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Research question: Can smartphones be used to detect individual and population-level changes in cough frequency that correlate with the incidence of coronavirus disease 2019 (COVID-19) and other respiratory infections? Methods: This was a prospective cohort study carried out in Pamplona (Spain) between 2020 and 2021 using artificial intelligence cough detection software. Changes in cough frequency around the time of medical consultation were evaluated using a randomisation routine; significance was tested by comparing the distribution of cough frequencies to that obtained from a model of no difference. The correlation between changes of cough frequency and COVID-19 incidence was studied using an autoregressive moving average analysis, and its strength determined by calculating its autocorrelation function (ACF). Predictors for the regular use of the system were studied using a linear regression. Overall user experience was evaluated using a satisfaction questionnaire and through focused group discussions. Results: We followed-up 616 participants and collected >62 000 coughs. Coughs per hour surged around the time cohort subjects sought medical care (difference +0.77â coughs·h-1; p=0.00001). There was a weak temporal correlation between aggregated coughs and the incidence of COVID-19 in the local population (ACF 0.43). Technical issues affected uptake and regular use of the system. Interpretation: Artificial intelligence systems can detect changes in cough frequency that temporarily correlate with the onset of clinical disease at the individual level. A clearer correlation with population-level COVID-19 incidence, or other respiratory conditions, could be achieved with better penetration and compliance with cough monitoring.
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Research question: What is the impact of the duration of cough monitoring on its accuracy in detecting changes in the cough frequency? Materials and methods: This is a statistical analysis of a prospective cohort study. Participants were recruited in the city of Pamplona (Northern Spain), and their cough frequency was passively monitored using smartphone-based acoustic artificial intelligence software. Differences in cough frequency were compared using a one-tailed Mann-Whitney U test and a randomisation routine to simulate 24-h monitoring. Results: 616 participants were monitored for an aggregated duration of over 9â person-years and registered 62 325 coughs. This empiric analysis found that an individual's cough patterns are stochastic, following a binomial distribution. When compared to continuous monitoring, limiting observation to 24â h can lead to inaccurate estimates of change in cough frequency, particularly in persons with low or small changes in rate. Interpretation: Detecting changes in an individual's rate of coughing is complicated by significant stochastic variability within and between days. Assessing change based solely on intermittent sampling, including 24-h, can be misleading. This is particularly problematic in detecting small changes in individuals who have a low rate and/or high variance in cough pattern.
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BACKGROUND: Fifty-three percent of all cases of malaria in the Americas in 2019 came from Venezuela, where the epidemic is heavily focused south of the Orinoco river, and where most of the country's Amerindian groups live. Although the disease is known to represent a significant public health problem among these populations, little epidemiological data exists on the subject. This study aims to provide information on malaria incidence, geospatial clustering, and risk factors associated to Plasmodium falciparum infection among these groups. METHODS: This is a descriptive study based on the analysis of published and unpublished programmatic data collected by Venezuelan health authorities and non-government organizations between 2014 and 2018. The Annual Parasite Index among indigenous groups (API-i) in municipalities of three states (Amazonas, Bolivar, and Sucre) were calculated and compared using the Kruskal Wallis test, risk factors for Plasmodium falciparum infection were identified via binomial logistic regression and maps were constructed to identify clusters of malaria cases among indigenous patients via Moran's I and Getis-Ord's hot spot analysis. RESULTS: 116,097 cases of malaria in Amerindian groups were registered during the study period. An increasing trend was observed between 2014 and 2016 but reverted in 2018. Malaria incidence remains higher than in 2014 and hot spots were identified in the three states, although more importantly in the south of Bolivar. Most cases (73.3%) were caused by Plasmodium vivax, but the Hoti, Yanomami, and Eñepa indigenous groups presented higher odds for infection with Plasmodium falciparum. CONCLUSION: Malaria cases among Amerindian populations increased between 2014 and 2018 and seem to have a different geographic distribution than those among the general population. These findings suggest that tailored interventions will be necessary to curb the impact of malaria transmission in these groups.
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Malária Falciparum/epidemiologia , Plasmodium falciparum/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Incidência , Indígenas Sul-Americanos , Lactente , Recém-Nascido , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise Espacial , Venezuela/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Tracheostomy is one of the most frequent techniques in intensive care units (ICU). Fiberoptic bronchoscopy (FB) is a safety measure when performing a percutaneous dilatational tracheostomy (PDT), but the controversy surrounding the routine use of FB as part of the procedure remains open. National surveys in some European countries showed that the use of FB is non-standardized. Retrospective studies have not shown a significant difference in complications between procedures performed with or without a bronchoscope. International guidelines have not been able to establish recommendations regarding the use of FB in PDT due to lack of evidence. DESIGN: This is a multicenter (three centers at the time of publishing this paper) randomized controlled clinical trial to examine the safety of percutaneous tracheostomy using FB. We will include all consecutive adult patients admitted to the ICU in whom percutaneous tracheostomy for prolonged mechanical ventilation is indicated and with no exclusion criteria for using FB. Eligible patients will be randomly assigned to receive blind PDT or PDT under endoscopic guidance. All procedures will be performed by experienced intensivists in PDT and FB. A Data Safety and Monitoring Board (DSMB) will monitor the trial. The primary outcome is the incidence of perioperative complications. DISCUSSION: FB is a safe technique when performing PDT although its use is not universally accepted in all ICUs as a routine practice. Should PDT be monitored routinely with endoscopic guidance? This study will assess the role of FB monitoring during PDT. TRIAL REGISTRATION: ClinicalTrials.gov NCT04265625. Registered on February 11, 2020.
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Broncoscopia , Traqueostomia , Adulto , Broncoscopia/efeitos adversos , Dilatação/efeitos adversos , Europa (Continente) , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Traqueostomia/efeitos adversosAssuntos
Miíase/diagnóstico , Animais , Criança , Dípteros/anatomia & histologia , Feminino , HumanosRESUMO
BACKGROUND: Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. METHODS: Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. FINDINGS: All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). INTERPRETATION: Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. FUNDING: ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra.
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The pharmacological properties of melatonin are well known. However, there is noticeable the lack of clinical trials that confirm the efficacy, security, absence of side effects in the short and long term, and the effective doses of melatonin. This point is especially important in diseases with high morbidity and mortality including COVID-19. There is not treatment for COVID-19, and several anti-inflammatory and antiviral molecules are being tested, and different vaccines are in preparation. Although the SARS-CoV-2 pandemic is apparently improving, it is expected new resurges next fall. Thus, looking for an effective treatment of COVID-19 is mandatory. Melatonin has significant anti-inflammatory, antioxidant, and mitochondrial protective effects, and its efficacy has been demonstrated in multiple experimental models of disease and in a clinical trial in sepsis. Because COVID-19 courses with a severe septic response, multiple reviews proposing melatonin as a treatment for COVID-19 have been published. Nevertheless, there is a lack of experimental and clinical data on the use of melatonin on SARS-CoV-2 infection. Accordingly, we designed a clinical trial with an injectable formulation of melatonin for intravenous perfusion in ICU patients suffering from COVID-19 that has been just approved by the Spanish Agency of Medicines and Medical Devices (AEMPS). The trial will allow by the first time understand the doses and efficacy of melatonin against COVID-19.
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Antioxidantes/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Melatonina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , COVID-19 , Humanos , Infusões Intravenosas , Pandemias , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Malaria is expanding rapidly across Venezuela, spreading outwards from traditional high transmission regions in the southeast of the country, but the lack of official data make it impossible to understand the reasons for this expansion and to estimate its real magnitude. This study aims to evaluate the epidemiological characteristics driving the re-emergence of malaria in Mérida, a state in the west of Venezuela, where no cases have been reported since 2003, and also to study the clinical presentation of the disease in patients presenting with malaria. METHODS: Thirty-three patients who presented with anemia and fever and with a microscopic diagnosis of malaria were examined and interviewed. Data were collected in standardized forms and analyzed. One-way analysis of variance was used to study differences among patients infected with different parasites. RESULTS: Twenty-two patients were from the Zulia state and eleven were from the Mérida state, mainly from the lowlands south of Lake Maracaibo. Six of these patients traveled to the Bolívar state between 2017 and 2019. Thirteen patients presented with the WHO criteria for severe malaria.Conclusions:Domestic migration to the southeast of Venezuela may have played an important role in the expansion of malaria in previously existing endemic areas of transmission and also in the increase in the number of cases of severe malaria.
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Hospitalização , Malária , Hospitais , Humanos , Malária/epidemiologia , Viagem , Venezuela/epidemiologiaRESUMO
Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, viral, tickborne disease. In Europe, cases have been reported only in the southeastern part of the continent. We report two autochthonous cases in Spain. The index patient acquired the disease through a tick bite in the province of Ávila - 300 km away from the province of Cáceres, where viral RNA from ticks was amplified in 2010. The second patient was a nurse who became infected while caring for the index patient. Both were infected with the African 3 lineage of this virus. (Funded by Red de Investigación Cooperativa en Enfermedades Tropicales [RICET] and Efficient Response to Highly Dangerous and Emerging Pathogens at EU [European Union] Level [EMERGE].).
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Vírus da Febre Hemorrágica da Crimeia-Congo/isolamento & purificação , Febre Hemorrágica da Crimeia , Colo/patologia , Busca de Comunicante , Evolução Fatal , Feminino , Vírus da Febre Hemorrágica da Crimeia-Congo/classificação , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Febre Hemorrágica da Crimeia/patologia , Febre Hemorrágica da Crimeia/transmissão , Febre Hemorrágica da Crimeia/virologia , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Reação em Cadeia da Polimerase , EspanhaRESUMO
BACKGROUND: In the current epidemic of Ebola virus disease, health-care workers have been transferred to Europe and the USA for optimised supportive care and experimental treatments. We describe the clinical course of the first case of Ebola virus disease contracted outside of Africa, in Madrid, Spain. METHODS: Herein we report clinical, laboratory, and virological findings of the treatment of a female nurse assistant aged 44 years who was infected with Ebola virus around Sept 25-26, 2014, while caring for a Spanish missionary with confirmed Ebola virus disease who had been medically evacuated from Sierra Leone to La Paz-Carlos III University Hospital, Madrid. We also describe the use of experimental treatments for Ebola virus disease in this patient. FINDINGS: The patient was symptomatic for 1 week before first hospital admission on Oct 6, 2014. We used supportive treatment with intravenous fluids, broad-spectrum antibiotics, and experimental treatments with convalescent plasma from two survivors of Ebola virus disease and high-dose favipiravir. On day 10 of illness, she had acute respiratory distress syndrome, possibly caused by transfusion-related acute lung injury, which was managed without mechanical ventilation. Discharge was delayed because of the detection of viral RNA in several bodily fluids despite clearance of viraemia. The patient was discharged on day 34 of illness. At the time of discharge, the patient had possible subacute post-viral thyroiditis. None of the people who had contact with the patient before and after admission became infected with Ebola virus. INTERPRETATION: This report emphasises the uncertainties about the efficacy of experimental treatments for Ebola virus disease. Clinicians should be aware of the possibility of transfusion-related acute lung injury when using convalescent plasma for the treatment of Ebola virus disease. FUNDING: La Paz-Carlos III University Hospital.
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Doença pelo Vírus Ebola/terapia , Assistentes de Enfermagem , Doenças Profissionais/etiologia , Plasma , Síndrome do Desconforto Respiratório/etiologia , Lesão Pulmonar Aguda/etiologia , Adulto , Amidas/uso terapêutico , Antivirais/uso terapêutico , Feminino , Humanos , Doenças Profissionais/terapia , Isolamento de Pacientes , Pirazinas/uso terapêutico , Síndrome do Desconforto Respiratório/terapia , Espanha , Superinfecção/etiologia , Reação Transfusional , Carga ViralRESUMO
OBJECTIVES: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A (2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between the timing of antiviral administration and intensive care unit (ICU) outcomes. METHODS: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection. Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint. Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality. RESULTS: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients required mechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy and were included in the study group. All patients received oseltamivir for a median duration of 10 days (interquartile range 8-14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groups were comparable in terms of main clinical variables. ICU length of stay (22.7â±â16.7 versus 18.4â±â14.2 days; Pâ=â0.03), hospital length of stay (34.0â±â20.3 versus 27.2â±â18.2 days; Pâ=â0.001) and MV days (17.4â±â15.2 versus 14.0â±â12.4; Pâ=â0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than in ET (21.5%; ORâ=â1.9; 95% CI 1.06-3.41). A multivariate model identified ET (ORâ=â0.44; 95% CI 0.21-0.87) as an independent variable associated with reduced ICU mortality. These results were confirmed by propensity score analysis (ORâ=â0.44; 95% CI 0.22-0.90; Pâ<â0.001). CONCLUSIONS: Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.