Current Medical Research and Opinion最新文献

There remains considerable interest in the therapeutic use of combinations of levothyroxine (LT4) and triiodothyronine (liothyronine, T3) in the management of hypothyroidism, especially where hypothyroid-like symptoms persist on optimised LT4 monotherapy. This interest appears to be increasing, despite the lack of consistent identification of clinical benefit in people with hypothyroidism in randomised trials going back two decades. Guidelines support an individualised trial of addition of T3 to LT4 for symptomatic patients on optimised LT4. A new generation of clinical trials seeks to address this issue, using thyroid-specific instruments to measure patient-reported outcomes, among other innovations. Safety is the other critical element of the therapeutic profile of a drug. In this article, we review the safety of treatment LT4 + T3, with an emphasis on side-effects suggestive of thyrotoxicosis (overtreatment with thyroid hormones). Randomised trials that evaluated LT4 + T3 did not raise clear or consistent safety issues with this treatment. This was despite the use of regimens with a lower ratio of LT4:T3 (usually 4-10:1) than recommended currently by clinical experts in the field. In addition, a real-world analysis of side-effects of a commercial LT4 + T3 treatment (LT4:T3 ratio 5:1) that were reported spontaneously to a pharmacovigilance database revealed a low rate of reports, both overall and with regard to symptoms possible reminiscent of thyrotoxicosis. Safety concerns regarding the possibility of iatrogenic thyrotoxicosis appear unlikely to limit the future guideline-driven therapeutic use of LT4:T3 combinations with a ratio of these ingredients of around 15:1.

Objectives: Polyethylene glycol recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are used to prevent or treat chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). This study aimed to compare the efficacy and safety of same-day versus next-day PEG-rhG-CSF administration following chemotherapy and the effects of 3 mg versus 6 mg dosages.

Methods: We retrospectively analyzed cohort data of patients with breast cancer who underwent chemotherapy and received PEG-rhG-CSF either within 24 h (same-day group) or 24 h (next-day group) after chemotherapy. The incidences of CIN and FN were assessed in each chemotherapy cycle between the two groups. The primary endpoint was the incidence of FN in the first cycle and throughout all cycles. The secondary endpoints included the incidences of various grades of CIN (CIN1-CIN4), antibiotic use, chemotherapy regimen modifications, and overall safety.

Results: Among the 2385 chemotherapy cycles with prophylactic PEG-rhG-CSF in 620 patients, 798 and 1587 cycleswere in the same-day and next-day group, respectively. No statistically significant differences were observed in the incidence of FN in the first cycle or across all cycles, CIN1-4, or adverse reactions between the two groups. However, the same-day group exhibited significantly higher rates of antibiotic use (2.88% vs. 0.42%, p = .03) and chemotherapy regimen modification (4.68% vs. 1.45%, p < .001). Subgroup analysis indicated no differences in outcomes for the 6 mg dosage, but a significantly lower incidence of CIN was observed in the same-day group receiving 3 mg (p = .025).

Conclusions: These findings suggest that same-day administration of PEG-rhG-CSF is as effective and safe as next-day administration in preventing FN and CIN during chemotherapy.

Cancer remains a major global cause of death, posing significant treatment challenges. The interactions between tumor cells and the tumor microenvironment (TME) are crucial in influencing tumor initiation, progression, metastasis, and treatment response. There has been significant research and clinical interest in targeting the TME as a therapeutic approach in cancer, with advancements being made through drug development. Histamine binds to HRH1 receptors on the TME, which inhibit CD8+ T cell activity, promote tumor growth, and contribute to resistance against immunotherapy. By inhibiting CD8+ T cells, the effectiveness of immunotherapies targeting these cells is reduced. By blocking the HRH1 pathway, H1-antihistamines can mitigate this suppression and enhance the response to immunotherapies that target CD8+ T cells. Therefore, understanding the role of histamine and its potential impact on T cells and the role of H1-antihistamines in improving immune-oncology (I/O) agents' efficacy ultimately could lead to more effective cancer therapies. The objective of this review is to examine the current literature to investigate the potential role of H1-antihistamines on the effectiveness of I/O drugs and their role in enhancing treatment against cancer. We conducted a comprehensive literature search, which included multiple databases including PubMed, Google Scholar, and EMBASE, as well as a search of oncology congresses. Our literature review initially identified thirty studies. Twenty-three of these were excluded for failing to meet inclusion criteria, which varied from study design to the type of antihistamines and patient populations involved. The clinical studies investigated the effect of different generations of H1-antihistamines in combination with I/O treatments on patients' outcomes. The findings from these studies indicated that patients using H1-antihistamines concomitantly with I/O agents experienced longer median overall survival (mOS), progression-free survival (mPFS), or improved survival compared to those who did not use antihistamines. Additionally, these trials differentiated between cationic and non-cationic H1-antihistamines, revealing that users of cationic antihistamines had overall better outcomes in terms of longer mOS and mPFS. The assessed trials were consistent in their comparisons of quantitative and qualitative, efficacy, and safety outcomes.

Objective: The purpose of this study was to conduct a systematic investigation of the potential of artificial intelligence (AI) models in the prediction, detection of diagnostic biomarkers, and progression of diabetic kidney disease (DKD). In addition, we compared the performance of non-logistic regression (LR) machine learning (ML) models to conventional LR prediction models.

Methods: Until January 30, 2024, a comprehensive literature review was conducted by investigating databases such as Medline (via PubMed) and Cochrane. Research that is inclusive of AI or ML models for the prediction, diagnosis, and progression of DKD was incorporated. The area under the Receiver Operating Characteristic Curve (AUROC) served as the principal outcome metric for assessing model performance. A meta-analysis was performed utilizing MedCalc statistical software to calculate pooled AUROC and assess the performance differences between LR and non-LR models.

Results: A total of 57 studies were included in the meta-analysis. The pooled AUROC of AI or ML model was 0.84 (95% CI = 0.81-0.86, p < 0.0001) for analyzing prediction of DKD, 0.88 (95%CI = 0.84-0.92, p < 0.0001) for detecting diagnostic biomarkers, and 0.80 (95% CI = 0.77-0.82, p < 0.0001) for analyzing progression of DKD. The pooled AUROC of LR and non-LR ML models exhibited no significant differences across all categories (p > 0.05), except for the random forest (RF) model, which displayed a statistically significant increase in predictive accuracy compared to LR for DKD occurrence (p < 0.04).

Conclusion: ML models showed solid DKD prediction effectiveness, with pooled AUROC values over 0.8, suggesting good performance. These data demonstrated that non-LR and LR models perform similarly in overall CKD management, but the RF model outperforms the LR model, particularly in predicting the occurrence of DKD. These findings highlight the promise of AI technologies for better DKD management. To improve model reliability, future study should include extended follow-up periods as well as external validation.

Objective: To determine the preferences regarding injection, medication frequency and complexity of GLP1 receptor agonists among patients with type 2 diabetes, treatment-naïve for such drugs in Spain. Additionally, patients' willingness to pay according to these attributes was evaluated.

Methods: A discrete-choice experiment survey designed to evaluate patients' preferences over three attributes discriminating by age, sex and patients experience with previous injectable treatment was fulfilled by patients. The resulting model was analyzed using a conditional (fixed-effects) logistic regression.

Results: A total of 180 patients (63.35 ± 11.49 years, 63.28% men, 48.41% with previous cardiovascular disease, 54.69% with a time of evolution of diabetes >10 years) recruited from 5 health care centers in Spain completed the survey. Patients viewed positively weekly injections (vs daily injections), but rated negatively a complex preparation of the dose (vs simple preparation). Whereas naïve patients for injectable medications did not consider administration timing of importance, no naïve patients considered it relevant. No relevant differences were observed according to age or gender. Patients were willing to pay 83.25€for a "no preparation required" dose. No naïve and naïve patients were willing to pay 34.61€ and 14.35€; p = 0.000, to change daily injection for a weekly injection.

Conclusions: Patients highly valued the avoidance of injections, with weekly dosing clearly preferred over daily dosing, as well as reducing the treatment complexity. These findings may provide a better understanding of what patients prefer and value in their treatment and provide guidance for clinicians making therapeutic decisions regarding treatments of patients with type 2 diabetes.

Cancer stem cells (CSCs) are cancer cells that can self-renew and give rise to tumors. The multipotency of CSCs enables the generation of diverse cancer cell types and their potential for differentiation and resilience against chemotherapy and radiation. Additionally, specific biomarkers have been identified for them, such as CD24, CD34, CD44, CD47, CD90, and CD133. The CSC model suggests that a subset of CSCs within tumors is responsible for tumor growth. The tumor microenvironment (TME), including fibroblasts, immune cells, adipocytes, endothelial cells, neuroendocrine (NE) cells, extracellular matrix (ECM), and extracellular vesicles, has a part in shielding CSCs from the host immune response as well as protecting them against anticancer drugs. The regulation of cancer stem cell plasticity by cancer-associated fibroblasts (CAFs) occurs through specific signaling pathways that differ among various types of cancer, utilizing the IGF-II/IGF1R, FAK, and c-Met/FRA1/HEY1 signaling pathways. Due to the intricate dynamics of CSC proliferation, controlling their growth necessitates innovative approaches and much more research. Our current review speculates an outline of how the TME safeguards stem cells, their interaction with CSCs, and the involvement of the immune and inflammatory systems in CSC differentiation and maintenance. Several technologies have the ability to identify CSCs; however, each approach has limitations. We discuss how these methods can aid in recognizing CSCs in several cancer types, comprising brain, breast, liver, stomach, and colon cancer. Furthermore, we explore different immunotherapeutic strategies targeting CSCs, including stimulating cancer-specific T cells, modifying immunosuppressive TMEs, and antibody-mediated therapy targeting CSC markers.

The populations in countries that have the highest number of individuals with chronic kidney disease (CKD) are the low and middle-income countries which are ethnically diverse. The regional and international data highlighting the need for continuous monitoring of renal function warrants that such countries use equations that give the best estimates of glomerular filtration rate for their settings. While chronic disease conditions such as diabetes and hypertension are the main conditions associated with CKD in adult populations and complicated urinary tract infections and congenital anomalies in the kidney and the urinary tract in the young, the management of patients with CKD at any age can be impacted by medical and non-biological factors. This communication seeks to posit issues that may be germane to consider when using the CKD-EPI 2021 equations in the adult and young adult populations. These equations, by excluding the race factor, have put the spotlight on the relevance of the cultural and economic context concerning the management of renal patents. The social determinants of health, how an individual defines their gender, the cultural acceptance of such or the lack thereof, factors influencing the choice of the test, communication, and technology among others may all affect renal care. These issues together may have a greater impact on renal patient care and outcome than racial disparity. While the racial divide may have been a driver for differential treatment in developed nations with different ethnic groups they may be less so when compared with more homogenous populations.

Background: This study aimed to describe the life impacts of intravesical therapies for non-muscle invasive bladder cancer (NMIBC) from a patient perspective.

Methods: A cross-sectional online survey design was used. Adults with NMIBC (and no other cancer) treated intravesically in the prior 12 months were recruited from US patient online communities. Individuals participating in a clinical trial or treated with erdafitinib were excluded. Participants' treatment experiences were evaluated using a questionnaire comprising (a) custom questions reported on 11-point numerical rating scales and (b) validated patient reported outcome (PRO) measures for bladder symptom burden and work productivity.

Results: Among 171 survey participants, most received bacillus Calmette-Guérin (BCG) (83%), intravesical gemcitabine (28%), or gemcitabine + docetaxel (13%) during the past year. Participants generally felt adequately informed about treatment, felt expectation of treatment matched actual experience, and expressed intent to complete the full treatment course and willingness to try different treatments if needed. Participants reported disease symptom burden of 42.6/72 on the NFBlSI-18 scale. Employed participants reported 51% work impairment and 59% overall work productivity loss due to NMIBC.

Conclusions: Participants recently treated with intravesical therapies expressed intent to complete the full treatment course and willingness to try new therapies if needed. Participants reported high NMIBC symptom burden and work impairment negatively impacting their well-being, despite receiving intravesical treatment.