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Diet is thought to be one of the leading causes of bone mineral loss in aging people. In this study, we explored the potential impact of a vegetarian diet on bone mineral density (BMD) in adult Taiwanese men and women. This was a cross-sectional study of the relationship between diet (vegetarian versus non-vegetarian) and BMD and the incidence of osteoporosis. Bone mineral density was determined in a cohort of 1865 adult male and female patients who underwent routine examination in a regional teaching hospital in Taiwan between February 2003 and February 2004. Subjects with definite vertebral problems, known osteopathy, or poor posture were excluded. Dual-energy X-ray absorptiometry (DEXA) was used to determine BMD, on the right hip in men and on lumbar vertebrae L2 to L4 in women. The subjects were grouped according to sex and diet, and were then stratified by age within each of the four groups. The outcome measures were the BMD value and the incidence of osteopenia or osteoporosis according to defined criteria. Bone mineral density gradually declined with increasing age in Taiwanese men, while Taiwanese women showed a precipitous decrease in BMD after the 5(th) decade. However, no statistical differences in BMD were observed between vegetarians and non-vegetarians of either sex. The proportion of subjects with osteopenia or osteoporosis also appeared comparable between vegetarians and non-vegetarians of either sex. BMD shows an age-related decline in Taiwanese men and women, and eating a vegetarian diet does not appear to affect this decline. [ABSTRACT FROM AUTHOR]

Background: While the nephrotoxicity of lead and cadmium is well-established, the impact of low-level exposure on risk of chronic kidney disease (CKD) and long-term health outcomes, especially in CKD patients, remains unclear. This study examines the association between low-level lead and cadmium exposure with risks of CKD and long-term mortality., Method: We analyzed data from adult participants of 2003-2012 National Health and Nutrition Examination Survey in the United States. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2. Elevated blood lead (≥ 1.5 μg/dL) and cadmium (≥ 0.4 μg/L) levels were assessed for their associations with CKD and all-cause mortality, with survival tracked until December 31, 2019., Results: Among the 24,810 participants (mean age 44.4 years, 48.9% male), 1,309 (3.9%) had CKD. Lead and cadmium levels were significantly higher in participants with CKD compared to those without. Elevated lead (OR: 1.41, 95% CI: 1.15-1.74) and cadmium (OR: 1.23, 95% CI: 1.03-1.46) levels were both associated with increased CKD risk, with the highest risk in those with both lead ≥ 1.5 μg/dL and cadmium ≥ 0.4 μg/L (OR: 1.65, 95% CI 1.27-2.14). During a median follow-up of 141 months, 2,255 participants died (7.0 per 10,000 person-months). Elevated cadmium was associated with higher mortality risk in CKD (HR: 1.42, 95% CI: 1.07-1.88) and non-CKD populations (HR: 1.40, 95% CI: 1.24-1.58), while lead levels were not significantly associated with mortality in either group. Participants with both elevated lead and cadmium had a significantly higher mortality risk (HR: 1.32, 95% CI: 1.13-1.54)., Conclusion: Low-level cadmium and lead exposure are linked to increased CKD risk, with cadmium also associated with higher long-term mortality in both CKD and non-CKD populations. These findings highlight the need for public health efforts to reduce exposure and further research on long-term impacts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aims to evaluate the effectiveness of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing the post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as long COVID, and reducing all-cause mortality among older patients. A retrospective cohort study was conducted using the TriNetX database. The study cohort consisted of older patients (age ≥ 65 years) with their first COVID-19 illness between January 1, 2022, and May 31, 2024. Participants were divided into vaccinated and unvaccinated groups based on their vaccination status. Propensity score matching (PSM) was used to balance baseline characteristics. Cox regression models and log-rank tests were applied to estimate the hazard ratio (HR) for PASC and all-cause mortality during 30-180 days of follow-up. The study included 189 059 geriatric patients who contracted SARS-CoV-2, with 5615 vaccinated and 183 444 unvaccinated. After PSM, each group contained 5615 patients. Vaccinated patients exhibited a significantly lower incidence of PASC symptoms (HR = 0.852, 95% CI: 0.778-0.933, p = 0.0005), particularly anxiety and depression, with a HR of 0.710 (95% CI: 0.575-0.878, p = 0.0015). Vaccination was also significantly associated with reduced all-cause mortality (HR = 0.231, 95% CI: 0.136-0.394, p < 0.0001). The findings highlight the effectiveness of COVID-19 vaccination in mitigating the development of PASC and decreasing mortality among older patients., (© 2024 Wiley Periodicals LLC.)

Objective: To investigate the effectiveness of oral antiviral agents - nirmatrelvir - ritonavir or molnupiravir in non-hospitalized COVID-19 patients aged < 60 years., Methods: This retrospective cohort study analyzed data of patients aged 18-60 years diagnosed with COVID-19 between 1 January 2022, and 30 June 2023. Propensity score matching was used to balance the demographic and clinical characteristics of patients receiving oral antivirals (nirmatrelvir - ritonavir or molnupiravir) and untreated controls. The primary outcome was a composite of all-cause emergency department visits, hospitalizations, or mortality within 30 days. The secondary outcomes included each individual component of the primary composite outcome., Results: Two matched cohorts (antiviral group and control group) comprising 52,585 patients with balanced baseline characteristics were created using propensity score-matching. During follow-up period, the antiviral group demonstrated a lower risk of the primary outcome than the control group (hazard ratio [HR] 0.772, 95% confidence interval [CI] 0.736-0.808, p  < 0.001). The antiviral group also exhibited a reduced risk of individual secondary outcomes, including emergency department visits (HR 0.780, 95% CI, 0.738-0.825), hospitalization (HR 0.755, 95% CI, 0.715-0.840), and mortality (HR 0.297, 95% CI, 0.147-0.600)., Conclusion: Oral antiviral agents were associated with lower risks of all-cause emergency department visits, hospitalizations, and mortality in non-hospitalized COVID-19 patients aged < 60 years.

Background: Semaglutide has shown potential liver benefits in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). However, no direct comparisons have been made between semaglutide and other antidiabetic medications, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), thiazolidinediones (TZD), and dipeptidyl peptidase-4 inhibitors (DPP-4i), regarding liver outcomes in patients with both NAFLD and T2D., Methods: This retrospective cohort study utilized the TriNetX electronic health record database, a multinational and multi-institutional database. Adults with NAFLD and T2D who received their first prescription for either semaglutide or other antidiabetic medications were included. New users of semaglutide were matched 1:1 via propensity score matching with users of SGLT2i, DPP-4i, and TZD. The primary outcome was major adverse liver outcome (MALO), a composite end point consisting of decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. Secondary outcomes included the individual components of MALO and all-cause mortality., Results: A total of 648,070 adult patients with T2D and NAFLD were identified, and patients were categorized into three different comparison groups based on their drug of interest. Semaglutide was associated with a lower risk of MALO compared to SGLT2i (adjusted hazard ratio [aHR], 0.73; 95% CI 0.60-0.88), DPP-4i (aHR, 0.72; 95% CI 0.56-0.86), and TZD (aHR, 0.76; 95% CI 0.56-0.99). Additionally, semaglutide was linked to a lower risk of all-cause mortality compared to SGLT2i (aHR, 0.62; 95% CI 0.53-0.72), DPP-4i (aHR, 0.42; 95% CI 0.36-0.49), and TZD (aHR, 0.67; 95% CI 0.54-0.83)., Conclusion: Semaglutide is associated with better liver outcomes and a lower risk of all-cause mortality compared to SGLT2i, DPP-4i, and TZD in patients with NAFLD and T2D., Competing Interests: Declarations. Competing interests: The authors state that they have no conflicts of interest. Ethics approval and consent to participate: The Institutional Review Board of the Chi Mei Medical Center approved the study protocol. Written informed consent was not required because TriNetX contains anonymized data. Consent for publication: All authors consent to the publishing of this article., (© 2024. Asian Pacific Association for the Study of the Liver.)

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 21 January 2024. Randomized controlled trials investigating the clinical efficacy of inhaled antibiotics for VAP prevention were included., Results: Seven randomized controlled trials, 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, 0.69; 95% confidence interval [CI], 0.51-0.92). However, there were no significant differences in mortality (risk ratio, 0.90; 95% CI, 0.74-1.09), length of stay in ICU (mean difference [MD], 0.10 d; 95% CI, -0.91 to 1.1), and hospital (MD, 0.30 d; 95% CI, -1.82 to 2.43), and mechanical ventilation duration (MD, 0.45 d; 95% CI, -0.45 to 1.35) between groups., Conclusions: 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 mechanical ventilation duration was not statistically significant., Competing Interests: Declaration of competing interests All authors affirm that no conflict of interest exists., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

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.

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., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Context: Investigating the co-occurrence of obstructive sleep apnea (OSA) and primary aldosteronism (PA) is crucial for understanding their interrelation., Objective: This work aimed to evaluate the prevalence of OSA in individuals diagnosed with PA and to assess the prevalence of PA within the OSA population, with a specific focus on hypertensive individuals., Methods: An exhaustive search was performed across PubMed, Embase, CINAHL, Scopus, and Web of Science up to September 2023, without restrictions on language or publication date. Studies were selected based on their focus on the prevalence of OSA in PA patients and vice versa, specifically in hypertensive individuals. Data were extracted using standard guidelines, focusing on patient characteristics, prevalence rates, and other relevant clinical parameters., Results: Proportional meta-analysis using a random-effects model revealed a 59.8% prevalence of OSA in hypertensive PA patients, with 45.4% exhibiting moderate-to-severe OSA. Meta-regression showed no significant effect of age, sex, body mass index, antihypertensive medication, systolic blood pressure, diastolic blood pressure, or serum potassium on OSA prevalence. However, a significant positive association was found with the glomerular filtration rate (GFR) (P < .001). Subgroup analysis also revealed that a hyperfiltration rate (GFR ≥ 100 mL/min per 1.73 m2) may be associated with a higher prevalence of OSA (71%, P value for interaction < .01). Among hypertensive OSA patients, 11.2% had PA., Conclusion: A substantial prevalence of OSA in individuals with PA was identified, demonstrating a complex interplay between these conditions in hypertensive patients. Notably, the prevalence of OSA was significantly associated with kidney hyperfiltration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

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., (© 2024. The Author(s).)

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., (© 2024 Wiley Periodicals LLC.)

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.

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., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

The 5-year survival is poor for stage IV non-small cell lung cancer (NSCLC). Recently, cell immunotherapy has emerged as a new treatment strategy. This study aimed to evaluate the efficacy and safety of Immune killer cells (IKC) in patients with stage IV NSCLC after the failure of prior chemotherapy. This study enrolled 26 patients with stage IV NSCLC who failed at least two lines of chemotherapy with or without targeted therapy. The IKC was given alone weekly for 24 weeks. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), pain intensity, quality of life (QOL), and safety. The median PFS for the intent-to-treat (ITT) population (i.e., all enrolled patients) was 3.8 month. In the per-protocol (PP) population (i.e., patients receiving > 12 IKC infusions), the median PFS was 5.6 months. Moreover, the ITT population showed a 1-year survival rate of 60.0%, while that for the PP population was 85.7%. Only 7 out of 200 AEs (3.5%) were related to the IKC infusion, and they were all rated as grade 1 in severity. The IKC infusion was well tolerated. This novel immunotherapy prolonged the PFS and improved the survival compared with historical data. It might be a potential treatment strategy for stage IV NSCLC patient who failed prior chemotherapy.ClinicalTrials.gov identifier: NCT03499834., (© 2024. The Author(s).)

Objectives: This study examined the effectiveness of nirmatrelvir plus ritonavir (NMV-r) and molnupiravir (MOV) in treating COVID-19 among chronic kidney disease (CKD) patients., Methods: This retrospective cohort study, using the TriNetX research network, identified stage 3-5 CKD and end-stage kidney disease (ESKD) patients with non-hospitalized COVID-19 between 1 January 2022, and 31 May 2023. Propensity score matching (PSM) was used to compare patients on NMV-r or MOV (antiviral group) against those not receiving these treatments (control group). The primary composite outcome was the cumulative hazard ratio (HR) for all-cause hospitalization or death within the 30-day follow-up., Results: After PSM, two balanced cohorts of 6,275 patients each were established. The antiviral group exhibited a lower incidence of all-cause hospitalization or mortality (5.93% vs. 9.53%; HR: 0.626; 95% CI: 0.550-0.713) than controls. Additionally, antiviral recipients were associated with a lower risk of all-cause hospitalization (HR: 0.679; 95% CI: 0.594-0.777) and mortality (HR: 0.338; 95% CI: 0.227-0.504). The beneficial effects of antiviral agents were consistent across sex, age, vaccination status, antiviral type, and CKD stage., Conclusion: Oral antiviral agents could be associated with lower rates of all-cause hospitalization or death among non-hospitalized COVID-19 patients with CKD.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: Despite its demonstrated benefits in improving cardiovascular risk profiles, the association of tirzepatide with mortality and cardiovascular and kidney outcomes compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) remains unknown., Objective: To investigate the association of tirzepatide with mortality and adverse cardiovascular and kidney outcomes compared with GLP-1 RAs in patients with type 2 diabetes., Design, Setting, and Participants: This retrospective cohort study used US Collaborative Network of TriNetX data collected on individuals with type 2 diabetes aged 18 years or older initiating tirzepatide or GLP-1 RA between June 1, 2022, and June 30, 2023; without stage 5 chronic kidney disease or kidney failure at baseline; and without myocardial infarction or ischemic or hemorrhagic stroke within 60 days of drug initiation., Exposures: Treatment with tirzepatide compared with GLP-1 RA., Main Outcomes and Measures: The primary outcome was all-cause mortality, and secondary outcomes included major adverse cardiovascular events (MACEs), the composite of MACEs and all-cause mortality, kidney events, acute kidney injury, and major adverse kidney events. All outcomes were analyzed using Cox proportional hazards regression models., Results: There were 14 834 patients treated with tirzepatide (mean [SD] age, 55.4 [11.8] years; 8444 [56.9%] female) and 125 474 treated with GLP-1 RA (mean [SD] age, 58.1 [13.3] years; 67 474 [53.8%] female). After a median (IQR) follow-up of 10.5 (5.2-15.7) months, 95 patients (0.6%) in the tirzepatide group and 166 (1.1%) in the GLP-1 RA group died. Tirzepatide treatment was associated with lower hazards of all-cause mortality (adjusted hazard ratio [AHR], 0.58; 95% CI, 0.45-0.75), MACEs (AHR, 0.80; 95% CI, 0.71-0.91), the composite of MACEs and all-cause mortality (AHR, 0.76; 95% CI, 0.68-0.84), kidney events (AHR, 0.52; 95% CI, 0.37-0.73), acute kidney injury (AHR, 0.78; 95% CI, 0.70-0.88), and major adverse kidney events (AHR, 0.54; 95% CI, 0.44-0.67). Treatment with tirzepatide was associated with greater decreases in glycated hemoglobin (treatment difference, -0.34 percentage points; 95% CI, -0.44 to -0.24 percentage points) and body weight (treatment difference, -2.9 kg, 95% CI, -4.8 to -1.1 kg) compared with GLP-1 RA. An interaction test for subgroup analysis revealed consistent results stratified by estimated glomerular filtration rate, glycated hemoglobin level, body mass index, comedications, and comorbidities., Conclusions and Relevance: In this study, treatment with tirzepatide was associated with lower hazards of all-cause mortality, adverse cardiovascular events, acute kidney injury, and adverse kidney events compared with GLP-1 RA in patients with type 2 diabetes. These findings support the integration of tirzepatide into therapeutic strategies for this population.

Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI's pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2·insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.

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.

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., (© 2024 Wiley Periodicals LLC.)

Objectives: This study investigated the outcomes of underweight patients with COVID-19 and the effectiveness of antiviral agents in this population., Methods: A retrospective cohort study using theTriNetX research network was conducted. Propensity score matching (PSM) was employed to balance the first cohort involving COVID-19 patients with underweight and normal-weight. In the second cohort, underweight patients receiving antiviral agents and untreated individuals were matched using PSM. The primary outcome was a composite of all-cause hospitalization and death during the 7-30-day follow-up period., Results: After PSM, the first cohort including each group of 13,502 patients with balanced baseline characteristics were identified for comparing the outcome of patients with underweight and normal weight. The underweight group had a higher risk of the composite primary outcome than those with normal weight (hazard ratio [HR], 1.251; 95% confidence interval [CI], 1.132-1.382). The second cohort included each 884 underweight patients with and without receiving antivirals.Compared with untreated patients, those receiving antiviral treatment had a lower risk of composite primary outcomes (HR, 0.426; 95% CI, 0.278-0.653)., Conclusion: Underweight status may be associated with a higher risk of all-cause hospitalization and death in patients with COVID-19.Among underweight patients, antiviral agents demonstrated clinically beneficial effects.

With the coming of a rapidly aging society, individuals born in the baby boom era after World War II are now facing the challenges of aging. From late middle age to successful aging, what are the perceptions and responses of these quasi-seniors? With this in mind, referring to Phelan's successful aging scale, the researchers developed the 4P Strategies (Physical, Psychological, Prospect, and Place and Relationships) tailored for quasi-seniors. Based on grounded theory, the results of 12 sessions of focused interviews (involving a total of 93 interviewees between the ages of 55 and 75; 41 males and 52 females; 48 not retired and 45 retired) were matched with the 4P Strategies. The results were the following: (1) regarding the Physical factor, the interviewees were shocked by their physical decline, and they had begun to devise strategies for health preservation and exercise; (2) regarding the Psychological factor, in order to mentally adapt, the interviewees agreed that moderate stress relief was absolutely necessary; (3) regarding the Prospect factor: the interviewees felt that one should make financial plans early, contemplate the value of life, and more actively learn and realize one's dreams; and (4) regarding the Place and Relationships factor, the interviewees aimed to rebuild their close relationships with their spouses, family members, and old friends and had polarized views regarding where to live in their old age. On the whole, the most discussed issue among the interviewees was where to live in their old age. Many had their own views and plans and did not stick to traditional views; however, they took the opinions of their significant others into account. During the interviews, interviewees wished to understand the responses of their peers to serve as a reference for their own decisions, and they realized that successful aging also required learning. This study aimed to encourage quasi-seniors about to enter their old age and help them to learn how to positively respond to aging as well as work towards a happy life with successful aging. This study could fill in gaps in research involving individuals in this age group and provide a reference for relevant policies.

Objectives: This study aimed to investigate the association between vitamin D deficiency (VDD) and post-acute outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: This retrospective study used the TriNetX research network to identify COVID-19 patients between January 1 and November 30, 2022. Patients were matched using propensity score matching (PSM) and divided into VDD (< 20 ng/mL) and control (≥ 20 ng/mL) groups. The primary outcome was a composite of post-COVID-19 condition (identified by ICD-10 code), all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period (90-180 days) after the diagnosis of COVID-19., Results: From an initial recruitment of 42,674 non-hospitalized patients with COVID-19 and known 25(OH)D status, a VDD group of 8300 was identified and propensity matched with 8300 controls. During the follow-up period, the VDD group had a higher risk of the primary outcome than did the control group [hazard ratio (HR) = 1.122; 95% confidence interval (CI) = 1.041-1.210]. The VDD group also had a higher risk of all-cause ED visits (HR = 1.114; 95% CI = 1.012-1.226), all-cause hospitalization (HR = 1.230; 95% CI = 1.105-1.369), and all-cause death (HR = 1.748; 95% CI = 1.047-2.290) but not post-COVID-19 condition (HR = 0.980; 95% CI = 0.630-1.523), individually., Conclusion: Among the COVID-19 patients, VDD might be associated with a higher risk of all-cause ED visits, hospitalization, and death during the post-acute phase., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Backgruound: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined., Methods: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis., Results: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group., Conclusion: Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Background: The 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., Methods: This 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., Results: After 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)., Conclusion: There were no significant differences in clinical outcomes between older adult patients with COVID-19 reinfection and those with primary infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tey, Tsai, Wu, Liu, Chuang, Hsu, Huang, Lai and Hsu.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Tsai, Wang, Wu, Liu, Hsu, Huang, Chuang, Sheu and Lai.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 10 6 GXCPC1, N = 5) and high dose (4 × 10 7 GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV-r) in treating patients with COVID-19 who have preexisting cardiovascular diseases (CVDs)., Methods: Patients with underlying CVDs and COVID-19 were included from the TriNetX network. We employed a 1:1 propensity score matching to create two comparable cohorts: patients receiving NMV-r and those not receiving NMV-r. The primary outcome was the composite outcome of all-cause hospitalization or death within 30 days., Results: Propensity score matching yielded two matched cohorts of 10,847 patients each. The composite outcomes of all-cause hospitalization or death within 30 days were 2.2% (239 patients) in the NMV-r cohort and 4.7% (512 patients) in the control cohort, indicating reduced risk in the NMV-r cohort (hazard ratio [HR], 0.475; 95% confidence interval [CI], 0407-0.533). The NMV-r cohort exhibited lower risks of all-cause hospitalization (HR, 0.525; 95% CI, 0.449-0.615) and mortality (HR, 0.113; 95% CI, 0.052-0.246) compared with the control group. A similar trend was observed across most of the subgroups., Conclusions: Our findings indicate that NMV-r to treat COVID-19 could reduce all-cause hospitalization and death in patients with CVDs.

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

Objective: To investigate the association between nirmatrelvir plus ritonavir (NMV-r) and the outcomes of non-hospitalized obese patients with coronavirus disease 2019 (COVID-19)., Methods: This retrospective cohort study used the TriNetX research network to identify non-hospitalized obese adult patients with COVID-19 between 1 January 2022 and 30 June 2023. Propensity score matching was used to match patients receiving NMV-r (NMV-r group) with those not receiving NMV-r (control group). The primary outcome was the compositive outcome of all-cause emergency department (ED) visits, hospitalization or death during the 30-day follow-up period., Results: Using propensity score matching methods, two cohorts of 30,969 patients each with balanced baseline characteristics were identified. During the follow-up period, the NMV-r group had a lower risk of all-cause ED visits, hospitalization or death [4.80% (n=1489) vs 5.50% (n=1705); hazard ratio (HR) 0.900, 95% confidence interval (CI) 0.839-0.965]. Compared with the control group, the NMV-r group had a lower risk of all-cause ED visits (HR 0.812, 95% CI 0.740-0.891) and all-cause mortality (HR 0.089, 95% CI 0.027-0.288). The lower risk in the NMV-r group compared with the control group was observed consistently in most subgroup analyses according to body mass index (30.0-34.9 kg/m 2 : HR 0.68, 95% CI 0.55-0.82; 35.0-39.9 kg/m 2 : HR 0.67, 95% CI 0.52-0.87), age (4-64 years: HR 0.83, 95% CI 0.75-0.92; ≥65 years: HR 0.88, 95% CI 0.79-0.98), sex (men: HR 0.69, 95% CI 0.60-0.79; women: HR 0.69, 95% CI 0.63-0.76) and vaccination status (unvaccinated: HR 0.75, 95% CI 0.70-0.81)., Conclusion: NMV-r is associated with reduced risk of all-cause ED visits, hospitalization and death for non-hospitalized obese patients with COVID-19. Accordingly, these findings support the use of NMV-r in obese patients., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

This study investigated the risk of post-COVID-19 conditions in older patients with COVID-19 compared to those with influenza, and how age impacts this relationship. Patients aged ≥65 years with COVID-19 or influenza were identified using the TriNetX network. The risk of post-COVID-19 conditions was compared between survivors of COVID-19 and influenza, followed by a comparison of post-COVID-19 conditions risk between patients aged 65-74 years and those aged over 75 years. Compared with influenza survivors, post-COVID-19 conditions were significantly more prevalent in patients with COVID-19 (hazard ratio [HR], 1.534; 95% confidence interval [CI]: 1.405-1.675). Specifically, COVID-19 survivors have a significantly higher risk of experiencing abnormal breathing (HR, 2.052; 95% CI: 1.757-2.397), fatigue (HR, 1.587; 95% CI: 1.322-1.905), anxiety/depression (HR, 1.587; 95% CI: 1.322-1.905), cognitive symptoms (HR, 1.667; 95% CI: 1.295-2.146) and cough (HR, 1.250; 95% CI: 1.006-1.553) compared with the influenza group. Contrastingly, no significant difference was observed in the risk of any post-COVID-19 condition between COVID-19 survivors aged 65-74 years and those aged over 75 years (HR, 0.994; 95% CI: 0.920-1.073). However, a lower incidence of cognitive symptoms was observed in patients aged 65-74 years compared to those aged ≥75 years (HR, 0.543; 95% CI: 0.445-0.661). In conclusion, compared with influenza, older patients have a higher risk of developing post-COVID-19 conditions after SARS-CoV-2 infection, and those aged over ≥75 years may have an increased risk of developing cognitive symptoms compared to those aged 65-74 years., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The effect of anemia on the post-acute outcome of patients with severe acute respiratory syndrome coronavirus 2 infection was unclear. This study aimed to investigate the potential association between nutritional deficiency anemia (NDA) status and post-acute sequelae of patients with SARS-CoV-2 infection. This retrospective cohort study included patients with coronavirus disease (COVID-19) from January 1, 2022 to November 30, 2022 using the TriNetX research network. The patients were grouped into the NDA group comprising patients diagnosed with NDA and the control group comprising patients without NDA, and propensity score matching (PSM) was performed to balance the two groups. The primary outcome was a composite of post-COVID-19 condition, all-cause hospitalization, and all-cause death. The secondary outcomes were any individual outcomes of the primary composite. The follow-up period was set at 90-180 days after COVID-19 diagnosis. Two cohorts comprising 15 446 nonhospitalized patients with COVID-19 in each group with balanced baseline characteristics were created using PSM. During the follow-up period, the NDA group demonstrated a higher risk of the composite primary outcome, including post-COVID-19 condition, all-cause hospitalization, or all-cause death (hazard ratio [HR], 1.896; 95% confidence interval [CI] =  1.757-2.045). Regarding secondary outcomes, the NDA group was associated with worse outcomes, including post-COVID-19 condition (HR, 1.992; 95% CI = 1.403-2.828), all-cause hospitalization (HR, 1.856; 95% CI = 1.714-2.009), and all-cause death (HR, 3.922; 95% CI = 2.910-5.285) compared to the control group. Among nonhospitalized patients with COVID-19, NDA was associated with a higher risk of post-COVID-19 condition, all-cause hospitalization, and all-cause death during the 90-180-day follow-up period., (© 2023 Wiley Periodicals LLC.)

Study Objective: This meta-analysis aimed at identifying the risk factors for and their strengths in predicting difficult mask ventilation (MV) through a systematic approach., Design: Meta-analysis of observational studies., Setting: Operating room., Intervention: Airway- or patient-related risk factors for difficult MV reported in over 20% of eligible studies identified through literature review., Patients: Adults receiving anesthetic induction with requirement of MV., Measurements: Databases including EMBASE, MEDLINE, Google Scholar, and Cochrane Library were searched from inception to July 2022. The primary outcomes were the identification of commonly reported risk factors for MV and a comparison of their strengths in difficult MV prediction, while the secondary outcomes were the prevalence of difficult MV in the general population and those with obesity., Main Results: Meta-analysis of 20 observational studies involving 335,846 patients identified 13 risk factors with predictive strengths (all p < 0.05): neck radiation (OR = 5.0, five studies, n = 277,843), increased neck circumference (OR = 4.04, 11 studies, n = 247,871), obstructive sleep apnea (OSA) (OR = 3.61, 12 studies, n = 331,255), presence of beard (OR = 3.35, 12 studies, n = 295,443), snoring (OR = 3.06, 14 studies, n = 296,105), obesity (OR = 2.99, 11 studies, n = 278,297), male gender (OR = 2.76, 16 studies, n = 320,512), Mallampati score III-IV (OR = 2.36, 17 studies, n = 335,016), limited mouth opening (OR = 2.18, six studies, n = 291,795), edentulous (OR = 2.12, 11 studies, n = 249,821), short thyroid-mental distance (OR = 2.12, six studies, n = 328,311), old age (OR = 2, 11 studies, n = 278,750), and limited neck movement (OR = 1.98, nine studies, n = 155,101). The prevalence of difficult MV was 6.1% (16 studies, n = 334,694) and 14.4% (four studies, n = 1152) in the general population and those with obesity, respectively., Conclusions: Our results demonstrated the strengths of 13 most common risk factors for predicting difficult MV, which may serve as an evidence-based reference for clinicians to incorporate into their daily practice., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier Inc.)

Background: In intensive care units (ICUs), both continuous and intermittent feeding are commonly used for early enteral nutrition (EN). However, whether continuous feeding is a preferable feeding modality compared to intermittent feeding remains unclear. Therefore, this meta-analysis assessed the clinical efficacy of both EN feeding modalities in critically ill patients., Methods: The PubMed, Embase, and Cochrane Library databases were searched from their inception dates to December 29, 2022. The search did not involve language restrictions (PROSPERO CRD42022371756). Randomized controlled trials (RCTs) comparing the clinical efficacy and safety of continuous feeding and intermittent feeding in critically ill patients in ICUs were included., Results: We included 13 RCTs involving 785 patients. Compared with intermittent feeding, continuous feeding was associated with a lower mortality rate (relative risk [RR], 0.68; 95% confidence interval [CI], 0.47, 0.98; p = 0.04) but a higher risk of constipation (RR, 1.57; 95% CI, 1.02, 2.43; p = 0.04). Trial sequential analysis (TSA) for mortality rate presented a cumulative Z-curve crossing the traditional boundary, but the curve did not cross the TSA boundary for benefit. No significant differences were found in the aspiration/pneumonia rate (RR, 1.19; 95% CI, 0.51, 2.75; p = 0.69), diarrhea rate (RR, 0.82; 95% CI, 0.58, 1.16; p = 0.26), or increased gastric residual volumes (RR, 1.05; 95% CI, 0.58, 1.90; p = 0.86) between the groups., Conclusion: Despite the low certainty of evidence, compared with intermittent feeding, continuous feeding may reduce the mortality rate in critically ill patients in ICU. Additional studies are needed to provide more evidence and validate the findings., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: A comprehensive network meta-analysis comparing the effects of individual sodium-glucose cotransporter 2 (SGLT2) inhibitors on patients with and without comorbidities including diabetes mellitus (DM), heart failure (HF), and chronic kidney disease (CKD) has not been previously conducted., Methods: We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomized controlled trials up to March 28, 2023. Network meta-analysis using a random-effects model was conducted to calculate risk ratios (RRs). Risk of Bias tool 2.0 was used to assess bias, and CINeMA to assess the certainty of evidence. In the subgroup analysis, the SGLT2 inhibitors were classified into highly (dapagliflozin, empagliflozin, and ertugliflozin) and less selective SGLT2 inhibitors (canagliflozin and sotagliflozin)., Results: A total of fourteen trials with 75,334 patients were analyzed. Among these, 40,956 had taken SGLT2 inhibitors and 34,378 had not. One of the main results with particular findings was empagliflozin users had a significantly lower risk of all-cause death compared to dapagliflozin users in DM population (RR: 0.81, 95% CI 0.69-0.96). In HF population, sotagliflozin users had a borderline significantly lower risk of CV death or hospitalization for HF (HHF) than dapagliflozin users (RR: 0.90, 95% CI 0.80-1.01). In non-HF population, those who used canagliflozin had a significantly lower risk of CV death or HHF compared with those who used dapagliflozin (RR: 0.75, 95% CI 0.58-0.98). At last, for HF patients, those who used less selective SGLT2 inhibitors had a significantly lower risk of MACEs compared to those who used highly selective SGLT2 inhibitors (RR: 0.75, 95% CI 0.62-0.90)., Conclusions: Our network meta-analysis revealed that empagliflozin users with diabetes experienced a lower risk of dying from any cause than those using dapagliflozin. Additionally, canagliflozin users demonstrated a reduced risk of cardiovascular death or HHF compared to dapagliflozin users in those without HF. In HF patients, less selective SGLT2 inhibitors showed superior CV composite outcomes, even surpassing the performance of highly selective SGLT2 inhibitors., Trial Registration: PROSPERO [CRD42022361906]., (© 2023. The Author(s).)

This study was aimed at investigating the risk of cytomegalovirus (CMV) disease among coronavirus disease 2019 (COVID-19) survivors. In this retrospective cohort study, we used the TriNetX research network to identify adults with and without COVID-19 between January 1, 2022 and December 31, 2022. Propensity score matching was used to match the patients with and without COVID-19. The primary outcome was the risk of CMV disease during the 90-day follow-up period. Two matched cohorts comprising 2 501 634 patients with balanced baseline characteristics were created using propensity score matching. During the follow-up period, patients with COVID-19 had a higher risk of CMV disease than those without COVID-19 (hazard ratio [HR], 2.55; 95% confidence interval: 2.01-3.23). The higher risk of CMV disease in the COVID-19 cohort compared with that of the non-COVID-19 cohort remained unchanged in the subgroup analyses by sex (men: HR, 1.85 [1.38-2.47]; women: HR, 2.31 [1.63-3.27]), age (18-64 years: HR, 2.21 [1.71-2.85]; ≥65 years: HR, 1.97 [1.20-3.25]), obesity (HR, 1.54 [1.04-2.30]), diabetes mellitus (HR, 1.50 [1.08-2.08]), cancer (HR, 3.10 [1.95-4.92]), glucocorticoid use (HR, 3.14 [2.45-4.02]), transplantation (HR, 1.38 [1.08-1.77]), and unvaccinated status (HR, 2.37 [1.82-3.08]). In conclusion, COVID-19 can increase the risk of CMV disease. Clinicians should be aware of the risk of CMV disease in patients with COVID-19., (© 2023 Wiley Periodicals LLC.)

Introduction: Studies on association of α-klotho levels with mortality risk in general population are relatively scarce and inconclusive. Therefore, we conducted a population-based cohort study to investigate the relationship between soluble α-klotho and all-cause mortality in a nationally representative sample of middle-aged and older adults in the United States (U.S.)., Methods: The study population was 2007-2016 National Health and Nutrition Examination Survey (NHANES) participants, totaling 13,583 adults aged 40-79 years. Participants were divided into 7 groups by septile of α-klotho levels. We linked the NHANES data to the National Death Index to determine participants' survival status. End of follow-up was participants' death date or December 31, 2019., Results: We observed that males, current smokers, older age, higher body mass index, and lower estimated glomerular filtration rate correlated to lower α-klotho levels, while hepatitis C virus infection correlated to higher α-klotho. The population mortality rate was 11.8 per 10,000 person-months (1,490 deaths); group 1 (the first septile) had higher mortality risk compared with group 2 through group 7. By weighted Cox regression with adjustment for potential confounders, we found that group 2 through group 6, but not group 7, were associated with 25% to 35% lower risk of all-cause mortality compared with group 1. When compared with group 4, we observed that both group 1 (HR: 1.46, 95% CI 1.13-1.88) and group 7 (HR: 1.38, 95% CI 1.09-1.74) were associated with higher mortality risk., Conclusion: In summary, among middle-aged and older U.S. adults, we observed a non-linear association between soluble α-klotho and all-cause mortality, with individuals at the two extremes at increased risk of death., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chuang, Wang, Huang and Jiang.)

Although a novel oral antiviral agent can improve short-term COVID-19 outcomes, its effects on the long-term outcomes, namely the risk of major adverse cardiovascular events (MACEs), remains unknown. This retrospective cohort study used the TriNetX research network to identify nonhospitalized adult patients with COVID-19 between March 1, 2020, and January 1, 2022. A propensity score matching method was used to form two matched cohorts with and without receiving nirmatrelvir-ritonavir (NMV-r) or molnupiravir. The primary outcome was the incidence of MACEs within a 30-day to 1-year period following a diagnosis of COVID-19. Two cohorts of each 80 888 patients with balanced baseline characteristics were formed using propensity score matching. During the follow-up period, 976 patients in the study group and 1609 patients in the control group developed MACE. Overall, the study group had a significantly lower risk of MACE than the control group (hazard ratio [HR], 0.683; 95% confidence interval: 0.630-0.739). The significantly lower HRs of overall MACEs were consistently observed in most subgroup analyses (age: >41-≤64 years: 0.60 [0.52-0.89]; age: ≥65 years: 0.68 [0.62-0.76]; women: 0.63 [0.57-0.71]; men: 0.62 [0.55-0.70]; vaccinated: 0.74 [0.63-0.88]; unvaccinated: 0.66 [0.60-0.73]; NMV-r; 0.65 [0.59-0.71]; and molnupiravir: 0.75 [0.61-0.92]). In conclusion, novel oral antiviral agents, namely NMV-r and molnupiravir, were effective in reducing long-term MACEs among nonhospitalized patients with COVID-19, particularly when treated with NMV-r or in patients aged ≥40 years. These findings suggest the potential role of novel antiviral agents as a preventive measure to reduce further adverse cardiovascular outcomes., (© 2023 Wiley Periodicals LLC.)