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BACKGROUND: Ventilator-associated pneumonia (VAP) constitutes a considerable challenge for patients in intensive care units (ICUs) and necessitates the development of effective preventive strategies. This study aimed to evaluate the clinical efficacy of inhaled antibiotics for preventing VAP. METHODS: PubMed, Embase, and ClinicalTrials.gov were searched until January 21, 2024. Randomized controlled trials (RCTs) investigating the clinical efficacy of inhaled antibiotics for VAP prevention were included. RESULTS: Seven RCTs, involving 1465 patients, of whom 734 were classified as the study group receiving inhaled antibiotics and 731 as the control group receiving placebo were included in this meta-analysis. Overall, the occurrence of VAP was significantly lower in the study group than in the control group (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.51 to 0.92). However, there were no significant differences in mortality (RR, 0.90; 95% CI, 0.74 to 1.09), length of stay in ICU (mean difference [MD], 0.10 days; 95% CI, -0.91 to 1.1) and hospital (MD, 0.30 days; 95% CI, -1.82 to 2.43), and mechanical ventilation (MV) duration (MD, 0.45 days; 95% CI, -0.45 to 1.35) between groups. CONCLUSION: Inhaled antibiotics hold promise for mitigating the risk of VAP among critically ill patients. However, their impact on mortality, length of stay in ICU and hospital, and MV duration was not statistically significant.

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Although the recombinant zoster vaccine (RZV) has demonstrated efficacy in reducing the risk of herpes zoster (HZ) for individuals aged 50 years and older, its effectiveness in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. This study was conducted to assess the effect of RZV on the risk of HZ in COPD patients. A multi-institutional propensity score-matched retrospective cohort study was conducted using the TriNetX Research network, including individuals aged 40 years or older with COPD from January 1, 2018, to December 31, 2022. Patients with a history of HZ or prior zoster vaccination were excluded. The primary outcome was HZ occurrence, with secondary outcomes including severe and nonsevere HZ. After propensity score matching, each 17 431 patients receiving RZV and unvaccinated patients were included. The vaccinated group had a significantly lower risk of HZ compared to the unvaccinated group (HR, 0.62; [95% confidence intervals] 95% CI, 0.51-0.75, p < 0.01). Similar risk reductions were observed for nonsevere HZ (HR, 0.61; 95% CI, 049-0.75, p < 0.01) and severe HZ (HR, 0.53; 95% CI, 0.38-0.73, p < 0.01). Further subgroup analyses demonstrated consistent risk reductions across age (50-59, 60-69, 70-79, and ≥80 years), sex, and comorbidities, except for individual aged 40-49 years. This study confirms the effectiveness of RZV in reducing HZ risk in patients with COPD aged 50 years and older, supporting its administration in this population. However, vaccination rates remain low, highlighting the need for improved vaccination strategies in this high-risk group. Efforts to enhance vaccine uptake are warranted to reduce HZ morbidity.

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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 < 0.001). Stratified analyses by age, SARS-CoV-2 variant, vaccination status, and infection status consistently supported this association. Non-hospitalized individuals with COVID-19 demonstrated a higher risk of new-onset asthma (aHR, 1.27; 95% CI, 1.22-1.33; p < 0.001); however, no significant differences were observed in hospitalized and critically ill groups. The study also identified an increased risk of subsequent bronchiectasis following COVID-19 (aHR, 1.30; 95% CI, 1.13-1.50; p < 0.001). In contrast, there was no significant difference in the hazard of chronic obstructive pulmonary disease between the groups (aHR, 1.00; 95% CI, 0.95-1.06; p = 0.994). CONCLUSION: This study offers convincing evidence of the association between COVID-19 and the subsequent onset of asthma and bronchiectasis. It underscores the need for a multidisciplinary approach to post-COVID-19 care, with a particular focus on respiratory health.

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BACKGROUND: This study assessed the effect of hydrocortisone-fludrocortisone combination therapy on the mortality of patients with septic shock. METHODS: A literature search was conducted using Medline, Embase, the Cochrane Library, ClinicalTrials.gov, and other databases for articles published until October 1, 2023. Only clinical studies that assessed the clinical efficacy and safety of hydrocortisone-fludrocortisone therapy for the treatment of septic shock were included. The primary outcome was the in-hospital mortality rate. RESULTS: Seven studies with a total of 90, 756 patients were included. The study group exhibited lower in-hospital mortality rates (40.8% vs. 42.8%; OR, 0.86; 95% CI, 0.80-0.92). Compared to the control group, the study group also had lower intensive care unit (ICU) mortality (OR, 0.77; 95% CI, 0.63-0.95), 28-day mortality (OR, 0.85; 95% CI, 0.72-1.00), 90-day mortality (OR, 0.85; 95% CI, 0.71-1.01), 180-day mortality (OR, 0.82; 95% CI, 0.68-0.90), and one-year mortality (OR, 0.70; 95% CI, 0.42-1.16). Subgroup analyses showed a similar trend, particularly prominent in the pooled analysis of randomized clinical trials, multicenter studies, and ICU patients, the study drug regimen involved hydrocortisone at a dose of 50 mg every 6 h in combination with fludrocortisone at 50 µg daily, with the control group receiving either placebo or standard care. Hydrocortisone-fludrocortisone also increased vasopressor-free days and reduced vasopressor duration, without elevating the risk of adverse events. CONCLUSIONS: This study emphasizes the potential survival benefits of hydrocortisone-fludrocortisone combination therapy for patients with septic shock and its additional advantages, including reduced vasopressor use.

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Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006-1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18-64 years old (HR 1.853, 95% CI 1.002-3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118-3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343-12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18-64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18-64 years and those with cardiovascular risk factors.

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Aspergillus is a common filamentous fungus found in various natural environments, with spores frequently inhaled by humans. While healthy individuals typically resist infection, immunocompromised individuals and those with pre-existing lung diseases are at higher risk for aspergillosis. Chronic pulmonary aspergillosis (CPA) often develops in individuals with conditions like tuberculosis and chronic obstructive pulmonary disease. Recent studies in Taiwan reveal a significant incidence of CPA among elderly patients with these underlying conditions. The most common clinical manifestations include cavitation, nodules, and consolidation in the lungs. Aspergillus-specific IgG antibodies have emerged as key diagnostic markers, with varying optimal cut-off values across different regions. Studies indicate a strong correlation between high IgG levels and severe CPA, alongside associations with specific radiographic features. Additionally, elevated inflammatory markers such as IL-1ß and TNF-α are linked to poor outcomes, emphasizing the need for early detection and intervention. The preferred treatment regimen consists of itraconazole, voriconazole, posaconazole, and isavuconazole, with itraconazole and voriconazole being the most extensively documented in the context of CPA. Overall, this review underscores the importance of localized diagnostic validation and comprehensive studies to improve the understanding and treatment of CPA in Taiwan.

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Objectives: This study investigated the clinical effectiveness of molnupiravir for treating non-hospitalized COVID-19 patients with pre-existing psychiatric disorder. Methods: This 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. Results: Two 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. Conclusion: Molnupiravir 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.

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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.

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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.

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OBJECTIVES: This study assessed the effectiveness of the oral antiviral agents nirmatrelvir - ritonavir (NMV-r) and molnupiravir (MOV) for treating mild-to-moderate coronavirus disease 2019 (COVID-19) in patients with COPD. METHODS: This retrospective cohort study extracted data from the TriNetX platform and examined 94,984 COVID-19 patients with preexisting COPD from 1 January 2022, to 1 October 2023. Patients receiving NMV-r or MOV (study group) were compared with those not receiving oral antiviral agents (control group) after propensity score matching (PSM). RESULTS: After PSM, 7,944 patients were classified into the study and control groups. The primary composite outcome of all-cause hospitalization, or death in 30 days was reported in 458 (5.7%) patients in the study group and 566 (7.1%) patients in the control cohort, yielding a hazard ratio [HR] of 0.79 (95% confidence interval [CI]: 0.70-0.89; Table 2). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (HR, 0.87; 95% CI: 0.76-0.99) and death (HR: 0.21, 95% CI: 0.13-0.35). CONCLUSIONS: This study revealed that oral antivirals - NMV-r or MOV might improve clinical outcomes in patients with preexisting COPD and COVID-19. However, only a small proportion of preexisting COPD patients with COVID-19 received oral antiviral treatment.

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This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

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BACKGROUND: This meta-analysis was conducted to compare the efficacy of ceftazidime-avibactam combination therapy with that of monotherapy in the treatment of carbapenem-resistant Gram-negative bacterial (CR-GNB). METHODS: A literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was conducted until September 1, 2023. Only studies that compared CZA combination therapy with monotherapy for CR-GNB infections were included. RESULTS: A total of 25 studies (23 retrospective observational studies and 2 prospective studies) involving 2676 patients were included. There was no significant difference in 30-day mortality between the study group receiving combination therapy and the control group receiving monotherapy (risk ratio [RR] 0.91; 95% confidence interval [CI] 0.71-1.18). In addition, no significant differences were observed between the study and the control group in terms of in-hospital mortality (RR 1.00; 95% CI 0.79-1.27), 14-day mortality (RR 1.54; 95% CI 0.24-9.91), 90-day mortality (RR 1.18; 95% CI 0.62-2.22), and clinical cure rate (RR 0.95; 95% CI 0.84-1.08). However, the combination group had a borderline higher microbiological eradication rate than the control group (RR 1.15; 95% CI 1.00-1.32). CONCLUSIONS: Compared to monotherapy, CZA combination therapy did not yield additional clinical benefits. However, combination therapy may be associated with favorable microbiological outcomes.

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OBJECTIVES: This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. METHODS: Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. RESULTS: Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599-0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328-0.451) and all-cause death (HR: 0.110; 95% CI: 0.053-0.228) compared with the control group. CONCLUSION: NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

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INTRODUCTION: The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity. AREA COVERED: This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety. EXPERT OPINION: Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline's efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline's adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline's role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections.

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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.

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OBJECTIVES: This study investigated the association between nirmatrelvir plus ritonavir (NMV-r) or molnupiravir and the outcomes of non-hospitalized high-risk patients with COVID-19 during Omicron XBB subvariants. METHODS: The retrospective cohort study used the TriNetX US collaborative network to identify non-hospitalized high-risk adult patients with COVID-19 between 1 February 2023, and 31 August 2023. Propensity score matching (PSM) was used to match patients receiving NMV-r or MOV (the study group) with those not receiving antivirals (the control group). RESULTS: Using PSM, two cohorts of 17,654 patients each with balanced baseline characteristics were identified. During the follow-up period, the study group had a lower risk of all-cause hospitalization, or death (3.2% [n = 564] versus 3.8% [n = 669]; HR, 0.796; 95% confidence interval [CI], 95% CI, 0.712-0.891). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (3.1% vs. 3.4%; HR, 0.847; 95% CI, 0.754-0.950) and mortality (0.1% vs. 0.4%; HR, 0.295; 95% CI, 0.183-0.476). CONCLUSION: The use of novel oral antiviral including NMV-r or MOV can be associated with a lower risk of all-cause hospitalization, or death in non-hospitalized high-risk patients with COVID-19 during Omicron XBB wave.