Relevance of NAT2 genotype and clinical factors to risk for antituberculosis drug-induced liver injury.

The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and NAT2 gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing of antituberculosis (ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB; p < 0.05). There was a significant difference in the distribution of NAT2 metabolic phenotypes between the study group and the control group (p < 0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.

N-acetyltransferase 2 genetic polymorphisms and anti-tuberculosis-drug-induced liver injury: a correlation study.

Background: Considering the genetic characteristics of people with anti-tuberculosis (TB)-drug-induced liver injury (ATDILI), genetic factors and their consequences for treatment need to be studied. Objective: The correlation between N-acetyltransferase 2 (NAT2) genetic polymorphisms and ATDILI was analysed. Methods: In this study, the liver and coagulation functions of 120 patients with TB were monitored dynamically for at least 3 months. The genetic polymorphisms of patients were detected by pyrosequencing, and the acetylation types of liver damage and the distribution of NAT2 genetic polymorphisms were compared and analysed. Results: The results showed that there were significant differences in the distribution of alleles and acetylation types among different groups (p < 0.05). In patients with grade 4 liver injury (liver failure), any two alleles were included, i.e., *6 and *7. Specifically, patients with fast acetylation genotypes accounted for 42.4% (14/33), those with intermediate acetylated genotypes accounted for 55.2% (32/58), and patients with slow acetylation genotypes accounted for 65.5% (19/29). Conclusion: Patients with slow acetylation genotypes had higher rates of liver failure and liver injury than those with intermediate and fast acetylation genotypes, and patients with slow acetylation genotypes containing any two alleles (*6 and *7) had a higher rate of liver failure than those with other alleles. In summary, the time of liver injury in patients with slow acetylation genotypes was earlier than the total average time, and the time of liver function recovery in patients with fast acetylation genotypes was shorter than the total average time.

Xpert MTB/RIF Improves the Prognosis of Multidrug-Resistant Tuberculosis Patients Through Faster Diagnosis and Earlier Targeted Treatment: A Prospective Cohort Study.

Objective: To evaluate the effectiveness of Xpert MTB/RIF in patients with multidrug-resistant tuberculosis (MDR-TB). Methods: Seventy-five patients with MDR-TB were enrolled in this prospective cohort study and were divided into two groups. The observation group were given standardized anti-MDR-TB treatment regimen (6ZAmLfxPtoCs/18ZLfxPtoCs) immediately when they had two positive sputum Xpert MTB/RIF results of RIF resistance. The control group were not given standardized anti-MDR-TB regimen until culture-based drug-susceptibility testing suggested MDR-TB. Treatment effect index, foci absorption, conversion of sputum, treatment outcomes, and adverse reactions were observed. Fisher's exact test and chi-square test were used to compare the differences between groups. Results: Treatment effect index of the observation group significantly out-performed the control group (24/34, 70.6% vs. 17/38, 44.7%, p = 0.027). At the 6th month of treatment course, observation group achieved significantly higher conversion (28/34, 82.3% vs. 23/38, 60.5%, p = 0.042). The foci absorption, cavity change, conversion at the 24th month of course, or treatment outcome between two groups were not statistically different. Conclusion: Xpert MTB/RIF helps MDR-TB patients to start rational treatment regimen earlier and reach earlier sputum conversion.

Increased levels of lactate dehydrogenase and hypertension are associated with severe illness of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is amid an ongoing pandemic. It has been shown that patients with cardiovascular comorbidities are at higher risk of severe illness of COVID-19. AIM: To find out the relationship between cardiovascular comorbidities and severe illness of COVID-19. METHODS: The clinical data of 140 COVID-19 patients treated from January 22, 2020 to March 3, 2020 at our hospital were retrospectively collected. The clinical characteristics were compared between patients with mild illness and those with severe illness. RESULTS: There were 75 male patients and 65 female patients (53.6% vs 46.4%). The mean age was 45.4 ± 14.6 years (range, 2-85 years). Most of the patients had mild illness (n = 114, 81.4%) and 26 patients had severe illness (18.6%). The most common symptom was fever (n = 110, 78.6%), followed by cough (n = 82, 58.6%) and expectoration (n = 51, 36.4%). Eight patients were asymptomatic but were positive for severe acute respiratory syndrome coronavirus 2 RNA. Patients with severe illness were significantly more likely to be hypertensive than those with mild illness [(10/26, 38.4%) vs (22/114, 19.3%), P = 0.036]. The levels of lactate dehydrogenase were significantly higher in the severe illness group than in the mild illness group (299.35 ± 68.82 vs 202.94 ± 63.87, P < 0.001). No patient died in either the severe illness or the mild illness group. CONCLUSION: Hypertension and elevated levels of lactate dehydrogenase may be associated with severe illness of COVID-19.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

BACKGROUND: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). METHODS: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: a multicenter study.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Epidemiological Features of 105 Patients Infected with the COVID-19.

OBJECTIVE: To investigate and evaluate the clinical features of patients infected with the 2019 novel coronavirus (COVID-19) outside of Wuhan. METHODS: 105 patients admitted to our hospital with clinical- and laboratory-confirmed COVID-19 infection were studied. Data were collected from January 17, 2020 to March 5, 2020. RESULTS: 105 patients (57 male and 48 female) were confirmed to have COVID-19 infection. Among the 105 patients, 55 (52%) had made short trips to Wuhan during the two weeks before the onset of illness, and these were the first-generation confirmed cases. An exact date of close contact with someone in Wenzhou with confirmed or suspected COVID-19 infection from Wuhan (the second-generation confirmed cases) could be provided by 38 (36%) patients. Of the remaining patients, six (6%; the third-generation confirmed cases) were familial clusters of the second-generation confirmed cases, three (3%) had no definite epidemiological features, and 16 (15%) were from the same location as for the case report. CONCLUSION: Due to the infectiousness of COVID-19, patients with infections should be diagnosed and treated as early as possible after developing fever symptoms or showing other clinical characteristics or imaging features. With respect to high-risk cases, we must focus on any complications that arise and take effective measures to treat them immediately. This will significantly improve the prognosis of patients with severe infections.

Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study.

Background: The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. Methods: This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Results: Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. Conclusion: The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events.