RESUMO
(1) Background: COVID-19 has evolved during seven epidemic waves in Spain. Our objective was to describe changes in mortality and severity in our hospitalized patients. (2) Method: This study employed a descriptive, retrospective approach for COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) until 31 December 2022. (3) Results: A total of 5510 admissions for COVID-19 were recorded. The first wave accounted for 1823 (33%) admissions and exhibited the highest proportion of severe patients: 65% with bilateral pneumonia and 83% with oxygen saturation under 94% during admission and elevated levels of CRP, IL-6, and D-dimer. In contrast, the seventh wave had the highest median age (79 years) and comorbidity (Charlson: 2.7), while only 3% of patients had bilateral pneumonia and 3% required intubation. The overall mortality rate was 10.3%. The first wave represented 39% of the total. The variables related to mortality were age (OR: 1.08, 1.07-1.09), cancer (OR: 1.99, 1.53-2.60), dementia (OR: 1.82, 1.20-2.75), the Charlson index (1.38, 1.31-1.47), the need for high-flow oxygen (OR: 6.10, 4.94-7.52), mechanical ventilation (OR: 11.554, 6.996-19.080), and CRP (OR: 1.04, 1.03-1.06). (4) Conclusions: The variables associated with mortality included age, comorbidity, respiratory failure, and inflammation. Differences in the baseline characteristics of admitted patients explained the differences in mortality in each wave. Differences observed between patients admitted in the latest wave and the earlier ones suggest that COVID-19 has evolved into a distinct disease, requiring a distinct approach.
Assuntos
COVID-19 , Epidemias , Humanos , Idoso , COVID-19/epidemiologia , Estudos Retrospectivos , Hospitais , HospitalizaçãoRESUMO
Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.
Assuntos
COVID-19 , Adulto , Humanos , Mesilato de Imatinib , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Resultado do TratamentoRESUMO
Coronavirus disease 2019 (COVID-19) infection in elderly patients is more aggressive and treatments have shown limited efficacy. Our objective is to describe the clinical course and to analyze the prognostic factors associated with a higher risk of mortality of a cohort of patients older than 80 years. In addition, we assess the efficacy of immunosuppressive treatments in this population. We analyzed the data from 163 patients older than 80 years admitted to our institution for COVID-19, during March and April 2020. A Lasso regression model and subsequent multivariate Cox regression were performed to select variables predictive of death. We evaluated the efficacy of immunomodulatory therapy in three cohorts using adjusted survival analysis. The mortality rate was 43%. The mean age was 85.2 years. The disease was considered severe in 76.1% of the cases. Lasso regression and multivariate Cox regression indicated that factors correlated with hospital mortality were: age (hazard ratio [HR] 1.12, 95% confidence interval [CI]: 1.03-1.22), alcohol consumption (HR 3.15, 95% CI: 1.27-7.84), CRP > 10 mg/dL (HR 2.67, 95% CI: 1.36-5.24), and oxygen support with Venturi Mask (HR 6.37, 95% CI: 2.18-18.62) or reservoir (HR 7.87, 95% CI: 3.37-18.38). Previous treatment with antiplatelets was the only protective factor (HR 0.47, 95% CI: 0.23-0.96). In the adjusted treatment efficacy analysis, we found benefit in the combined use of tocilizumab (TCZ) and corticosteroids (CS) (HR 0.09, 95% CI: 0.01-0.74) compared to standard treatment, with no benefit of CS alone (HR 0.95, 95% CI: 0.53-1.71). Hospitalized elderly patients suffer from a severe and often fatal form of COVID-19 disease. In this regard, several parameters might identify high-risk patients upon admission. Combined use of TCZ and CS could improve survival.
Assuntos
Corticosteroides/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Tratamento Farmacológico da COVID-19 , COVID-19/mortalidade , Idoso de 80 Anos ou mais , COVID-19/virologia , Comorbidade , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Espanha/epidemiologia , Análise de SobrevidaRESUMO
The pharmacological inhibition of soluble epoxide hydrolase (sEH) has been suggested as a potential therapy for the treatment of pain and inflammatory diseases through the stabilization of endogenous epoxyeicosatrienoic acids. Numerous potent sEH inhibitors (sEHI) have been developed, however many contain highly lipophilic substituents limiting their availability. Recently, a new series of benzohomoadamantane-based ureas endowed with potent inhibitory activity for the human and murine sEH was reported. However, their very low microsomal stability prevented further development. Herein, a new series of benzohomoadamantane-based amides were synthetized, fully characterized, and evaluated as sEHI. Most of these amides were endowed with excellent inhibitory potencies. A selected compound displayed anti-inflammatory effects with higher effectiveness than the reference sEHI, TPPU.
Assuntos
COVID-19 , Amidas , Humanos , Mesilato de Imatinib/uso terapêutico , Pirazinas , SARS-CoV-2 , Resultado do TratamentoAssuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Pulmão/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19 , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Ritonavir/administração & dosagem , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Visceral Leishmaniasis (VL) is a serious protozoal disease endemic in diverse areas, including the southern area of Madrid (Spain), where an outbreak was detected in 2009. The objective of this work is to analyze bone marrow alterations in VL patients and elaborate a diagnostic model with the aim to improve the early detection of this disease. The usual diagnostic methods, as the observation of the parasite on a bone marrow aspirate, have frequent false negatives, and the high sensitivity methods, as PCR and ELISA, are delayed or are not always available. METHODS: This observational study evaluated bone marrow parameters of adult patients with clinical suspicion of VL, in which a bone marrow aspiration was performed but Leishmania was not directly observed, during the period 2009-2014. The patients finally diagnosed of VL by other methods (VL group, n=41), and the patients in which the VL was not diagnosed (non-VL group, n=20) were compared. A multivariant model was elaborated and externally validated. RESULTS: The final multivariant model includes percentage of myeloid series, percentage of plasma cells and quantification of megakaryocytes in the bone marrow, with an area under the ROC curve of 0.87 (0.78-0.96). The model performed well in the external validation. CONCLUSION: In cases of VL suspicion and when the parasite is not observed in the bone marrow aspiration, the proposed model could be useful in discriminating between patients with and without VL, allowing to take a therapeutic decision while awaiting the definitive diagnosis.
Assuntos
Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/parasitologia , Exame de Medula Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Adulto JovemRESUMO
OBJECTIVE: The objective of this study was to predict the diagnosis of bacteraemia as a function of the time at which the automated BacT/Alert system continuously detects microorganism growth. METHODS: A retrospective study of a database of 1334 patients with a positive blood culture between January 2011 and June 2013 was conducted. Together with the final blood culture results and the patient's history, growth was then analysed to assess whether it represented true bacteraemia or bacterial contamination. The earliest detection times of bacterial growth in each batch of blood cultures were analysed in a blinded fashion after classification. RESULTS: In total, 590 batches of blood cultures corresponded to true bacteraemia and 744 to bacterial contamination. In the bacteraemia group, the median growth time was 12.72 h (interquartile range (IQR) 10.08-17.58 h). In the contaminated blood culture group, the median growth time was 20.6h (IQR 17.04-32.16 h) (p<0.001). Analysis of the receiver operating characteristics (ROC) curve (area under the curve 0.80, 95% confidence interval 0.771-0.826) showed that 90% of the contaminants grew after 14.7h (sensitivity 90.5%, specificity 63.4%, positive predictive value (PPV) 65.9%, negative predictive value (NPV) 90.7%). Forty-five percent of the bacteraemia organisms grew in under 12h (sensitivity 45.3%, specificity 95%, PPV 87.8%, NPV 68.7%). Microorganisms such as Candida sp and Bacteroides sp presented median growth times significantly longer than those of the other microorganisms. The administration of antibiotics in the week prior to bacteraemia was found to delay the growth time of microorganisms (p<0.001). CONCLUSIONS: Knowing the time to detection of microorganism growth can help to distinguish between true bacteraemia and bacterial contamination, thus allowing more timely clinical decisions to be made, before definitive microorganism identification.
Assuntos
Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Técnicas Bacteriológicas/métodos , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de TempoRESUMO
BACKGROUND: Arrival of inmigrants from malaria endemic areas has led to a emergence of cases of this parasitic disease in Spain. The objective of this study was to analyse the high incidence rate of imported malaria in Fuenlabrada, a city in the south of Madrid, together with the frequent the lack of chemoprophylaxis, for the period between 2004 and 2014. Both pregnant women and HIV risk groups have been considered. METHODS: Retrospective descriptive study of laboratory-confirmed malaria at the Fuenlabrada University Hospital, in Madrid, during a 10-year period (2004-2014). These data were obtained reviewing medical histories of the cases. Relevant epidemiological, clinical and laboratory results were analysed, with focus on the following risk groups: pregnant women and individuals with HIV. RESULTS: A total of 185 cases were diagnosed (90.3 % Plasmodium falciparum). The annual incidence rate was 11.9/100,000 inhabitants/year. The average age was 30.8 years (SD: 14.3). Infections originating in sub-Saharan Africa comprised the 97.6 % of the cases. A total of 85.9 % were Visiting Friends and Relatives. Only a 4.3 % completed adequate prophylaxis. A total of 14.28 % of the fertile women were pregnant, and 8 cases (4.3 %) had HIV. None of them in these special groups completed prophylaxis. CONCLUSIONS: The incidence rate in Fuenlabrada is higher than in the rest of Spain, due to the large number of immigrants from endemic areas living in the municipality. However, the results are not representative of all the country. It seems to be reasonable to implement prevention and pre-travel assessment programs to increase chemoprophylaxis. Pregnancy tests and HIV serology should be completed for all patients to improve prophylactic methods.