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1.
Lancet ; 395(10236): 1569-1578, 2020 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-32423584

RESUMO

BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.

2.
Trials ; 21(1): 422, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448345

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , China , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Infusões Intravenosas , Masculino , Estudos Multicêntricos como Assunto , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
3.
Artigo em Inglês | MEDLINE | ID: mdl-32385638

RESUMO

BACKGROUND: Brainstem auditory evoked potentials (BAEPs) have been widely monitored to prevent hearing loss (HL) during microvascular decompression (MVD) for hemifacial spasm (HFS); however, their predictive value is still unclear. The aim of this study is to investigate the predictive values of the maximum changes in BAEPs and define the best warning indicator and a cutoff value (CV) during HFS-MVD. METHODS: The clinical data of 93 HFS-MVD patients were retrospectively analysed. The maximum change rates of the latency and amplitude of waves I, III, and V and the interpeak latencies (IPLs) I-III, I-V, and III-V, when BAEPs change most during MVD, were defined. Pure tone audiometry was performed to evaluate hearing loss (HL). Logistic regression, propensity score, receiver operating curve (ROC), and area under the curve (AUC) were used to identify the predictive value of relevant indexes and to determine the CV (with the largest Youden index) of the best index at different levels of HL. RESULTS: The AUCs of BAEPs for predicting HL were 0.98, 0.92, and 0.84 for 50 dB, 30 dB, and 10 dB, respectively. The amplitude of wave V (AwV) was the best single predictive index at all three HL levels. The CV of AwV was 55% (50 dB), 46% (30 dB), and 34% (10 dB). At 50 dB HL, the predictive value of IPLs I-V (AUC 0.89 with CV 0.6 ms) was better than that of LwV (AUC 0.82 with CV 1 ms). CONCLUSION: BAEPs can predict HL well. AwV is the best single predictive index of all BAEPs. The reduction of AwV by 34% (watching), 46% (reporting), and 55% (warning) can be used as a sliding-scale warning sign. In addition, IPLs I-V (> 0.6 ms) and LwV (> 1 ms) should also be observed and reported during MVD.

5.
Lancet ; 395(10229): 1054-1062, 2020 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-32171076

RESUMO

BACKGROUND: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. METHODS: In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. FINDINGS: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 µg/mL (18·42, 2·64-128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. INTERPRETATION: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 µg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.


Assuntos
Infecções por Coronavirus/mortalidade , Escores de Disfunção Orgânica , Planejamento de Assistência ao Paciente , Pneumonia Viral/mortalidade , Medição de Risco , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Doenças Cardiovasculares/complicações , China , Técnicas de Laboratório Clínico , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Complicações do Diabetes , Progressão da Doença , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Pandemias , Isolamento de Pacientes , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Adulto Jovem
6.
N Engl J Med ; 382(19): 1787-1799, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32187464

RESUMO

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Betacoronavirus/genética , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Análise de Intenção de Tratamento , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Gravidade do Paciente , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ritonavir/efeitos adversos , Tempo para o Tratamento , Falha de Tratamento , Carga Viral
7.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32004165

RESUMO

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Assuntos
Betacoronavirus , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Adulto , Idoso , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/terapia , Tomografia por Raios X , Resultado do Tratamento
8.
Lancet ; 395(10223): 497-506, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31986264

RESUMO

BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. METHODS: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. FINDINGS: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. INTERPRETATION: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. FUNDING: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adulto , Distribuição por Idade , Idoso , China/epidemiologia , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/transmissão , Tosse/epidemiologia , Tosse/virologia , Feminino , Febre/epidemiologia , Febre/virologia , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Mialgia/epidemiologia , Mialgia/virologia , Pneumonia Viral/complicações , Pneumonia Viral/transmissão , Prognóstico , Radiografia Torácica , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/virologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Adulto Jovem
9.
J Infect Dis ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31822885

RESUMO

BACKGROUND: A synergistic effect of combination therapy with favipiravir and oseltamivir has been reported in pre-clinical models of influenza. However, no data are available on the clinical effectiveness of combination therapy in severe influenza. METHODS: Data from two separate prospective studies of influenza adults were used to compare outcomes between combination and oseltamivir monotherapy. Outcomes includes rate of clinical improvement, defined as a decrease of 2 categories on a 7-category ordinal scale, and viral RNA detectability over time. Sub-hazard ratio (sHR) was estimated by Fine and Gray model for competing risks. RESULTS: In total, 40 patients were treated with combination therapy and 128 with oseltamivir alone. Clinical improvement on Day 14 occurred in the combination group was higher than in monotherapy group (62.5% vs 42.2%, p=0.0247). The adjusted sHR for combination therapy was 2.06 (95%CI: 1.3-3.26). The proportion of undetectable viral RNA at day 10 was higher in the combination group than oseltamivir group (67.5% vs 21.9%, p<0.01). No significant differences were observed in mortality or other outcomes. CONCLUSIONS: Favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, and this strategy should be formally evaluated in a randomized controlled trial.

10.
BMC Pulm Med ; 19(1): 237, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818300

RESUMO

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in awake, spontaneously breathing and non-intubated patients (awake ECMO) may be a novel therapeutic strategy for severe acute respiratory distress syndrome (ARDS) patients. The purpose of this study is to assess the feasibility and safety of awake ECMO in severe ARDS patients receiving prolonged ECMO (> 14 days). METHODS: We describe our experience with 12 consecutive severe ARDS patients (age, 39.1 ± 16.4 years) supported with awake ECMO to wait for native lung recovery during prolonged ECMO treatment from July 2013 to January 2018. Outcomes are reported including the hospital mortality, ECMO-related complications and physiological data on weaning from invasive ventilation. RESULTS: The patients received median 26.0 (15.5, 64.8) days of total ECMO duration in the cohort. The longest ECMO support duration was 121 days. Awake ECMO and extubation was implemented after median 10.2(5.0, 42.9) days of ECMO. Awake ECMO was not associated with increased morbidity. The total invasive ventilation duration, lengths of stay in the ICU and hospital in the cohort were 14.0(12.0, 37.3) days, 33.0(22.3, 56.5) days and 46.5(27.3, 84.8) days, respectively. The hospital mortality rate was 33.3% (4/12) in the cohort. Survivors had more stable respiratory rate and heart rate after extubation when compared to the non-survivors. CONCLUSIONS: With carefully selected patients, awake ECMO is a feasible and safe strategy for severe pulmonary ARDS patients receiving prolonged ECMO support to wait for native lung recovery.

11.
Open Forum Infect Dis ; 6(3): ofz053, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30895200

RESUMO

Background: The objective of this study was to investigate the difference in disease severity between influenza A and B among hospitalized adults using a novel ordinal scale and existing clinical outcome end points. Methods: A prospective, observational study was conducted over the 2016-2018 influenza seasons in a central hospital. The primary outcome was the rate of clinical improvement, defined as a decline of 2 categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death), or hospital discharge up to day 28. Results: In total, 574 eligible patients were enrolled, including 369 (64.3%) influenza A cases and 205 (35.7%) influenza B cases. The proportion of patients with a worse ordinal scale at admission was higher in influenza A than influenza B (P = .0005). Clinical improvement up to 28 days occurred in 82.4% of patients with influenza A and 90.7% of patients with influenza B (P = .0067). The Cox model indicated that influenza B patients had a higher clinical improvement probability than influenza A cases (adjusted hazard ratio [HR], 1.266; 95% confidence interval [CI], 1.019-1.573; P = .0335). A similar pattern was observed in weaning oxygen supplement (adjusted HR, 1.285; 95% CI, 1.030-1.603; P = .0261). In-hospital mortality for influenza A was marginally higher than influenza B (11.4% vs 6.8%; P = .0782). Conclusions: Our findings indicated that hospitalized patients with influenza A were more ill and had delayed clinical improvement compared with those with influenza B virus infection.

12.
Pediatr Cardiol ; 40(4): 705-712, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30652193

RESUMO

OBJECTIVE: The bidirectional cavopulmonary shunt (BCPS) is an effective palliative procedure which has been widely used to boost outcome of the Fontan procedure. However, there is no standard duration time between these two procedures. Therefore, we investigated whether different time intervals between BCPS and Fontan procedure affects morbidity and mortality of Fontan patients. METHODS: Between 2004 and 2016, 210 post-BCPS patients underwent Fontan operation at Fuwai Hospital. The median interval between BCPS and Fontan procedure was 3.7 years (range 0.55-11.86 years) and this was used to divide study cohort into Group 1 (< 3.7 years; n = 124) and Group 2 (> 3.7 years; n = 86). We analyzed these patients retrospectively in terms of their preoperative characteristics and post-operative and follow-up results. RESULTS: Weight z-scores for age at BCPS (- 0.73 ± 1.39 vs - 1.17 ± 1.60, p < 0.05) was significantly higher in Group 2. However, saturation at room air before Fontan (76.42 ± 20.01 vs 82.85 ± 9.69, p < 0.001) was significantly higher in Group 1. The morbidity and mortality were similar between two groups. There were twelve hospital deaths (5.7%): eight (8/124, 6.5%) presented in Group 1 and four (4/86, 4.7%) in Group 2. On multi-variable analysis, risk factors for death were prolonged mechanical ventilation [hazard ratio (HR) 1.02, p = 0.004] and single right ventricle (HR 7.17, p = 0.03). After a mean follow-up of 4.95 years (range 0.74-13.62 years), one patient in Group 1 died of heart failure 13 months after Fontan procedure. The overall Fontan failure in Group 1 was similar to that in Group 2 (2.7% vs 2.6%, p = 0.985). The incidence of arrhythmias and re-intervention were not different between the two groups. CONCLUSIONS: Fontan procedure could be performed safely in patient who stayed in long duration between Fontan procedure and BCPS without affecting the operative and long-term follow-up results. However, for post-BCPS patients with severe hypoxemia, earlier age at Fontan might be a good choice.


Assuntos
Técnica de Fontan/métodos , Cardiopatias Congênitas/cirurgia , Fatores Etários , Criança , Pré-Escolar , Feminino , Técnica de Fontan/mortalidade , Cardiopatias Congênitas/mortalidade , Humanos , Lactente , Estudos Longitudinais , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento
13.
Front Oncol ; 8: 461, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30406028

RESUMO

Background: We aimed to investigate the interaction between prediabetes and the ABO blood types in predicting esophageal squamous cell carcinoma (ESCC)-specific mortality by analysing data from the FIESTA study on normal/prediabetic patients with ESCC. Methods: Total 1,857 normal/prediabetic patients with ESCC who underwent three-field lymphadenectomy between January 2000 and December 2010 and survived hospitalization were analyzable, with follow-up beginning in 2000 and ending in 2015. Results: At the end of the follow-up, there were 1,161 survivors and 696 non-survivors. The follow-up time ranged from 0.5 to 180 months. The cumulative survival rates in normal patients were obviously better than in prediabetic patients. The cumulative survival rates were significantly higher in normal patients than in prediabetic patients for the blood types O and A (Log-rank test P < 0.05), while no significance was detected for the blood types B and AB. Adjusted risk estimates for ESCC-specific mortality for prediabetic patients relative to normal patients were statistically significant in the blood type B- group (hazard ratio [HR]: 1.71; 95% confidence interval [CI]: 1.33-2.20; P < 0.001), but not in the blood type B+ group (HR: 1.12; 95% CI: 0.77-1.64; P = 0.5544). Conclusions: Our findings indicate that prediabetes can predict the significant risk of ESCC-specific mortality in Chinese Han patients with the blood types O and A.

17.
BMC Cancer ; 18(1): 785, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30081869

RESUMO

BACKGROUND: As we previously reported, the presence of preoperative metabolic syndrome can predict the significant risk of gastric cancer mortality. As a further extension, we evaluated the prediction of three lipid derivatives generated from triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDLC and LDLC) at baseline for postoperative gastric cancer mortality by prospectively analysing 3012 patients. The three lipid derivatives included the ratio of TC minus HDLC to HDLC known as atherogenic index (AI), the ratio of TG to HDLC abbreviated as THR and the ratio of LDLC to HDLC abbreviated as LHR. METHODS: Gastric cancer patients who received gastrectomy between January 2000 and December 2010 were consecutively recruited from Fujian Cancer Hospital. Follow-up assessment was implemented annually before December 2015. RESULTS: Finally, there were 1331 deaths from gastric cancer and 1681 survivors, with a median follow-up time of 44.05 months. 3012 patients were evenly randomized into the derivation group and the validation group, and both groups were well balanced at baseline. Overall adjusted estimates in the derivation group were statistically significant for three lipid derivatives (hazard ratio [HR]: 1.20, 1.17 and 1.19 for AI, THR and LHR, respectively, all P < 0.001), and were reproducible in the validation group. The risk prediction of three lipid derivatives was more obvious in males than females, in patients with tumor-node-metastasis stage I-II than stage III-IV, in patients with intestinal-type than diffuse-type gastric cancer, in patients with normal weight than obesity, and in patients without hypertension than with hypertension, especially for AI and LHR, and all results were reproducible. Calibration and discrimination statistics showed good reclassification performance and predictive accuracy when separately adding three lipid derivatives to baseline risk model. A prognostic nomogram was accordingly built based on significant attributes to facilitate risk assessment, with a good prediction capability. CONCLUSIONS: Our results indicate that preoperative lipid derivatives, especially AI and LHR, are powerful predictors of postoperative gastric cancer mortality, with more obvious prediction in patients of male gender or with tumor-node-metastasis stage I-II or intestinal-type gastric cancer, and in the absence of obesity or hypertension before gastrectomy.


Assuntos
Biomarcadores Tumorais/sangue , Colesterol/sangue , Técnicas de Apoio para a Decisão , Gastrectomia/mortalidade , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Triglicerídeos/sangue , Idoso , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Gastrectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
18.
J Cancer ; 9(16): 2885-2894, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123357

RESUMO

Objectives: We here attempted to evaluate the prediction of different "ABO" blood groups for postsurgical gastric cancer-specific mortality by using data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Methods: Initially, a total of 3413 patients with gastric cancer were consecutively enrolled between January 2000 and December 2010 to receive radical gastrectomy, and they were followed up until December 2015. Study patients were divided into the "O+" group and the blood type "O-" group. Results: Of 2781 eligible patients, 1116 (40.1%) were in the "O+" group and 1665 (59.9%) in the "O-" group, with mortality rate of being 45.0% (n = 502) and 45.3% (n = 755), respectively. A 1:1 propensity score match between the "O+" and the "O-" groups was used. After adjustment, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), high total cholesterol and high low-density lipoprotein cholesterol, had non-overlapping 95% confidence intervals between the "O+" and the "O-" groups and simultaneously had detectable statistical significance in either group only. A forward method in the multivariate-adjusted COX model was employed and there were five shared risk factors between both groups, including diabetes mellitus, low high-density lipoprotein cholesterol, regional lymph node metastasis, tumor size and TNM stage. Further nomogram plot revealed that presurgical risk factors selected can better predict the risk of early gastric cancer-specific mortality (C-index: 0.737 for the "O-" group and 0.751 for the "O+" group). Conclusions: Our findings indicated that the prognostic factors differed between postsurgical gastric cancer patients with "O+" and "O-" blood types.

19.
J Renin Angiotensin Aldosterone Syst ; 19(2): 1470320318770546, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29716409

RESUMO

OBJECTIVES: We conducted a meta-analysis of published studies on the angiotensin-converting enzyme ( ACE) gene insertion/deletion (I/D) polymorphism associated with the risk of chronic obstructive pulmonary disease, as well as with pulmonary function and circulating angiotensin-converting enzyme changes. METHODS: A literature search, quality assessment and data extraction were completed independently and in duplicate. RESULTS: A total of 16 articles were meta-analysed, including 12 articles (2113 patients and 8786 controls) for chronic obstructive pulmonary disease risk and eight articles (11,664 subjects) for pulmonary and circulating phenotypes. In overall and subgroup analyses, no significance was noted between the I/D polymorphism and chronic obstructive pulmonary disease risk under all genetic models ( P>0.05), without heterogeneity or publication bias. Carriers of II, ID and II plus ID genotypes had significantly lower levels of circulating angiotensin-converting enzyme than those with the DD genotype (weighted mean difference -13.35, -8.13 and -10.74 U/L, respectively, P<0.001). For forced expiratory volume in one second (FEV1)/forced vital capacity, carriers of the DD genotype had marginally lower levels than those with the DD genotype (weighted mean difference -1.66, P=0.034). Furthermore in the case of FEV1 of 50% or greater of predicted FEV1, FEV1 was marginally lower in ID genotype carriers than DD genotype carriers (weighted mean difference -3.50, P=0.056). CONCLUSIONS: Our meta-analytical findings demonstrated that the ACE gene I/D polymorphism was not associated with the risk of chronic obstructive pulmonary disease.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Mutação INDEL/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/genética , Humanos , Fenótipo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Análise de Regressão , Testes de Função Respiratória , Fatores de Risco
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