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Abstract Background The study assessed the association between COVID-19 and new-onset obstructive airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis among vaccinated individuals recovering from COVID-19 during the Omicron wave. Methods This multicenter retrospective cohort study comprised 549,606 individuals from the U.S. Collaborative Network of TriNetX database, from January 8, 2022, to January 17, 2024. The hazard of new-onset obstructive airway diseases between COVID-19 and no-COVID-19 groups were compared following propensity score matching using the Kaplan–Meier method and Cox proportional hazards model. Results After propensity score matching, each group contained 274,803 participants. Patients with COVID-19 exhibited a higher risk of developing new-onset asthma than that of individuals without COVID-19 (adjusted hazard ratio (aHR), 1.27; 95% CI, 1.22–1.33; p

Introduction: Photokeratoconjunctivitis (PKC) is primarily caused by welding. However, inappropriate use of germicidal lamps, which have been widely used following the COVID-19 outbreak, can also cause PKC. Our goal in this study was to investigate the incidence of and changes in the causes of PKC during the coronavirus 2019 (COVID-19) pandemic. Methods: We conducted a single-center, retrospective observational study. The health records of patients who visited the emergency department in a tertiary care hospital from January 1, 2018–December 31, 2021 and were diagnosed with PKC, were reviewed. We then conducted an analysis to compare the characteristics of PKC before and after COVID-19 began and the features of PKC caused by welding and germicidal lamps. Results: There were 160 PKC cases with a clear etiology before the COVID-19 pandemic and 147 cases during the COVID-19 pandemic. No significant differences in age and gender were detected between the two groups. The incidence of PKC induced by the use of germicidal lamps during the COVID-19 pandemic was significantly higher (10.2%) than the incidence before the pandemic (3.1%). The ratio of females to males in the germicidal lamp subgroup was significantly higher than the ratio in the welding subgroup. Limitations included incomplete information due to the retrospective nature of the study, underestimation of incidence, and possible recall bias. Conclusion: In the era of COVID-19, clinicians should be aware of the hazards of germicidal lamps. Although the COVID-19 pandemic seems to show signs of easing, new infectious diseases that require protective measures could still emerge in the future. Therefore, injuries related to germicidal lamps deserve more public health attention.

Backgrounds: The effectiveness of oral antiviral therapy including nirmatrelvir plus ritonavir and molnupiravir in managing COVID-19 among individuals with pre-existing lung cancer was unclear. Therefore, this study was conducted to evaluate the usefulness of antiviral agents in the management of COVID-19 among patients with lung cancer. Methods: Utilizing data from the TriNetX – a global health research network, a retrospective cohort study was conducted involving 2484 patients diagnosed with both lung cancer and COVID-19. Propensity score matching (PSM) was employed to create well-balanced cohorts. The study assessed the primary outcome of all-cause hospitalization or mortality within a 30-day follow-up. Results: After PSM, the oral antiviral group exhibited a significantly lower risk of the primary composite outcome compared to the control group (6.1 % vs. 9.9 %; HR: 0.60; 95 % CI: 0.45–0.80). This association was consistent across various subgroups according to age, sex, vaccine status, type of oral antiviral agent, and lung cancer characteristics. Additionally, the oral antiviral group showed a lower risk of all-cause hospitalization (HR: 0.73; 95 % CI: 0.54–0.99) and a significantly lower risk of mortality (HR: 0.16; 95 % CI: 0.06–0.41). Conclusion: The study suggests a favorable impact of oral antiviral therapy on the outcomes of COVID-19 in individuals with lung cancer and support the potential utility of oral antiviral agents in improving outcomes in this vulnerable population.

ObjectivesThis study investigated the clinical effectiveness of molnupiravir for treating non-hospitalized COVID-19 patients with pre-existing psychiatric disorder.MethodsThis retrospective cohort study used the TriNetX research network to identify patients with psychiatric disorder who experienced non-hospitalized COVID-19 between 1 January 2022, and 1 May 2023. The propensity score matching (PSM) method was used to match patients receiving molnupiravir (treated group) with those who did not (untreated group). The outcome included short-term outcomes - the composite of all-cause hospitalization or death within 30 days and the risk of post-COVID-19 conditions up to a year after COVID-19 diagnosis.ResultsTwo groups of 9,421 patients, each with balanced baseline characteristics, were identified using the PSM method. During the 30-day follow-up, treated group was associated with a reduced risk of hospitalization or mortality compared to untreated group (HR, 0.760; 95% CI, 0.665–0.869). Compared to untreated group, treated group also exhibited a decreased risk of experiencing post-COVID-19 conditions, including chest/throat pain (HR, 0.615; 95% CI, 0.543–0.696), abnormal breathing (HR, 0.761; 95% CI, 0.687–0.884), abdominal symptoms (HR, 0.748; 95% CI, 0.674–0.831), fatigue (HR, 0.718; 95% CI, 0.638–0.808), headache (HR, 0.753; 95% CI, 0.665–0.852), cognitive symptoms (HR, 0.769; 95% CI, 0.630–0.940), myalgia (HR, 0.647; 95% CI, 0.530–0.789), cough (HR, 0.867; 95% CI, 0.770–0.978), and palpitation (HR, 0.641; 95% CI, 0.534–0.770) during the 1-year follow-up.ConclusionMolnupiravir could be associated with lower rates of all-cause hospitalization or death and also lower risk of post-COVID-19 condition among non-hospitalized COVID-19 patients with pre-existing psychiatric disorder.

Abstract Background To date, no studies have investigated the prevalence of post-COVID-19 conditions in patients with Intellectual and Developmental Disabilities (IDD). Addressing this research gap is crucial, as understanding post-COVID-19 conditions in IDD patients can improve care planning, and it is essential not to overlook this vulnerable population in COVID-19 studies. This study was aimed at investigating the prevalence of post-COVID-19 conditions in patients with IDD and compare their risk with that of the general population. Methods Using the TriNetX network, we identified patients with and without an IDD who had COVID-19. Subsequently, we compared the risk of developing any post-COVID-19 condition between these two groups, during the 90–180-day follow-up after SARS-CoV-2 infection. Results During the follow-up, patients with an IDD exhibited a significantly higher prevalence of post-COVID-19 conditions compared to the general population (hazard ratio [HR], 1.120; 95% confidence interval [CI]: 1.053–1.191). Specifically, COVID-19 survivors with IDD had a significantly increased risk of experiencing abnormal breathing (HR, 1.216; 95% CI: 1.077–1.373), abdominal symptoms (HR, 1.259; 95% CI: 1.128–1.406), fatigue (HR, 1.397; 95% CI: 1.216–1.606), anxiety/depression (HR, 1.157; 95% CI: 1.050–1.274), cognitive symptoms (HR, 1.828; 95% CI: 1.529–2.186), myalgia (HR, 1.325; 95% CI: 1.077–1.631), sleep disturbances (HR, 1.481; 95% CI: 1.148–1.910), and cough (HR, 1.315; 95% CI: 1.146–1.508) compared to the non-IDD group. Conclusions Patients with IDD might be associated with a higher risk of post-COVID-19 conditions following SARS-CoV-2 infection compared to the general population.

Background: Primary Aldosteronism (PA) is a common subtype of hypertension that increases the risk of adverse cardiovascular and kidney events. The impact of COVID-19 on patients with PA is not well understood.This study aimed to investigate the impact of COVID-19 on patients with PA and compare their outcomes with hypertensive patients with essential hypertension. Methods: A cohort study was conducted using data from the Trinetx platform, including 9,817,307 participants enrolled between January 1, 2020, and July 31, 2022. The study group consisted of participants who tested positive for PCR SARS-CoV-2. The primary outcome was critical care and all-cause mortality, while the secondary outcomes were major adverse cardiac events (MACE) or major adverse kidney events (MAKE). The study included 4814 patients with PA and 4814 hypertensive controls. Results: Patients with PA had a higher risk of critical outcomes than the hypertensive control group (adjusted hazard ratio [aHR] 1.14, p = 0.001). Moreover, they had higher risks of MACE (aHR 1.32, p

Abstract Background Few studies have directly compared the risk and magnitude of post-acute sequelae following COVID-19 and influenza, and most of these studies were conducted before emergence of the Omicron. This study investigated the prevalence of post-COVID conditions and the long-term risk of emergency department (ED) visits, hospitalizations, and deaths in patients with COVID-19 and compared their risk with that of patients with influenza. Methods A retrospective study based on the TriNetX databases, a global health research network. We identified patients with COVID-19 and influenza who required hospitalization between January 1, 2022, and January 1, 2023. We compared the risk of developing any post-COVID conditions between the two groups and also analyzed each post-COVID-19 condition and all-cause ED visits, hospitalizations, and deaths in both populations during the follow-up 90–180 days. Results Before matching, 7,187 patients with COVID-19 were older (63.9 ± 16.7 vs. 55.4 ± 21.2) and were predominantly male (54.0% vs. 45.4%), and overweight/obese (16.1% vs. 11.2%) than 11,266 individuals with influenza. After propensity score matching, 6,614 patients were identified in each group, resulting in well-balanced baseline characteristics. During follow-up, the COVID-19 group had a higher incidence of any post-COVID-19 condition when compared with the influenza group (17.9% vs. 13.0%), with a hazard ratio (HR) of 1.398 (95% CI, 1.251–1.562). Compared to the influenza group, the COVID-19 group had a significantly higher incidence of abnormal breathing (HR, 1.506; 95% CI, 1.246–1.822), abdominal symptoms (HR, 1.313; HR, 1.034–1.664), fatigue (HR, 1.486; 95% CI, 1.158–1.907), and cognitive symptoms (HR, 1.815; 95% CI, 1.235–2.668). Moreover, the COVID-19 group had a significantly higher risk of the composite outcomes during all-cause ED visits, hospitalizations, and deaths when compared with the influenza group (27.5% vs. 21.7; HR, 1.303; 95% CI, 1.194–1.422). Conclusions This study indicates that hospitalized COVID-19 patients are at a higher risk of long-term complications when compared with influenza survivors.

Background: Previous studies have revealed higher mortality rates in patients of severe influenza coinfected with invasive pulmonary aspergillosis (IPA) than in those without the coinfection; nonetheless, the clinical outcome of IPA in critically ill patients without influenza remains unclear. Patients and methods: This retrospective study was conducted in three institutes. From 2016–2018, all adult patients diagnosed with IPA in the intensive care units (ICUs) were identified. The logistic regression was used to identify the potential risk factors associated with in-hospital mortality in patients with non-influenza IPA. The stratified analysis of IPA patients with and without antifungal therapy was also performed. The final model was established using a forward approach, selecting variables with p-values less than 0.05. Results: Ninety patients were included during the study period, and 63 (70%) were men. The most common comorbidity was diabetes mellitus (n = 24, 27%), followed by solid cancers (n = 22, 24%). Antifungal therapy was administered to 50 (56%) patients, mostly voriconazole (n = 44). The in-hospital mortality rate was 49% (n = 44). Univariate analysis revealed that the risk factors for mortality included daily steroid dose, APACHE II score, SOFA score, C-reactive protein (CRP) level, carbapenem use, antifungal therapy, and caspofungin use. Multiple regression analysis identified four independent risk factors for mortality: age (Odds ratio [OR], 1.052, p = 0.013), daily steroid dose (OR, 1.057, p = 0.002), APACHE II score (OR, 1.094, p = 0.012), and CRP level (OR, 1.007, p = 0.008). Furthermore, the multivariable analysis identified that more physicians would initiate antifungal therapy for patients with prolonged steroid use (p = 0.001), lower white blood cell count (p = 0.021), and higher SOFA score (p = 0.048). Thus, under the selection bias, the independent risk factors for mortality in the antifungal treatment subgroup were daily steroid dose (OR, 1.046, p = 0.001) and CRP (OR, 1.006, p = 0.018), whereas the independent risk factor for mortality in the untreated group became APACHE II score (OR, 1.232, p = 0.007). Conclusions: Patients with IPA had a substantially high mortality. Overall, age, steroid use, APACHE II score, and CRP level were identified as the independent risk factors for mortality in patients in the ICU.

Background: The efficacy of inhaled corticosteroid (ICS) in the treatment of patients with COVID-19 has been evaluated in randomized controlled trials (RCTs), however, their findings are not consistent. Methods: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar were searched to June 10, 2023. Only RCTs that investigated the clinical efficacy and safety of ICS for patients with COVID-19 were included. Results: Eleven RCTs were included. ICS users had significantly higher rate of symptom alleviation at day 14 than the control group (risk ratio [RR], 1.13; 95% CI, 1.04–1.23; I2 = 42%). Additionally, no significant difference between the ICS users and the control group was observed in the composite outcome of urgent care, emergency department (ED) visit or hospitalization (RR, 0.43; 95% CI, 0.08–2.48; I2 = 85%) and hospitalization or death (RR, 0.85; 95% CI, 0.64–1.12; I2 = 0%). Finally, ICS user had a non-significantly lower risk of death at day 28 than the control group (0.63% vs 0.99%; RR, 0.82; 95% CI, 0.43–1.56; I2 = 0%). Conclusions: Additional ICS use, particularly inhaled budesonide may help symptom relief in patients with COVID-19. However, ICS use did not help reduce the risk of urgent care, ED visit, hospitalization, or death.

Background: Enterobacterales carrying blaNDM represent an emerging challenge in treating infectious diseases. In this study, we aimed to investigate the characteristics of blaNDM-producing Enterobacterales from three hospitals in southern Taiwan. Methods: Enterobacterales strains that were nonsusceptible to more than one carbapenem (ertapenem, meropenem, imipenem, or doripenem) were collected from hospitalized patients. Molecular typing for New Delhi metallo-β-lactamase (NDM) and antibiotic susceptibility tests were performed, followed by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and plasmid analysis by PCR-based replicon typing. Results: A total of 1311 carbapenem-nonsusceptible Enterobacterales were isolated from 2017 to 2021. blaNDM-encoding genes were detected in 108 isolates, with 53 (49.1%) harboring blaNDM-1 and 55 (50.9%) harboring blaNDM-5. The rate of blaNDM-1 detection among isolates decreased to 2% in 2021. However, the rate of E. coli harboring blaNDM-5 increased from 1% to 12% of total isolates during the study period. Of 47 NDM-5-positive E. coli isolates, 44 (93.6%) were ST8346 with high genetic relatedness. E. coli ST8346 isolates showed high-level resistance to both carbapenems and aminoglycosides. Most (38 out of 47, 80.9%) blaNDM-5-harboring E. coli isolates co-harbored blaOXA-181. We analyzed the regions harboring blaNDM-5 in E. coli ST8346 via PCR amplification. blaNDM-5 and blaOXA-181 were located on two separate plasmids, IncF and IncX3, respectively. Conclusion: The dissemination of E. coli ST8346 caused an increase in blaNDM-5 and blaOXA-181 co-harboring Enterobacterales in southern Taiwan, which show high-level resistance to both carbapenems and aminoglycosides. We identified a distinct IncF plasmid encoding blaNDM-5 that has the potential for rapid spread and needs further surveillance.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health crisis, exacerbating issues like malnutrition due to increased metabolic demands and reduced intake during illness. Malnutrition, a significant risk factor, is linked to worse outcomes in patients with COVID-19, such as increased mortality and extended hospital stays. This retrospective cohort study investigated the relationship between malnutrition and clinical outcomes within 90–180 days using data obtained from the TriNetX database. Patients aged >18 years diagnosed with COVID-19 between 1 January 2022, and 31 March 2024 were enrolled in the study. The propensity score-matching (PSM) method was used to match patients with malnutrition (malnutrition group) and those without malnutrition (control group). The primary composite outcome was the cumulative hazard ratio (HR) for post-COVID-19 condition, all-cause hospitalization, and all-cause mortality between 90 days and 180 days after COVID-19 diagnosis. The secondary outcomes were the individual components of the primary outcomes. Two cohorts, each consisting of 15,004 patients with balanced baseline characteristics, were identified using PSM. During the 90–180-day follow-up period, the malnutrition group exhibited a higher incidence of all-cause hospitalization, mortality, or post-COVID-19 condition (HR = 2.315, 95% confidence interval: 2.170–2.471, p < 0.0001). Compared with patients with COVID-19 without malnutrition, those with malnutrition may be associated with a higher risk of adverse clinical outcomes.

Abstract Background This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia (sCAP). Methods A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality. Results A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio [RR], 0.61; 95% CI 0.44 to 0.85; p

Abstract Background The benefit of inpatient comprehensive geriatric assessment on patient survival and function has been demonstrated among frail older patients. However, the influence of outpatient geriatric evaluation and management (GEM) on clinical outcomes remains debated. This study aimed to update the research evidence detailing the effect of outpatient GEM on survival and nursing-home admission through a comparison with conventional care. Methods Cochrane Library, EMBASE, and MEDLINE databases were searched up to January 29th, 2022, to identify randomized controlled trials (RCTs) including older people over age 55 that compared outpatient GEM with conventional care on mortality (primary outcome) and nursing-home admission (secondary outcome) during a follow-up period of 12 to 36 months. Results Nineteen reports from 11 studies that recruited 7,993 participants (mean age 70–83) were included. Overall, outpatient GEM significantly reduced mortality (risk ratio (RR) = 0.87, 95% confidence interval (CI) = 0.77–0.99, I 2 = 12%). For the subgroup analysis categorized by different follow-up periods, its prognostic benefit was only disclosed for 24-month mortality (RR = 0.68, 95% CI = 0.51–0.91, I 2 = 0%), but not for 12- or 15 to 18-month mortality. Furthermore, outpatient GEM had significantly trivial effects on nursing-home admission during the follow-up period of 12 or 24 months (RR = 0.91, 95% CI = 0.74–1.12, I 2 = 0%). Conclusions Outpatient GEM led by a geriatrician with a multidisciplinary team improved overall survival, specifically during the 24-month follow-up period. This trivial effect was demonstrated in rates of nursing-home admission. Future research on outpatient GEM involving a larger cohort is warranted to corroborate our findings.

From January 2020 to December 2022, there was a total of 8,872,955 confirmed COVID-19 cases in Taiwan. In addition, a total of 15,253 COVID-19 related deaths were reported. During these three years, the government and health authority did many efforts to response this pandemic. In the early pandemic, Taiwan Central Epidemic Command Center was established in the early 2020 to organize associated resource, develop effective policy and implement strict intervention. In response to COVID-19 pandemic, many infection control policy and interventions, including universal mask wearing with increasing production of face mask, hand hygiene, border control, introduce of digital technology incorporating big data, quarantine of COVID-19 cases, travel and gathering restriction, were implemented. In the meanwhile, two COVID-19 vaccines, namely MVC-COV1901 and UB-612, have been developed under the support of government. Furthermore, MVC-COV1901 was taken into clinical practice after received emergency use approval. In addition, two traditional Chinese medicines, including NRICM101 and NRICM102 showed their promising effect against SARS-CoV-2 infection and were recommended as potential therapeutic options for COVID-19. During the pandemic, the nonpharmacologic intervention help reduce many infectious diseases, especially for airborne/droplet-transmitted diseases. However, COVID-19 exhibited some adverse impacts on the healthcare systems, such as emergency medical service on out of hospital cardiac arrest, cancer screening, HIV screening and prevention services, and public health, namely the psychosocial status of healthcare workers. Although the outbreak of SARS-CoV-2 infections may gradually subsided, we should keep monitoring its associated impact and appropriately response to this pandemic.

ABSTRACT: Objective: Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection. Methods: PubMed, Web of Science, and Cochrane Library were searched from their inception to 29 November 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included. Results: A total of six studies meeting selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-d mortality when compared with other carbapenems (10.7% [46/431] vs. 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40–0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenem groups (mean differences, -6.02 d; 95% CI, -9.39 to -2.64). No significant differences were noted between ertapenem and other carbapenem groups in terms of rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97–1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97–1.06). Conclusions: Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections.

BackgroundThe outcomes of older adult people acquiring SARS-CoV-2 reinfection was unclear. This study aimed to compare the outcomes of older adult patients with COVID-19 reinfection and those with primary infection.MethodsThis retrospective cohort study used electronic medical records from the TriNetX Research Network. Older adult patients (aged ≥65 years) with COVID-19 between January 1, 2022, and December 31, 2022, were included in the study. The patients were subsequently categorized into reinfection or primary infection groups, according to whether they manifested two distinct COVID-19 episodes with an intervening period of more than 90 days. Propensity score matching was performed for covariate adjustment between the reinfection and primary infection groups. The primary outcome was a composite outcome, including emergency department visits, hospitalization, intensive care unit admission, mechanical ventilation use, and mortality, following primary infection and reinfection.ResultsAfter matching, 31,899 patients were identified in both the reinfection and primary infection groups. The risk of primary composite outcomes was 7.15% (n = 2,281) in the reinfection group and 7.53% (n = 2,403) in the primary infection group. No significant difference in the primary outcome was observed between groups (HR, 0.96; 95% CI, 0.91 to 1.02, p = 0.17). In addition, there was no significant differences between the reinfection and primary infection groups in terms of emergency department visit (HR, 1.03; 95% CI, 0.95 to 1.11, p = 0.49), all-cause hospitalization (HR, 0.94; 95% CI, 0.86 to 1.02, p = 0.14), intensive care unit admission (HR, 0.92; 95% CI, 0.67 to 1.28, p = 0.62), mechanical ventilation use (HR,1.35 95% CI, 0.69 to 2.64 p = 0.38), and all-cause mortality (HR, 0.94; 95% CI, 0.74 to 1.20, p = 0.62).ConclusionThere were no significant differences in clinical outcomes between older adult patients with COVID-19 reinfection and those with primary infection.

Background: The effectiveness of the novel oral antiviral agents, nirmatrelvir plus ritonavir and molnupiravir, in treating COVID-19 in patients with nonalcoholic fatty liver disease is unclear.Objective: To assess the effectiveness of novel oral antiviral agents against COVID-19 among patients with nonalcoholic fatty liver diseases.Methods: This retrospective cohort study used the TriNetX Research Network to identify non-hospitalized patients with COVID-19 and nonalcoholic fatty liver disease between 1 January 2022, and 30 June 2023. Propensity score matching was used to form two matched cohorts treated with or without nirmatrelvir-ritonavir or molnupiravir.Results: In the two matched cohorts of 6,358 patients each, the use of novel oral antiviral agents was associated with a significantly lower risk of all-cause emergency department visits, hospitalization, or mortality (6.59% versus 8.24%; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.70–0.91). The novel antiviral group had a significantly lower risk of all-cause emergency department visits (HR, 0.85; 95% CI, 0.74–0.99). Additionally, the incidence of hospitalization was significantly lower in the oral antiviral group than in the control group (HR, 0.71; 95% CI, 0.55–0.90). There were no deaths in the oral antiviral group but 12 deaths in the control group.Conclusion: Novel oral antiviral agents are beneficial for treating COVID-19 in patients with nonalcoholic fatty liver disease.

Background: The association between N-acetylcysteine (NAC) and COVID-19 remains undetermined; therefore, this meta-analysis assessed the clinical efficacy of NAC in the treatment of patients with COVID-19. Methods: This study searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for studies published from their inception to December 17, 2022. Only randomized controlled trials (RCTs) that assessed the clinical efficacy of NAC for patients with COVID-19 were included. Results: Five RCTs involving 651 patients were included. There was no significant difference in mortality between the study group receiving NAC and the control group (15.6 % [50/320] vs. 32.3 %, [107/331]; risk ratio [RR]: 0.58; 95 % confidence interval [CI]: 0.24–1.40). In addition, the two groups did not differ with respect to the incidence of invasive mechanical ventilation (RR: 0.93; 95 % CI: 0.65–1.33), the risk of intensive care unit (ICU) admission (RR: 0.86; 95 % CI: 0.62–1.21), the length of hospital stay (mean difference [MD]: 0.17 days; 95 % CI: −0.67–1.01), and the length of ICU stay (MD: −0.77 days; 95 % CI: −2.97–1.42). Conclusions: The administration of NAC did not improve the clinical outcomes of patients with COVID-19; its routine use is not recommended for patients with SARS-CoV-2 infections.

The influence of inhaled corticosteroids (ICS) on COVID-19 outcomes remains uncertain. To address this, we conducted a systematic review and meta-analysis, analyzing 30 studies, to investigate the impact of ICS on patients with COVID-19. Our study focused on various outcomes, including mortality risk, hospitalization, admission to the intensive care unit (ICU), mechanical ventilation (MV) utilization, and length of hospital stay. Additionally, we conducted a subgroup analysis to assess the effect of ICS on patients with chronic obstructive pulmonary disease (COPD) and asthma. Our findings suggest that the prior use of ICS did not lead to significant differences in mortality risk, ICU admission, hospitalization, or MV utilization between individuals who had used ICS previously and those who had not. However, in the subgroup analysis of patients with COPD, prior ICS use was associated with a lower risk of mortality compared to non-users (OR, 0.95; 95% CI, 0.90-1.00). Overall, while the use of ICS did not significantly affect COVID-19 outcomes in general, it may have beneficial effects specifically for patients with COPD. Nevertheless, more research is needed to establish a definitive conclusion on the role of ICS in COVID-19 treatment. PROSPERO registration number: CRD42021279429.

ABSTRACT Viral load quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical measure for monitoring clinical responses of patients with COVID-19. The cobas SARS-CoV-2 Duo (Roche Molecular Systems, Inc.) uses the cobas 6800/8800 platform and is an automated real-time reverse transcription PCR (RT-PCR) assay for the qualitative detection of SARS-CoV-2 RNA (ORF1a and ORF1a/b non-structural regions) in nasal and nasopharyngeal specimens. This assay also performs quantitation of the SARS-CoV-2 RNA level in the collected specimen. The precision, accuracy, and linearity of the cobas SARS-CoV-2 Duo test were assessed and correlated with the cycle threshold (Ct) value of the cobas SARS-CoV-2 assay, and the cobas Liat SARS-CoV-2 and influenza A/B assay (Inf A/B) (cobas Liat) in 201 clinical nasopharyngeal swab specimens. The analytical measurement range of the cobas SARS-CoV-2 Duo has been verified to be 1.0E + 02 IU/mL to 1.0E + 09 IU/mL. The between- and within-run precision evaluation and the linearity results (R 2 = 0.9961) of the cobas SARS-CoV-2 Duo were acceptable based on the verification criteria. A total of 201 nasopharyngeal specimens were evaluated. The positive, negative, and total agreements between the cobas SARS-CoV-2 Duo and the cobas SARS-CoV-2 assay were 93.5% (157 of 168), 75% (33 of 44), and 92.5% (186 of 201), respectively. The qualitative results (Ct values) from the cobas SARS-CoV-2 and the cobas Liat demonstrated good agreement with the quantitative results from the cobas SARS-CoV-2 Duo assay. In conclusion, the diagnostic performance of the cobas SARS-CoV-2 Duo assay is appropriate. It is a precise, accurate, and sensitive method for the detection of SARS-CoV-2 RNA and is comparable to two qualitative assays. IMPORTANCE Quantitative SARS-CoV-2 tests for viral load are necessary to guide patient treatment, as well as to determine infection control measures and policies. Although the real-time RT-PCR assays can report the Ct value to estimate the viral load, there are several serious concerns regarding the use of Ct values. Importantly, Ct values can vary significantly among between- and within-run methods. The diagnostic performance of the cobas SARS-CoV-2 Duo is appropriate. It is a precise, accurate, and sensitive method for the detection of SARS-CoV-2 RNA and is comparable to two qualitative assays (the cobas SARS-CoV-2 and the Liat cobas SARS-CoV-2 and Inf A/B). In contrast, using the Ct value to estimate viral load is not reliable, and utilization of a quantitative detection test, such as the cobas SARS-CoV-2 Duo, to accurately measure the viral load is needed.

Background Patients with chronic liver disease (CLD) have a higher risk of mortality when infected with severe acute respiratory syndrome coronavirus 2. Although the fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and albumin-bilirubin grade (ALBI) score can predict mortality in CLD, their correlation with the clinical outcomes of CLD patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to investigate the association between the liver severity and the mortality in hospitalized patients with non-cirrhotic CLD and COVID-19. Methods This retrospective study analyzed 231 patients with non-cirrhotic CLD and COVID-19. Clinical characteristics, laboratory data, including liver status indices, and clinical outcomes were assessed to determine the correlation between liver status indices and the mortality among patients with non-cirrhotic CLD and COVID-19. Results Non-survivors had higher levels of prothrombin time-international normalized ratio (PT-INR), alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein (hs-CRP) and lower albumin levels. Multivariable analysis showed that ALBI grade 3 (odds ratio (OR): 22.80, 95% confidence interval (CI) [1.70–305.38], p = 0.018), FIB-4 index ≥ 3.25 (OR: 10.62, 95% CI [1.12–100.31], p = 0.039), PT-INR (OR: 19.81, 95% CI [1.31–299.49], p = 0.031), hs-CRP (OR: 1.02, 95% CI [1.01–1.02], p = 0.001), albumin level (OR: 0.08, 95% CI [0.02–0.39], p = 0.002), and use of vasopressors (OR: 4.98, 95% CI [1.27–19.46], p = 0.021) were associated with the mortality. Conclusion The ALBI grade 3 and FIB-4 index ≥ 3.25, higher PT-INR, hsCRP levels and lower albumin levels could be associated with mortality in non-cirrhotic CLD patients with COVID-19. Clinicians could assess the ALBI grade, FIB-4 index, PT-INR, hs-CRP, and albumin levels of patients with non-cirrhotic CLD upon admission.

AbstractObjective This study evaluated the clinical efficacy and safety of interleukin-1 (IL-1) blockade for patients with COVID-19.Methods The PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library databases were searched for relevant articles from their inception to 25 September 2022. Only randomized clinical trials (RCTs) that assessed the clinical efficacy and safety of IL-1 blockade in the treatment of patients with COVID-19 were included.Results This meta-analysis included seven RCTs. No significant difference in the all-cause mortality rate of patients with COVID-19 was observed between the IL-1 blockade and control groups (7.7 vs. 10.5%, odds ratio [OR] = 0.83, 95% confidence interval [CI] 0.57–1.22; I2 = 18%). However, the study group was at significantly lower risk of requiring mechanical ventilation (MV) compared with the control group (OR = 0.53, 95% CI 0.32–0.86; I2 = 24%). Finally, the risk of adverse events was similar between the two groups.Conclusions IL-1 blockade does not provide increased survival benefits in hospitalized patients with COVID-19, but it may reduce the need for MV. Furthermore, it is a safe agent for use in the treatment of COVID-19.>

Background: The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear. Methods: We performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3. Results: Twelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664–1.499; p = 0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408; 95% CI=0.693–2.858; p = 0.344 in ICS monotherapy, and pooled OR=1.225; 95% CI=0.533–2.815; p = 0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715; 95% CI=0.415–1.230; p = 0.225) and asthma (pooled OR=1.081; 95% CI=0.970–1.206; p = 0.160). Conclusions: The use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection.

At present, there are more than 560 million confirmed cases of the coronavirus disease 2019 (COVID-19) worldwide. Although more than 98% of patients with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection can survive acute COVID, a significant portion of survivors can develop residual health problems, which is termed as long COVID. Although severe COVID-19 is generally associated with a high risk of long COVID, patients with asymptomatic or mild disease can also show long COVID. The definition of long COVID is inconsistent and its clinical manifestations are protean. In addition to general symptoms, such as fatigue, long COVID can affect many organ systems, including the respiratory, neurological, psychosocial, cardiovascular, gastrointestinal, and metabolic systems. Moreover, patients with long COVID may experience exercise intolerance and impaired daily function and quality of life. Long COVID may be caused by SARS-CoV-2 direct injury or its associated immune/inflammatory response. Assessment of patients with long COVID requires comprehensive evaluation, including history taking, physical examination, laboratory tests, radiography, and functional tests. However, there is no known effective treatment for long COVID. Based on the limited evidence, vaccines may help to prevent the development of long COVID. As long COVID is a new clinical entity that is constantly evolving, there are still many unknowns, and further investigation is warranted to enhance our understanding of this disease.

Objective: To investigate the clinical efficacy of vitamin C-containing therapy for patients with sepsis. Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception to July 27, 2022. Only randomized controlled trials (RCTs) comparing vitamin C-containing therapy and placebo or alternative treatment for patients with sepsis were included, and the primary outcome was all-cause mortality. Results: Sixteen RCTs involving a total of 2985 patients were included in this meta-analysis. Overall, no significant difference in 28-day mortality was observed between the study group, who received vitamin C-containing treatment, and the control group (odds ratio [OR], 0.87; 95% confidence interval [CI]: 0.71–1.08; P = .20). In subgroup analysis of eight RCTs focusing on patients with septic shock, there was no significant difference in 28-day mortality between the study and control groups (OR, 1.09; 95% CI: 0.89–1.34; P = .41). In addition, no significant difference was observed between the study and control groups in intensive care unit-mortality (OR, 1.03; 95% CI: 0.84–1.25; P = .81), in-hospital mortality (OR, 1.06; 95% CI: 0.85–1.13; P = .60), and 90-day mortality (OR, 1.23; 95% CI: 0.75–2.02; P = .40). Conclusions: The results of this systematic review and meta-analysis indicated that adjunctive vitamin C-containing therapy did not help improve the clinical outcomes of patients with sepsis/septic shock. Our findings do not support the additional use of vitamin C for septic patients.

Aim This meta-analysis aimed to assess the usefulness of colchicine in patients with COVID-19.Methods PubMed, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Clinicaltrials.gov were searched for relevant randomised controlled trials (RCTs) published between database inception and November 12, 2021. Only RCTs that compared the clinical efficacy and safety of colchicine with other alternative treatments or placebos in patients with COVID-19 were included.Results Overall, 7 RCTs involving 16,024 patients were included; 7,794 patients were in the study group receiving colchicine and 8,230 were in the control group receiving placebo or standard treatment. The study and control groups had similar risk of mortality (odds ratio [OR], 1.00; 95% CI, 0.91–1.09; I2 = 0%). No significant difference was observed between the study and control groups in terms of the need for non-invasive ventilation (OR, 0.92; 95% CI, 0.83–1.03; I2 = 0%), the need for mechanical ventilation (OR, 0.64; 95% CI, 0.32–1.32; I2 = 58%), and length of hospital stay (mean difference, −0.42 days; 95% CI, −1.95 to 1.11; I2 = 62%). In addition, colchicine was associated with significantly higher risks of gastrointestinal adverse events (OR, 1.81; 95% CI, 1.56–2.11; I2 = 0%) and diarrhoea (OR, 2.12; 95% CI, 1.75–2.56; I2 = 9%).Conclusions Colchicine does not improve clinical outcomes in patients with COVID-19, so it did not support the additional use of colchicine in the treatment of patients with COVID-19.Key messageColchicine could not reduce the mortality of patients with COVID-19.No significant difference was observed between the colchicine and comparators in terms of the need for non-invasive ventilation, need for mechanical ventilation, and length of hospital stay.Colchicine was associated with a higher risk of gastrointestinal adverse events.

Objectives: This meta-analysis investigated the use of fluvoxamine for the treatment of nonhospitalized patients with COVID-19. Methods: PubMed, Web of Science, Ovid medline, Embase, Scopus, Cochrane Library databases, and ClinicalTrials.gov were searched for studies published before June 25, 2022. Only clinical studies that compared the efficacy and safety of fluvoxamine with other alternatives or placebos in the treatment of nonhospitalized patients with COVID-19 were included. Results: Four studies with 1814 patients, of whom 912 received fluvoxamine, were included in this study. Compared with the control group receiving placebo or no therapy, the study group receiving fluvoxamine demonstrated a lower risk of hospitalization and emergency department (ED) visits (odds ratio [OR], 0.59; 95 % CI, 0.44–0.79; I2 = 26 %). In addition, the rate of hospitalization remained significantly lower in patients who received fluvoxamine than in the control group (OR, 0.69; 95 % CI, 0.51–0.94; I2 = 36 %). Although the study group demonstrated a lower risk of requirement of mechanical ventilation and intensive care unit admission, and mortality than the control group, these differences were nonsignificant. Finally, fluvoxamine use was associated with a similar risk of adverse events as that observed in the control group. Conclusion: Fluvoxamine can be safely used in nonhospitalized patients with COVID-19 and can reduce the hospitalization rate or ED visits in these patients.

The emergence of the monkeypox outbreak in early 2022 has posed a new global health threat. As of July 8, 2022, 9069 laboratory-confirmed cases have been reported, and most of them are from non-endemic countries. The monkeypox virus is an enveloped double-stranded DNA virus, and preliminary genetic data suggest that the 2022 monkeypox virus belongs to the West African clade. In the current outbreak, human-to-human transmission has been the primary transmission mode. Although direct skin-to-skin contact with lesions during sexual activities can spread the virus, it remains unclear whether monkeypox can spread through sexual contact, specifically through contaminated body fluids. The typical presentation of monkeypox includes prodromal symptoms, followed by a rash that usually begins within 1–3 days of symptom onset, and the skin lesions can last for 2–4 weeks and then gradually resolve. However, the monkeypox outbreak in 2022 may exhibit atypical features. A definite diagnosis of monkeypox virus infection requires nucleic acid amplification testing via the polymerase chain reaction method. Supportive care is essential, and antiviral therapy is not considered for all affected patients, but recommended for those at highrisk for severe diseases. The mitigation of monkeypox outbreaks include enhanced case detection, case isolation, contact tracing, and post-exposure vaccination. In conclusion, the current monkeypox outbreak is a new threat during the COVID-19 pandemic. Clinicians should be aware of this new situation, which presents a different scenario from those of prior outbreaks. Global health systems should develop effective strategies to mitigate the spread of monkeypox.

Purpose: To compare the clinical effectiveness of branded versus generic piperacillin-tazobactam for treating severe community-acquired pneumonia (CAP). Patients and methods: We identified patients with severe CAP who received piperacillin-tazobactam based on a nine-center registry database. Furthermore, we classified the patients in three hospitals, which used only branded piperacillin-tazobactam as the study group, and the patients in six other hospitals, which used both branded and generic products as the control group. Results: A total of 472 patients (n = 263 in the study group and n = 209 in the control group) with severe CAP were included. The study group using branded piperacillin-tazobactam had higher odds of clinical cure (adjusted odds ratio [OR] = 3.77, 95 % confidence interval [CI], 1.93–7.37) and lower odds of treatment failure (adjusted OR = 0.28, 95 % CI, 0.13–0.58) than the control group receiving either branded or generic piperacillin-tazobactam. In addition, the study group was associated with higher odds of clinical effectiveness (adjusted OR = 2.95, 95 % CI, 1.46–6.11), less odds of clinical ineffectiveness (adjusted OR = 0.39, 95 % CI, 0.18–0.81), and lower risk of in-hospital mortality (adjusted OR = 0.39, 95 % CI, 0.21–0.73). Conclusion: Based on the findings of the present study using indirect comparison, the clinical effectiveness of generic piperacillin-tazobactam for treating patients with severe CAP might not be as good as that of brand-name products.

Background: This study was conducted to compare the number of cases of non-airborne/droplet-transmitted notifiable infectious disease (NID) before and after COVID-19 pandemic. Methods: This study used an open database - National Notifiable Diseases Surveillance System to collect the epidemiological data of NIDs. Ten fecal-oral-, six vector-borne-, four direct-contact, and four sexually-transmitted NIDs between pandemic period (defined as from January 2020 to December 2021) and the pre-pandemic period (defined as the period from January 2018 to December 2019) were included for the analysis. Results: Overall, the annual case number of these 24 non-airborne/droplet-transmitted NIDs was 19,186, 19,101, 19,567, and 19,863 in 2018, 2019, 2020 and 2021, respectively. The overall case number in the pandemic period was higher than those in pre-pandemic period (39,430 vs 38,287) and the monthly case number was significantly higher in pandemic period than pre-pandemic period (1643 vs 1595, p

ObjectivesWe assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned extubation.MethodsWe searched the Pubmed, Embase, the Cochrane databases and ClinicalTrial.gov registration for articles published through September 29, 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacies of systemic corticosteroids and other therapeutics for preventing postextubation stridor and reintubation were included. The primary outcome was postextubation stridor and the secondary outcome was reintubation.ResultsThe 11 assessed RCTs reported 4 nodes: methylprednisolone, dexamethasone, hydrocortisone, and placebo, which yielded 3 possible pairs for comparing the risks of post extubation stridor and 3 possible pairs for comparing the risks of reintubation. The risk of postextubation stridor was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients (dexamethasone: OR = 0.39; 95% CI = 0.22–0.70; methylprednisolone: OR = 0.22; 95% CI = 0.11–0.41). The risk of postextubation stridor was significantly lower in methylprednisolone-treated patients than in hydrocortisone-treated: OR = 0.24; 95% CI = 0.08–0.67) and dexamethasone-treated patients: OR = 0.55; 95% CI = 0.24–1.26). The risk of reintubation was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients: (dexamethasone: OR = 0.34; 95% CI = 0.13–0.85; methylprednisolone: OR = 0.42; 95% CI = 0.25–0.70). Cluster analysis showed that dexamethasone- and methylprednisolone-treated patients had the lowest risks of stridor and reintubation. Subgroup analyses of patients with positive cuff-leak tests showed similar results.ConclusionsMethylprednisolone and dexamethasone were the most effective agents against postextubation stridor and reintubation.

ObjectivesTo investigate the in vitro activity of antibiotic combinations against Stenotrophomonas maltophilia isolates and their associated biofilms.MethodsThirty-two S. maltophilia clinical isolates with at least twenty-five different pulsotypes were tested. The antibacterial activity of various antibiotic combinations against seven randomly selected planktonic and biofilm-embedded S. maltophilia strains with strong biofilm formation was assessed using broth methods. Extraction of bacterial genomic DNA and PCR detection of antibiotic resistance and biofilm-related genes were also performed.ResultsThe susceptibility rates of levofloxacin (LVX), fosfomycin (FOS), tigecycline (TGC) and sulfamethoxazole-trimethoprim (SXT) against 32 S. maltophilia isolates were 56.3, 71.9, 71.9 and 90.6%, respectively. Twenty-eight isolates were detected with strong biofilm formation. Antibiotic combinations, including aztreonam-clavulanic (ATM-CLA) with LVX, ceftazidime-avibactam (CZA) with LVX and SXT with TGC, exhibited potent inhibitory activity against these isolates with strong biofilm formation. The antibiotic resistance phenotype might not be fully caused by the common antibiotic-resistance or biofilm-formation gene.ConclusionS. maltophilia remained resistant to most antibiotics, including LVX and β-lactam/β-lactamases; however, TGC, FOS and SXT still exhibited potent activity. Although all tested S. maltophilia isolates exhibited moderate-to-strong biofilm formation, combination therapies, especially ATM-CLA with LVX, CZA with LVX and SXT with TGC, exhibited a higher inhibitory activity for these isolates.

Objectives: This meta-analysis of randomized controlled trials (RCTs) investigated the usefulness of mesenchymal stromal cells (MSCs) to treat patients with COVID-19. Methods: PubMed, Embase, Ovid MEDLINE, the Cochrane Library, and Clinicaltrials.gov were searched for RCTs published before November 7, 2021. Only RCTs that compared the clinical efficacy and safety of MSCs with other alternative treatments or placebos in the treatment of patients with COVID-19 were included. Results: Six RCTs were included, in which the MSC and control groups consisted of 158 and 135 patients, respectively. The patients who received MSCs had a significantly lower 28-day mortality rate (7.6% vs 21.5%; OR, 0.18; 95% CI, 0.06–0.52; I2 = 0%) and significantly higher clinical improvement rate (OR, 6.05; 95% CI, 2.31–15.83; I2 = 0%) than the controls. The patients who received MSCs were associated with a similar risk of adverse events (AEs) and serious AEs to the control group (AEs: OR, 33; 95% CI, 0.09–1.18; I2 = 59%; serious AEs: OR, 0.30; 95% CI, 0.02–4.41; I2 = 53%). Conclusions: MSC treatment may help to improve the clinical outcomes of patients with COVID-19. In addition, MSC treatment appears to be a safe therapeutic option for patients with COVID-19.

Objectives: This study assessed the efficacy and safety of novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations in adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). Methods: PubMed, Web of Science, the Cochrane Library, Ovid MEDLINE, Embase and EBSCO databases were searched for randomised controlled trials (RCTs) published before 13 September 2020. Only RCTs comparing the treatment efficacy of novel BL/BLI combinations with other antibiotics for HAP/VAP in adult patients were included in this integrated analysis. Results: Three RCTs were included and no significant difference in clinical cure rate of test of cure was observed between the novel BL/BLI combinations and comparators [odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.81–1.27; I2 = 35%]. The 28-day all-cause mortality was 16.2% and 17.6% for patients receiving novel BL/BLI combinations and comparators, respectively, and no significant difference was noted (OR = 0.90, 95% CI 0.69–1.16; I2 = 11%). Compared with comparators, novel BL/BLI combinations were associated with a similar microbiological response (OR = 1.06, 95% CI 0.73–1.54; I2 = 64%) and a similar risk of adverse events (AEs) [treatment-emergent AEs (TEAEs): OR = 1.04, 95% CI 0.83–1.30; I2 = 0%; serious AEs: OR = 1.14, 95% CI 0.79–1.63; I2 = 68%; treatment discontinuation for TEAE: OR = 0.90, 95% CI 0.62–1.31; I2 = 11%). Conclusion: Clinical and microbiological responses of novel BL/BLI combinations in the treatment of HAP/VAP were similar to those of other available antibiotics. These combinations also shared a similar safety profile to comparators.

IntroductionBeta-blockers are widely prescribed to manage hypertension and cardiovascular diseases and have been suggested as an attractive therapy to improve the prognosis of sepsis. Herein, we investigated the potential benefits of premorbid selective beta-blocker use in sepsis with a real-world database and explored the underlying mechanism by in vivo and in vitro experiments.MethodsA total of 64,070 sepsis patients and 64,070 matched controls who were prescribed at least one anti-hypertensive drug for more than 300 days within 1 year were selected for the nested case–control study. Female C57BL/6 J mice and THP-1 cells stimulated with lipopolysaccharide (LPS) were used for studying systemic responses during sepsis to validate our clinical findings.ResultsThe risk of sepsis was lower in current selective beta-blocker users than in non-users (adjusted OR (aOR), 0.842; 95% CI, 0.755–0.939), and in recent users than in non-users (aOR, 0.773; 95% CI, 0.737–0.810). A mean daily dose of ≥0.5 DDD was associated with a lower risk of sepsis (aOR, 0.7; 95% CI, 0.676–0.725). Metoprolol, atenolol, and bisoprolol users had lower risk of sepsis than non-users. In a LPS-induced sepsis mouse model, mice pre-fed with atenolol had significantly reduced mortality. While atenolol had some mild effects on LPS-induced release of inflammatory cytokines in septic mice, it significantly reduced serum soluble PD-L1 levels. Notably, atenolol treatment reversed the negative correlation of sPD-L1 with inflammatory cytokines in septic mice. Moreover, atenolol markedly downregulated the PD-L1 expression on LPS-stimulated THP-1 monocytes/macrophages via targeting ROS-induced NF-κB and STAT3 activation.ConclusionAtenolol pretreatment can reduce sepsis mortality in mice, and in vivo and in vitro studies of PD-L1 expression suggest a role for atenolol in the modulation of immune homeostasis. These findings may contribute to the reduced incidence of sepsis in hypertensive patients with premorbid treatment with selective beta-blockers, especially atenolol.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly become a global threaten since its emergence in the end of 2019. Moreover, SARS-CoV-2 infection could also present with co-infection or secondary infection by other virus, bacteria, or fungi. Among them, mucormycosis is a rare but aggressive fungal disease and it mainly affects patients particularly with poorly controlled diabetes mellitus with diabetic ketoacidosis (DKA). We here did a comprehensive review of literature reporting COVID-19 associated with mucormycosis (CAM) cases, which have been reported worldwide. The prevalence is higher in India, Iran, and Egypt than other countries, particularly highest in the states of Gujarat and Maharashtra in India. Poor diabetic control and the administration of systemic corticosteroids are the common precipitating factors causing mucormycosis in the severe and critical COVID-19 patients. In addition, COVID-19 itself may affect the immune system resulting in vulnerability of the patients to mucormycosis. Appropriate treatments of CAM include strict glycemic control, extensive surgical debridement, and antifungal therapy with amphotericin B formulations.

Background: Anti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear. Methods: A literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation. Results: A total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86–0.97, I2 = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV1 from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, −0.86, 95% CI, −1.92 – 0.19, I2 = 0%; FEV1, mean difference, 0.01, 95% CI, −0.01 – 0.03, I2 = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99–1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72–1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85–1.01) when compared with the placebo. Conclusion: Anti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.

The emergence of antimicrobial resistance among microorganisms is a serious public health concern, and extended-spectrum β-lactamases (ESBL)-producing Enterobacterales is one of the major concerns among antibiotic-resistant bacteria. Although the prevalence of ESBL in Enterobacterales has been increasing with time, the prevalence of ESBL could differ according to the species, hospital allocation, sources of infections, nosocomial or community acquisitions, and geographic regions. Therefore, we conducted a comprehensive review of the epidemiology of ESBL-producing Enterobacterales in Taiwan. Overall, the rates of ESBL producers are higher in northern regions than in other parts of Taiwan. In addition, the genotypes of ESBL vary according to different Enterobacterales. SHV-type ESBLs (SHV-5 and SHV-12) were the major types of Enterobacter cloacae complex, but Serratia marcescens, Proteus mirabilis, Escherichia coli, and Klebsiella pneumoniae were more likely to possess CTX-M-type ESBLs (CTX-M-3 and CTX-M-14). Moreover, a clonal sequence type of O25b-ST131 has been emerging among urinary or bloodstream E. coli isolates in the community in Taiwan, and this clone was potentially associated with virulence, ESBL (CTX-M-15) production, ciprofloxacin resistance, and mortality. Finally, the evolution of the genetic traits of the ESBL-producing Enterobacterales isolates helps us confirm the interhospital and intrahospital clonal dissemination in several regions of Taiwan. In conclusion, continuous surveillance in the investigation of ESBL production among Enterobacterales is needed to establish its long-term epidemiology.

ObjectivesThis study investigated the inhibitory effect of Lactobacillus spp. with prebiotics against Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing Klebsiella pneumoniae using both in vitro experiments and animal models.MethodsThirty-three Lactobacillus spp. strains were confirmed by 16S rDNA sequencing, and four different PFGE genotyped KPC-2-producing K. pneumoniae strains were selected for investigation. In vitro studies, including broth microdilution assays, changes in pH values in lactobacilli cultures with different prebiotics, time-kill tests of Lactobacillus spp. against KPC-2-producing K. pneumoniae and further in vivo Lactobacillus alone or in combination with prebiotics against KPC-2-producing K. pneumoniae in an animal model, were performed.ResultsThe lower pH value of the cell-free supernatant was associated with a lower minimal inhibitory percentage of the Lactobacillus strain against KPC-2-producing K. pneumoniae. Furthermore, lactulose/isomalto-oligosaccharide/inulin and fructo-oligosaccharide can enhance the inhibitory effect of all 107 CFU/ml Lactobacillus strains against KPC001. Three Lactobacillus strains (LYC1154, LYC1322, and LYC1511) that could be persistently detected in the stool were tested for their ability to reduce the amount of KPC001 in the feces individually or in combination. A significantly better effect in reducing the amount of KPC001 was observed for the combination of three different Lactobacillus species than for each of them alone. Furthermore, their inhibitory effect was enhanced after adding lactulose or isomalto-oligosaccharide (both p

Purpose: The aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza. Methods: PubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included. Results: Three RCTs enrolling 3771 patients (baloxavir group, n = 1451; oseltamivir group, n = 1288; placebo group, n = 1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], −1.29 h; 95% CI, −6.80 to 4.21; I2 = 0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, −26.32 h; 95% CI, −33.78 to −18.86; I2 = 0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69–0.98; I2 = 0%) and placebo (OR, 0.79; 95% CI, 0.66–0.96; I2 = 0%). Conclusions: The findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.

Abstract Background The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. Methods We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). Results Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI − 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI − 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). Conclusions In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.

BackgroundFor the intensivists, accurate assessment of the ideal timing for successful weaning from the mechanical ventilation (MV) in the intensive care unit (ICU) is very challenging.PurposeUsing artificial intelligence (AI) approach to build two-stage predictive models, namely, the try-weaning stage and weaning MV stage to determine the optimal timing of weaning from MV for ICU intubated patients, and implement into practice for assisting clinical decision making.MethodsAI and machine learning (ML) technologies were used to establish the predictive models in the stages. Each stage comprised 11 prediction time points with 11 prediction models. Twenty-five features were used for the first-stage models while 20 features were used for the second-stage models. The optimal models for each time point were selected for further practical implementation in a digital dashboard style. Seven machine learning algorithms including Logistic Regression (LR), Random Forest (RF), Support Vector Machines (SVM), K Nearest Neighbor (KNN), lightGBM, XGBoost, and Multilayer Perception (MLP) were used. The electronic medical records of the intubated ICU patients of Chi Mei Medical Center (CMMC) from 2016 to 2019 were included for modeling. Models with the highest area under the receiver operating characteristic curve (AUC) were regarded as optimal models and used to develop the prediction system accordingly.ResultsA total of 5,873 cases were included in machine learning modeling for Stage 1 with the AUCs of optimal models ranging from 0.843 to 0.953. Further, 4,172 cases were included for Stage 2 with the AUCs of optimal models ranging from 0.889 to 0.944. A prediction system (dashboard) with the optimal models of the two stages was developed and deployed in the ICU setting. Respiratory care members expressed high recognition of the AI dashboard assisting ventilator weaning decisions. Also, the impact analysis of with- and without-AI assistance revealed that our AI models could shorten the patients’ intubation time by 21 hours, besides gaining the benefit of substantial consistency between these two decision-making strategies.ConclusionWe noticed that the two-stage AI prediction models could effectively and precisely predict the optimal timing to wean intubated patients in the ICU from ventilator use. This could reduce patient discomfort, improve medical quality, and lower medical costs. This AI-assisted prediction system is beneficial for clinicians to cope with a high demand for ventilators during the COVID-19 pandemic.

Background: This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). Methods: Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. Results: All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2–21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. Conclusions: Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.