Drugs - Real World Outcomes最新文献

Background: The combination of regorafenib and immune checkpoint inhibitor (ICI) has been the most popular second-line systemic therapy for advanced hepatocellular carcinoma (HCC). However, considering the good anti-tumor performance of lenvatinib, combined immunotherapy on the basis of lenvatinib after first-line lenvatinib failure is also popular in clinical practice. This study aimed to compare the efficacy and safety of regorafenib plus ICI (TACE-R-I) versus lenvatinib plus ICI (TACE-L-I) in patients with advanced HCC after lenvatinib failure.

Methods: In this single-center retrospective study, 164 patients with advanced HCC were enrolled from January 2019 to March 2024 in China. All patients were aged ≥ 18 years, clinically or pathologically diagnosed with HCC. All patients received trans-arterial chemoembolization (TACE) as local treatment. Overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were compared between groups. The Cox regression model was used to analyze the factors associated with OS and PFS.

Results: We compared 77 patients from each group after propensity score matching (PSM). There was no significant difference in the OS (p = 0.255) or PFS (p = 0.387) between groups. However, in the subgroup (distant metastases, Barcelona Clinic Liver Cancer (BCLC) stage C or tumor thrombus), the TACE-R-I group showed better survival benefit than the TACE-L-I group. The multivariable Cox regression model suggested that BCLC stage and alpha-fetoprotein (AFP) were independently associated with OS. Distant metastases, tumor thrombus and Child-Pugh were independent associated factors for PFS (p < 0.05). The frequency of grade ≥ 3 TRAEs was not significantly different between groups (p ≥ 0.05).

Conclusion: Our study demonstrated that in patients with greater tumor burden, the TACE-R-I group showed better OS and PFS benefits than the TACE-L-I group. However, in the overall population of HCC patients, there was no significant difference in efficacy and safety between the groups.

Background and objective: Vildagliptin sustained release (XR), a formulation that provides vildagliptin 100 mg with a once-daily dose administration, is a recent introduction to manage type 2 diabetes mellitus in India. This study aimed to evaluate the effectiveness and tolerability of vildagliptin XR in patients with type 2 diabetes in real-world clinical settings.

Methods: This was an observational, prospective, multicenter, cohort study conducted in India, which included patients with type 2 diabetes uncontrolled on metformin XR monotherapy with glycated hemoglobin (HbA1c) > 7.00%. Vildagliptin XR was added to their ongoing treatment. The primary endpoint was a change in HbA1c from baseline to 3 months. Secondary endpoints were changes in fasting plasma glucose, postprandial plasma glucose, percentage of patients achieving HbA1c < 7.00% at 3 months, and assessment of efficacy, tolerability, and safety.

Results: A total of 1691 patients from 118 centers were enrolled in this study, having a mean (standard deviation) age of 53.10 (11) years and a mean (standard deviation) HbA1c of 8.44 (1.35) %. At the end of the study, vildagliptin XR significantly reduced the mean HbA1c by 1.02% points (95% confidence interval 0.93-1.12; p < 0.001) from baseline. The mean fasting plasma glucose and postprandial plasma glucose levels were significantly reduced by 28.44 mg/dL (95% confidence interval 26.64-30.25; p < 0.001) and 48.45 mg/dL (95% confidence interval 45.91-50.99; p < 0.001), respectively, with vildagliptin XR, at the end of study. During the study duration, 34.7% of patients achieved their glycemic target (HbA1c < 7.0%) and there were three reported adverse events (all mild in severity).

Conclusions: Results demonstrated that vildagliptin XR (100 mg once daily) significantly improved HbA1c and other glycemic parameters in Indian patients with type 2 diabetes and was well tolerated.

Clinical trial registration: The study was registered under the Clinical Trials Registry India (CTRI/2022/01/039112).

Background: Studies on medicinal cannabis (MC) have primarily investigated effects on diseases and symptoms, while there is only sparse knowledge on patients' health-related quality of life. Our aim was, firstly, to compare the health-related quality of life of patients (MC users and non-users) within four specified diagnostic indications (multiple sclerosis, paraplegia, neuropathy, and nausea and vomiting after chemotherapy) with that of patients with other diagnostic indications (MC users only) and the adult population (non-users only). Secondly, we estimate the associations between use of MC and health-related quality of life for patients in the four specified diagnostic indications.

Methods: We collected data on quality-adjusted life years (QALYs), using EQ-5D-3L, and patients' self-reported use of MC in a Danish nationwide online survey distributed to 23,846 patients in October 2020. We compared QALY scores of all groups using a two-tailed t-test, listed QALY scores of MC users versus non-users, and investigated associations between QALY score and MC use using unadjusted and adjusted linear regression analyses. Significance level was set to p-value < 0.05.

Results: A total of 9265 patients took part in the survey. All diagnostic indications had a statistically significant lower QALY score than the adult population (0.87). Paraplegia patients had the lowest QALY score, being 0.36 lower, followed by other diagnostic indication (- 0.34), multiple sclerosis (- 0.20), neuropathy (- 0.13), and nausea and vomiting after chemotherapy (- 0.06). MC users had a statistically significant lower QALY score than non-users (0.44 vs 0.74). Users redeeming 1-6 and ≥ 7 MC prescriptions (except for paraplegia patients) had a statistically significant lower QALY score than non-users, ranging between 0.11-0.24 and 0.26-0.32 lower than non-users, accordingly. Although, it should be noted that the number of users was small when stratifying by number of prescriptions.

Conclusion: Patients with either multiple sclerosis, paraplegia, neuropathy, or nausea and vomiting after chemotherapy had a significantly lower health-related quality of life than individuals from the adult population. Users of medicinal cannabis also had a significantly lower health-related quality of life compared with non-users, in all diagnostic indications.

Background and objectives: Accumulating pediatric efficacy and safety data on drug use is inherently challenging yet essential. This study aimed to analyze the frequency and compute the odds of pediatric drug-associated liver injury across age groups (early childhood, middle childhood, and adolescence) and therapeutic categories using adverse drug reactions (ADRs) reporting data spanning nearly two decades.

Methods: We analyzed the reports of suspected ADRs occurring in children and adolescents in the Taiwan National Adverse Drug Reaction Reporting System during the period from May 1998 until July 2017. Standardized Medical Dictionary for Regulatory Activities Queries were utilized to identify suspected hepatic ADRs. Outcome patterns across age groups were compared using the chi-squared test, and disproportionality analysis was employed to calculate reporting odds ratios (RORs) of hepatic versus nonhepatic reports.

Results: Among 16,673 reports, 484 (2.9%) were identified as suspected hepatic ADRs, involving 193 distinct drugs. The mean age of affected individuals was 8.2 years. Outcome types in adolescents were predominantly serious (91.8%). Antibacterials for systemic use (18.8%) and antiepileptics (8.7%) were the most frequently implicated therapeutic categories. Drugs with high ADR occurrence rates and significant RORs included oxacillin (5.2%; ROR: 12.07), methotrexate (4.1%; ROR: 9.07), and phenobarbital (2.7%; ROR: 5.04). Some medications exhibited higher ratios of used-versus-recommended doses, suggesting inappropriate dosing.

Conclusions: Pediatric drug-associated liver injury was not uncommon and may result in serious outcomes. This study underscores the need for heightened vigilance in administering certain high-risk drugs and attentiveness in proper dosing for children, including adolescents.

Anti-seizure medications (ASMs) are specific types of anticonvulsants used to treat epileptic seizures. However, several studies have shown an association between ASMs and an increased risk of hematological disorders, such as thrombocytopenia, aplastic anemia, and platelet function disorders leading to prolonged bleeding times. This review explores the existing literature on this topic, investigating a wide variety of ASMs, ranging from first-generation medications to newer ones. A comprehensive search was conducted on all the currently approved ASMs using PubMed and Google Scholar: review articles, clinical trials, meta-analysis, observational studies, case reports, and relevant animal studies were identified. We extracted 15 ASMs including valproic acid (VPA), carbamazepine, phenytoin, phenobarbital, diazepam, clonazepam, lamotrigine, levetiracetam, oxcarbazepine, felbamate, topiramate, pregabalin, lacosamide, cannabidiol (CBD), and perampanel that contain considerable literature regarding different coagulopathies. An in-depth review of over 140 studies revealed a robust association between ASM-induced changes and the onset of bleeding disorders via several different mechanisms. Polytherapy, the use of multiple ASMs, also emerged as a significant risk factor for the development of coagulopathies. This review highlights the potential link between ASMs and bleeding disorders, emphasizing the importance of considering this risk during treatment planning. By understanding these associations, healthcare providers can optimize patient outcomes and minimize bleeding risks. Additionally, this review identifies the need for further research to bridge current knowledge gaps in clinical pharmacology related to ASMs and bleeding disorders.

Introduction: This study aimed to investigate the association between the 2023 Beers criteria for inappropriate prescribing and different health outcomes among community-dwelling older individuals after a 1-year follow-up period and to assess the use and factors associated with inappropriate prescribing.

Methods: This longitudinal population study spanning from 2017 to 2018 included 490 community-dwelling older adults (≥60 years old) receiving care from family medicine teams in the city of São João del-Rei, Brazil. The 2023 Beers criteria was used to identify potentially inappropriate medications (PIMs). Community health workers carried out interviews assessing different health outcomes, such as cognition, sleep, mental health, quality of life, successful aging, and life satisfaction. Generalized estimating equations were used to evaluate whether the presence of PIMs was longitudinally associated with diverse outcomes following the 1-year follow-up period.

Results: A total of 255 (52%) of the participants used at least one PIM. The most common PIMs were benzodiazepines (36.5-38.3%), followed by proton pump inhibitors (16.2-18.4%) and sulfonylureas (9.8-10.6%). Some sociodemographic factors (e.g., marital status and race) and clinical factors (e.g., difficulties in activities of daily living and the number of diseases) were associated with the presence and/or number of PIMs at baseline. In the longitudinal analysis, the presence of PIMs exhibited associations with a spectrum of outcomes observed after a 1-year follow-up period. These outcomes included diminished physical quality of life (B = -0.21; p = 0.030), disrupted sleep patterns (B = 1.14; p < 0.001), compromised mental health-depression (B = 1.04; p = 0.041), stress (B = 2.00; p = 0.001), and anxiety (B = 1.26; p = 0.004), successful aging (B = -1.92; p = 0.033), and satisfaction with life (B = -0.77; p = 0.013).

Conclusion: The use of at least one PIM, according to the 2023 Beers criteria, was high and associated with worse health outcomes. This underscores the imperative for healthcare professionals to exercise caution when prescribing medications to older patients.

Background and objective: Performing lipid testing after statin initiation is recommended to monitor response. Inadequate response may indicate non-adherence, which is associated with an increased risk of cardiovascular events and increased costs. Group-based trajectory modeling is an approach to establish probabilistic developmental trajectories of adherence, differentiating individuals by their distinct longitudinal medication-taking behaviors. We examined whether lipid testing is associated with distinct trajectories of statin adherence among individuals enrolled in a Medicare fee-for-service plan in the USA.

Methods: A retrospective cohort study was conducted using the Centers for Medicare & Medicaid Chronic Condition Warehouse 5% sample of Medicare fee-for-service data between 2006 and 2015. Statin use and lipid testing were identified using claims data. The proportion of days covered was calculated for each 30 days after the index date, which was used to estimate the probability of belonging to each potential adherence trajectory.

Results: In a cohort of 138,101 statin initiators, four statin adherence trajectory groups were identified. The four groups were differentiated as "rapid decline" (21.53%), "gradual decline" (10.25%), "decline first then improve later" (26.47%), and "high adherence" (41.75%). Compared with "high adherence," initiators who had lipid tests within 360 days after statin initiation were less likely to fall into "rapid decline" (adjusted odds ratio: 0.661; 95% confidence interval 0.641-0.683), "gradual decline" (adjusted odds ratio: 0.834; 95% confidence interval 0.801-0.868), and "decline first then improve later" groups (adjusted odds ratio: 0.936; 95% confidence interval 0.910-0.962).

Conclusions: Lipid testing is positively associated with greater use of statin medication across different adherence trajectories in the present study.

Background: The humanized anti-disialoganglioside-2 monoclonal antibody naxitamab was approved in the USA in 2020 for the treatment of patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor. Treatment with naxitamab under expanded access was initiated by physicians from the Children's Hospital of Fudan University, Shanghai, China, in August 2021.

Objective: We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab under expanded access in China from 1 August 2021 to 31 July 2022.

Methods: We assessed patient demographics and the safety profile of naxitamab over multiple treatment cycles.

Results: At the data cutoff, 41 patients with relapsed/refractory high-risk neuroblastoma had received a total of 150 treatment cycles (451 infusions) of naxitamab. The median number of cycles completed was three; 13 patients (32%) were receiving ongoing naxitamab treatment. The median patient age was 3 years (range 1-9 years) and 63% were female. Overall, ARs were reported in 89/150 cycles (59%); serious ARs were reported in 23/150 cycles (15%). The cumulative reporting rate (ARs/cycle) decreased after 3 versus 12 months of expanded access: all ARs (8.7-4.6), serious ARs (0.9-0.3), hypotension (1.4-1.0), flushing (0.7-0.5), cough (0.6-0.3), pain (0.5-0.2), and hypoxia (0.3-0.2).

Conclusions: During the first 12 months of expanded access treatment in China, 41 patients received naxitamab therapy with a cumulative 451 infusions administered. Over the course of this expanded access program, a reduction in the AR rate, including serious ARs, was observed as more patients were initiated and proceeded to later treatment cycles. While additional research is needed, the observed decrease in the AR rate may be attributed to clinicians' increased knowledge of AR management and hands-on experience with naxitamab-treated patients.