Clinico-pathological discrepancies in the diagnosis of causes of death in adults in Mozambique: A retrospective observational study

Background Clinico-pathological discrepancies are more frequent in settings in which limited diagnostic techniques are available, but there is little information on their actual impact. Aim We assessed the accuracy of the clinical diagnoses in a tertiary referral hospital in sub-Saharan Africa by comparison with post-mortem findings. We also identified potential risk factors for misdiagnoses. Methods One hundred and twelve complete autopsy procedures were performed at the Maputo Central Hospital (Mozambique), from November 2013 to March 2015. We reviewed the clinical records. Major clinico-pathological discrepancies were assessed using a modified version of the Goldman and Battle classification. Results Major diagnostic discrepancies were detected in 65/112 cases (58%) and were particularly frequent in infection-related deaths (56/80 [70%] major discrepancies). The sensitivity of the clinical diagnosis for toxoplasmosis was 0% (95% CI: 0­37), 18% (95% CI: 2­52) for invasive fungal infections, 25% (95% CI: 5­57) for bacterial sepsis, 34% (95% CI: 16­57), for tuberculosis, and 46% (95% CI: 19­75) for bacterial pneumonia. Major discrepancies were more frequent in HIV-positive than in HIV-negative patients (48/73 [66%] vs. 17/39 [44%]; p = 0.0236). Conclusions Major clinico-pathological discrepancies are still frequent in resource constrained settings. Increasing the level of suspicion for infectious diseases and expanding the availability of diagnostic tests could significantly improve the recognition of common life-threatening infections, and thereby reduce the mortality associated with these diseases. The high frequency of clinico-pathological discrepancies questions the validity of mortality reports based on clinical data or verbal autopsy.

Contribution of the clinical information to the accuracy of the minimally invasive and the complete diagnostic autopsy

Embora o diagnóstico de autópsia inclua rotineiramente uma avaliação completa de todos os resultados patológicos disponíveis e também de qualquer dado clínico disponível, a contribuição dessas informações clínicas para o rendimento diagnóstico da autópsia não foi analisada. Nosso objetivo foi determinar em que medida o uso de dados clínicos melhora a acurácia diagnóstica da autópsia diagnóstica completa (ACD) e da autópsia minimamente invasiva (MIA), um procedimento patológico simplificado post-mortem projetado para locais de baixa renda. Um total de 264 procedimentos acoplados MIA e CDA (112 adultos, 57 mortes maternas, 54 crianças e 41 neonatos) foram realizados no Hospital de Maputo, Moçambique. Comparamos os diagnósticos obtidos pelo MIA cego para dados clínicos (MIAb), o MIA adicionando a informação clínica (MIAc) e o CDA cego para informação clínica (CDAb), com os resultados do padrão-ouro, o CDA com dados clínicos, comparando a Classificação Internacional de Doenças, códigos da Décima Revisão e as principais classes diagnósticas obtidas com cada estratégia de avaliação (MIAb, MIAc, CDAb, CDAc). Os dados clínicos aumentaram a coincidência diagnóstica com o MIAb com o padrão-ouro em 30 (11%) de 264 casos e modificaram o diagnóstico CDAb em 20 (8%) de 264 casos. O aumento da concordância entre MIAb e MIAc com o padrão-ouro foi significativo nos óbitos neonatais (κ aumentando de 0,404 para 0,618, P = .0271), adultos (κ aumentando de 0,732 para 0,813, P = .0221) e maternos (κ aumentando de 0,485 para 0,836, 0.; P < .0001). Em conclusão, o uso de informações clínicas aumenta a precisão do MIA e do CDA e pode fortalecer o desempenho do MIA em ambientes com recursos limitados.

Signos predictores de crecimiento precoz de la hemorragia intracerebral en la tomografía computarizada sin contraste y mortalidad / Signs predicting early growth of intracerebral haemorrhage in computer tomography without enhancement and mortality

Introducción. La hemorragia intracerebral está asociada a una elevada morbimortalidad y su aumento de volumen en fases iniciales conlleva un peor pronóstico. El signo de la mezcla, la densidad heterogénea, la morfología irregular y un nivel líquido en el hematoma se relacionan con un crecimiento precoz del hematoma. Objetivo. Determinar si esas cuatro características se asocian a una mayor mortalidad a los 7, 30 y 90 días de ocurrida la hemorragia intracerebral. Pacientes y métodos. Estudio de cohortes retrospectivo que incluyó a todos los pacientes atendidos en nuestro hospital, entre 2010 y 2015, por una hemorragia intracerebral espontánea con tomografía computarizada cerebral realizada en las primeras seis horas tras el inicio de los síntomas. Resultados. De los 158 pacientes incluidos, 23 (14,6%) presentaban signo de la mezcla, 39 (24,7%) heterogeneidad, 53 (33,5%) irregularidad y 33 (20,9%) nivel líquido. En el análisis bivariante, sólo la heterogeneidad y la irregularidad se asociaron a mayor mortalidad a los 7, 30 y 90 días. En el análisis por regresión logística multivariante, el tratamiento previo con antiagregante plaquetario, una puntuación en la escala de coma de Glasgow menor de 13 y la irregularidad se asociaron a una mayor mortalidad en los siete primeros días. Conclusión. El estudio muestra asociación entre la irregularidad del hematoma y la mortalidad en los siete primeros días. La irregularidad permitiría identificar a pacientes con peor pronóstico, en los que una vigilancia estricta, especialmente de factores relacionados con el crecimiento del hematoma, podría mejorar su pronóstico

Introduction. Intracerebral haemorrhage is associated with high morbidity and mortality, and an increase in its volume in the early phases entails a poorer prognosis. The blend sign, the heterogeneous density, the irregular morphology and a fluid level in the haematoma are related to an early growth of the haematoma. Aim. To determine whether these four characteristics are associated with greater mortality at 7, 30 and 90 days of the occurrence of the intracerebral haemorrhage. Patients and methods. A retrospective cohort study that included all the patients attended in our hospital between 2010 and 2015 for spontaneous intracerebral haemorrhage with a computed tomography brain scan performed in the first six hours following the onset of symptoms. Results. Of the 158 patients included in the sample, 23 (14.6%) presented blend sign; 39 (24.7%), heterogeneity; 53 (33.5%), irregularity; and 33 (20.9%), fluid level. In the bivariate analysis, only heterogeneity and irregularity were associated with increased mortality at 7, 30 and 90 days. In the multivariate logistic regression analysis, previous treatment with an antiplatelet drug, a score on the Glasgow Coma Scale below 13 and irregularity were associated with higher mortality in the first seven days. Conclusion. The study shows an association between irregularity of the haematoma and mortality in the first seven days. Irregularity would allow identification of patients with a more unfavourable prognosis; in these cases, strict surveillance, especially of factors related to the growth of the haematoma, could improve their prognosis

Postmortem interval and diagnostic performance of the autopsy methods

Postmortem studies, including the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), an innovative approach to post-mortem sampling and cause of death investigation, are commonly performed within 24 hours after death because the quality of the tissues deteriorates over time. This short timeframe may hamper the feasibility of the procedure. In this study, we compared the diagnostic performance of the two postmortem procedures when carried out earlier and later than 24 hours after death, as well as the impact of increasing postmortem intervals (PMIs) on the results of the microbiological tests in a series of 282 coupled MIA/CDA procedures performed at the Maputo Central Hospital in Mozambique between 2013 and 2015. 214 procedures were conducted within 24 hours of death (early autopsies), and 68 after 24 hours of death (late autopsies). No significant differences were observed in the number of non-conclusive diagnoses (2/214 [1%] vs. 1/68 [1%] p = 0.5645 for the CDA; 27/214 [13%] vs. 5/68 [7%] p = 0.2332 for the MIA). However, increasing PMIs were associated with a raise in the number of bacteria identified (rate: 1.014 per hour [95%CI: 1.002-1.026]; p = 0.0228). This increase was mainly due to rising numbers of bacteria of the Enterobacteriaceae family and Pseudomonas genus strains. Thus, performing MIA or CDA more than 24 hours after death can still render reliable diagnostic results, not only for non-infectious conditions but also for many infectious diseases, although, the contribution of Enterobacteriaceae and Pseudomonas spp. as etiological agents of infections leading to death may be overestimated.

Healthcare providers' views and perceptions on post-mortem procedures for cause of death determination in Southern Mozambique

Background: The minimally invasive autopsy (MIA) is being investigated as an alternative to the complete diagnostic autopsy (CDA), gold standard for CoD determination, in settings where CDA is unfeasible and/or unacceptable. We aimed to explore healthcare providers' views and perceptions on theoretical and factual acceptability of the CDA and the MIA. Methods: A qualitative study, combining ethnographic and grounded-theory approaches, was conducted within a project aiming to validate the MIA tool against the CDA for CoD investigation. We present data on in-depth and semi-structured interviews of 33 healthcare providers operating within the formal and informal health services in Southern Mozambique. MIA perception was analysed through the theory of diffusion of innovations. Results: All participants considered CDA useful for CoD determination. CDA was perceived reliable, but the unpleasant nature of the procedure and its associated infection risk were the main perceived disadvantages. Participants considered the MIA simple, easy and quick to perform; likely to meet families' expectations to know the CoD, and able to provide evidence-based knowledge for disease management. Concerns were raised on its reliability compared to the CDA. Family's emotional status and accessibility to decision-makers were mentioned as principal barriers for MIA performance. The main jeopardizing factors for MIA implementation were the shortage of required resources and the significant proportion of people dying at home. Key facilitators for MIA acceptance included the need for the support from community and religious leaders, provision of clear information to the community, and accompaniment to bereaved families

Validity of a minimally invasive autopsy for cause of death determination in stillborn babies and neonates in Mozambique: An observational study

Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs)-the gold standard for cause of death determination-are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed. Methods and findings: In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56-0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18-0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction. Conclusions: The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.

Validity of a minimally invasive autopsy tool for cause of death determination in pediatric deaths in Mozambique: An observational study

Background: In recent decades, the world has witnessed unprecedented progress in child survival. However, our knowledge of what is killing nearly 6 million children annually in low- and middle-income countries remains poor, partly because of the inadequacy and reduced precision of the methods currently utilized in these settings to investigate causes of death (CoDs). The study objective was to validate the use of a minimally invasive autopsy (MIA) approach as an adequate and more acceptable substitute for the complete diagnostic autopsy (CDA) for pediatric CoD investigation in a poor setting. Methods and findings: In this observational study, the validity of the MIA approach in determining the CoD was assessed in 54 post-neonatal pediatric deaths (age range: ≥1 mo to 15 y) in a referral hospital of Mozambique by comparing the results of the MIA with those of the CDA. Concordance in the category of disease obtained by the two methods was evaluated by the Kappa statistic, and the sensitivity, specificity, and positive and negative predictive values of the MIA diagnoses were calculated. A CoD was identified in all cases in the CDA and in 52/54 (96%) of the cases in the MIA, with infections and malignant tumors accounting for the majority of diagnoses. The MIA categorization of disease showed a substantial concordance with the CDA categorization (Kappa = 0.70, 95% CI 0.49-0.92), and sensitivity, specificity, and overall accuracy were high. The ICD-10 diagnoses were coincident in up to 75% (36/48) of the cases. The MIA allowed the identification of the specific pathogen deemed responsible for the death in two-thirds (21/32; 66%) of all deaths of infectious origin. Discrepancies between the MIA and the CDA in individual diagnoses could be minimized with the addition of some basic clinical information such as those ascertainable through a verbal autopsy or clinical record. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation.

Asociación entre miastenia grave y lupus eritematoso sistémico: ¿es seguro el uso de hidroxicloroquina? / Association between myasthenia gravis and systemic lupus erythematosus: is it safe to use hydroxychloroquine?

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Validity of a Minimally Invasive Autopsy for Cause of Death Determination in Adults in Mozambique: An Observational Study

There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique. Methods and findings: In this observational study, coupled MIAs and CDAs were performed in 112 deceased patients. The MIA analyses were done blindly, without knowledge of the clinical data or the results of the CDA. We compared the MIA diagnosis with the CDA diagnosis of cause of death. CDA diagnoses comprised infectious diseases (80; 71.4%), malignant tumors (16; 14.3%), and other diseases, including non-infectious cardiovascular, gastrointestinal, kidney, and lung diseases (16; 14.3%). A MIA diagnosis was obtained in 100/112 (89.2%) cases. The overall concordance between the MIA diagnosis and CDA diagnosis was 75.9% (85/112). The concordance was higher for infectious diseases and malignant tumors (63/80 [78.8%] and 13/16 [81.3%], respectively) than for other diseases (9/16; 56.2%). The specific microorganisms causing death were identified in the MIA in 62/74 (83.8%) of the infectious disease deaths with a recognized cause. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation. Conclusions: A simple MIA procedure can identify the cause of death in many adult deaths in Mozambique. This tool could have a major role in improving the understanding and surveillance of causes of death in areas where infectious diseases are a common cause of mortality