-analytic Markov cohort model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. Results: The most effective strategies were FIT and COL. The IHBR to move from COL to FIT has an expected incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. gFOBT was dominated by FIT. Moving from COL to FIT has an ICER of 15000 EUR/LYG. Conclusions: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.

Background. In state-transition models (STMs), decision problems are conceptualized using health states and transitions among those health states after predefined time cycles. The naive, commonly applied method (C) for cycle length conversion transforms all transition probabilities separately. In STMs with more than 2 health states, this method is not accurate. Therefore, we aim to describe and compare the performance of method C with that of alternative matrix transformation methods. Design. We compare 2 alternative matrix transformation methods (Eigenvalue method [E], Schure-Padé method [SP]) to method C applied in an STM of 3 different treatment strategies for women with breast cancer. We convert the given annual transition matrix into a monthly-cycle matrix and evaluate induced transformation errors for the transition matrices and the long-term outcomes: life years, quality-adjusted life-years, costs and incremental cost-effectiveness ratios, and the performance related to the decisions. In addition, we applied these transformation methods to randomly generated annual transition matrices with 4, 7, 10, and 20 health states. Results. In theory, there is no generally applicable correct transformation method. Based on our simulations, SP resulted in the smallest transformation-induced discrepancies for generated annual transition matrices for 2 treatment strategies. E showed slightly smaller discrepancies than SP in the strategy, where one of the direct transitions between health states was excluded. For long-term outcomes, the largest discrepancy occurred for estimated costs applying method C. For higher dimensional models, E performs best. Conclusions. In our modeling examples, matrix transformations (E, SP) perform better than transforming all transition probabilities separately (C). Transition probabilities based on alternative conversion methods should therefore be applied in sensitivity analyses.

Budget impact analyses (BIAs) describe changes in intervention- and disease-related costs of new technologies. Evidence on the quality of BIAs for cancer screening is lacking. We systematically reviewed the literature and methods to assess how closely BIA guidelines are followed when BIAs are performed for cancer-screening programs. Systematic searches were conducted in MEDLINE, EMBASE, EconLit, CRD (Centre for Reviews and Dissemination, University of York), and CEA registry of the Tufts Medical Center. Eligible studies were BIAs evaluating cancer-screening programs published in English, 2010–2018. Standardized evidence tables were generated to extract and compare study characteristics outlined by the ISPOR BIA Task Force. Nineteen studies were identified evaluating screening for breast (5), colorectal (6), cervical (3), lung (1), prostate (3), and skin (1) cancers. Model designs included decision-analytic models (13) and simple cost calculators (6). From all studies, only 53% reported costs for a minimum of 3 years, 58% compared to a mix of screening options, 42% reported model validation, and 37% reported uncertainty analysis for participation rates. The quality of studies appeared to be independent of cancer site. “Gray” literature was not searched, misinterpretation is possible due to limited information in publications, and focus was on international methodological guidelines rather than regional guidelines. Our review highlights considerable variability in the extent to which BIAs evaluating cancer-screening programs followed recommended guidelines. The annual budget impact at least over the next 3–5 years should be estimated. Validation and uncertainty analysis should always be conducted. Continued dissemination efforts of existing best-practice guidelines are necessary to ensure high-quality analyses.

For the evaluation of infectious-diseases interventions, the transmissible nature of such diseases plays a central role. Agent-based models (ABM) allow for dynamic transmission modeling but publications are limited. We aim to provide an overview of important characteristics of ABM for decision-analytic modeling of infectious diseases. A case study of dengue epidemics illustrates model characteristics, conceptualization, calibration and model analysis. First, major characteristics of ABM are outlined and discussed based on ISPOR and ISPOR-SMDM Good Practice guidelines. Second, in our case study, we modeled a dengue outbreak in Cebu City (Philippines) to assess the impact interventions to control the relative growth of the mosquito population. Model outcomes include prevalence and incidence of infected persons. The modular ABM simulates persons and mosquitoes over an annual time horizon considering daily time steps. The model was calibrated and validated. ABM is a dynamic, individual-level modeling approach that is capable to reproduce direct and indirect effects of interventions for infectious diseases. The ability to replicate emerging behavior and to include human behavior or the behavior of other agents is a distinguishing modeling characteristic (e.g., compared to Markov models). Modeling behavior may, however, require extensive calibration and validation. The analyzed hypothetical effectiveness of dengue interventions showed that a reduced human-mosquito ratio of 1:2.5 during rainy seasons leads already to a substantial decrease of infected persons. ABM can support decision-analyses for infectious diseases including disease dynamics, emerging behavior, and providing a high level of reusability due to modularity.

Liberal internationalism has been in crisis for a while now. Yet, until recently its supporters have argued that its prospects are better than ever since the successful spread of liberal principles, practices and institutions in the international sphere provides the necessary basis for reform. Alas, recent political developments do not support these expectations. In fact, the Brexit vote, the Trump election, and the rise of populism more generally challenge liberalism in the domestic sphere and aim to unravel its international achievements. But the idea that these movements are therefore liberalism's nemesis does not quite follow. Providing a theoretical and historical analysis of liberalism, this article shows that the separation of domestic and international politics is constitutive of liberalism itself. The successful extension of liberal principles into the international sphere undermines this separation and thus liberalism itself. Ironically, therefore, the prospects of liberal internationalism are dependent on the reestablishment of a clear divide between domestic and international politics. And this, I argue, is precisely the goal of contemporary populist movements.

Aim: To provide an overview of thresholds for incremental cost–effectiveness ratios (ICERs) representing willingness-to-pay (WTP) across multiple countries and insights into exemptions pertaining to the ICER (e.g., cancer). To compare ICER thresholds to individual country's estimated ability-to-pay. Materials & methods: We included AHRQ/USA, BIQG-GOEG/Austria, CADTH/Canada, DAHTA@DIMDI/Germany, DECIT-CGATS/Brazil, HAS/France, HITAP/Thailand, IQWiG/Germany, LBI-HTA/Austria, MSAC/Australia, NICE/England/Wales and SBU/Sweden. ICER thresholds were derived from systematic literature/website search/expert surveys. WTP was compared with ATP using Spearman's rank correlation. Results: Two general and explicitly acknowledged thresholds (England/Wales, Thailand), implicit thresholds in six countries and different ICER thresholds/decision-making rules in oncology were identified. Correlation between WTP and ability-to-pay was moderate. Discussion: Our overview supports country-specific discussions on WTP and on how to define value(s) within societies.

Summary Background The Oncotyrol – Center for Personalized Cancer Medicine is an international and interdisciplinary alliance combining research and commercial competencies to accelerate the development, evaluation and translation of personalized healthcare strategies in cancer. The philosophy of Oncotyrol is to collaborate with relevant stakeholders and advance knowledge "from bench to bedside to population and back". Oncotyrol is funded through the COMET Excellence Program by the Austrian government via the national Austrian Research Promotion Agency (FFG). This article focuses on the role of health technology assessment (HTA) and outcomes research in personalized cancer medicine in the context of Oncotyrol. Methods Oncotyrol, which currently comprises approximately 20 individual projects, has four research areas: Area 1: Biomarker and Drug Target Identification; Area 2: Assay Development and Drug Screening; Area 3: Innovative Therapies; Area 4: Health Technology Assessment and Bioinformatics. Area 4 translates the results from Areas 1 to 3 to populations and society and reports them back to Area 3 to inform clinical studies and guidelines, and to Areas 1 and 2 to guide further research and development. Results In a series of international expert workshops, the Oncotyrol International Expert Task Force for Personalized Cancer Medicine developed the Methodological Framework for Early Health Technology Assessment and Decision Modeling in Cancer and practical guidelines in this field. Further projects included applications in the fields of sequential treatment of patients with chronic myeloid leukemia (CML), benefit-harm and cost-effectiveness evaluation of prostate cancer screening, effectiveness and cost-effectiveness of multiple cervical cancer screening strategies, and benefits and cost-effectiveness of genomic test-based treatment strategies in breast cancer. Conclusion An interdisciplinary setting as generated in Oncotyrol provides unique opportunities such as systematically coordinating lab and bench research, product development, clinical studies and decision science/HTA and transparent joint planning of research and development with a partnership of researchers, manufacturers and health policy decision makers. However, generating a joint research and legal framework with numerous partners from different sectors can be challenging, particularly in the starting period of such an endeavor. The journey to translational personalized medicine through multidisciplinary collaborations may still be long and difficult, but it is evident that it must be continued to turn vision into reality.

The attempt to recover the international origins of social and political thought is motivated by the unsatisfactory fragmentation of modern knowledge – by its failure to account for the intimate connections between theory and history in general and its international dimension in particular – and seeks to overcome these divides. This article provides an analysis of the theory/history divide and its role for the fragmentation of modern knowledge. Theoretically, it shows, this divide is rooted in, and reproduced by, the epistemic foundations of modern knowledge. Historically, the modern episteme arises from a crisis of imperial politics in the 18th century. This analysis suggests that theory, history, and the international are products rather than origins of modern social and political thought. These historical origins thus do not provide the basis for more integrated forms of knowledge. They do, however, reveal how the fragmentation of knowledge itself simultaneously serves and obscures the imperialist dimension of modern politics.