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Medicina (Kaunas, Lithuania) Jun 2024Inflammatory proteins and their prognostic value in patients with carotid artery stenosis (CAS) have not been adequately studied. Herein, we identified CAS-specific...
Inflammatory proteins and their prognostic value in patients with carotid artery stenosis (CAS) have not been adequately studied. Herein, we identified CAS-specific biomarkers from a large pool of inflammatory proteins and assessed the ability of these biomarkers to predict adverse events in individuals with CAS. Samples of blood were prospectively obtained from 336 individuals (290 with CAS and 46 without CAS). Plasma concentrations of 29 inflammatory proteins were determined at recruitment, and the patients were followed for 24 months. The outcome of interest was a major adverse cardiovascular event (MACE; composite of stroke, myocardial infarction, or death). The differences in plasma protein concentrations between patients with vs. without a 2-year MACE were determined using the independent -test or Mann-Whitney test to identify CAS-specific prognostic biomarkers. Kaplan-Meier and Cox proportional hazards analyses with adjustment for baseline demographic and clinical characteristics were performed to assess the prognostic value of differentially expressed inflammatory proteins in predicting a 2-year MACE in patients with CAS. The mean age of the cohort was 68.8 (SD 10.2) years and 39% were female. The plasma concentrations of two inflammatory proteins were significantly higher in individuals with a 2-year MACE relative to those without a 2-year MACE: IL-6 (5.07 (SD 4.66) vs. 3.36 (SD 4.04) pg/mL, = 0.03) and CD163 (233.825 (SD 230.306) vs. 159.673 (SD 175.669) pg/mL, = 0.033). Over a follow-up period of 2 years, individuals with elevated levels of IL-6 were more likely to develop MACE (HR 1.269 (95% CI 1.122-1.639), = 0.042). Similarly, over a 2-year period, patients with high levels of CD163 were more likely to develop MACE (HR 1.413 (95% CI 1.022-1.954), = 0.036). The plasma levels of inflammatory proteins IL-6 and CD163 are independently associated with adverse outcomes in individuals with CAS. These CAS-specific prognostic biomarkers may assist in the risk stratification of patients at an elevated risk of a MACE and subsequently guide further vascular evaluation, specialist referrals, and aggressive medical/surgical management, thereby improving outcomes for patients with CAS.
Topics: Humans; Female; Carotid Stenosis; Male; Biomarkers; Aged; Middle Aged; Prospective Studies; Inflammation; Receptors, Cell Surface; Prognosis; Interleukin-6; Proportional Hazards Models; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Kaplan-Meier Estimate; Myocardial Infarction; Cardiovascular Diseases; Stroke
PubMed: 38929614
DOI: 10.3390/medicina60060997 -
Serum Endocan Is a Risk Factor for Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis.Medicina (Kaunas, Lithuania) Jun 2024: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and...
: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and angiogenesis. We aimed to investigate the link between endocan and aortic stiffness in maintenance hemodialysis (HD) patients. : After recruiting HD patients from a medical center, their baseline characteristics, blood sample, and anthropometry were assessed and recorded. The serum endocan level was determined using an enzyme immunoassay kit, and carotid-femoral pulse wave velocity (cfPWV) measurement was used to evaluate aortic stiffness. : A total of 122 HD patients were enrolled. Aortic stiffness was diagnosed in 53 patients (43.4%), who were found to be older ( = 0.007) and have a higher prevalence of diabetes ( < 0.001) and hypertension ( = 0.030), higher systolic blood pressure ( = 0.011), and higher endocan levels ( < 0.001), when compared with their counterparts. On the multivariate logistic regression model, the development of aortic stiffness in patients on chronic HD was found to be associated with endocan [odds ratio (OR): 1.566, 95% confidence interval (CI): 1.224-2.002, < 0.001], age (OR: 1.040, 95% CI: 1.001-1.080, = 0.045), and diabetes (OR: 4.067, 95% CI: 1.532-10.798, = 0.005), after proper adjustment for confounders (adopting diabetes, hypertension, age, systolic blood pressure, and endocan). The area under the receiver operating characteristic curve was 0.713 (95% CI: 0.620-0.806, < 0.001) for predicting aortic stiffness by the serum endocan level, at an optimal cutoff value of 2.68 ng/mL (64.15% sensitivity, 69.57% specificity). Upon multivariate linear regression analysis, logarithmically transformed endocan was proven as an independent predictor of cfPWV (β = 0.405, adjusted R change = 0.152; < 0.001). : The serum endocan level positively correlated with cfPWV and was an independent predictor of aortic stiffness in chronic HD patients.
Topics: Humans; Vascular Stiffness; Male; Proteoglycans; Female; Middle Aged; Renal Dialysis; Risk Factors; Neoplasm Proteins; Aged; Adult; Pulse Wave Analysis; ROC Curve; Biomarkers; Logistic Models; Cross-Sectional Studies
PubMed: 38929601
DOI: 10.3390/medicina60060984 -
Diagnostics (Basel, Switzerland) Jun 2024Major cardiovascular events (MACEs) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques are diagnosed...
Major cardiovascular events (MACEs) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques are diagnosed and treated with percutaneous coronary intervention (PCI). During this procedure, coronary angiography (CAG) remains the most widely used guidance modality for the evaluation of the affected blood vessel. The measurement of the blood vessel diameter is an important factor to consider in order to decide if stent colocation is suitable for the intervention. In this regard, a small blood vessel (<2.75 mm) is majorly left without stent colocation; however, small vessel coronary artery disease (SvCAD) is a significant risk factor for the recurrence of MACEs, maybe due to the lack of a standardized treatment related to the diameter of the affected blood vessel; therefore, a more precise measurement is needed. The use of CAG for the measurement of the blood vessel diameter has some important limitations that can be improved with the use of newer techniques such as intravascular ultrasound (IVUS), although at higher costs, which might explain its underuse. To address differences in blood vessel diameter measurements and identify specific cases where IVUS might be of additional benefit for the patient, we conducted a retrospective study in patients who underwent PCI for MACEs with affection for at least one small blood vessel. We compared the measurements of the affected small blood vessels' diameter obtained by CAG and IVUS to identify cases of reclassification of the affected blood vessel; additionally, we underwent a multivariate analysis to identify risk factors associated with blood vessel reclassification. We included information from 48 patients with a mean ± SD age of 69.1 ± 11.9 years; 70.8% were men and 29.2% were women. The mean diameter with CAG and IVUS was 2.1 mm (95% CI 1.9-2.2), and 2.8 (2.8-3.0), respectively. The estimated difference was of 0.8 mm (95% CI 0.7-0.9). We found a significant positive low correlation in diameter measurements of small blood vessels obtained with CAG and IVUS (r = 0.1242 = 0.014). In total, 37 (77%) patients had a reclassification of the affected blood vessel with IVUS. In 21 cases, the affected blood vessel changed from a small to a medium size (2.75-3.00 mm), and in 15 cases, the affected vessel changed from a small to a large size (<3.00 mm). The Bland-Altman plot was used to evaluate agreement in measurements with CAG and IVUS. The change in blood vessel classification with IVUs was important for the decision of intervention and stent collocation. The only variable associated with reclassification of blood vessels after adjustment in a multivariate analysis was T2D (type 2 diabetes) ( = 0 0.035). Our findings corroborate that blood vessels might appear smaller with CAG, especially in patients with T2D; therefore, at least in these cases, the use of IVUS is recommended over CAG.
PubMed: 38928727
DOI: 10.3390/diagnostics14121312 -
Brain Sciences Jun 2024The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear...
BACKGROUND
The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear temporal sequence demonstrated previously.
METHODS
Data were derived from four waves (2011 baseline and 2013, 2015, and 2018 follow-ups) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 17,708 participants aged 45 years or older who had baseline data on both sarcopenia status and depressive symptoms in 2011 were included in the study. For the two cohort analyses, a total of 8092 adults without depressive symptoms and 11,292 participants without sarcopenia in 2011 were included. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Depressive symptoms were defined as a score of 20 or higher on the 10-item Center for Epidemiologic Studies Depressive Scale (CES-D-10). Cox proportional hazard regression models were conducted to examine the risk of depressive symptoms and sarcopenia risk, while cross-lagged panel models were used to examine the temporal sequence between depressive symptoms and sarcopenia over time.
RESULTS
During a total of 48,305.1 person-years follow-up, 1262 cases of incident depressive symptoms were identified. Sarcopenia exhibited a dose-response relationship with a higher risk of depressive symptoms (HR = 1.7, 95%CI: 1.2-2.3 for sarcopenia, and HR = 1.5, 95%CI: 1.2-1.8 for possible sarcopenia, trend < 0.001). In the second cohort analysis, 240 incident sarcopenia cases were identified over 39,621.1 person-years. Depressive symptoms (HR = 1.5, 95%CI: 1.2-2.0) are significantly associated with a higher risk of developing sarcopenia after multivariable adjustment ( < 0.001, Cross-lagged panel analyses demonstrated that depressive symptoms were associated with subsequent sarcopenia (β = 0.003, < 0.001). Simultaneously, baseline sarcopenia was also associated with subsequent depressive symptoms (β = 0.428, < 0.001).
CONCLUSION
This study identified a bidirectional relationship between depressive symptoms and sarcopenia. It seems more probable that baseline sarcopenia is associated with subsequent depressive symptoms in a stronger pattern than the reverse pathway. The interlinkage indicated that maintaining normal muscle mass and strength may serve as a crucial intervention strategy for alleviating mood disorders.
PubMed: 38928593
DOI: 10.3390/brainsci14060593 -
BMC Endocrine Disorders Jun 2024Limited studies have investigated the relationship between Anti-Müllerian hormone (AMH) and metabolic syndrome (MetS), yielding inconclusive results. This study aimed...
BACKGROUND
Limited studies have investigated the relationship between Anti-Müllerian hormone (AMH) and metabolic syndrome (MetS), yielding inconclusive results. This study aimed to examine the relationship between AMH levels and MetS and its components in women from a general population.
METHODS
This prospective study recruited 769 women. Generalized Estimating Equation (GEE) models analyzed longitudinal trends of MetS components. Cox proportional hazard models evaluated effect of age-specific AMH tertiles on MetS occurrence, adjusting for confounders.
RESULTS
The GEE analysis indicated that women in the third tertile exhibited higher mean FPG compared to those in the first tertile of age-specific AMH (3 mg/dL; 95% CI: 0.40, 5.60; P = 0.024); however, this association became non-significant after adjustment. Notably, the second tertile showed a significant decrease in FPG mean changes over time (-0.69 mg/dL; 95% CI: -1.31, -0.07; P = 0.030). Women in the second and third tertiles of age-specific AMH demonstrated lower mean HDL-C compared to the first tertile (-2.96 mg/dL; 95% CI: -4.67, -1.26; P < 0.001 and -2.63 mg/dL; 95% CI: -4.31, -0.96; P = 0.002, respectively). The association between HDL-C changes and the second tertile remained significant after adjustment (-1.91 mg/dL; 95% CI: -3.68, -0.14; P = 0.034). No significant associations were observed between age-specific AMH tertiles and TG and SBP/DBP. Cox models revealed no significant differences in the hazard ratio of MetS between AMH tertiles after adjusting for confounders.
CONCLUSION
Despite minor variations in MetS components, AMH levels did not affect MetS risk in women from a general population.
Topics: Humans; Anti-Mullerian Hormone; Metabolic Syndrome; Female; Prospective Studies; Middle Aged; Adult; Biomarkers; Follow-Up Studies; Risk Factors; Aged; Prognosis
PubMed: 38926704
DOI: 10.1186/s12902-024-01627-z -
Scientific Reports Jun 2024This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We...
This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13-0.87, P = 0.024). When stratified by dose, short-term NRT use (8-28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16-0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36-1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.
Topics: Humans; Male; Female; Smoking Cessation; Glaucoma; Middle Aged; Macular Degeneration; Retrospective Studies; Cataract; Taiwan; Aged; Adult; Smoking; Tobacco Use Cessation Devices; Incidence; Varenicline
PubMed: 38926484
DOI: 10.1038/s41598-024-65813-8 -
The Journal of Nutrition, Health & Aging Jun 2024Diet can modulate systemic inflammation, while inflammation is a critical contributory factor of frailty. However, longitudinal data on the association between dietary...
OBJECTIVES
Diet can modulate systemic inflammation, while inflammation is a critical contributory factor of frailty. However, longitudinal data on the association between dietary inflammatory index (DII) and frailty are limited, and the intermediate mechanisms remain unclear. This study aimed to examine the association between DII and incident frailty and the potential mediating roles of frailty-related biomarkers.
DESIGN
Prospective cohort study.
SETTING
The Mr. OS and Ms. OS (Hong Kong) study.
PARTICIPANTS
A total of 3,035 community-dwelling men and women aged above 65 years without frailty at baseline were included.
MEASUREMENTS
DII scores were calculated using the locally validated food frequency questionnaire. Incident frailty at year four was defined using the Fried frailty phenotype. Logistic regression was used to examine the association between DII and frailty onset. Mediation analysis was used to explore the mediating roles of frailty-related biomarkers in the DII-frailty association.
RESULTS
During four years of follow-up, 208 individuals developed frailty. Compared with the lowest tertile of DII, the highest tertile was associated with an increased risk of incident frailty (OR: 1.82; 95% CI: 1.17-2.82; p = 0.008) after adjustment for relevant confounders. The DII-frailty association was significant in men but not in women. Furthermore, increasing serum homocysteine, decreasing serum folate, and reducing estimated glomerular filtration rate (eGFR) mediated 11.6%, 7.1%, and 9.6 % of the total relation between DII and frailty onset, respectively.
CONCLUSION
In this cohort study, a pro-inflammatory diet was associated with a higher risk of frailty onset, mediated by homocysteine, folate, and renal function.
PubMed: 38924861
DOI: 10.1016/j.jnha.2024.100304 -
PloS One 2024Postoperative patients with ostomies experience significant changes in their lives as a result of the device implantation. Self-care is important to improve their health... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Postoperative patients with ostomies experience significant changes in their lives as a result of the device implantation. Self-care is important to improve their health outcomes. Telehealth provides an opportunity to expand access to self-care education.
AIM
This is a multicenter, non-inferiority randomized, open-label, controlled trial to evaluate the non-inferiority of a telehealth intervention to the standard in-person approach in improving self-care behaviors.
METHODS AND ANALYSIS
Three hundred and eighty-four patients aged ≥ 18 years, with a recently placed ostomy, no stomal/peristomal complications, and documented cognitive integrity will be randomly assigned (1:1) to receive either a telehealth intervention (four remote educational sessions) or a standard educational approach (four in-person sessions) delivered in outpatient settings. Every session (remote and in-person) will occur on Days 25, 32, 40, and 60 after discharge. Follow-ups will occur 1, 3, and 6 months after the last intervention session. Primary outcome is self-care maintenance measured using the Ostomy Self-care Index (OSCI). Secondary outcomes include self-care monitoring, self-care management, self-efficacy (OSCI), quality of life (Stoma specific quality of Life), depression (Patient Health Questionnaire-9), adjustment (Ostomy Adjustment Inventory-23), stomal and peristomal complication rates, healthcare services utilization, mobility, and number of working days lost. Analyses will be performed per intention-to-treat and per protocol.
ETHICS AND DISSEMINATION
This study has been approved by the Institutional Review Board of the main center (registration number: 119/22). Following completion of the trial, dissemination meetings will be held to share the results of the study with the participants and the health-care team. Adoption of telehealth technologies for ostomy patients can improve service organization by ensuring better integration and continuity of care. If the remote intervention produces comparable effects to the in-person intervention, it would be wise to make telehealth education an alternative treatment for addressing the educational needs of uncomplicated postoperative ostomy patients.
TRIAL REGISTRATION
ClinicalTrials.gov (identifier number: NCT05796544).
Topics: Humans; Telemedicine; Self Care; Ostomy; Patient Education as Topic; Quality of Life; Female; Male; Adult
PubMed: 38924038
DOI: 10.1371/journal.pone.0303015 -
JAMA Network Open Jun 2024There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization.
IMPORTANCE
There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization.
OBJECTIVE
To compare rates of premature death, suicide, and nonlethal intentional self-harm after psychiatric discharge with rates in the general population and investigate associations of these outcomes with relevant variables associated with the index psychiatric hospitalization.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included all residents from Catalonia, Spain (7.6 million population), who had psychiatric hospitalizations between January 1, 2014, and December 31, 2018, and were older than 10 years at the index (first) hospitalization. Follow-up was until December 31, 2019. Statistical analysis was performed from December 1, 2022, through April 11, 2024.
EXPOSURES
Socioeconomic status, psychiatric diagnoses, duration of index hospitalization, and number of previous psychiatric hospitalizations.
MAIN OUTCOMES AND MEASURES
Postdischarge premature death (ie, all-cause death before age 70 years) and suicide (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code range X60-X84), identified using mortality data, and postdischarge nonlethal intentional self-harm, identified using electronic health record and self-harm case register data. Standardized mortality ratios (SMRs) compared rates of premature death and suicide between the cohort and the general population. Fully adjusted, multivariable, cause-specific Cox proportional hazards regression models for the 3 outcomes were fitted.
RESULTS
A total of 49 108 patients discharged from psychiatric hospitalization were included (25 833 males [52.6%]; mean [SD] age at discharge, 44.2 [18.2] years). During follow-up, 2260 patients (4.6%) died prematurely, 437 (0.9%) died by suicide, and 4752 (9.7%) had an episode of nonlethal intentional self-harm. The overall SMR for premature death was 7.5 (95% CI, 7.2-7.9). For suicide, SMR was 32.9 (95% CI, 29.9-36.0) overall and was especially high among females (47.6 [95% CI, 40.2-54.9]). In fully adjusted sex-stratified hazard models, postdischarge premature death was associated with cognitive disorders (adjusted hazard ratio [AHR], 2.89 [95% CI, 2.24-3.74] for females; 2.59 [95% CI, 2.17-3.08] for males) and alcohol-related disorders (AHR, 1.41 [95% CI, 1.18-1.70] for females; 1.22 [95% CI, 1.09-1.37] for males). Postdischarge suicide was associated with postdischarge intentional self-harm (AHR, 2.83 [95% CI, 1.97-4.05] for females; 3.29 [95% CI, 2.47-4.40] for males), with depressive disorders (AHR, 2.13 [95% CI, 1.52-2.97]) and adjustment disorders (AHR, 1.94 [95% CI, 1.32-2.83]) among males, and with bipolar disorder among females (AHR, 1.94 [95% CI, 1.21-3.09]). Postdischarge intentional self-harm was associated with index admissions for intentional self-harm (AHR, 1.95 [95% CI, 1.73-2.21] for females; 2.62 [95% CI, 2.20-3.13] for males) as well as for adjustment disorders (AHR, 1.48 [95% CI, 1.33-1.65] for females; 1.99 [95% CI, 1.74-2.27] for males), anxiety disorders (AHR, 1.24 [95% CI, 1.10-1.39] for females; 1.36 [95% CI, 1.18-1.58] for males), depressive disorders (AHR, 1.54 [95% CI, 1.40-1.69] for females; 1.80 [95% CI, 1.58-2.04] for males), and personality disorders (AHR, 1.59 [95% CI, 1.46-1.73] for females; 1.43 [95% CI, 1.28-1.60] for males).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients discharged from psychiatric hospitalization, risk for premature death and suicide was significantly higher compared with the general population, suggesting individuals discharged from psychiatric inpatient care are a vulnerable population for premature death and suicidal behavior.
Topics: Humans; Male; Female; Patient Discharge; Middle Aged; Self-Injurious Behavior; Adult; Retrospective Studies; Spain; Suicide; Mortality, Premature; Aged; Adolescent; Mental Disorders; Young Adult; Hospitals, Psychiatric
PubMed: 38922620
DOI: 10.1001/jamanetworkopen.2024.17131 -
Journal of Cardiovascular Development... Jun 2024(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large,...
(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA < 0.01; LVEF < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock ( = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.
PubMed: 38921673
DOI: 10.3390/jcdd11060173