Ya‐Wen Tsai

Background: Chronic obstructive pulmonary disease (COPD) is frequently complicated by acute respiratory failure, pneumonia, exacerbations, and premature mortality, particularly in patients with comorbid type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) possess anti-inflammatory and metabolic properties that may confer protective effects against COPD-related respiratory complications, but comparative evidence remains limited. Methods: We conducted a retrospective cohort study using data from the TriNetX global federated health research network. Adults aged 40 years or older with both COPD and T2D who newly initiated GLP-1RAs, dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), or metformin between 1 January 2017 and 31 May 2025 were identified. An active-comparator, new-user design with 1:1 propensity score matching was applied. The primary outcome was incident acute respiratory failure. Secondary outcomes included all-cause mortality, all-cause hospitalization, acute exacerbation of COPD, and pneumonia, assessed over 1 year of follow-up. Results: After propensity score matching, GLP-1RA use was associated with significantly lower risk of acute respiratory failure compared with DPP-4is (HR, 0.77; 95% CI, 0.73–0.81), SUs (HR, 0.80; 95% CI, 0.76–0.84), and metformin (HR, 0.91; 95% CI, 0.85–0.98). GLP-1RA use was also consistently associated with reduced risks of all-cause mortality, all-cause hospitalization, acute exacerbation of COPD, and pneumonia across all three comparator groups. Subgroup analyses demonstrated consistent protective trends across sex, age, exacerbation history, and inhaled bronchodilator regimen. Conclusions: In patients with COPD and T2D, initiation of GLP-1RAs was associated with significantly lower risks of acute respiratory failure, pneumonia, acute exacerbation, hospitalization, and all-cause mortality compared with DPP-4is, SUs, and metformin. These findings suggest that GLP-1RA therapy may offer meaningful respiratory and survival benefits in this high-risk population.

Preventing the progression of coronavirus disease 2019 (COVID-19) is a critical issue, particularly in patients with comorbidities such as asthma. However, real-world data on the effectiveness of oral antivirals in patients with asthma and non-severe COVID-19 are limited. This study was conducted to evaluate the effectiveness of 2 oral antivirals, nirmatrelvir/ritonavir (NMV-r) and molnupiravir, in reducing adverse outcomes in asthmatic patients with non-severe COVID-19. This retrospective cohort study included non-hospitalized adults with asthma who were diagnosed with COVID-19 between January 1, 2022, and March 16, 2024, using data from the TriNetX Research Network. The study group received NMV-r or molnupiravir; the control group received no antivirals. Covariates were balanced between the groups using propensity score matching. The primary outcome was the composite incidence of all-cause mortality, all-cause hospitalization, and mechanical ventilation use within 30 days. After matching, each group comprised 19,235 patients. The study group showed significantly lower composite primary outcome (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.49–0.66). Specifically, the study group was associated with significantly lower risk of all-cause hospitalization (HR: 0.59; 95% CI: 0.50–0.69) and all-cause mortality (HR: 0.34; 95% CI: 0.16–0.73) and mechanical ventilation requirements (HR: 0.08; 95% CI: 0.01–0.58). Significantly risk reduction was also observed in subgroups including both sexes, different ages, those with hypertension, dyslipidemia, diabetes mellitus, those receiving NMV-r, and those who had received less than 1 dose and more than 3 doses of vaccine. Our findings suggest oral antivirals, particularly NMV-r, reduce adverse outcomes in asthmatic patients with non-severe COVID-19.

Objectives: This study investigates the impact of semaglutide on obstructive sleep apnea (OSA) risk and clinical outcomes in individuals with obesity. Methods: A retrospective cohort study was conducted using the TriNetX platform, which includes electronic health records from approximately 150 million patients across 149 healthcare organizations. Two cohorts were analyzed: (1) individuals with obesity to evaluate the incidence of new-onset OSA and (2) individuals with OSA and obesity to assess clinical outcomes. Propensity score matching was applied to balance baseline characteristics between semaglutide users and control groups. Primary outcomes included new-onset OSA incidence (obesity cohort) and a composite endpoint of all-cause mortality, major adverse cardiovascular events (MACEs), and major adverse kidney events (MAKEs) (OSA with obesity cohort). Results: In the obesity cohort (n = 191 273 in each group), semaglutide use was significantly associated with a reduced the risk of new-onset OSA (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.60-0.63; P < .0001). Stratified analyses confirmed consistent benefits across subgroups. In the OSA with obesity cohort (n = 40 123 in each group), semaglutide use was associated with lower risk of adverse composite outcomes (HR, 0.72; 95% CI, 0.66-0.78; P < .0001), as well as reductions in all-cause mortality (HR, 0.37; 95% CI, 0.31-0.45), MACE (HR, 0.72; 95% CI, 0.65-0.79), and MAKE (HR, 0.54; 95% CI, 0.48-0.60). Sensitivity analyses confirmed robustness against unmeasured confounders. Conclusions: Semaglutide was associated with a significant reduction in OSA risk among individuals with obesity and improved clinical outcomes in those with comorbid obesity and OSA.

Background This study investigated whether preoperative use of sodium-glucose cotransporter 2 inhibitors (SGLT2is), known for their cardio-renal benefits in type 2 diabetes (T2DM), reduces postoperative acute kidney injury (AKI) after metabolic and bariatric surgery (MBS). Methods The TriNetX research network was used to analyze propensity-matched patients with T2DM who underwent MBS between 2010 and 2024. We compared patients who received SGLT2is (discontinued ≥ 1 week before surgery) with those using other antidiabetic medications. The primary outcome was AKI within 30 days after surgery. Secondary outcomes included risks of mortality, intensive care unit (ICU) admission, acute myocardial infarction/stroke, eGFR decline to < 60 mL/min/1.73 m², and ketoacidosis. Results After matching, 4364 patients were included (n = 2182 for each group). The incidence of AKI was identical between the groups (1.88% in both, OR 1.00, 95% CI 0.65–1.55, P = 1.00). No significant differences were observed in mortality, ICU admission, acute myocardial infarction/stroke, eGFR decline to < 60 mL/min/1.73 m², or ketoacidosis at 30-day follow-up. Subgroup analyses based on baseline CKD status, empagliflozin use, and diabetes duration largely supported the robustness of the findings. Notably, among patients with diabetes duration > 1 year, SGLT2is use was significantly associated with a lower risk of eGFR decline to < 60 mL/min/1.73 m² (17.7% vs. 21.2%; OR 0.80, 95% CI 0.65–0.97; P = 0.024). Conclusions Preoperative SGLT2is use in patients undergoing MBS is associated with a reduced risk of GFR decline in those with longer-duration diabetes, suggesting potential renoprotective benefits. No increased risk of adverse outcomes was observed when these medications were discontinued ≥ 1 week before surgery.

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.

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.

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.

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.