Years Of Treatment Research Articles

Changes in the treatment landscape of metastatic hormone-sensitive prostate cancer: A multicenter study.

118 Background: A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). Methods: We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan–Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. Results: In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Analysis of annual treatment choice trends revealed an increasing preference for ARSIs with ADT. Kaplan–Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grade 3–4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. Conclusions: For patients with mHSPC, initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes.

Patient-reported outcomes and functional assessments of patients with Alkaptonuria in a 3-year Nitisinone treatment trial

Alkaptonuria is a rare disorder of tyrosine catabolism caused by deficiency of homogentisate 1,2-dioxygenase that leads to accumulation of homogentisic acid (HGA). Deposition of HGA-derived polymers in connective tissue causes progressive arthropathy of the spine and large joints, cardiac valvular disease, and genitourinary stones beginning in the fourth decade of life. Nitisinone, a potent inhibitor of the upstream enzyme, 4-hydroxyphenylpyruvate dioxygenase, dramatically reduces HGA production. As such, nitisinone is a proposed treatment for alkaptonuria. A randomized clinical trial of nitisinone in alkaptonuria confirmed the biochemical efficacy and tolerability of nitisinone for patients with alkaptonuria but the selected primary outcome did not demonstrate significant clinical benefit. Given that alkaptonuria is a rare disease with slow progression and variable presentation, identifying outcome parameters that can detect significant change during a time-limited clinical trial is challenging. To gain insight into patient-perceived improvements in quality of life and corresponding changes in physical function associated with nitisinone use, we conducted a post-hoc per protocol analysis of patient-reported outcomes and a functional assessment. Analysis revealed that nitisinone-treated patients showed significant improvements in complementary domains of the 36-Item Short-Form Survey (SF-36) and 6-min walk test (6MWT). Together, these findings suggest that nitisinone improves both quality of life and function of patients with alkaptonuria. The observed trends support nitisinone as a therapy for alkaptonuria.

Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer

The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival. To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy. This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included women aged 18 years or older with early ERBB2-positive, axillary node-negative or axillary node-positive breast cancer who were enrolled from January 3, 2008, to December 16, 2014, at 65 centers in 7 European countries. The current exploratory analysis was conducted after achieving the maximum attainable follow-up data when the last patient enrolled had completed the last scheduled visit in December 2022. Chemotherapy consisted of 3 cycles of docetaxel administered at 3-week intervals followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide at 3-week intervals. Trastuzumab was administered in both groups for 9 weeks concomitantly with docetaxel. In the 9-week group, no further trastuzumab was administered after chemotherapy, whereas in the 1-year group, trastuzumab was continued after chemotherapy to complete 1 year of administration. The primary objective was disease-free survival (DFS). Distant DFS and OS were secondary objectives. Survival between groups was compared using the Kaplan-Meier method and log-rank test or univariable Cox proportional hazards regression. Among the 2174 women analyzed, median age was 56 years (IQR, 48-64 years). The median follow-up time was 8.1 years (IQR, 8.0-8.9 years); 357 DFS events and 176 deaths occurred. Trastuzumab for 9 weeks was associated with shorter DFS compared with trastuzumab for 1 year (hazard ratio [HR], 1.36; 90% CI, 1.14-1.62); 10-year DFS was 80.3% in the 1-year group vs 78.6% in the 9-week group. The 5-year and 10-year OS rates were comparable between the 9-week and 1-year groups (95.0% vs 95.9% and 89.1% vs 88.2%, respectively; HR for all time points, 1.20; 90% CI, 0.94-1.54). In multivariable analyses, 9-week treatment was associated with shorter DFS compared with 1-year treatment (HR for recurrence or death, 1.36; 95% CI, 1.10-1.68; P = .005), but there was no between-group difference in OS (HR, 1.22; 95% CI, 0.90-1.64; P = .20). Only 4 patients (0.2%) died of a cardiac cause. In this secondary analysis of a randomized clinical trial, 1-year vs 9-week adjuvant trastuzumab was associated with improved DFS among patients with ERRB2-positive breast cancer receiving chemotherapy, but there was no significant difference in OS between the groups. ClinicalTrials.gov Identifier: NCT00593697.

Rapid and Sustained Effect of Ixekizumab on Patient Global, Spinal Pain, Stiffness, and Fatigue in Chinese Patients with Radiographic Axial Spondyloarthritis.

Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase3 study in China. In this Chinese phase3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80mg every 4weeks (IXEQ4W; starting dose 160mg) or placebo for 16weeks. At week16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week16. Improvements were maintained through week52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. ClinicalTrials.gov identifier NCT04285229.

Utilization and affordability of health insurance coverage for rare disease drugs in a first-tier city in Northeast China from 2018 to 2021: a study based on the health insurance claims database

ObjectiveThe accessibility issue of orphan drugs in China is prominent. Based on real-world data from a tier-one city in Northeast China, this study aims to analyze the current usage and affordability of orphan drugs for rare diseases.MethodsThe data was sourced from the health insurance claims data of a certain city from 2018 to 2021, including a total of 16 orphan drugs. The utilization of orphan drugs is assessed using four indicators: frequency of medical insurance claims, medication cost, defined daily doses (DDDs), and defined daily drug cost (DDDc). Affordability is measured using the concept of catastrophic health expenditure (CHE).ResultsBetween January 2018 and December 2021, there were a total of 2,851 medical insurance claims in the city, with a total medication costs of $3.08 million. Overall, during the study, there was a year-on-year increase in the utilization frequency of individual rare disease drugs in the city, with DDDs rising from 140.22 in 2018 to 3983.63 in 2021. Additionally, the annual medication costs of individual drugs showed a consistent upward trend, increasing from $10,953.53 in 2018 to $120,491.36 in 2021. However, the DDDc of individual drugs decreased from $398.12 in 2018 to $96.65 in 2021.The number of sales and the amount of sales for orphan drugs in community pharmacies have significantly increased. Prior to medical insurance coverage, out of the 16 orphan drugs, 9 drugs had annual treatment costs exceeding CHE for urban residents, and 15 drugs had annual treatment costs exceeding CHE for rural residents. After medical insurance coverage, there were no drugs with out-of-pocket costs exceeding CHE for urban residents, while 8 drugs had out-of-pocket costs exceeding CHE for rural residents. Furthermore, both before and after medical insurance coverage, the four treatment drugs for idiopathic pulmonary arterial hypertension were more affordable compared to the four treatment drugs for multiple sclerosis.ConclusionThe usage frequency of orphan drugs in a certain city increased gradually, but the disease burden remained heavy. More policy support should be provided to the priority rare disease populations, and the rare disease medical security and diagnosis and treatment systems should be improved.

Care Patterns and Barriers to Outpatient Care for Adults With AML Following Intensive Chemotherapy at NCCN Member Institutions.

Prolonged hospitalization following intensive (re)induction chemotherapy for acute myeloid leukemia (AML), while standard, is costly and resource intense, limits inpatient bed capacity, and negatively impacts quality of life. Early hospital discharge (EHD) following completion of chemotherapy has proven safe as an alternative at select institutions, but is not widely implemented. From February 2023 through May 2023, the NCCN Best Practices Committee conducted a survey evaluating AML hospitalization patterns, care models, and barriers to EHD at its 33 member institutions. A total of 30 (91%) institutions completed the survey; two-thirds treat >100 patients with AML annually and 45% treat more than half of these with intensive chemotherapy. In the (re)induction setting, 80% of institutions keep patients hospitalized until blood count recovery, whereas 20% aim to discharge patients after completion of chemotherapy if medically stable and logistically feasible. The predominant reasons for the perceived need for ongoing hospitalization were high risk of infection, treatment toxicities, and lack of nearby/accessible housing. There was no significant association between ability to practice EHD and annual AML volume or treatment intensity patterns (P=.60 and P=.11, respectively). In contrast, in the postremission setting, 87% of centers support patients following chemotherapy in the outpatient setting unless toxicities arise requiring readmission. Survey responses showed that 80% of centers were interested in exploring EHD after (re)induction but noted significant barriers, including accessible housing (71%), transportation (50%), high toxicity/infection rate (50%), high transfusion burden (50%), and limited bed availability for rehospitalization (50%). Hospitalization and care patterns following intensive AML therapy vary widely across major US cancer institutions. Although only 20% of surveyed centers practice EHD following intensive (re)induction chemotherapy, 87% do so following postremission therapy. Given the interest in exploring the EHD approach given potential advantages of EHD for both patients and health care systems, strategies to address identified medical and logistical barriers should be explored.

Switching to Intravitreal Brolucizumab after Ranibizumab or Aflibercept Using Treat and Extend Regimen for Neovascular Age-Related Macular Degeneration in Japanese Patients: 1-Year Results and Factors Associated with Treatment Responsiveness.

Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903-0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013-0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept.

Impact of smoking on cost-effectiveness of 10-48 years of periodontal care.

The study aims were (1) to explore whether "periodontal treatment" consisting of surgical therapy (flap, resective, or regenerative) or scaling and root planing treatment with long-term periodontal maintenance treatment, is cost-effective in terms of preventing periodontitis-attributable tooth extraction and replacement by implant-supported crowns ("extraction/replacement"); (2) to assess the effect of cigarette smoking on this cost-effectiveness. Data for this observational retrospective study were collected from dental charts of patients who had received periodontal therapy and at least annual follow-up visits for >10 years were analyzed by linear regression generalized estimating equations and generalized linear models. Among 399 adults (199 males, 200 females), those with the least mean annual treatment cost experienced the greatest mean annual costs for extraction/replacement, indicating general cost-effectiveness. Cigarette smoking adversely impacted this cost-effectiveness, with current heavy smokers experiencing no cost-effectiveness. Former smokers with Grade C periodontitis benefitted most, whereas smoking did not influence cost-effectiveness for Grade B periodontitis. Assessed by mean annual costs of "extraction/replacement," periodontal treatment was cost-effective, which decreased in a dose-response manner by former and current smoking intensity. Cigarette smoking should be factored into treatment planning and cost-effective analyses of periodontal treatment. Smoking cessation should be encouraged.

Rational use of short-term anorectic drugs for one-year effective treatment of obesity: An analysis of four studies.

Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity. This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed. The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation. The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%. Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

The Effects of Conservative Treatment on Geometric Morphology of the Spine and Thoracic Cage in Patients with Adolescent Idiopathic Scoliosis: A 1-Year Follow-up

ABSTRACT Introduction The thoracic cage has a direct relation with the spine and thereby scoliosis affects spinal morphology. The aim of the study is to investigate the effects of a 1-year conservative treatment on the geometric morphology of the spine and thoracic cage in patients with adolescent idiopathic scoliosis (AIS). Methods Thirty-six patients with AIS were assessed retrospectively for the initiation of conservative treatment and at 1-year follow-up. Patients were divided into two groups based on the intervention method: exercises-only group (ExG) and brace plus exercises group (BrG). The posteroanterior and lateral radiograph of each patient were measured in terms of spinal morphology including coronal, sagittal, transverse spinal, and thoracic cage parameters. Besides, the success rate of the conservative treatment was recorded by the sum of the stabilization and correction of each patient. Results No significant difference was found in the thoracic dimensions, thoracic geometry, and coronal and transverse plane parameters in ExG group (P &gt; 0.05). The spine height increased (P = 0.006), whereas other parameters did not change (P &gt; 0.05) in BrG. Lumbar lordosis decreased in ExG group (P = 0.025). The total success rate of the conservative treatment in AIS patients was 75%. The success rate of ExG and BrG was 68.4% and 82.4%, respectively. Conclusions The conservative treatment including both bracing and exercise seems to provide an additional elongation over the spine height without causing a negative effect in the spine and thoracic cage geometry in AIS. Clinical Relevance Bracing and exercise treatment do not have a negative impact on thoracic cage geometry in AIS.

Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year

We evaluated the efficacy and safety of 1-year treatment with nilotinib (Tasigna®) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150–300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized ‘responsive’ when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30–49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).

Once in Three-Year Deep-Banding and Annual Shallow-Banding of P, K and Cu Fertilizer Effects on Crops and Soil Nutrients

Deep-banding of the immobile nutrients (P, K, and Cu) is considered one technique that may improve crop production under temperate dryland systems, where moister soil conditions prevail at seeding followed by relatively drier soil during the growing period. The objectives were to compare growth and yield of canola (Brassica napus L.), field pea&amp;rsquo;s (Pisum sativum L.) and wheat (Triticum aestivum L.); and nutrient concentrations in crops and soil from once in three-year deep-banding (12.5-15 cm) and annual shallow-banding (3.75 to 5 cm diagonally deeper than seeding depth) of P, K and Cu under direct seeding systems. Small plot trials were conducted at the three sites; representing Brown (Dark Brown Chernozem), Black (Black Chernozem), and Grey (Dark Grey Luvisol) soil zones in Alberta, Canada; which represent crop growing conditions for most areas of western Canada. The nine treatments were annual shallow-banding and once in three year deep-banding of P, K, Cu and PKCU nutrients plus a control (no P, K, or Cu fertilizer). Applied thrice the recommended rate for deep-banding (in 2018) treatments and the recommended rate for the annual shallow-banding treatments in 2018, 2019 and 2020. All three phases of pea&amp;rsquo;s-wheat-canola rotation were grown at each site to generate nine years of data for each crop. The density, height, NDVI (normalized difference vegetation index) and biomass of plants, yield for crops and nutrient concentrations in seed and biomass of crops and soil showed significantly positive responses to P, K, and PKCu additions in some cases; generally not linked to the deep or shallow placement of tested nutrients. Changes in nutrient concentrations in seed and biomass of crops in response to nutrient additions were not consistent. Treatments with P showed response more often than with the K and Cu. The soil P and Cu concentrations increased in response to their additions in some cases, but no change was observed from the K addition. Once in three-year deep-banding or annual shallow-banding methods were equally effective. The findings provide another option (once in three year deep-banding) for applying the P, K and Cu fertilizers.

Transposition of the distal urethra: 10-year treatment results

Introduction. Post-coital cystitis is not a separate nosologic unit, but belongs to recurrent urinary tract infection. Surgical interventions are only recommended in cases where conservative treatment fails to provide relief.Objective. To evaluate the results of post-coital cystitis prophylaxis in urethral transposition.Materials &amp; methods. A retrospective study of 46 patients who underwent surgical treatment in the volume of transposition of the distal urethra from 2011 to 2013 was conducted in the clinic of Urology of MSUMD based on the Spasokukotsky Moscow Clinical Hospital.Results. Based on subjective reports from patients, urethral transposition was found to be effective in 71.7% of cases. Half of the participants reported no recurrence of cystitis within the past year, and over half (67%) reported no inflammatory episodes after undergoing surgery.Conclusion. The findings suggest that urethral transposition is an effective and relatively safe treatment option for patients with post-coital cystitis who have failed to respond to conservative treatments.

Efficacy and safety of subcutaneous immunotherapy with polymerized allergen mixtures in polyallergic patients – ARES observational study

ABSTRACT Background Administration of allergen mixtures of many components comprises the most common approach for American allergists regarding the management of polyallergic patients. European allergists, however, are more reluctant to this type of treatment due to the potential drawbacks of mixing extracts. Research design and methods To assess the efficacy and safety of subcutaneous immunotherapy (SCIT) with polymerized allergen mixtures without dilutional effect in polyallergic patients. This observational, prospective, multicenter study included patients (between 5 and 60 years) with respiratory allergic diseases that had been prescribed with SCIT with mixtures of two pollen or mite extracts. Changes in Symptoms and Medication Score (SMS) and in rhinitis quality of life questionnaire (RQLQ), subjective clinical improvement, treatment satisfaction and tolerability were assessed after the 1-year treatment. Results A total of 115 patients were included in the assessment. Mean global SMS decreased from 3.5 (SD = 1.1) to 1.6 (SD = 1.2) points, with a mean absolute reduction of 1.6 (SD = 1.3) points in the RQLQ score (p < 0.001, Wilcoxon test). General subjective clinical improvements and a good treatment satisfaction and tolerability were observed. Conclusion SCIT with polymerized allergen mixtures from either pollen or mite extracts proved to be an effective and safe treatment option for polyallergic patients suffering from allergic respiratory diseases.

Semaglutide Concurrently Improves Vascular and Liver Indices in Patients With Type 2 Diabetes and Fatty Liver Disease.

The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known. To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study. Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P < .05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (-6% vs -4%, P = .048 and -11% vs -9%, P = .039), augmentation index (AIx) (-59% vs -52%, P = .041 and -70% vs -57%, P = .022), and pulse wave velocity (PWV) (-6% vs -3.5%, P = .019 and -12% vs -10%, P = .036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores. Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD.

Analysis toolkit for evaluation of drug titration practice in acute lymphoblastic leukemia maintenance.

During the 2-year maintenance treatment phase (MT) of acute lymphoblastic leukemia (ALL), personalized patient-specified titration of oral antimetabolite drug doses is required to ensure maximum tolerated systemic drug exposure. Drug titration is difficult to implement in practice and insufficient systemic drug exposure resulting from inadequate dose titration increases risk of ALL relapse. We developed an open-source R-based analytical toolkit, including the allMT R package and an interactive web-based R Shiny VIATAMIN application, to evaluate antimetabolite drug titration during MT. Evaluation is initiated with basic visualization analysis of drug titration, in both individual patients and patient cohorts. Observations are supplemented with descriptive analyses of hematological toxicity frequency and prescriber compliance rates with protocol drug titration rules. In individual patients, visual and quantitative analyses indicate recurring potentially correctable suboptimal drug titration patterns. In patient cohorts, the toolkit enables evaluation of the impact of interventions to optimize MT drug titration. Incorporation of the toolkit in a forthcoming clinical decision support system for MT would enable real-time examination and course correction of drug titration practice. Future versions will be enhanced to include other variables that influence drug titration practice, including clinical toxicity data and later, pharmacological markers of antimetabolite, adherence, and drug activity.

Washed Microbiota Transplantation Is Associated With Improved Lipid Profiles: Long-Term Efficacy and Safety in an Observational Cohort From South China.

Dyslipidemia is one of the main risk factors of chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a significant improvement effect on patients with hyperlipidemia and hypolipemia in the Chinese population. The purpose of this study was to further explore the long-term efficacy and safety of WMT in patients with hyperlipidemia. Clinical data of patients who received WMT for multicourse were collected. Changes of blood lipid indexes before and after WMT, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein A, and Apolipoprotein B. A total of 124 patients were enrolled, including 56 cases in the hyperlipidemia group and 68 cases with normal lipids. The mean observation time was 787.80 ± 371.45 days, and the longest follow-up time was 1,534 days. TC and non-HDL-C in the hyperlipidemia group with 1-4 courses of WMT were significantly reduced ( P < 0.05); TG decreased significantly after the second course ( P < 0.05); low-density lipoprotein cholesterol also significantly decreased after the fourth course of treatment ( P < 0.05); TG, TC, and non-HDL-C significantly decreased in single course, double course, and multiple course, respectively ( P < 0.05). In terms of time period, over 1 year, the improvement in multicourse treatment was more significant than the single and double-course ones. In terms of comprehensive efficacy, WMT restored 32.14% of patients in the hyperlipidemia group to the normal lipid group ( P < 0.001), of which 30.00% recovered to the normal lipid group within 1 year ( P = 0.004) and 65.38% were reassigned to the normal lipid group over 1 year ( P = 0.003). In addition, over the 1-year treatment period, WMT significantly degraded the high-risk and medium-risk groups of atherosclerotic cardiovascular disease risk stratification in hyperlipidemia cases. There were no serious adverse events. WMT had a long-term improvement effect on patients with hyperlipidemia. The effect of multiple courses over 1 year was more significant than that of single/double courses and also had a significant destratification effect on the risk of atherosclerotic cardiovascular disease with high safety. Therefore, WMT provides a safe and long-term effective clinical treatment for patients with dyslipidemia.

Impact of pembrolizumab treatment duration on overall survival and prognostic factors in advanced non-small cell lung cancer: a nationwide retrospective cohort study

The efficacy of front-line pembrolizumab has been established in studies that limit treatment duration to 2 years, but decision to stop pembrolizumab after 2 years is often at physician's discretion. ATHENA is a retrospective cohort study using a comprehensive administrative database aimed firstly at exploring the optimal duration of pembrolizumab and secondly real-life prognosis factors in patients with advanced non-small cell lung cancer (NSCLC). Using the French National Health Insurance database (SNDS), we identified patients with incident lung cancer in France from 2015 to 2022. Treatments and patients' characteristics were extracted or inferred from hospital, outpatient care, pharmacy delivery reports. The duration's hazard ratio (HR) was estimated with Cox model weighted by inverse of propensity score to account for confounding. Prognostics factors in first line population were identified with Cox model selected by a LASSO procedure. 391,106 patients with lung cancer were identified, of whom 43,359 received up-front pembrolizumab for an advanced disease. There were 67% (29,040/43,359) of male and the median age at diagnosis was 65 years old. After a median follow-up time of 25.9 months (min-max, [0-97.6]), the median overall survival (OS) after pembrolizumab initiation in first line was 15.7 [CI 95, 15.3-16.0] months. In multivariable analysis, several covariables were independently associated with worse OS, including male sex with chemo-immunotherapy, age, hospital category, high deprivation index, inpatient hospitalization for first pembrolizumab, and history of diabetes, diuretic, beta blocker, painkiller prescription. At landmark time of 29 months after pembrolizumab initiation, continuation beyond 2 years was not associated with better OS than a fixed 2-year treatment, HR=0.97 [0.75-1.26] p=0.95. This study supports the notion that stopping pembrolizumab after 2 years could be safe for patients with advanced NSCLC. However, because observational studies are prone to confounding and selection bias, causality cannot be affirmed. This study did not receive any specific grant.

Early Intestinal Ultrasound in Severe Ulcerative Colitis Identifies Patients at Increased Risk of 1-Year Treatment Failure and Colectomy

Abstract Background and Aims Reliable and easily accessible objective markers of disease activity to predict long-term treatment outcomes in severe ulcerative colitis [UC] are missing. We aimed to investigate if intestinal ultrasound [IUS] might predict long-term outcomes in hospitalised patients with severe UC, treated with intravenous [IV] corticosteroids. Methods Hospitalised patients with severe UC and IUS inflammation (bowel wall thickness [BWT] &amp;gt; 3.0 mm) starting IV corticosteroids were recruited at three university hospitals in Denmark. IUS was performed before treatment and 48 ± 24 h, 6 ± 1 days, and 3 months after treatment initiation. Time until colectomy or need for new interventions was registered together with Mayo score at 3 months and partial Mayo score [pMayo] at 12 months. Follow-up time was 12 months. Results In the final analysis, 56 patients were included; 45 [80%] patients needed intervention, including nine colectomies, during the 12-month follow-up. After 48 ± 24 h, no patient with a BWT &amp;lt; 3 mm needed a colectomy, p = 0.04. BWT ≥ 4 mm showed an increased risk of colectomy {odds ratio 9.5 (95% confidence interval [CI] 1.5–186), p = 0.03}, whereas a BWT ≥ 3 mm showed an increased risk of intervention (3.6 [1.1–12.5], p = 0.03). A BWT ≥ 4 mm resulted in a significantly shorter time until both colectomy, p = 0.03, and treatment intensification (mean days 75 [95% CI 24–127] vs 176 [119–233], p = 0.005). However, neither IUS parameters nor pMayo score, C-reactive protein [CRP], haemoglobin, or p-albumin could predict remission at 3 and 12 months. Conclusion BWT, assessed at 48 h post intravenous corticosteroid initiation in patients hospitalised with severe UC, may identify patients with an increased risk of short- and long-term colectomy and predict a more aggressive short-term disease course.

Puberty suppression in adolescents with gender dysphoria: an emerging issue with multiple implications.

Controversy exists over puberty suppression (PS) in adolescents with gender dysphoria (GD). PS is preferentially achieved with GnRH analogues. By preventing the development of secondary sex characteristics, PS may improve psychological functioning, well-being, quality of life, emotional and behavioral (especially internalizing) problems and depressive symptoms, thus decreasing suicidality. PS can also extend the diagnostic period and give transgender adolescents time to explore their gender identity. GnRHa may also decrease the need for feminization/masculinization surgery. However, 2-year treatment with GnRHa may result in bone mass accrual retardation (decrease in BMD/BMAD z-scores), growth velocity deceleration (decrease in height SDS), increase in fat mass, temporary pause in oocyte/sperm maturation. The most common side effects of GnRHa are hot flashes, mood fluctuations, fatigue and headache. They are usually mild and rarely lead to GnRHa discontinuation. Based on current scientific evidence, PS could be recommended to adolescents who meet the diagnostic criteria of gender incongruence (by DSM-5 and/or ICD-11) and have long-lasting intense GD, which aggravates with puberty onset. Before initiating PS, possible mental issues should be addressed and informed consent (by the adolescent/caregiver) should be given, after counseling on probable reproductive effects of GnRHa. GnRHa can only be started after the adolescent has entered Tanner stage 2. Nevertheless, published studies are inadequate in number, small in size, uncontrolled and relatively short-term, so that it is difficult to draw safe conclusions on efficacy and safety of GnRHa. Large long-term randomized controlled trials are needed to expand knowledge on this controversial issue and elucidate the benefit and risks of PS.