Current Medical Research and Opinion最新文献

Objective: We aim to explore the concept of distance and journey to goal, and consideration of these 2 elements a priori when choosing LLT.

Methods: Modelling of expected % LDL-C reductions was carried out on a range of hypothetical patients' baseline LDL-C values prior to any LLT being commenced. Therapies were then added in a stepwise manner based on the pathway demonstrated in current national guidance and compared with goal achievement on a novel LLT optimization pathway implemented in Morecambe Bay NHS Trust.

Results: Modelling of a stepwise lipid management pathway shows that high-intensity statin monotherapy is not sufficient in most modelled baseline LDL-C scenarios to achieve guideline-recommended goals. Furthermore, ezetimibe second line may preclude 3^rd line injectable prescribing and lead to "ezetimibe limbo" where the patient is now below the reimbursement threshold for injectable prescribing but still not achieving their LDL-C target. Overall goal achievement is poor across the spectrum of modelled LDL-C levels. In contrast, by following the Morecambe Bay pathway all patients on statin for the range of hypothetical baseline LDL-C levels can reach an LDL-C target of < 1.8 mmol/L.

Conclusions: This study identifies a therapeutic gap when following a stepwise approach highlighted by recent national guidance. Our proposal of a novel pathway highlights that the order in which drugs are added is important in the context of national reimbursement thresholds and allows LDL-C goal to be reached in a timely manner, regardless of the starting baseline LDL-C level.

Background: High-sensitivity cardiac troponins (Hs-cTns) are reliable indicators of myocardial injury, but their relationship with cardiovascular outcomes remains less understood. This study explores the association between adverse cardiac events and Hs-cTnT levels exceeding 14 ng/L in patients with stable CAD.

Methods: Thirteen pertinent studies were identified using specific keywords from a pool of 208 articles retrieved from PubMed, Scopus, and Google Scholar, spanning 2013 to 2023. The primary outcomes included all-cause mortality (ACM), myocardial infarction (MI), cardiovascular death (CVD), rehospitalization due to decompensated heart failure (RDHF), need for revascularization, and stroke. Comprehensive meta-analysis (CMA) was employed to analyze the data for odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using I² statistics, and both qualitative assessment (Newcastle-Ottawa Scale) and quantitative analysis (Egger's and Beggs test, funnel plots) were conducted.

Results: The analysis included 29,115 participants (74.72% male) with a mean age of 68.34 years. It revealed a significantly elevated risk of ACM among stable CAD patients with Hs-cTnT levels >14 ng/L compared to those with levels <14 ng/L (11.2% vs. 3.3%; OR = 5.46; 95% CI = 1.53-19.54; p = 0.009). Similarly, higher risks were observed for MI (10.9% vs 3.6%; OR = 3.12; 95% CI = 0.98-9.95, p = 0.053), CVD (8.1% vs. 2.1%; OR = 3.37; 95% CI = 1.74-6.50; p < 0.0001), and RDHF (6.62% vs. 0.92%; OR = 9.46; 95% CI = 4.65-19.24; p < 0.0001). Notably, major adverse cardiovascular events (MACE) exhibited a stronger association with Hs-cTnT levels (18.2% vs 7.81%; OR = 1.89; 95% CI = 0.80-4.43; I² = 97%; p = 0.14) compared to Hs-cTnI levels (20.1% vs 21.1%; OR = 1.30; 95% CI = 1.03-1.64; I² <0.0001%; p = 0.03).

Conclusion: Elevated levels of Hs-cTnT (>14 ng/L) are significantly associated with increased risks of RDHF and ACM in patients with stable CAD. Further large-scale prospective studies are warranted to refine risk assessment strategies and mitigate cardiovascular mortality in this population.

Objective: To compare the efficacy and safety of insulin degludec biosimilar B01411 (HS-IDeg) with originator insulin degludec-Tresiba (NN-IDeg) in Chinese patients with type 2 diabetes mellitus (T2DM) who were inadequately controlled on oral antidiabetic drugs (OADs) for at least 3 months.

Methods: This multicenter, randomized, open-label, parallel-group, active-controlled, phase 3 study enrolled 362 participants with T2DM. Participants were stratified according to whether the insulin secretagogue (sulfonylurea or glinide) had been used before the screening and then randomized 1:1 to receive once-daily subcutaneous injections of HS-IDeg (n = 180) or NN-IDeg (n = 182) for 18 weeks. The primary endpoint was the change from baseline in glycated hemoglobin (HbA_1c) to week 18.

Results: At week 18, the least squares (LS) mean change in HbA_1c from baseline was -1.34% (95% CI -1.47 to -1.21) and -1.25% (95% CI -1.38 to -1.12) with HS-IDeg and NN-IDeg, respectively. The LS mean difference (HS-IDeg minus NN-IDeg) in HbA_1c at week 18 was -0.09% (95% CI -0.28 to 0.10), demonstrating non-inferiority of HS-IDeg to NN-IDeg. Participants achieving HbA_1c <7.0% at week 18 were 34.5% and 29.5% with HS-IDeg and NN-IDeg, respectively. Mean decreases in fasting plasma glucose and standard deviation of blood glucose were similar between both groups. Safety and tolerability, including hypoglycemia, adverse events, and weight change were similar between both groups. No severe hypoglycemia and no death occurred in the study.

Conclusions: HS-IDeg and NN-IDeg demonstrated similar efficacy and safety over 18 weeks of treatment in Chinese patients with T2DM who had inadequate responses to OADs for at least 3 months.

Background: To review the literature to outline findings from clinical trials assessing interventions for metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on androgen receptor-axis-targeted (ARAT) therapies.

Methods: A systematic literature review was performed to identify trials that assessed the efficacy and safety of interventions used in patients that progressed on prior ARAT therapies. A literature search was conducted using the OVID platform that searched the EMBASE, MEDLINE, and CENTRAL bibliographic databases.

Results: Of the 10,114 citations identified, a total of 36 studies representing 33 unique trials were included in the review. Of the 33 trials, 21 were randomized controlled trials and 12 were single-arm trials. A total of 11 were phase III trials, 13 were phase II trials, and 2 were phase I trials. The majority of included trials were open-label (n = 29) and the remaining were double-blind (n = 4). A total of 16 trials evaluated ARAT based therapies, 7 trials evaluated taxane-based treatments, 10 trials evaluated PARP inhibitors, 8 trials evaluated immunotherapies, and 8 trials evaluated other therapies (i.e. cabozantinib, mitoxantrone, radium-223,¹⁷⁷[Lu-177]-PNT2002,¹⁷⁷Lu-PSMA-617, samotolisib).

Conclusions: This systematic review demonstrated there are limited effective treatment options in this patient population. Unlike other cancer types, immunotherapy agents appear to provide little to no benefit. Conversely, agents such as taxane-based chemotherapy (e.g. cabazitaxel) and radionuclide therapy provide the most value in this patient population. Further research is needed to explore new therapies in this disease area and to optimize existing treatment strategies with more effective combination therapies.

Introduction: Corticobasal syndrome (CBS) is a rare form of atypical parkinsonism, most commonly caused by neurodegenerative disorders. Autoimmune underlying conditions are extremely rare, and anti-Yo antibody-associated CBS has not been reported yet.

Case report: Herein, we describe a case of a 68-year-old woman presenting with progressive dysarthria, gait instability and difficulty using her left hand with subacute deterioration during the last 3 months. Neurological examination revealed asymmetrical parkinsonism and pyramidal syndrome, reflex myoclonus and dystonia of her left upper limb, accompanied by apraxia of her left lower limb, fulfilling the criteria for possible CBS. Neuroimaging showed asymmetric frontoparietal atrophy, while cerebrospinal fluid and dopamine transporter imaging were normal. Prior to our evaluation, antineuronal autoantibody testing indicated positive anti-Yo antibodies. There was mild improvement after second IVIG cycle, and further investigation revealed no tumor.

Conclusion: Although autoimmune etiology of this case cannot be certain, it highlights the potential expansion of the clinical spectrum of anti-Yo-associated paraneoplastic syndrome.

Atrial fibrillation (AF) is associated with increased morbidity and mortality. Inflammation and oxidative stress play critical roles in AF occurrence and its complications. Therefore, evaluating the circulating levels of inflammatory and oxidative stress biomarkers and their possible applications in AF diagnosis and management have been the focus of many efforts. The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and neutrophil-to-lymphocyte ratio (NLR) are two non-invasive, available, and established markers that serve as indicators of inflammation and oxidative stress. This review summarizes the current literature regarding alterations in the NLR, MHR, and other composite markers of systemic inflammation in AF patients. Moreover, this review discusses the clinical performance of these markers in predicting AF occurrence, recurrence, and disease outcomes. The PubMed, Scopus, and ScienceDirect online databases were searched for relevant studies using appropriate keywords, including "atrial fibrillation", "monocyte to high-density lipoprotein cholesterol ratio", and "neutrophil to lymphocyte ratio". The results of this review revealed the association of elevated levels of systemic inflammatory markers, specifically the NLR and MHR with AF and its complications. This finding indicates the potential role of subclinical inflammation in the development of AF, emphasizing its consideration in both the prevention and treatment of AF and associated complications. Despite these promising findings, the utilization of these markers in routine clinical settings faces challenges, including low specificity and sensitivity and varying cut-off values across different studies.

Objective: Talquetamab is the first GPRC5D-targeting bispecific antibody approved for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). This matching-adjusted indirect comparison (MAIC) study was conducted to compare the effectiveness of talquetamab vs selinexor-dexamethasone (sel-dex) and vs belantamab mafodotin (belamaf) in patients with TCE RRMM.

Methods: An unanchored MAIC was performed using individual patient-level data from patients treated with subcutaneous talquetamab 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W) from MonumenTAL-1 (NCT03399799/NCT04636552) and published summary data for sel-dex from STORM (NCT02336815) and belamaf from DREAMM-2 (NCT0325678). Patients from MonumenTAL-1 who met key eligibility criteria for STORM and DREAMM-2 were included. Outcomes of interest were overall response rate (ORR), complete response or better (≥CR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results: After adjustment for cross-trial differences, patients treated with both dosing schedules of talquetamab showed significantly better ORR, ≥CR, and DOR vs sel-dex and significantly higher ORR and ≥ CR vs belamaf; DOR was relatively similar to belamaf. PFS was significantly improved with talquetamab Q2W and numerically in favor of talquetamab QW vs sel-dex and significantly improved with both dosing schedules of talquetamab vs belamaf. OS was significantly improved with both dosing schedules of talquetamab vs sel-dex and was numerically in favor of both dosing schedules of talquetamab vs belamaf.

Conclusion: These analyses show superior effectiveness of both talquetamab dosing schedules vs sel-dex and vs belamaf for most outcomes and highlight talquetamab as an effective treatment option for patients with TCE RRMM.

Depression is a serious psychiatric disorder with a high incidence of morbidity and mortality and psilocybin with psychotherapy has emerged as a promising potential in the treatment of depressive disorders. A review of psilocybin use in patients with depressive disorders is presented.A search was conducted investigating the use of psilocybin in patients with depressive disorders and treatment resistant depression via PubMed/MEDLINE, EMBASE, and Google Scholar in October 2023; all publication types were permitted and limited for English-language. Keyword search terms included: "psilocybin" or "psychedelics" and "depression", or "major depressive disorder", or "treatment-resistant depression". Controlled and uncontrolled clinical trials utilizing psilocybin with psychological support for major depressive disorder and treatment-resistant depression, as well as in patients with depression and cancer related anxiety have demonstrated immediate and sustained antidepressant and anxiolytic effects. Psilocybin has a favorable safety profile and was well-tolerated in clinical trials. Psilocybin's abuse potential is low and clinical research suggests the potential of psilocybin to produce rapid and lasting antidepressant effects up to 12 months post-treatment. Psilocybin may offer a valuable contribution as an option to the currently available pharmacological and psychotherapeutic agents for patients with major depressive disorders, treatment-resistant depression as well as for patients with depression and comorbid terminal cancer. Future studies are needed to demonstrate these findings and any synergistic interaction between psilocybin and the psychological support offered to patients during sessions.

Background: COPD management and therapy have been periodically revised to support a more patient-specific approach. Several concerns remain in primary care, such as the proper choice of initial treatment, medication adherence, and missing values for spirometry investigations. These concerns may be exacerbated by inconsistencies between the GOLD23 report and reimbursement criteria, as per the Italian NOTA99, especially for what concerns the assessment of disease severity and related treatment choice. We therefore examined the perception and knowledge of general practitioners (GPs) on COPD management and treatment.

Methods: We conducted an exploratory e-Delphi study among 600 GPs. The study examined the COPD-related GP's access to spirometry evaluations in primary care clinics; knowledge on early recognition of COPD and related clinical concerns; perception of the clinical application of the NOTA99; the place in therapy of the triple LABA/LAMA/ICS combination.

Results: Among 466 participating GPs (response rate: 70.3%; mean age 52, SD: 14.2; mean years of experience: 21.3, SD: 15) had a good level of knowledge about the GOLD 2023 document and the reimbursement criteria for COPD medications. Nevertheless, a low (34%) direct access to spirometry was reported, along with absence of consensus on the proper choice of initial treatment (especially of use of LABA/LAMA combination), and the re-evaluation of free-triple therapy LABA/LAMA/ICS through specialist's referral.

Conclusions: This study captured the domains on which further training for GPs might be implemented to improve the management and treatment of COPD. An extension of this e-Delphi to a larger GPs' panel might further confirm these findings.