Analytical and clinical evaluation of four commercial SARS-CoV-2 serological immunoassays in hospitalized patients and ambulatory individuals.

BACKGROUND: This study aimed to compare four anti-SARS-CoV-2 immunoassays in populations presenting different clinical severity levels. METHODS: Three populations were included: "severe-to-critical" ICU-hospitalized patients (n = 18), "mild-to-moderate" hospitalized patients (n = 16) and non-hospitalized symptomatic patients (n = 24). Four commercial immunoassays were analyzed and validated: anti-IgG ARCHITECT® (Abbott), anti-Total antibodies (Ab) VITROS® (Ortho Clinical Diagnostics), anti-IgG NovaLisa® (NovaTec Immundiagnostica) and Healgen® IgM and IgG (Zhejiang Orient Gene Biotech). Sensitivities were evaluated according to days post-symptoms onset (pso). Specificities were evaluated on SARS-CoV-2-negative control sera collected before January 2020. RESULTS: A majority of severe-to-critically ill patients showed detectable Ab already at day 14 and sensitivities reached 100 % after 22 days pso. For patients with "mild-to-moderate" illness, sensitivities increased by at least 5-fold from day 0 to day 14 pso. Non-hospitalized symptomatic individuals already seroconverted at day 14 days pso with 100 % sensitivities for Total Ab VITROS®. Specificities were evaluated at 97 % for ARCHITECT® and NovaLisa®, 98 % for VITROS® and at 94 % for Healgen® combined IgM and IgG. Five "severe-to-critically" ill patients presented high positive Ab levels for at least 16 weeks pso. CONCLUSION: The Ab levels and the evaluated sensitivities, representing the true positive rate, increased overtime and were related to the COVID-19 severity. Automated Total Ab immunoassay showed better sensitivities and specificity for immunological surveillance and vaccine evaluation.

Performance of three generations of Xpert MRSA in routine practice: approaching the aim?

The aim of this study was to evaluate retrospectively the performance of the Xpert MRSA assay in routine practice and its current use in the intensive care unit (ICU) setting of our hospital, since a pre-emptive isolation strategy has been applied. A total of 6473 patients were routinely screened with ESwab for methicillin-resistant Staphylococcus aureus (MRSA) using three generations of rapid real-time polymerase chain reaction (PCR) (Cepheid GeneXpert) over three consecutive periods of time. Performance was evaluated using broth enrichment culture as the reference method. Our results show that the last generation of Xpert MRSA (NxG) assay is more specific (99.2% vs. 97.9%) but not more sensitive (77.8% vs. 86.9%) than the third generation. Considering the low prevalence of MRSA in our hospital, we obtained an overall low positive predictive value. In conclusion, it remains difficult to abandon the reference method in routine practice considering the possible implications of an erroneous MRSA result in the ICU.

Score test for familial aggregation in probands studies: application to Alzheimer's disease.

When studying familial aggregation of a disease, the following two-stage design is often used: first select index subjects (cases and controls); then record data on their relatives. The likelihood corresponding to this design is derived and a score test of homogeneity is proposed for testing the hypothesis of no-aggregation. This test takes into account the selection procedure and allows adjustment to be made for explanatory variables. It appears as the sum of three terms: a pure test of homogeneity, a test of comparison of observed minus expected cases in the two groups, and a term which adjusts for the possible unequal probabilities of disease of the index subjects. Asymptotic efficiency and a simulation study show that the proposed test is superior to either the pure homogeneity test or tests based on the comparison of numbers of affected in the two groups. The test statistic, which has an asymptotically standard normal distribution, is applied to a study of familial aggregation of early-onset Alzheimer's disease for which a highly significant value (9.46) is obtained: this is the highest value among the three tests compared, in agreement with the simulation study. A logistic normal model is fitted to the data, taking account of the selection procedure: it allows to estimate the regression parameters and the variance of the random effect; the likelihood ratio test for familial aggregation seems less powerful than the score test.

Test of homogeneity of binary data with explanatory variables.

Apparent heterogeneity of the risk of a disease in different groups may be explained by subject-specific risk factors unequally distributed in these groups. We propose a score test of homogeneity that allows adjustment for known risk factors of the disease. The test is based on a random-effect logistic regression model and requires only simple computations in addition to a conventional logistic regression method. The score test is applied to the study of geographical heterogeneity of cognitive impairment in elderly using a sample of 3,318 subjects scattered in 75 parishes. It is shown that an apparent heterogeneity disappears when taking into account subject-specific risk factors. This test may also be useful for studying familial aggregation of a disease.

The intraclass correlation coefficient: distribution-free definition and test.

A definition of the intraclass correlation coefficient is given on the basis of a general class of random effect model. The conventional intraclass correlation coefficient and the intracluster correlation coefficient for binary data are both particular cases of the generalized coefficient. We derive the score test for the hypothesis of null intraclass correlation in the exponential family. The statistic does not depend on the particular distribution in this family and is related to the pairwise correlation coefficient. The test can be adjusted for explanatory variables.

Functional status of elderly people treated for asthma-related symptoms: a population based case-control study.

There are few data on the disability caused by asthma in elderly subjects. The aim of this survey was to assess the functional status of a population aged 65 years or more, being treated for asthma-related symptoms. A representative sample of 3,777 elderly people, living at home in the South-West of France, was surveyed using a standardized questionnaire on factors of ageing and their consequences. To assess the functional status, five scales were used: Activities of Daily Living (ADL); Instrumental Activities of Daily Living (IADL); Rosow and Breslau scale; Mobility; and a Subjective Health Scale. Patients treated for asthma-related symptoms were identified by means of their use of the anti-asthma drugs mentioned in the questionnaire. In a second stage, the presence of asthma-related symptoms was further established by enquiring from their general practitioners and by direct questioning of the patients. Among 135 subjects taking anti-asthma drugs, 83 (61%) had positive responses to specific questions, either from their doctors or from themselves, allowing them to be identified as "asthmatic". In comparison with a control group matched for age and sex (n = 166; two controls for each patient), asthmatic patients had a higher dependence in the IADL scale, a greater self-assessment of poor health, and a greater handicap in mobility. However, they had the same level of ADL disability as controls. Despite adjustment for residential area, depressive symptoms, Mini Mental Status (MMS) Exam score, visual and auditory impairment, and joint pain, patients treated for asthma still had a higher risk of disability in daily life, and a poorer subjective health than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Components of drinking water and risk of cognitive impairment in the elderly.

The relation between aluminum, fluorine, calcium, and pH in drinking water and the risk for cognitive impairment was studied using data collected in 1988-1989 in a population-based survey of 3,777 French men and women aged 65 years and older (the Paquid study). Cognitive impairment was defined as a score lower than 24 on the Mini-Mental State Examination. Data related to drinking water came from two prospective measurement surveys whose reliability was checked by a variability study. A mixed effects logistic regression was performed, adjusting for the effects of the age, sex, educational level, and occupation of the participants. A significant protective effect was found for high calcium concentration (odds ratio = 0.8 for a concentration > or = 75 mg vs. < 75 mg, p = 0.015). For aluminum, no significant effect was found when pH was not included in the model, but the results showed a weak interaction between aluminum and pH. When the four variables (calcium, aluminum, pH, and aluminum x pH interaction) were considered in the statistical analysis as a group, this group was significantly related to cognitive impairment (p = 0.01).

Cerebral and functional aging: first results on prevalence and incidence of the Paquid cohort.

Paquid is an interdisciplinary study designed to investigate cerebral and functional aging. A cohort of 3,777 community residents living in two administrative areas of South-Western France was selected. A standardized questionnaire was administered at home by trained psychologists. The same procedure was applied one and three years after the baseline data collection. The identification of demented subjects was made with a two-step procedure. The first step is a systematic screening by the psychologists using the DSM-III criteria for dementia. Subjects who fulfilled the DSM-III criteria were examined by a neurologist. Diagnosis of dementia is confirmed according to the NINCDS-ADRDA criteria. The Paquid cohort is complemented by a random sample of 357 institutionalized subjects. First results of prevalence and incidence rates show an exponential increase of dementia with age.

[Prevalence of dementia in Gironde (France)]. / Prévalence de la démence en Gironde (France).

The objective of the study is to estimate the prevalence of dementia using the data of the Paquid cohort. A sample of 3,149 subjects aged 65 years and older living at home or in institution was randomly chosen in Gironde (France). A questionnaire and psychometric tests were used to evaluate cognitive functioning and the presence of dementia was assessed through DSM III Diagnostic and Statistical Manual of mental disorders (ed. III) criteria. Hachinski scale and work group NINCDS-ADRDA criteria were applied to confirm the presence of dementia and identify Alzheimer's disease. Overall prevalence was estimated to 4.3%. No difference was found between men and women. The prevalence increased with age with nearly a doubling every 5 years of age. In institution, dementia frequency remained stable. The relative risk of a demented subject to be institutionalized with regard to a non demented subject decreased with age.