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PURPOSE: Molecular screening for Mycobacterium tuberculosis (MTB) can lead to rapid empirical treatment inception and reduce hospitalization time and complementary diagnostic tests. However, in low-prevalence settings, the cost-benefit balance remains controversial due to the high cost. METHODS: We used a Markov model to perform an economic analysis to evaluate the profit after implementing molecular MTB screening (Period B) compared with conventional culture testing (Period A) in respiratory samples from 7,452 consecutive subjects with presumed tuberculosis (TB). RESULTS: The proportion of positivity was comparable between both periods (P > 0.05), with a total of 2.16 and 1.78 samples/patient requested in periods A and B, respectively (P < 0.001). The mean length of hospital stay was 8.66 days (95%CI: 7.63-9.70) in Period B and 11.51 days (95%CI: 10.15-12.87) in Period A (P = 0.001). The healthcare costs associated with diagnosing patients with presumed TB were reduced by 717.95 per patient with PCR screening. The probability of remaining hospitalized and the need for a greater number of outpatient specialty care visits were the variables with the most weight in the model. CONCLUSION: Employing PCR as an MTB screening method in a low-prevalence setting may increase the profits to the system.
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Análise Custo-Benefício , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Feminino , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/economia , Técnicas de Diagnóstico Molecular/métodos , Adulto , Idoso , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/economia , Cadeias de Markov , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose/economia , Adulto JovemRESUMO
The effect of COVID-19 booster vaccination on SARS-CoV-2 T-cell mediated immune responses in elderly nursing home residents has not been explored in depth. Thirty-nine elderly nursing home residents (median age, 91 years) were included, all fully vaccinated with mRNA vaccines. The frequency of and the integrated mean fluorescence (iMFI) for peripheral blood SARS-CoV-2-Spike reactive IFN-γ-producing CD4+ or CD8+ T cells before and after the first (Pre-3D and Post-3D) and second (Pre-4D and Post-4D) vaccine booster doses was determined using flow cytometry for an intracellular staining method. 3D increased significantly (p = 0.01) the percentage of participants displaying detectable SARS-CoV-2-T-cell responses compared with pre-3D (97% vs. 74%). The magnitude of the increase was statistically significant for CD8+ T cells (p = 0.007) but not for CD4+ T cells (p = 0.77). A trend towards higher frequencies of peripheral blood SARS-CoV-2-CD8+ T cells was observed post-3D compared with pre-3D (p = 0.06). The percentage of participants with detectable SARS-S-CoV-2 CD4+ T-cell responses decreased post-4D (p = 0.035). Following 4D, a nonsignificant decrease in the frequencies of both T cell subsets was noticed (p = 0.94 for CD8+ T cells and p = 0.06 for CD4+ T cells). iMFI data mirrored that of T-cell frequencies. The kinetics of SARS-CoV-2 CD8+ and CD4+ T cells following receipt of 3D and 4D were comparable across SARS-CoV-2-experienced and -naïve participants and between individuals receiving a homologous or heterologous vaccine booster. 3D increased the percentage of elderly nursing home residents displaying detectable SARS-CoV-2 T-cell responses but had a marginal effect on T-cell frequencies. The impact of 4D on SARS-CoV-2 T-cell responses was negligible; whether this was due to suboptimal priming or rapid waning could not be ascertained.
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Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Casas de Saúde , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Idoso de 80 Anos ou mais , Masculino , Glicoproteína da Espícula de Coronavírus/imunologia , Feminino , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Linfócitos T CD4-Positivos/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , Idoso , Interferon gama , Vacinas de mRNARESUMO
PURPOSE: Comparing the performance of commercially available SARS-CoV-2 T-cell immunoassay responses may provide useful information for future observational or intervention studies as well as to their potential customers. METHOD: Whole blood was collected from a total of 183 subjects fully vaccinated against COVID-19: 55 healthy controls (Group 1), 50 hematological patients (Group 2), 50 chronic kidney disease patients (Group 3), and 28 elderly nursing home residents (Group 4). Samples were tested with the Roche Elecsys® IGRA (Interferon-gamma release assay) SARS-CoV-2 test (Roche Diagnostics, Rotkreuz, Switzerland), the Euroimmun SARS-CoV-2 test (Euroimmun, Lubeck, Germany), the SARS-CoV-2 T Cell Analysis Kit (Miltenyi Biotec, Bergisch Gladbach, Germany), and a flow-cytometry for intracellular cytokine (IFN-γ) staining-based immunoassay (FC-ICS). RESULTS: Overall, the Roche Elecsys® assay returned the highest number of positive results (151/179; 84.3%), followed by the Euroimmun test (127/183; 69%), and the FC-ICS (135/179; 75%). The Kappa coefficient of agreement was best between IGRAs (0.64). Most discordant results across assays involved patients from Group 2. Overall, IFN-γ concentrations measured by both IGRAs correlated strongly (rho = 0.78; 95% CI 0.71-0.84; P < 0.001) irrespective of the study group. The frequencies of SARS-CoV-2-reactive IFN-γ T cells and IFN-γ concentrations measured by the IGRAs correlated moderately for CD4+ T cells, however, weakly for CD8+ T cells. SARS-CoV-2-experienced participants displayed stronger responses than SARS-CoV-2-naïve when IGRAs, rather than FC-ICS, were used. CONCLUSION: The SARS-CoV-2 immunoassays evaluated in the present study did not return interchangeable qualitative or quantitative results either in seemingly healthy individuals or in immunosuppressed patients.
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Vacinas contra COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , Testes de Liberação de Interferon-gama , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Testes de Liberação de Interferon-gama/métodos , Testes de Liberação de Interferon-gama/normas , Idoso , Adulto , Vacinas contra COVID-19/imunologia , Linfócitos T/imunologia , Idoso de 80 Anos ou mais , Interferon gama/sangue , Interferon gama/imunologia , Imunoensaio/métodosRESUMO
PURPOSE: The significant proportion of asymptomatic patients and the scarcity of genotypic analysis of lymphogranuloma venereum (LGV), mainly among men who have sex with men (MSM), triggers a high incidence of underdiagnosed patients, highlighting the importance of determining the most appropriate strategy for LGV diagnosis, at both clinical and economical levels. MATERIALS AND METHODS: We conducted L1-L3 serovar detection by molecular biology in stored Chlamydia trachomatis-positive samples from MSM patients with HIV, another STI or belonging to a Pre-exposure prophylaxis program, to make a cost effectiveness study of four diagnostic strategies with a clinical, molecular, or mixed approach. RESULTS: A total of 85 exudates were analyzed: 35urethral (31 symptomatic/4 positive) and 50 rectal (22 symptomatic/25 positive), 70/85 belonging to MSM with associated risk factors. The average cost per patient was 77.09 and 159.55 for clinical (Strategy I) and molecular (Strategy IV) strategies respectively. For molecular diagnosis by genotyping of all rectal exudate samples previously positive for CT (Strategy II), the cost was 123.84. For molecular diagnosis by genotyping of rectal and/or urethral exudate samples from all symptomatic patients (proctitis or urethritis) with a previous positive result for CT (Strategy III), the cost was 129.39. The effectiveness ratios were 0.80, 0.95, 0.91, and 1.00 for each strategy respectively. The smallest ICER was 311.67 for Strategy II compared to Strategy I. CONCLUSIONS: With 30% asymptomatic patients, the most cost-effective strategy was based on genotyping all rectal exudates. With less restrictive selection criteria, thus increasing the number of patients with negative results, the most sensitive strategies tend to be the most cost-effective, but with a high incremental cost-effectiveness ratio.
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Linfogranuloma Venéreo , Minorias Sexuais e de Gênero , Masculino , Humanos , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/epidemiologia , Chlamydia trachomatis/genética , Homossexualidade Masculina , Análise de Custo-Efetividade , GenótipoRESUMO
In this single-center prospective study, we evaluated the performance to the MALDI-ToF MS based method in conjunction with lateral flow immunochromatographic (LFIC) in urine specimens for rapid diagnosis of bacterial Urinary Tract Infection (UTI) and detection of carbapenemase and/or extended-spectrum ß- lactamase (ESBL) enzymes produced by the involved bacteria, compared to standard culture, and antimicrobial susceptibility testing/genotypic resistance markers characterization performed on culture-grown colonies. In addition, a cost-benefit analysis comparing this approach against standard procedures was conducted. A total of 324 urines were included in the study, of which 288 (88.9 %) yielded concordant results by the MALDI-ToF MS and conventional culture (Kappa agreement, 0.82; P<0.001). Direct LFIC testing could be carried out in 249/324 urines. Bacterial species carrying ß-lactam genotypic resistance markers were identified in 35 urines (35 CTX-M and 2 OXA-48). Two ESBL-producing Escherichia coli were missed by LFIC (Kappa agreement with standard procedures of 0.96; P<0.001). The cost-benefit analysis indicated that our novel approach resulted in an improvement of clinical outcomes (less need of outpatient care) with a marginal incremental cost (2.59).
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Infecções Bacterianas , Infecções Urinárias , Humanos , Análise Custo-Benefício , Estudos Prospectivos , beta-Lactamases/genética , Bactérias/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Escherichia coli/química , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia , LasersRESUMO
Epithermal bonanza-type ores, characterized by weight-percent contents of e.g., gold and silver in a few mm to cm, are generated by mixtures of magmatic-derived hydrothermal brines and external fluids (e.g., meteoric) that transport a variety of metals to the site of deposition. However, the low solubilities of precious metals in hydrothermal fluids cannot justify the high concentrations necessary to produce such type of hyper-enriched metal ore. Here we show that boiling metal-bearing brines can produce, aggregate, and accumulate metal nanomaterials, ultimately leading to focused gold + silver ± copper over-enrichments. We found direct nano-scale evidence of nanoparticulate gold- and/or silver-bearing ores formed via nonclassical growth (i.e., nanomaterial attachment) during boiling in an intermediate-sulfidation epithermal bonanza. The documented processes may explain the generation of bonanzas in metal-rich brines from a range of mineral deposit types.
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We developed and evaluated a simple, low-cost matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS)-based method for the detection of meropenem (MER) resistance in Pseudomonas aeruginosa directly from blood. A volume of 50 µL of positive-flagged blood culture (BC) was transferred in 450 µL brain heart infusion (BHI) broth to microtubes either containing MER (test) or not (control) at 25 or 50 mg/L. P. aeruginosa was categorized as resistant or susceptible on the basis of whether or not the isolates could be identified, respectively, in the presence of the antibiotic (3 h of incubation). When using BCs spiked with 99 P. aeruginosa isolates (64 MER-resistant and 35 MER-susceptible) the method correctly classified 88/99 isolates (88.9%). Correct categorization was achieved in 23/23 (100%) of P. aeruginosa isolates (17 MER-susceptible and 6 MER-resistant) from prospectively collected BCs. Our method may prove useful for early targeted or adjustment of empirical therapy in patients with P. aeruginosa bloodstream infections.
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Hemocultura , Pseudomonas aeruginosa , Humanos , Meropeném/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Antibacterianos/farmacologia , Meios de Cultura , Testes de Sensibilidade MicrobianaRESUMO
Recent studies have reported the significant role of Au-bearing nanoparticles in the formation of hydrothermal gold deposits. Despite the ever-increasing understanding of the genesis and stability of Au-bearing nanoparticles, it is still unknown how they behave when exposed to hydrothermal fluids. Here, we study the nanostructural evolution of Au-Ag nanoparticles hosted within Co-rich diarsenides and sulfarsenides of a natural hydrothermal deposit. We use high-resolution transmission electron microscopy to provide a singular glimpse of the complete melting sequence of Au-Ag nanoparticles exposed to the hydrothermal fluid during coupled dissolution-precipitation reactions of their host minerals. The interaction of Au-Ag nanoparticles with hydrothermal fluids at temperatures (400-500 ºC) common to most hydrothermal gold deposits may promote melting and generation of Au-Ag nanomelts. This process has important implications in noble metal remobilization and accumulation during the formation of these deposits.
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Economic assessment is required to gauge the value of implementing PCR syndromic platforms in the microbiology laboratory for the diagnosis of community-acquired acute gastroenteritis (AGE) in pediatric and adult in- and outpatients. A cost-benefit analysis was conducted from a health care system perspective using BD MAX Enteric Bacterial, Bacterial Plus, and Virus panels. Two 6-month periods were selected, in which either conventional procedures (in 2017) or BD MAX PCR multiplex panels (in 2018) were used. We retrospectively reviewed medical records of all patients with positive results and a representative sample of negative ones. A Markov model was used to represent transition probabilities between different health care states from time of stool microbiological study until completion of AGE-episode-associated health care. A total of 1,336 medical records were reviewed (829 in 2018 and 507 in 2017), showing overall a significantly higher positivity rate in 2018 than in 2017 (26% versus 6%, P < 0.001). The total cost per individual associated with health care for AGE was 314 in 2018 and 341 in 2017; when we only considered the pediatric cohort, the figures were 271 and 456, respectively. Using Tornado sensitivity analyses, we found that the three variables that most influenced the model in descending order of weight were the probability of longer hospital stays, the probability of returning to the emergency room (ER), and the probability of hospitalization from the ER. Use of BD MAX enteric PCR platforms for the diagnosis of community-acquired AGE instead of a non-PCR-based conventional approach results in an incremental benefit from a health care perspective in the general population, particularly children. IMPORTANCE The implementation of multiplex molecular panels allows microbiological laboratories to quickly, sensitively, and accurately diagnose acute infectious gastroenteritis. This methodology therefore allows faster decisions regarding treatment and infection control measures. Economic evaluations are required to gauge the value of implementing these syndromic PCR platforms in a community-based acute gastroenteritis setting. We studied the potential clinical and cost benefits, in terms of both their impact on laboratory costs and the subsequent costs of managing patients.