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Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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COVID-19 , Estudio de Asociación del Genoma Completo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , COVID-19/genética , Caracteres Sexuales , Sitios Genéticos , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND: SARS-CoV-2 variant tracking is key to the genomic surveillance of the COVID-19 pandemic. While next-generation sequencing (NGS) is commonly used for variant determination, it is expensive and time-consuming. Variant-specific PCR (vsPCR) is a faster, cheaper method that detects specific mutations that are considered variant-defining. These tests usually rely on specific amplification when a mutation is present or a specific melting temperature peak after amplification. CASE PRESENTATION: A discrepant result between vsPCR and NGS was found in seventeen SARS-CoV-2 samples from Galicia, Spain. A cluster of BA.1 Omicron SARS-CoV-2 variant showed a BA.2-like melting temperature pattern due to a point mutation (C21772T) downstream the deletion of the spike amino acids 69/70. As the 69/70 deletion is widely used for differentiation between BA.1 and BA.2 by vsPCR, C21772T can cause BA.1 samples to be misinterpreted as BA.2. Over a thousand BA.1 sequences in the EpiCoV database contain this mutation. CONCLUSIONS: To our knowledge, this is the first case of a point mutation causing a vsPCR algorithm to misclassify BA.1 samples as BA.2. This is an example of how mutations in the probe target area of vsPCR tests based on melting curve analysis can lead to variant misclassification. NGS confirmation of vsPCR results is relevant for the accuracy of the epidemiological surveillance. In order to overcome the possible impact of novel mutations, diagnostic tools must be constantly updated.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Mutación Puntual , Pandemias , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa , MutaciónRESUMEN
OBJECTIVE: The objective is to describe the main characteristics of patients with systemic lupus erythematosus (SLE) in Argentina and to examine the influence of ethnicity on the expression of the disease. PATIENTS AND METHODS: RELESSAR is a multicentre register carried out by 106 researchers from 67 rheumatologic Argentine centres. It is a cross-sectional study of SLE (1982/1997 ACR) patients. RELESSAR electronic database includes demographic, cumulative SLE manifestations, SELENA-SLEDAI, SLICC-SDI, Katz's severity and Charlson's comorbidity indexes and treatment patterns. RESULTS: We included 1,610 patients, 91.7% were female with a median age at diagnosis of 28.1 ± 12.8; 96.2% met ≥4 ACR 1982/97 criteria. Frequent manifestations were arthritis (83.5%), malar rash (79.5%), photosensitivity (75.3%), haematological (63.8%) and renal disease (47.4%), antinuclear antibodies (96%), anti-dsDNA (66.5%) and anti-Smith antibodies (29%). The mean Selena-SLEDAI score at last visit was 3.18 (SD 4.3) and mean SDI was 1 (SD 1.3). The accumulated treatments most frequently used were antimalarials (90.4%), corticosteroids (90%), azathioprine (31.8%), intravenous cyclophosphamide (30.2%), mycophenolate mofetil or mycophenolic acid (24.5%), methotrexate (19.3%), belimumab 5.3% and rituximab 5.1%. Refractory lupus was diagnosed in 9.3% of the cases. The main causes of death were lupus activity (25.0%), activity and concomitant infections (25.0%), infections (18.2%), vascular disease (13.6%) and cancer (4.5%). Mortality was associated with higher SLEDAI, Katz, damage indexes and comorbidities. Of the 1610 patients included, 44.6% were Caucasian, 44.5% Mestizo, 8.1% Amerindian and 1.2% Afro-Latin American. Mestizo patients had higher male representation, low socioeconomic status, more inadequate medical coverage, fewer formal years of education and shorter disease duration. Polyadenopathies and Raynaud's phenomenon were more frequent in Caucasians. In the logistic regression analysis higher damage index (OR 1.28, CI 95% 1.02-1.61, p = 0.03) remained associated to mestizo ethnicity. CONCLUSIONS: This study represents the largest number of adult patients with SLE studied in Argentina. Caucasian patients were differentiated by having Raynaud's phenomenon and polyadenopathy more frequently, while patients of Mestizo origin had higher damage indexes.
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Etnicidad , Lupus Eritematoso Sistémico , Argentina/epidemiología , Estudios Transversales , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Masculino , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.
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Enfermedades del Sistema Digestivo/etiología , Lupus Eritematoso Sistémico/complicaciones , Sistema de Registros , Adulto , Comorbilidad , Enfermedades del Sistema Digestivo/epidemiología , Femenino , Humanos , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Array-based comparative genomic hybridization (aCGH) is a molecular analysis method for identifying chromosomal anomalies or copy number variants (CNVs) correlating with clinical phenotypes. The aim of our study was to identify the most significant clinical variables associated with a positive outcome of aCGH analyses to develop a simple predictive clinical score. METHODS: We conducted a cross-sectional study in a tertiary center comparing the genotype and phenotype of the cases. A score was developed using multivariate logistic regression. The best score cutoff point, sensitivity, specificity, positive and negative predictive values, and area under the curve were calculated with the receiver operating characteristic curve. RESULTS: aCGH identified structural chromosomal alterations responsible for the disorder in 13.7% (95% confidence interval [CI]: 10.9-16.5) of our sample (570 patients analyzed by aCGH). Based on the most frequent phenotypic characteristics among patients with a pathogenic CNV, we have created a checklist with the following items: alteration of the cranial perimeter, stature < percentile (p) 3, weight < p3, presence of brain malformations, ophthalmological malformations, two or more dysmorphic features in the same patient, and autism spectrum disorder diagnosis. Using a score ≥1.5 as the cutoff point for the test, we obtained a sensitivity of 82.4% (95% CI: 73.1-91.8) and a specificity of 54.2% (95% CI: 49.7-58.7). CONCLUSION: All individuals with a score of 1.5 or higher should be genetically screened by aCGH. This approach can improve clinical indications for aCGH in patients with neurodevelopmental disorders, but the scoring system should be validated in an external group.
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Lista de Verificación/métodos , Hibridación Genómica Comparativa/métodos , Secuenciación del Exoma/métodos , Pruebas Genéticas/métodos , Trastornos del Neurodesarrollo/genética , Lista de Verificación/normas , Niño , Preescolar , Hibridación Genómica Comparativa/normas , Estudios Transversales , Femenino , Pruebas Genéticas/normas , Humanos , Masculino , Trastornos del Neurodesarrollo/diagnóstico , Reproducibilidad de los Resultados , Secuenciación del Exoma/normasRESUMEN
BACKGROUND: To infer a reliable SARS-CoV-2 antibody protection level from a serological test, an appropriate quantitative threshold and solid equivalence across serological tests are needed. Additionally, tests should show a solid correlation with neutralising assays and with the protection observed in large population cohorts even against emerging variants. OBJECTIVES: We studied convalescent and vaccinated populations using 11 commercial antibody assays. Results were compared to evaluate discrepancies across tests. Neutralisation capacity was measured in a subset of the samples with a lentiviral-based assay. METHODS: Serum from convalescent (n = 121) and vaccinated individuals (n = 471, 260 with Comirnaty, 110 with Spikevax, and 96 with Vaxzevria) was assessed using 11 different assays, including two from Abbott, Euroimmun, Liaison, Roche, and Vircell, and one from Siemens. A spike protein-lentiviral vector with a fluorescent reporter was used for neutralisation assay of serum from convalescent (n = 26) and vaccinated (n = 39) individuals. RESULTS: Positivity ranged between 81.3 and 94.3% after infection and 99.4 and 99.7% after vaccination, depending on the assay. Both cohorts showed a high level of qualitative agreement across tests (Fleiss' kappa = 0.598 and 0.719 for convalescent and vaccinated respectively). Spikevax vaccine recipients showed the highest level of antibodies in all tests. Effectiveness of each test predicting SARS-CoV-2 neutralising capacity depended on assay type and target, with CLIA and anti-S being more effective than ELISA and anti-N assays, respectively. CONCLUSIONS: High-throughput immunoassays are good predictors of neutralising capacity. Updated targets and better standardisation would be required to find an effective correlate of protection, especially to account for antibodies against new variants.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been and remains one of the major challenges modern society has faced thus far. Over the past few months, large amounts of information have been collected that are only now beginning to be assimilated. In the present work, the existence of residual information in the massive numbers of rRT-PCRs that tested positive out of the almost half a million tests that were performed during the pandemic is investigated. This residual information is believed to be highly related to a pattern in the number of cycles that are necessary to detect positive samples as such. Thus, a database of more than 20,000 positive samples was collected, and two supervised classification algorithms (a support vector machine and a neural network) were trained to temporally locate each sample based solely and exclusively on the number of cycles determined in the rRT-PCR of each individual. Overall, this study suggests that there is valuable residual information in the rRT-PCR positive samples that can be used to identify patterns in the development of the SARS-CoV-2 pandemic. The successful application of supervised classification algorithms to detect these patterns demonstrates the potential of machine learning techniques to aid in understanding the spread of the virus and its variants.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Algoritmos , Aprendizaje Automático , Prueba de COVID-19RESUMEN
OBJECTIVES: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. RESULTS: A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3â¯vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival. CONCLUSION: The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates.
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Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Reumatología , Humanos , Estudios Retrospectivos , Lupus Eritematoso Sistémico/epidemiología , Vasculitis por Lupus del Sistema Nervioso Central/complicaciones , Vasculitis por Lupus del Sistema Nervioso Central/epidemiología , Vasculitis por Lupus del Sistema Nervioso Central/psicología , Sistema Nervioso CentralRESUMEN
OBJECTIVE: Lipid abnormalities contribute to the increased risk of premature atherosclerosis in patients with SLE. This study was undertaken to investigate changes in lipid profile after B-cell depletion therapy (BCDT) in patients with active SLE who had failed standard immunosuppressive therapy. METHODS: Twelve patients with refractory SLE treated with BCDT based on rituximab (two biweekly infusions of 1 g) were examined. Lipid profile and lupus activity were measured before the infusions and 1 year later. The control group consisted of 26 age- and sex-matched lupus patients not treated with BCDT. RESULTS: In the study group, the mean levels of total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterols were 4.6, 1.4 and 2.4 mmol/l at baseline and changed to 4.1, 1.6 and 2.0 mmol/l (P = NS, P = 0.04 and P = NS) at 1 year, respectively. The atherogenic index was 3.8 at baseline and decreased to 2.7 (P = 0.02). The triglyceride (TG) level was 2.1 mmol/l at baseline and decreased to 1.3 mmol/l (P = 0.04). BCDT was followed by a significant decrease in global BILAG scores and a drop in the mean dose of prednisolone at 1 year (P = 0.01). Reduction in disease activity was significantly associated with a reduction in total cholesterol and TG levels and an increase in HDL cholesterol levels. In the control group, there were no differences in any of the lipid determinations over a 1-year period. CONCLUSION. This provisional observational study suggests a favourable long-term effect of BCDT on the lipid profile of patients with refractory SLE, which correlated with decreasing activity of the disease.
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Antirreumáticos/uso terapéutico , Aterosclerosis/terapia , Linfocitos B/inmunología , Lípidos/sangre , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/terapia , Depleción Linfocítica/métodos , Adulto , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Estadística como Asunto , Tiempo , Adulto JovenRESUMEN
AIMS: To evaluate the role of human leukocyte antigen (HLA) class II DQB1*0201 and DQA1*0102 in the risk of antituberculosis drug (ATD)-induced hepatotoxicity (ATDH) in a cohort of tuberculosis patients of Caucasian origin from Spain. METHODS: Matched case-control study including active tuberculosis (TB) patients from Spain (Caucasian) treated with first-line ATD (Isoniazid, Rifampin, and Pyrazinamide). Presence or absence of HLA class II DQB1*0201 and DQA1*0102 alleles were compared between cases and controls. RESULTS: We included 110 TB patients, 55 ATDH cases, and 55 sex-matched controls. The analysis of the presence of HLA-DQB1*0201 and HLA-DQA*0102 did not show significative differences between both groups [presence of HLA-DQB1*0201 53.6% of the cases vs. 45.4% of the controls, OR: 1.63 95% CI (0.62-4.52) p = 0.38; presence of HLA-DQA*0102 7.5% of cases vs. 20% of controls, OR: 0.36 95% CI (0.08-1.23) p = 0.12]. After multivariate logistic regression analysis including in the model, other potential risk factors of hepatotoxicity HLA class II DQB1*0201 and DQA1*0102 alleles were not found significantly associated with the risk of development ATDH. We could not demonstrate an association between HLA-DQA1*0102 and HLA-DQB1*0201 with the risk of ATDH in this Caucasian population of Spanish origin.
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Respiratory protection is a factor which worries nursing professionals who take care of patients susceptible of transmitting microorganisms through the air more as every day passes. This type of protection covers the use of surgical or hygienic masks against the transmission of infection by airborne drops to the use of highly effective masks or respirators against the transmission of airborne diseases such as tuberculosis or SARS, a recently discovered disease. The adequate choice of this protective device and its correct use are fundamental in order to have an effective protection for exposed personnel. The authors summarize the main protective respiratory devices used by health workers, their characteristics and degree of effectiveness, as well as the circumstances under which each device is indicated for use.
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Microbiología del Aire , Personal de Salud , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Enfermería , Dispositivos de Protección Respiratoria , Diseño de Equipo , HumanosRESUMEN
Lung adenocarcinoma is one of the most frequent causes of malignant pleural effusions (MPE). The presence of MPE bears a poor prognosis. Although epigenetic changes are commonly related to human neoplasia, scarce date is available on patients with MPE. We aimed to estimate the prognostic value of DNA methylation of tumor suppressor genes from pleural fluid. Thirty patients with MPE due to lung adenocarcinoma were prospectively included. Methylation-specific (MS) PCR was used to study the methylation status of the promoter region of tumor suppressor genes p16/INK4a, MGMT, BRCA1 and RARß in pleural fluid. Clinical data and survival were collected. Survival analysis was performed using Kaplan-Meier plots and Cox regression. Hypermethylation in at least one gene was detected in 25 patients (83.3%). On multivariate analysis factors significantly associated with shorter survival were the lack of hypermethylation in any of the studied genes (hazard ratio = 9.3; p = 0.001), Charlson index ≥ 3 (hazard ratio = 9.6, p = 0.002) and no oncological treatment (hazard ratio = 11.1; p < 0.001). Analysis of aberrant promoter hypermethylation of tumor suppressor genes may be useful in predicting prognosis, but further studies are needed to validate our findings.
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Adenocarcinoma/genética , Metilación de ADN/genética , Genes Supresores de Tumor , Neoplasias Pulmonares/genética , Derrame Pleural Maligno/genética , Adenocarcinoma/mortalidad , Adenocarcinoma del Pulmón , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Genes p16 , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Derrame Pleural Maligno/mortalidad , Pronóstico , Regiones Promotoras Genéticas , Estudios Prospectivos , Receptores de Ácido Retinoico/genética , Análisis de Supervivencia , Proteínas Supresoras de Tumor/genéticaRESUMEN
UNLABELLED: Transbronchial needle aspiration (TBNA) of pulmonary lesions without endobronchial affectation in combination with transbronchial biopsy (TBB) has been shown to increase diagnostic performance. The objective of this present study was to analyze whether the combination of TBNA with conventional TBB is a cost-effective approach. METHODOLOGY: Ours is a prospective study that included patients with lung nodules or masses with no evidence of endobronchial lesions after flexible bronchoscopy in whom both TBNA and TBB were performed. We analyzed the additional diagnostic value, the impact of TBNA on the cost of the diagnosis and the minimum level of sensitivity required in order for TBNA combined with TBB to be considered a cost-effective diagnostic approach. RESULTS: Thirty-six patients were included in the study, 25 of whom were males. TBB reached a histologic diagnosis in 39% of the cases, and its combination with TBNA diagnosed 47%. The mean diameter of the lesions was significantly greater in the positive TBNA cases compared with the negative cases (31 vs. 23mm; p=0,034). The cost analysis did not show the additional TBNA to be more cost-effective, despite demonstrating greater diagnostic sensitivity. The minimum sensitivity required for TBNA combined with TBB to be considered a cost-effective approach was 88%. CONCLUSION: The contribution of TBNA to TBB in the diagnosis of lung nodules or masses without associated endobronchial lesions does not seem to justify the additional economic cost.
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Biopsia con Aguja/economía , Biopsia con Aguja/métodos , Neoplasias Pulmonares/economía , Neoplasias Pulmonares/patología , Anciano , Bronquios , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: To evaluate the diagnostic efficacy of pleural procedures, safety, delay and cost of the diagnosis of pleural effusion (PE) by analysing the parameters that are dependent on the area of patient management (outpatient or inpatient). PATIENTS AND METHODS: Prospective non-randomized study. Two groups were established depending on whether they were managed in a specific outpatient unit or as a conventional hospital inpatient, with the rest of the criteria being the same for the study of the PE. RESULTS: We included 60 outpatients and 34 inpatients. The median number of visits as an outpatient was 2 (range 2-3), and the time an inpatient was hospitalized was 13 (range 7.7-25-2) days. The number of analytical and imaging studies was significantly higher in the inpatient group. There were no differences in the number of cytology and pleural biopsies, or complications between groups. There were no differences in time to performing computed tomography. The number of days until the pleural biopsy and the time until to obtain a diagnosis was lower in the outpatient group. Mean total cost for an outpatient was euro1.352 and euro9.793,2 for inpatients. CONCLUSIONS: Management of ambulatory diagnosis of PE patients is highly cost-effective. The effectiveness and safety of forms of the study is at least similar. In this study, the mean cost for a hospitalised inpatient for a PE was 7.2 times higher than outpatient management.
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Derrame Pleural/diagnóstico , Derrame Pleural/economía , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVES: To evaluate the agreement and the association with FEV(1), FEV(6) and FEV(1)/FEV(6) measured with the Vitalograph-COPD-6 portable device and the FEV(1), FVC and FEV(1)/FVC by conventional spirometry, and to analyse the validity of this device to detect obstruction. METHODOLOGY: A cross-sectional, descriptive, prospective study, that included 180 subjects. A conventional spirometry and one with the Vitalograph-COPD-6 were sequentially performed on them. The agreement was analysed [kappa index and interclass correlation coefficient (ICC)], as well as the association [Pearson correlation coefficient (r)], area under the ROC curve (AUC) of the FEV(1)/FEV(6) in detecting obstruction, and the sensitivity, specificity, predictive values (PPV and NPV), and probability ratios (PR+ and PR-) of the different FEV(1)/FEV(6) cut-off points in the detection of obstruction. RESULTS: The prevalence of obstruction was 47%. The kappa index was 0.59 when an FEV(1)/FEV(6) < cut-off point of <0.7 was used. The ICC and the r between the FEV(1) measured by the two instruments, FEV(6) and FEV(1)/FEV(6) measured by the Vitalograph-COPD-6 and the FVC and FEV(1)/FVC determined by the spirometer were all greater than 0.92. The ROC AUC was 0.97. To detect obstruction, if the cut-off point of FEV(1)/FEV(6) (for COPD-6) was <0.70, the sensitivity, specificity, PPV, NPV, CR+ and CR- were, 58%, 100%, 100%, 73%, infinity and 0.42, respectively. For a cut-off point of <0.8, they were 96%, 76%, 78%, 96%, 3.8 and 0.05, respectively. CONCLUSIONS: The portable Vitalograph-COPD6 device is precise for the detection of airway obstruction. The best sensitivity/specificity of FEV(1)/FEV(6) was obtained with cut-off points greater than 0.7.
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Enfermedades Pulmonares Obstructivas/diagnóstico , Enfermedades Pulmonares Obstructivas/fisiopatología , Estudios Transversales , Diseño de Equipo , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función Respiratoria/instrumentación , Sensibilidad y Especificidad , EspirometríaRESUMEN
INTRODUCTION: Hartmann's operation has occasionally been criticised for its high morbidity-mortality and permanent stomas. To compare risk factors is difficult due to different severity scores for diverticulitis with no standardisation. We attempted to define the morbidity-mortality of Hartmann's operation for sigmoid diverticulitis with peritonitis Hinchey III-IV and to identify some factors associated with morbidity-mortality and non-restoration of intestinal continuity. PATIENTS AND METHOD: Retrospective analysis of 72 patients: age, gender, ASA score, length of time between symptoms and surgery, Hinchey's score, Mannheim index, preoperative creatinine and co-morbidities. RESULTS: Hinchey's score III, 75%. Male, 35. Median age, 66.5 years. Morbidity-mortality: 48.6% and 23.6%, respectively. ASA > 2 (p = 0.03) and age > 65 years (p = 0.03) in bivariate analysis; and ASA > 2 (p = 0.002) and a history of ischaemic cardiac disease (p = 0.04) in multivariate analysis were associated with postoperative complications. In bivariate analysis mortality was associated with ASA > 2 (p = 0.02), age > 65 years (p = 0.02), chronic obstructive pulmonary disease (p = 0.001), Mannhein index >or= 25 (p = 0.01) and pulmonary postoperative complications (p = 0.003). Multivariate analyses were statistical significant: chronic obstructive pulmonary disease (p = 0.001) and postoperative respiratory infection (p = 0.02). Fifty-five patients survived and 65.5% continued to restoration of intestinal continuity. Age > 65 years (p = 0.004) and ASA score > 2 at first operation (p = 0.004) were predictive for non-reversal of Hartmann's procedure. CONCLUSIONS: Hartmann's operation is highly associated with morbidity-mortality in severe peritonitis of sigmoid diverticular origin, Hinchey III-IV. The majority of patients have severe co-morbidities and high-grade risk factors which are related to the incidence of morbidity and mortality.