Current Medical Research and Opinion最新文献

Levothyroxine (LT4), being "narrow therapeutic index" drug, may lead to significant fluctuations in thyroid stimulating hormone (TSH) levels. Such fluctuations can result in clinically noteworthy disruptions in thyroid function and give rise to adverse clinical consequences. Consequently, regulatory standards for LT4 potency have been tightened, with the most stringent specifications requiring maintenance of potency within the range of 95-105% of the labeled dose throughout the entire shelf-life of the product. The LT4 new formulation with tightened specification adheres to these rigorous standards, demonstrating established bioequivalence to its older formulation while upholding an equivalent standard of safety and efficacy. Furthermore, the novel formulation exhibits enhanced stability and an extended shelf-life. Of paramount significance is its capacity to provide patients with accurate and consistent dosing, thereby effectively catering to their medical requirements. The primary objective of the Asia-Pacific advisory board meeting (held in June 2022 with endocrinologists, experts from India, Indonesia, Philippines, Thailand, Malaysia and Singapore) was to establish the importance of appropriate communication to HCPs, patients and other stakeholders regarding the LT4 new formulation. The aim of this brief review is to highlight the importance of communication with healthcare professionals that should focus on providing accurate information on the LT4 new formulation, emphasizing efficacy, safety, and bioequivalence with clear guidance and ensure that patients and clinicians are fully informed about any changes to medications such as LT4 to reduce the risk of unrelated adverse events being incorrectly attributed to the newer formulation.

Background: Macitentan, either as monotherapy or part of combination therapy, improved clinical outcomes in patients with pulmonary artery hypertension (PAH) in clinical trials. Evidence on the effectiveness and safety of macitentan administered in real-world clinical practice in China is limited.

Methods: This real-world, retrospective, multicenter chart review study was conducted at seven hospitals in China. Adult patients with a diagnosis of PAH who initiated macitentan and had medical assessments at 3-7 months after macitentan initiation were included. The primary outcomes were changes in the World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide from baseline to first follow-up visit (months 3-7). Serious adverse events (SAEs) and adverse drug reactions (ADRs) of macitentan were collected.

Results: From 30 August 2021 to 31 March 2022, 214 eligible patients were included in the safety analysis set and 105 patients were included in the analysis of effectiveness. At the first follow-up visit compared with baseline, significant changes in WHO-FC were observed (p = .04), 93.5% patients had their WHO-FC improved (25.8%) or maintained (67.7%). 6MWD changed by a mean (standard deviation [SD]) of 45.0 (81.4) meters (p < .001), with 94.7% having their 6MWD improved (34.7%) or maintained (60.0%). The mean (SD) of NT-proBNP decreased from 1667.4 (3233.0) ng/L to 1090.0 (2230.1) ng/L (p < .001). In the safety analysis set, 24 (11.2%) patients experienced at least one ADR and/or SAE. ADRs and SAEs were reported in 11 (5.1%) and 18 (8.4%), respectively. No deaths or unexpected safety events were observed.

Conclusion: This study provided real-world evidence on the clinical benefits and good tolerance of macitentan in Chinese patients with PAH treated in routine clinical practice.

Introduction: Substance use disorder (SUD) poses a significant public health challenge globally, with substantial impacts on physical and social well-being. This study investigates the interplay between abstinence self-efficacy (ASE), locus of control (LOC), perceived social support (PSS), and various socio-demographic and psychosocial factors among individuals undergoing SUD rehabilitation.

Methods: Researchers obtained permission from drug rehabilitation centers in Assam, India, and conducted orientation programs for prospective participants. A total of 144 participants, aged 18-65 years, predominantly from rural areas participated in the study. Data was collected through one-to-one interviews, covering socio-demographic history, drug abuse, and administering scales for ASE, LOC and PSS. Collected data underwent digitization and subsequent descriptive and inferential statistical analyses.

Results: Significant associations were found between ASE and socio-demographic variables, family dynamics, and drug use history, highlighting the importance of considering these factors in SUD rehabilitation. Disturbed family relationships were linked to diminished ASE and higher risk of relapse, emphasizing the role of family support in recovery. Additionally, a negative correlation was observed between ASE and LOC, suggesting that individuals with higher ASE tend to have a more internal locus of control, which positively influences recovery outcomes. Moreover, positive correlations were found between ASE and PSS, particularly from family members, underscoring the importance of social support in fostering recovery. Regression analysis further elucidated the relationships between ASE, LOC, and PSS, emphasizing the predictive value of LOC and the impact of family support on ASE.

Conclusion: Findings of this study have several implications for developing targeted interventions aimed at strengthening ASE, promoting internal locus of control, and enhancing social support systems.

Objective: To estimate the comparative efficacy of ciltacabtagene autoleucel (cilta-cel) versus idecabtagene vicleucel (ide-cel) in patients with relapsed/refractory multiple myeloma (RRMM) treated with 2-4 prior lines of therapy.

Methods: Matching adjusted indirect comparison (MAICs) were performed using individual patient-level data (IPD) for cilta-cel from CARTITUDE-1 and CARTITUDE-4 and published aggregated data for ide-cel from KarMMa-3. Cilta-cel patients who met inclusion criteria from KarMMa-3 were selected, and outcomes were compared against data for ide-cel using simulated IPD derived from aggregate-level data from KarMMa-3. Patient characteristics were adjusted by reweighting cilta-cel IPD to match the distribution of prognostic factors in KarMMa-3. Comparative efficacy was estimated for response outcomes using a weighted logistic regression analysis and for progression-free survival using a weighted Cox proportional hazards model.

Results: Patients treated with cilta-cel were 1.2 times more likely to achieve overall response (relative response ratio [RR]: 1.18 [95% confidence interval: 1.03-1.34]; p = 0.04), 1.3 times more likely to achieve very good partial response or better (RR: 1.34 [1.15-1.57]; p = 0.003), and 1.9 times more likely to achieve complete response or better (RR: 1.91 [1.54-2.37]; p < 0.0001) versus ide-cel patients from KarMMa-3. Cilta-cel was associated with a significant 49% reduction in risk of disease progression or death versus ide-cel (hazard ratio: 0.51 [95% confidence interval: 0.31, 0.84]; p = 0.0078).

Conclusion: For patients with triple-class exposed RRMM treated with 2-4 prior lines of treatment, cilta-cel was found to provide superior clinical benefit over ide-cel in terms of response and progression-free survival.

Malnutrition is a prevalent, yet often underdiagnosed and undertreated, condition in older adults. It is characterized by weight loss and/or reduced muscle mass due to diminished caloric intake, inflammation, and/or disease burden. In return, malnutrition can lead to diminished skeletal muscle functionality and disability, among others. Malnutrition plays a crucial role in the pathogenesis of two prevalent geriatric syndromes, namely sarcopenia and frailty. The complex interplay between malnutrition, sarcopenia, and frailty significantly impacts the older population, leading to increased morbidity, mortality, hospitalization rates, quality-of-life, and healthcare costs. Given the prognostic significance of malnutrition in geriatric care, recent guidelines emphasized the role of nutritional support in vulnerable populations. A group of vulnerable populations to malnutrition, sarcopenia, and frailty are older patients with hip fractures, cancer patients, and those with sarcopenic dysphagia. This article highlights the importance of individualized nutritional assessment and treatment in the management of vulnerable populations such as older patients with hip fractures, cancer, and those suffering from sarcopenic dysphagia. It presents practical protocols and guidelines that can be instrumental in enhancing the nutritional care of these groups, thereby improving their overall health outcomes.

Background: Efficacy of remdesivir for COVID-19 remains unclear. We updated our published systematic review to better inform on the use of remdesivir for COVID-19.

Methods: We searched for randomized controlled trials (RCTs) among hospitalized COVID-19 patients. Meta-analysis was conducted using an inverse variance, random-effects model, presenting relative risk (RR) or mean difference (MD) and their associated 95% confidence intervals (CIs). Statistical heterogeneity was calculated using the I² statistic. In addition, we conducted trial sequential analysis (TSA). Outcomes with additional data were clinical progression, hospitalization days, and all-cause mortality.

Results: We included nine RCTs (12,876 individuals). Three trials each were of a low, unclear, and a high risk of bias. Compared with no treatment/placebo, remdesivir (100 mg daily, over 10 days) significantly improved clinical progression (RR 1.06, CI 1.02-1.11), but did not significantly reduce hospitalization days (MD -0.48, CI -2.18-1.21) and all-cause mortality (RR 0.92, CI 0.84-1.01). TSA suggested that further information is not required to conclude on the efficacy of remdesivir in improving clinical progression, and that, while more information is required for hospitalization days and all-cause mortality, further RCTs to prove fewer hospitalization days may be futile, as efficacy of remdesivir for this outcome is unlikely.

Conclusions: Remdesivir appeared promising for COVID-19, but there is insufficient evidence of its efficacy. High quality RCTs are needed for a stronger evidence base.

Objective: To illustrate the challenges encountered when gathering rapidly synthesized evidence in response to the coronavirus disease 2019 (COVID-19) pandemic.

Methods: In this article, we describe the challenges encountered when we performed a systematic literature review (SLR) of randomized controlled trials (RCTs) on the efficacy and safety of treatments for severe COVID-19. The methods of the SLR are described in full, to show the context of our objectives. Then we use the results of the SLR to demonstrate the problems of producing synthesized evidence in this setting.

Results: Various challenges were identified during this SLR. These were primarily a result of heterogeneity in the study methodology of eligible studies. Definitions of the patient populations and outcome measurements were highly variable and the majority of studies demonstrated a high risk of bias, preventing quantitative synthesis of the collated evidence.

Conclusion: Consolidating evidence from RCTs evaluating COVID-19 interventions was problematic. Guidance is needed for scenarios with high rapid output in primary research.

Objective: Fexofenadine is a second-generation inverse agonist of H₁-receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood-brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria.

Methods: We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo.

Results: Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H₁-receptor occupancy (H₁RO) obtained from PET showed no H₁RO by fexofenadine, the receptor which is known to cause sedation of H₁ antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses.

Conclusion: Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating.

Objective: Several guidelines do not recommend beta-blocker as the first-line treatment for hypertension because of its inferior efficacy in stroke prevention. Combination therapy with beta-blocker is commonly used for blood pressure control. We compared the clinical outcomes in patients treated with amlodipine plus bisoprolol (A + B), a ß1-selective beta-blocker and amlodipine plus valsartan (A + V).

Methods: A population-based cohort study was performed using data from the Taiwan National Health Insurance Research Database. From 2012 to 2019, newly diagnosed adult hypertensive patients who received initial amlodipine monotherapy and then switched to A + V or A + B were included. The efficacy outcomes included all-cause death, atherosclerotic cardiovascular disease (ASCVD) event (cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization), hemorrhagic stroke, and heart failure. Multivariable Cox proportional hazards model was used to evaluate the relationship between outcomes and different treatments.

Results: Overall, 4311 patients in A + B group and 10980 patients in A + V group were included. After a mean follow-up of 4.34 ± 1.79 years, the efficacy outcomes were similar between the A + V and A + B groups regarding all-cause death (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [CI] 0.83-1.18), ASCVD event (aHR 0.97, 95% CI 0.84-1.12), and heart failure (aHR 1.06, 95% CI 0.87-1.30). The risk of hemorrhagic stroke was lower in A + B group (aHR 0.70, 95% CI 0.52-0.94). The result was similar when taking death into consideration in competing risk analysis. The safety outcomes were similar between the 2 groups.

Conclusions: There was no difference of all-cause death, ASCVD event, and heart failure in A + B vs. A + V users. But A + B users had a lower risk of hemorrhagic stroke.