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      Performance of the minimally invasive autopsy tool for cause of death determination in adult deaths from the Brazilian Amazon: an observational study

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          Abstract

          The uncertainty about the real burden of causes of death (CoD) is increasingly recognized by the international health community as a critical limitation for prioritizing effective public health measures. The minimally invasive autopsy (MIA) has shown to be a satisfactory substitute of the complete diagnostic autopsy (CDA), the gold standard for CoD determination in low- and middle-income countries. However, more studies are needed to confirm its adequate performance in settings with different epidemiology. In this observational study, the CoD obtained with the MIA were compared with the clinical diagnosis and the results of the CDA in 61 deaths that occurred in an infectious diseases referral hospital in Manaus, Brazilian Amazon. Concordance between the categories of diseases obtained by the three methods was evaluated by the Kappa statistic. Additionally, we evaluated discrepancies between clinical and complete diagnostic autopsy diagnoses. The MIA showed a substantial concordance with the CDA (Kappa = 0.777, 95% CI 0.608–0.946), and a perfect or almost perfect coincidence in specific diagnosis (ICD-10 code) between MIA and CDA was observed in 85% of the cases. In contrast, the clinical diagnosis showed a fair concordance with the CDA (Kappa = 0.311, 95% CI 0.071–0.552). Major clinico-pathological discrepancies were identified in 49% of cases. In conclusion, the MIA showed a substantial performance for CoD identification. Clinico-pathological discrepancies remain high and justify the need for post-mortem studies, even in referral hospitals. The MIA is a robust substitute of the CDA for CoD surveillance and quality improvement of clinical practice in low- and middle-income settings.

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          The online version of this article (10.1007/s00428-019-02602-z) contains supplementary material, which is available to authorized users.

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          Most cited references21

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          Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15–60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5–24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates—a measure of relative inequality—increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7–87·2), and for men in Singapore, at 81·3 years (78·8–83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Funding Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.
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            Changes in rates of autopsy-detected diagnostic errors over time: a systematic review.

            Substantial discrepanies exist between clinical diagnoses and findings at autopsy. Autopsy may be used as a tool for quality management to analyze diagnostic discrepanies. To determine the rate at which autopsies detect important, clinically missed diagnoses, and the extent to which this rate has changed over time. A systematic literature search for English-language articles available on MEDLINE from 1966 to April 2002, using the search terms autopsy, postmortem changes, post-mortem, postmortem, necropsy, and posthumous, identified 45 studies reporting 53 distinct autopsy series meeting prospectively defined criteria. Reference lists were reviewed to identify additional studies, and the final bibliography was distributed to experts in the field to identify missing or unpublished studies. Included studies reported clinically missed diagnoses involving a primary cause of death (major errors), with the most serious being those likely to have affected patient outcome (class I errors). Logistic regression was performed using data from 53 distinct autopsy series over a 40-year period and adjusting for the effects of changes in autopsy rates, country, case mix (general autopsies; adult medical; adult intensive care; adult or pediatric surgery; general pediatrics or pediatric inpatients; neonatal or pediatric intensive care; and other autopsy), and important methodological features of the primary studies. Of 53 autopsy series identified, 42 reported major errors and 37 reported class I errors. Twenty-six autopsy series reported both major and class I error rates. The median error rate was 23.5% (range, 4.1%-49.8%) for major errors and 9.0% (range, 0%-20.7%) for class I errors. Analyses of diagnostic error rates adjusting for the effects of case mix, country, and autopsy rate yielded relative decreases per decade of 19.4% (95% confidence interval [CI], 1.8%-33.8%) for major errors and 33.4% (95% [CI], 8.4%-51.6%) for class I errors. Despite these decreases, we estimated that a contemporary US institution (based on autopsy rates ranging from 100% [the extrapolated extreme at which clinical selection is eliminated] to 5% [roughly the national average]), could observe a major error rate from 8.4% to 24.4% and a class I error rate from 4.1% to 6.7%. The possibility that a given autopsy will reveal important unsuspected diagnoses has decreased over time, but remains sufficiently high that encouraging ongoing use of the autopsy appears warranted.
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              The value of the autopsy in three medical eras.

              To determine whether advances in diagnostic procedures have reduced the value of autopsies, we analyzed 100 randomly selected autopsies from each of the academic years 1960, 1970, and 1980 at one university teaching hospital. In all three eras about 10 per cent of the autopsies revealed a major diagnosis that, if known before death, might have led to a change in therapy and prolonged survival; another 12 per cent showed a clinically missed major diagnosis for which treatment would not have been changed. Among 1980 autopsies, renal disease and pulmonary embolus were less common causes of death than before, but systemic bacterial, viral, and fungal infections increased significantly and were missed clinically 24 per cent of the time. The introduction of radionuclide scans, ultrasound, and computerized tomography as diagnostic procedures did not reduce the use of conventional tests in patients who subsequently died and were studied by autopsy. Over-reliance on these new procedures occasionally contributed directly to missed major diagnoses. We conclude that advances in diagnostic technology have not reduced the value of the autopsy, and that a goal-directed autopsy remains a vital component in the assurance of good medical care.
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                Author and article information

                Contributors
                +34 93 2275450 , jordi@clinic.ub.es
                Journal
                Virchows Arch
                Virchows Arch
                Virchows Archiv
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0945-6317
                1432-2307
                14 June 2019
                14 June 2019
                2019
                : 475
                : 5
                : 649-658
                Affiliations
                [1 ]GRID grid.412290.c, ISNI 0000 0000 8024 0602, Universidade do Estado do Amazonas, ; Manaus, Amazonas 69850-000 Brazil
                [2 ]GRID grid.418153.a, ISNI 0000 0004 0486 0972, Fundação de Medicina Tropical Dr. Heitor Viera Dourado, ; Manaus, 69040-000 Brazil
                [3 ]GRID grid.5841.8, ISNI 0000 0004 1937 0247, ISGlobal-Hospital Clínic, , Universitat de Barcelona, ; Villarroel 170, 08036 Barcelona, Spain
                [4 ]GRID grid.410458.c, ISNI 0000 0000 9635 9413, Department of Pathology, , Hospital Clinic - Universitat de Barcelona, ; Villarroel 170, 08036 Barcelona, Spain
                [5 ]GRID grid.410458.c, ISNI 0000 0000 9635 9413, Department of Microbiology, , Hospital Clinic - Universitat de Barcelona, ; 08036 Barcelona, Spain
                [6 ]GRID grid.452366.0, ISNI 0000 0000 9638 9567, Centro de Investigação em Saúde de Manhiça (CISM), ; 1929 Maputo, Mozambique
                [7 ]GRID grid.450640.3, ISNI 0000 0001 2189 2026, National Council for Scientific and Technological Development (CNPq, Brasilia, Brazil) fellow, ; Brasília, Brazil
                [8 ]GRID grid.470120.0, ISNI 0000 0004 0571 3798, Department of Pathology, , Maputo Central Hospital, ; 1653 Maputo, Mozambique
                [9 ]GRID grid.8295.6, Faculty of Medicine, , Eduardo Mondlane University, ; 1653 Maputo, Mozambique
                [10 ]GRID grid.425902.8, ISNI 0000 0000 9601 989X, ICREA, , Catalan Institution for Research and Advanced Studies, ; Passeig de Lluís Companys 23, 08010 Barcelona, Spain
                [11 ]Paediatric Infectious Diseases Unit, Paediatrics Department, Hospital Sant Joan de Déu - Universitat de Barcelona, 8950 Barcelona, Spain
                [12 ]Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
                Article
                2602
                10.1007/s00428-019-02602-z
                6861203
                31201504
                37deaf58-7eb5-43c4-8738-643817291465
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 1 April 2019
                : 1 May 2019
                : 6 June 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP2068633
                Award ID: OPP2239002
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI23/00868
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Pathology
                cause of death,minimally invasive autopsy,complete autopsy,infectious diseases,clinico-pathological discrepancies

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