Current Medical Research and Opinion最新文献

Diabetes mellitus, stemming from either insulin resistance or inadequate insulin secretion, represents a complex ailment that results in prolonged hyperglycemia and severe complications. Patients endure severe ramifications such as kidney disease, vision impairment, cardiovascular disorders, and susceptibility to infections, leading to significant physical suffering and imposing substantial socio-economic burdens. This condition has evolved into an increasingly severe health crisis. There is an urgent need to develop new treatments with improved efficacy and fewer adverse effects to meet clinical demands. However, novel drug development is costly, time-consuming, and often associated with side effects and suboptimal efficacy, making it a major challenge. Artificial Intelligence (AI) and Machine Learning (ML) have revolutionized drug development across its comprehensive lifecycle, spanning drug discovery, preclinical studies, clinical trials, and post-market surveillance. These technologies have significantly accelerated the identification of promising therapeutic candidates, optimized trial designs, and enhanced post-approval safety monitoring. Recent advances in AI, including data augmentation, interpretable AI, and integration of AI with traditional experimental methods, offer promising strategies for overcoming the challenges inherent in AI-based drug discovery. Despite these advancements, there exists a notable gap in comprehensive reviews detailing AI and ML applications throughout the entirety of developing medications for diabetes mellitus. This review aims to fill this gap by evaluating the impact and potential of AI and ML technologies at various stages of diabetes mellitus drug development. It does that by synthesizing current research findings and technological advances so as to effectively control diabetes mellitus and mitigate its far-reaching social and economic impacts. The integration of AI and ML promises to revolutionize diabetes mellitus treatment strategies, offering hope for improved patient outcomes and reduced healthcare burdens worldwide.

Objective: To assess the screening efficiency of an multi-cancer early detection (MCED) test added to standard of care (SoC) screening, compared to SoC screening alone, among immunocompromised individuals, and to estimate the diagnostic workup costs associated with positive screening results.

Methods: We estimated the potential impact of cancer screening among immunocompromised individuals aged 50-79 years within the University of Utah Health system who underwent a stem cell/solid organ transplant or were diagnosed with a primary or secondary immunodeficiency disorder between January 2000 and February 2018. We derived cancer incidence rates from the Huntsman Cancer Institute Tumor Registry, and screening performance of SoC screening and an MCED test from published literature. Outcomes of screening efficiency included the true-positive to false-positive (TP:FP) ratio, diagnostic yield (DY), and cancer detection rate (CDR) for SoC screening alone and an incremental MCED test. Scenario and probabilistic sensitivity analyses were conducted.

Results: Among 4932 immunocompromised individuals aged 50-79 years, we estimated that 2595 tests would be done under SoC screening and assumed that all individuals received an additional MCED test. Adding an MCED test to SoC screening substantially improved screening efficiency (TP:FP = 1:1, DY = 5.15/1000 tests, CDR = 42.0%), compared to SoC screening alone (TP:FP = 1:99, DY = 1.23/1000 tests, CDR = 5.3%), assuming an MCED test with 100% uptake. Our findings were also robust to parameter uncertainty.

Conclusion: Adding an MCED test to complement existing screening may be a highly efficient strategy to increase the detection of cancers among immunocompromised individuals. These results could help to improve cancer prevention and detection efforts among individuals with multiple cancer risk factors.

Objectives: In the United States (US), prescription drug coverage is subject to prior authorization (PA) criteria, which may vary between health plans and may exceed drug label requirements. This study aimed to characterize profiles and treatment history of patients with treatment-resistant depression (TRD) who initiated esketamine nasal spray, by stringency of their health plans' PA criteria relative to the esketamine label.

Methods: Adults with evidence of TRD (≥2 antidepressant courses of adequate dose and duration) prior to initiating esketamine were identified using US insurance claims data (03/2016-02/2022). Based on health plan PA criteria for esketamine obtained from Managed Markets Insight & Technology data (05/2020-02/2022), patients were grouped into stringent (PA criteria exceeds label) and non-stringent (PA criteria less stringent or equal to label) cohorts. Patient treatment history before esketamine initiation was compared using Wilcoxon rank sum and Fisher's exact tests.

Results: The stringent cohort included 168 patients (mean age: 45 years, 63% female) and the non-stringent cohort included 400 patients (mean age: 45 years, 70% female). During the ongoing major depressive episode before esketamine initiation, the stringent versus non-stringent cohort completed 3.9 versus 3.8 antidepressant treatment courses, on average (p = 0.217); 94.6% versus 96.8% used augmentation therapy (p = 0.240), including 59.3% versus 58.1% with an antipsychotic (p = 0.844), respectively.

Conclusions: Regardless of health plan stringency, on average, patients exceeded US label-mandated number of antidepressant trials before esketamine initiation, which questions the need for health insurance plans PA criteria above label.

Background: Fatigue imposes a socioeconomic burden on patients with Crohn's disease (CD) and ulcerative colitis (UC). We assessed the prevalence of fatigue among patients with CD or UC and identified disease activity measures associated with fatigue.

Methods: Data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD) were analyzed separately for CD and UC. Fatigue was defined based on a subjective and dichotomic questionnaire. Patients indicated if they experienced fatigue within the last week. The overall prevalence of fatigue was analyzed using descriptive and contingency tables. Demographics, clinical characteristics, disease activity (measures include Physician's Global Assessment for both CD and UC, short CD Activity Index for CD, and Ulcerative Colitis Disease Activity Index for UC), symptoms, and patient-reported outcomes were compared between patients with and without fatigue. Multivariable logistic regression models were constructed to identify symptoms and disease activity measures associated with fatigue.

Results: The study included 903 patients with CD and 443 patients with UC. Fatigue was reported in 47.7% of patients with CD and 40.9% of patients with UC. In patients with CD, abdominal pain, bowel incontinence, depressive symptoms, reduced general well-being, and night-time bowel movements were associated with fatigue. In patients with UC, depressive symptoms, reduced general well-being, moderate or severe disease activity by the physician's global assessment, and night-time bowel movements were significantly associated with fatigue.

Conclusions: Fatigue is a common symptom among patients with CD or UC and is associated with higher levels of disease activity and reduced general well-being.

Background: Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types.

Methods: This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene.

Results: SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31-0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42-0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42-0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70-1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects.

Conclusion: SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.

Introduction: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjögren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases.

Case report: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy.

Conclusion: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations.

Objective: Quality of bowel preparation and patient compliance are among the most important indicators to assess the quality of colonoscopy. To investigate the independent factors associated with the quality of bowel preparation in subjects undergoing colonoscopy and its impact on compliance.

Methods: A total of 329 patient records were collected and were divided into an adequate bowel preparation group (272 cases) and an inadequate bowel preparation group (57 cases), or a compliant group (260 cases) and a non-compliant group (69 cases), based on bowel preparation quality or compliance. The quality of bowel preparation is evaluated using the Boston Bowel Preparation Scale. The comfort level of subjects during bowel preparation is assessed using the Kolcaba General Comfort Questionnaire (GCQ). Subjects' compliance was assessed according to a self-developed compliance questionnaire. Prediction analyses were conducted to identify factors associated with the quality of bowel preparation and compliance.

Results: Age, bowel preparation duration, history of bowel inadequacy, and laxative dosage showed statistical differences between the adequate and inadequate bowel preparation groups (p < 0.05). Age, bowel preparation duration, and laxative dosage were independent influencing factors of bowel preparation quality. Correlation analysis showed that GCQ scores were significantly negatively correlated with age, bowel preparation duration, laxative dose, defecation frequency, and colonoscopy duration (r < 0, p < 0.05), and positively correlated with sleep duration (r > 0, p < 0.05). In addition, age, gender, bowel preparation duration, and laxative dosage showed statistical differences between the compliant and non-compliant groups (p < 0.05). Logistic regression analysis revealed that age, bowel preparation duration, and laxative dosage were independent influencing factors of bowel preparation compliance. Age and bowel preparation duration were independent influencing factors for bowel preparation adequacy and compliance.

Conclusions: Age, bowel preparation duration, and laxative dosage are independent influencing factors for bowel preparation adequacy and compliance among patients undergoing colonoscopy at the First Affiliated Hospital, School of Medicine, Zhejiang University. It is recommended that a one-day low-residue diet combined with a 2000 mL laxative dosage be used as the bowel preparation protocol for the general colonoscopy population.

Objective: Vortioxetine has demonstrated safety and efficacy in improving symptoms of major depressive disorder (MDD), including overall functioning in real-world settings. This is the first study in a real-life clinical setting in India to evaluate effectiveness and safety of vortioxetine in patients with MDD.

Methods: This interventional, open-label study consisted of a 12-week treatment period with flexible doses of vortioxetine (5-20 mg/day) in adult patients (aged 18-65 years) with a confirmed MDD diagnosis. Effectiveness outcomes included change from baseline to week 12 in Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression-Severity (CGI-S) scores, along with CGI-Improvement (CGI-I) scores at week 12, using a mixed model for repeated measures. Adverse events (AEs) were recorded for safety outcome assessments.

Results: Of 395 patients who received vortioxetine, 42.3% were women mean age 38.9 years; 322 patients completed the study. Significant improvement in depressive symptoms was observed in change from baseline to week 12 least squares (LS) mean (SE) PHQ-9 total score (-9.36 [0.276]; p<.0001) and CGI-S score (-2.14 [0.065]; p<.0001). LS mean (SE) CGI-I score showed significant improvement at week 12 (1.93 [0.067]; p<.0001). Subgroup analysis across age, sex, disease severity, and body mass index showed significant improvements in depression symptoms and severity. A total of 35.4% (n = 140) of patients experienced treatment-emergent AEs (mostly mild-moderate); nausea and pruritus were the most frequent (6.6%, n = 26 each).

Conclusion: Safety and effectiveness of vortioxetine in improving symptoms of MDD over a 12-week period was demonstrated in a real-life clinical setting in India.

Clinical trial registration information: Open-label, flexible-dose study of vortioxetine in patients with major depressive disorder in India; Clinical Trials.gov ID: NCT04288895; https://www.clinicaltrials.gov/study/NCT04288895.

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.