Clinical therapeutics最新文献

Background: Metabolic-associated fatty liver disease (MAFLD) is a prevalent condition with significant health and economic burdens. Dietary interventions, such as intermittent fasting (IF) and low-calorie diets (LCD), have shown promise in managing MAFLD, but their comparative efficacy remains unclear.

Methods: This 10-month, parallel, single-blind randomized controlled trial compared the effects of a 16:8 IF diet with an LCD on 52 patients with MAFLD. Anthropometric, biochemical, liver enzyme, steatosis, fibrosis, inflammatory, and oxidative status parameters were assessed before and after the interventions.

Results: Both diets led to improvements in anthropometric measures and liver enzyme levels, with no significant differences between groups. However, the LCD group showed superior outcomes in reducing liver steatosis (-52.40 vs -44.63 dB/m; P < 0.001) and fibrosis (-0.74 vs -0.004 Kpa; P = 0.01) compared to the IF group. LCD also led to a significant decrease in serum triglycerides (-24.08 vs 11.22 mg/dL; P = 0.02), while neither intervention significantly affected inflammatory markers or oxidative status.

Conclusion: While both IF and LCD can be effective in managing MAFLD, LCD may offer additional benefits in terms of liver fat reduction and improvement in certain lipid parameters. These findings highlight the complexity of dietary interventions in MAFLD and the need for personalized approaches.

Objectives: To compare the risk of cardiovascular disease (CVD) and common solid cancers between JAK inhibitors (JAKi) versus TNF or IL-17 inhibitors, among people with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA).

Methods: We used real-world electronic health records data from a predominantly North American population of PsA or axSpA. Initiators of JAKi (tofacitinib or upadacitinib) and TNFi were 1:1 propensity score matched. Cox models were used to compare time to CVD (acute myocardial infarction, stroke or revascularization) or common solid cancers (breast, colorectal, lung or prostate) over 3 years. Analyses were repeated for JAKi versus IL-17i. We performed sensitivity analyses with follow-up over 1 or 5 years, in those aged ≥65 years, or those initiating treatment before 2021.

Results: The JAKi vs TNFi comparison included 2,200 matched individuals in each group over 3,092 and 4,618 person-years, respectively. Compared to TNFi, JAKi was not associated with higher risk of CVD (HR 0.977; 95% 0.632, 1.510) or cancer (HR 0.710; 0.462, 1.091) over 3 years' follow-up. JAKi vs IL-17i comparison included 2,287 individuals over 3,190 and 4,312 person-years, respectively. Compared to IL-17i, JAKi was not associated with risk of CVD (HR 1.114; 0.720,1.722) or cancer (HR 0.737; 0.484,1.122). Results across stratified analyses were directionally concordant.

Conclusions: These results are reassuring that among a large population of people with PsA or axSpA, JAKi was not associated with increased risk of CVD or common solid cancers, compared to TNFi or IL-17i initiators. Ongoing monitoring of cardiovascular and cancer risks is needed.

Purpose: To assess real-world effectiveness of sotrovimab for reducing severe clinical outcomes in patients with coronavirus disease 2019 (COVID-19) versus no treatment during the Delta/early Omicron variant periods.

Methods: Patients diagnosed with COVID-19 between May 26, 2021, and April 5, 2022, were identified from US administrative claims data (Komodo Health). Cohorts included early treatment (sotrovimab, other monoclonal antibodies, or antivirals), prophylaxis monoclonal antibody treatment, and untreated for COVID-19. Patient characteristics and severe clinical outcomes (assessed in the 29-day post-treatment period, including hospitalization, mortality, ventilatory support/extracorporeal membrane oxygenation [ECMO], and hospital length of stay) were described for all cohorts, with comparative effectiveness analysis conducted among matched cohorts of sotrovimab-treated and untreated patients.

Findings: In the descriptive analysis (N = 434,766 early treated; N = 2015 prophylaxis treated; N = 4,231,748 untreated), differences in age, comorbidity, and high-risk status were observed. Clinical outcomes occurred at low frequencies in all cohorts. In the effectiveness analysis (N = 34,160 sotrovimab treated; N = 68,320 untreated), treatment with sotrovimab significantly (P < 0.001 for all) reduced hospitalization (4.0% vs 4.7%), hospitalization and/or mortality (4.0% vs 5.2%), ventilatory support and/or ECMO (3.6% vs 6.5%), and length of inpatient stay (4.8 vs 6.2 days) versus no treatment. Stratification by age showed the significant reduction in the likelihood of 29-day all-cause hospitalization was only observed in patients aged >55 years, with greatest benefit observed among patients aged ≥65 years (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.49-0.63). Likelihood of all-cause hospitalization was lower among sotrovimab-treated versus untreated patients during the Delta (OR 0.66; 95% CI 0.57-0.76), Omicron BA.1 (OR 0.88; 95% CI 0.81-0.95), and BA.2 (OR 0.58; 95% CI 0.43-0.79) variant predominant periods.

Implications: Sotrovimab was associated with a reduced risk of severe clinical outcomes in patients with COVID-19 at high risk of progression during the Delta and early Omicron (BA.1 and BA.2) variant periods.

Purpose: Cardiopulmonary rehabilitation, which often follows major acute cardiac events, is traditionally focused on aerobic exercise and has been associated with decreased morbidity and mortality. Its benefit among cardiac surgery patients is less clear, as is the role of resistance-based exercise programs and their sex-specific effects. This study seeks to evaluate the safety and feasibility of a 12-week resistance training program in patients post cardiac surgery through a sex-specific lens.

Methods: We conducted a nonrandomized feasibility trial with a 12-week strength training exercise intervention. The primary outcome was safety and feasibility. Secondary outcomes included changes in strength, endurance, and functional capacity; and sex differences among these. Adult participants post open-heart surgery who had completed traditional cardiac rehabilitation were consented. Both patients who completed (cases) or did not complete (controls) a tailored 12-week resistance training program underwent comprehensive assessment of physiologic and physical fitness measures pre- and postintervention.

Findings: Nine participants enrolled in the trial, including 6 in the intervention arm (median age 61 years; 67% male) and 3 in the control arm (median age 66 years; 67% male). No serious adverse events were noted, indicating safety of the intervention. Participants completed a mean of 34.8/36 (96.7%) of sessions, indicating the feasibility of the program. Although not powered for statistical significance, patients experienced positive trends of improvement in measures of hand grip strength, endurance, and functional capacity with the intervention. When stratified, females experienced greater gains than males in these measures.

Implications: This proof-of-concept study found that resistance-based exercise after cardiac surgery is well tolerated and feasible. Although all patients experienced improvements in exercise parameters, females reported greater relative improvement than males.