First Year Of Treatment Research Articles

Should We Use bDMARDs as an Induction Therapy in Early and Severe Rheumatoid Arthritis? Results at 5years from the ERA UCLouvain Brussels Cohort.

This study sought to analyze the benefit of an early induction therapy with a biological disease-modifying anti-rheumatic drugs (bDMARD) during the first year of treatment with a 5-year follow-up in early rheumatoid arthritis (ERA). We included ERA patients from the UCLouvain Brussels cohort who met the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria and were naïve to DMARDs. ERA patients were divided into two groups according to whether they received an induction bDMARD therapy or a standard therapy with methotrexate (MTX). Clinical response after the induction treatment at 6 and 12months followed by a MTX maintenance therapy at 36 and 60months was evaluated. Data from 470 ERA patients were collected, 189 received a bDMARD and 281 initiated MTX alone. In the bDMARD group, disease activity and HAQ were higher at baseline. A total of 391 patients were followed up to 5years. We then divided each group into two subgroups according to the last treatment they received at 5years: bDMARD > MTX (n = 95), bDMARD > bDMARD (n = 59); MTX > MTX (n = 134), MTX > bDMARD (n = 103). During the induction, we observed a clinical response with a large number of patients achieving DAS28-CRP remission. According to a treat-to-target (T2T) approach, remission rate was stable on MTX monotherapy or rescued by the addition or prolongation of a bDMARD. Interestingly, bDMARD followed by a MTX maintenance therapy experienced a stable and sustained DAS28-CRP remission rate in 53% of the ERA patients at year 5. Long-term remission is an achievable goal in ERA. Our results suggest that a bDMARD induction therapy followed by MTX maintenance therapy could be an interesting option.

Polydrug use among patients on methadone medication treatment: Evidence from urine drug testing to inform patient safety.

Patients in methadone medication treatment for opioid use disorder (M-MOUD) typically have a complex history of opioid use, often in combination with other drugs. It is unknown how frequently M-MOUD patients experience persistent substance or polysubstance use. We measured trends in illicit substance use in a large, multistate population of M-MOUD patients and persistence of substance use in the first year of treatment. Retrospective cohort study of United States (US) M-MOUD patients from 2017 to 2021, focused on urine drug specimens provided for testing to Millennium Health, a third-party laboratory. Specimens were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Generalized estimating equations (GEE) were used to estimate the average trends in positivity during time in treatment. Specimens were obtained from clinics in 10 US states that provided at least 300 unique patients during the study period (Alaska, Arizona, Florida, Illinois, Kentucky, Minnesota, New Mexico, Ohio, Virginia and Washington). Patients with opioid use disorder receiving M-MOUD (n = 16 386). Positivity rates for heroin, fentanyl, methamphetamine and cocaine. From 2017 to 2021, yearly crude positivity rates for first collected specimens increased for fentanyl (13.1%-53.0%, P < 0.001), methamphetamine (10.6%-27.2%, P < 0.001) and cocaine (13.8%-19.5%, P < 0.001); for heroin positivity did not significantly change (6.9%-6.5%, P = 0.74). In regression models estimating patient trajectories from week 1 to week 52, marginal fentanyl positivity declined from 21.8% to 17.1% (incidence rate ratio [IRR] = 0.78, P < 0.001) and heroin positivity declined from 8.4% to 4.3% (IRR = 0.51, P < 0.001), but positivity for methamphetamine and cocaine did not significantly change, remaining at an average of 17.7% (IRR = 0.98, P = 0.53) and 9.2% (IRR = 0.96, P = 0.36), respectively. Between 2017 and 2021, United States patients presenting to opioid treatment programs increasingly tested positive for fentanyl, methamphetamine and cocaine. Methadone medication treatment for opioid use disorder appears to remain an effective intervention for reducing illicit opioid use.

Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML.

The achievement of major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) is a milestone in the therapeutic management of patients with newly diagnosed chronic myeloid leukemia (CML). We analyzed the predictive value of gene expression levels of ESPL1/Separase, PTTG1/Securin and PTTG1IP/Securin interacting protein for MMR achievement within 12 months. Relative expression levels (normalized to GUSB) of ESPL1, PTTG1 and PTTG1IP in white blood cells of patients (responders n = 46, non-responders n = 51) at the time of diagnosis were comparatively analyzed by qRT-PCR. 3D scatter plot analysis combined with a distance analysis performed with respect to a commonly calculated centroid center resulted in a trend to larger distances for non-responders compared to the responder cohort (p = 0.0187). Logistic regression and analysis of maximum likelihood estimates revealed a positive correlation of distance (cut-off) with non-achieving MMR within 12 months (p = 0.0388, odds ratio 1.479, 95%CI: 1.020 to 2.143). Thus, 10% of the tested non-responders (cut-off ≥ 5.9) could have been predicted already at the time of diagnosis. Future scoring of ESPL1, PTTG1 and PTTG1IP transcript levels may be a helpful tool in risk stratification of CML patients before initiation of TKI first = line treatment.

Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study

BackgroundAnti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. MethodsAll patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. ResultsAmong a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1–20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0–59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02–2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30–4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15–0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. ConclusionIn a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.

Оцінка ефективності комбінованої терапії препаратами рекомбінантного гормона росту та вітаміну D дітей препубертатного віку із соматотропною недостатністю

The treatment of somatotropic insufficiency (SI) remains one of the most important problems in paediatric endocrinology. Since 1985, recombinant growth hormone (rGH) has been widely used to correct the growth of children with SI. Sufficient clinical experience has been gained in the use of rGH preparations, and the efficacy and safety of rGH therapy in children and adolescents with various forms of short stature has been proven. However, there are a number of factors that can have a significant impact on the achievement of final height in adulthood, including a wide range of sensitivity to exogenous growth hormone (GH), the degree of endogenous GH deficiency, patient compliance, and other uncertain factors. Patients with GH deficiency require long-term treatment, the effectiveness of which decreases significantly over time, prompting the search for optimal treatment options. Purpose - to evaluate the effectiveness of combined therapy of pre-pubertal children with SI with rGH and vitamin D drugs. Materials and methods. 23 pre-pubertal children with isolated SI were examined, who took monotherapy with rGH for 3 years. When the effectiveness of monotherapy decreases, vitamin D are added to the treatment complex. The level of 25(OH)D in blood serum is determined by the immunochemiluminescence method on microparticles (Abbott, USA). The levels of GH and insulin-like growth factor-1 were studied by solid-phase enzyme immunoassay using Immulite 2000 XPI kits. Results. At the end of the first year of rGH monotherapy, all patients showed a significant (p&lt;0.05) increase in height. However, already after the second and third years of treatment, height velocity (HV) decreased in all patients. The increase in HV in the third year of treatment with rGH was significantly lower (p&lt;0.05) than in the first year. Thanks to the addition of vitamin D, the further decrease in HV was stopped after the third year of monotherapy with rGH. The increase in HV during the first year of combined therapy was significantly (p&lt;0.05) greater than during the third year of treatment with rGH monotherapy. The same trend was observed after the second year of combined therapy. Conclusions. In the presence of a decrease in the effectiveness of therapy with rGH after the first years of treatment, it is considered appropriate to use combined therapy of children with SI with rGH and vitamin D. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Management, Survival, and Costs of Pancreatic Cancer: Population-Based Observational Study in Catalonia

Few published studies comprehensively describe the characteristics of patients with pancreatic cancer and their treatment in clinical practice. This study aimed to describe the current clinical practice for treating pancreatic cancer in Catalonia, along with the associated survival and treatment costs. A retrospective observational cohort study in patients diagnosed with pancreatic cancer from 2014 to 2018, using data from the healthcare records of the Public Health System of Catalonia, was conducted. Treatment patterns and costs were described by age groups from 2014 to 2018, with survival reported until December 2021. The proportion of patients receiving surgery with curative intent was low, especially in older patients (23% of patients <60 years and 9% of patients ≥80 years). The percentage of patients treated with drugs for unresectable disease also decreased with age (45% of patients <60 years and 8% of patients ≥80 years). Although age was associated with significant differences in survival after curative surgery, no differences attributable to age were observed in patients who received pharmacological treatment for unresectable disease. In patients under 60 years of age, the mean cost of the first year of treatment was EUR 17,730 (standard deviation [SD] 5754) in those receiving surgery and EUR 5398 (SD 9581) in those on pharmacological treatment for unresectable disease. In patients over 80, the mean costs were EUR 15,339 (SD 2634) and EUR 1845 (SD 3413), respectively. Half of the patients diagnosed with pancreatic cancer did not receive specific treatment. Surgery with curative intent was associated with longer survival, but only 18% of (mostly younger) patients received this treatment. Chemotherapy was also used less frequently in patients of advanced age, though survival in treated patients was comparable across all age groups, so careful oncogeriatric assessment is advisable to ensure the most appropriate indication for eligibility in older patients. In general, earlier diagnosis and more effective pharmacological treatments are necessary to treat frail patients with high comorbidity, a common profile in older patients.

Immunological Signatures Associated With Ocrelizumab Treatment in Early RRMS: 12-Month Interim Analysis From the Ocrelizumab Phase IIIb (ENSEMBLE; NCT03085810) Immunological Substudy (S16.003)

Immunological Signatures Associated With Ocrelizumab Treatment in Early RRMS: 12-Month Interim Analysis From the Ocrelizumab Phase IIIb (ENSEMBLE; NCT03085810) Immunological Substudy (S16.003)

Abstract CT064: Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy, Flamingo-01

Abstract Background: GP2 is a biologic nine amino acid peptide of the HER2/neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. In a prospective, randomized, single-blinded, placebo-controlled, multicenter Phase IIb study, no recurrences were observed in the HER2+ population after 5 years of follow-up, if the patient was treated with GLSI-100, survived, and was followed for more than 6 months (p = 0.0338). Immunotherapy elicited a potent response measured by skin tests and immunological assays. Of the 146 patients that have been treated with GLSI-100 over 4 clinical trials, GLSI-100 was well-tolerated and no serious adverse events observed were considered related to the immunotherapy. Method: This Phase III trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy, 6 intradermal injections of GLSI-100 or placebo will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years for a total of 11 injections over 3 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up for a total of 4 years following the first year of treatment with trastuzumab-based therapy. Patients will be stratified based on residual disease status at surgery, hormone receptor status and region. Study Size - Interim Analysis: Approximately 498 patients will be enrolled. To detect a hazard ratio of 0.3 in invasive breast cancer free survival (IBCFS), 28 events will be required. An interim analysis for superiority and futility will be conducted when at least 14 events have occurred. This sample size provides 80% power if the annual rate of events in placebo patients is 2.4% or greater. Up to 100 non-HLA-A*02 subjects will be enrolled in an open-label arm. Eligibility Criteria: The patient population is defined by these key eligibility criteria: 1) HER2/neu positive and HLA-A*02; 2) Residual disease or High risk pCR (Stage III at presentation) post neo-adjuvant therapy; 3) Exclude Stage IV; and 4) Completed at least 90% of planned trastuzumab-based therapy. Trial Objectives: 1) To determine if GP2 therapy increases IBCFS; 2) To assess the safety profile of GP2; and 3) To monitor immunologic responses to treatment and assess relationship to efficacy and safety. Study Status: The study has been initiated at a number of sites in the US. The study is also expected to be opened in Spain, Germany, and France. Funding: This trial is supported by Greenwich LifeSciences. Citation Format: Snehal S. Patel, Jaye L. Thompson, Mira S. Patel, F. Joseph Daugherty, Mothaffar F. Rimawi. Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy, Flamingo-01 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT064.

Longitudinal evaluation on negative symptoms in young people at Ultra-High Risk (UHR) of psychosis: results from a 2-year follow-up study in a real-world care setting.

Negative Symptoms (NS) severely affect real-world functioning also in young people at UHR for developing psychosis. However, longitudinal research on beneficial effects of specialized treatments for NS in UHR people is still relatively scarce and inconclusive, especially in real-world care settings. The aims of the present research were: (1) to evaluate the longitudinal stability of NS levels in young UHR subjects treated within a specialized "Early Intervention in Psychosis" (EIP) program across a 2-year follow-up period, and (2) to investigate any relevant association of NS changes with the specific treatment components offered within the EIP program. One hundred UHR individuals (aged 12-25years) completed the Positive And Negative Syndrome Scale (PANSS). A multiple linear regression analysis was conducted to examine significant associations between longitudinal changes in NS severity levels and the EIP treatment components. Across the follow-up, a significant decrease in NS clinical severity was observed. This reduction was associated with the intensity of individual psychotherapy sessions provided in the first year of treatment, a shorter duration of untreated illness at entry and the 2-year longitudinal decrease in positive symptom levels. In conclusion, NS are relevant in UHR people, but decrease over time together with the delivery of specialized EIP interventions. Specifically, our results showed that individual psychotherapy may reduce the clinical severity of NS at least during the first year of treatment.

Baclofen and the Risk of Encephalopathy: A Real-World, Active-Comparator Cohort Study

ObjectiveTo quantify the risk of encephalopathy associated with oral baclofen compared with other muscle relaxants—tizanidine or cyclobenzaprine. Patients and MethodsWe conducted a new-user, active-comparator study of 2 pairwise cohorts using tertiary health system data from Geisinger Health in Pennsylvania (January 1, 2005, through December 31, 2018). Adults (aged ≥18 years) newly treated with baclofen or tizanidine were included in cohort 1. Adults newly treated with baclofen or cyclobenzaprine were included in cohort 2. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance the respective cohorts on 45 patient characteristics. Fine-Gray competing risk regression was used to estimate the risk of encephalopathy. ResultsCohort 1 included 16,192 new baclofen users and 9782 new tizanidine users. The 30-day risk of encephalopathy was higher in patients treated with baclofen vs tizanidine (IPTW incidence rate, 64.7 vs 28.3 per 1000 person-years) with an IPTW subdistribution hazard ratio (SHR) of 2.29 (95% CI, 1.43 to 3.67). This risk persisted through 1 year (SHR, 1.32 [95% CI, 1.07 to 1.64]). Similarly in cohort 2, baclofen vs cyclobenzaprine was associated with a greater risk of encephalopathy at 30 days (SHR, 2.35 [95% CI, 1.59 to 3.48]) that persisted through the first year of treatment (SHR, 1.94 [95% CI, 1.56 to 2.40]). ConclusionThe risk of encephalopathy was greater with baclofen vs tizanidine or cyclobenzaprine use. The elevated risk was apparent as early as 30 days and persisted through the first year of treatment. Our findings from routine care settings may inform shared treatment decisions between patients and prescribers.

Real life long-term efficacy and safety of rhGH therapy in children with SHOX deficiency.

This Italian survey aims to evaluate real-life long-term efficacy and safety of rhGH therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy. This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3, T4) and at near-final height (nFH) (T5), when available. 117 SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33years (74% prepubertal), 99 completed the 1st year of treatment, and 46 reached nFH. During rhGH therapy, growth velocity (GV) SDS and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14±0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (β -0.31, p = 0.030) and the GV during the first year of rhGH treatment (β 0.45, p = 0.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported. Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype.

Tyrame [N-(3-hydroxy-1:3:5(10)-estratrien-17β-yl)-4-hydroxy-phenethylamine], antithrombotic aminoestrogen that decreases microvesicle formation.

Estrogens that are used as contraceptives or in replacement therapy are associated with an increase in the risk for developing thrombosis, mainly during the first year of treatment and in women with associated risk factors. To synthesize, characterize and identify the anticoagulant, antiplatelet aggregation and microvesicle-reducing effect of the new aminoestrogen Tyrame. CD1 strain mice were used, which had Tyrame (0, 1 and 2 mg/100 g) subcutaneously administered. At 24 h, a blood sample was obtained to determine whole-blood clotting time, microvesicles concentration and inhibitory effect on platelet aggregation. Blood clotting time increased up to 1.5 times in comparison with the control. Platelet aggregation inhibition had different magnitude depending on the agonist agent employed, and was complete with collagen. Both effects had a dose-dependent relationship. The microvesicles decreased up to six times with respect to the control. Tyrame reduces platelet aggregation and microvesicle formation, which emphasizes its potential therapeutic utility as an estrogen free of thrombotic effects.

A randomized, open-label clinical trial in mild cognitive impairment with EGb 761 examining blood markers of inflammation and oxidative stress

Although beta-amyloid (Aβ) and phosphorylated tau remain the preferred targets for disease-modifying treatments (DMT) against Alzheimer’s disease (AD), part of the pathophysiological mechanisms of cognitive impairment are related to neuroinflammation and oxidative stress. In mild cognitive impairment (MCI), a prodromal stage of AD and other neurodegenerative conditions, the joint appearance of inflammation, oxidative stress, and metabolic alterations are the common pathways of neurotoxicity and neurodegeneration. The standardized extract of Ginkgo biloba EGb 761 interferes with the pathogenic mechanisms involved in both the development of cognitive impairment due to AD and that of vascular origin. The primary objective of this study is to compare changes in the levels of blood markers of inflammation and oxidative stress after treatment with EGb 761 in a cohort of 100 patients with MCI. In addition, we aim to assess changes in these blood markers during an additional 12-month extension phase in which patients in the control group will also receive EGb 761 and patients in the active group will extend their treatment duration. Secondary objectives include comparing changes in neuropsychiatric and cognitive test scores between the baseline (v0) and 12-month visits (v2). This study is a Phase IV, single-center, randomized, open-label, parallel-group clinical trial consisting of the 12-month follow-up of a cohort of participants with MCI [Global Deterioration Scale (GDS) = 3] and an extension with an additional 12-month follow-up. During the first 12 months, participants will be randomized into two arms: in one arm, patients will receive 1 daily tablet of EGb 761 240 mg orally (study group, n = 50), while in the other arm, patients will not receive EGb 761 and will undergo the same assessments as the treated group (control group, n = 50). After the first 12 months of the study, patients in the EGb 761-treated group will continue treatment, and patients in the control group will be offered one EGb 761 240 mg tablet per day orally. All participants will be monitored for an additional 12 months. A battery of blood markers of inflammation and oxidative stress will be quantified at v0, v1, v2, v3, and v4. The Olink Proteomics panel of inflammation markers (https://www.olink.com/products/inflammation/) will be used to evaluate 92 proteins associated with inflammatory diseases and related biological processes. The second panel measures 92 proteins involved in neurological processes. At v0, v2, and v4, neuropsychological and neurological evaluations will be conducted in addition to vital signs and anthropometric studies using a body composition monitor with bioimpedance technology (Tanita). Sixty percent of the 100 MCI patients recruited were women. The mean age was 73.1 years, and the mean time between symptom onset and MCI diagnosis was 2.9 years. The mean Mini-Mental State Examination (MMSE) score was 26.7. Depressive and anxiety disorders, as well as vascular risk factors, were the most frequent comorbidities among the cohort. The study is still ongoing, and results for the first year of treatment (v0, v1, v2) are expected by 2023. Individuals with MCI have an elevated risk of developing dementia. EGb 761 is used worldwide for the symptomatic treatment of cognitive disorders due to its neuroprotective effects. In experimental models and clinical observational studies, EGb 761 has shown strong antioxidant and anti-inflammatory activity. As a result, this study has been proposed to evaluate the antioxidant and anti-inflammatory effects on plasma markers and their potential clinical correlation with the progression of cognitive decline in patients with MCI.Trial registration: Registro Español de estudios clínicos (REec) number 2020-003776-41, ClinicalTrials.gov Identifier: NCT05594355.

Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms

IntroductionMyopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown...

MP76-03 PROCEDURAL COMPLICATIONS ASSOCIATED WITH MIST AND INVASIVE SURGERY COMPARED TO DISEASE PROGRESSION WITH MEDICAL THERAPY

You have accessJournal of UrologyCME1 Apr 2023MP76-03 PROCEDURAL COMPLICATIONS ASSOCIATED WITH MIST AND INVASIVE SURGERY COMPARED TO DISEASE PROGRESSION WITH MEDICAL THERAPY Steven Kaplan, Ronald Kaufman, Daniel Rukstalis, and Claus Roehrborn Steven KaplanSteven Kaplan More articles by this author , Ronald KaufmanRonald Kaufman More articles by this author , Daniel RukstalisDaniel Rukstalis More articles by this author , and Claus RoehrbornClaus Roehrborn More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003350.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To quantify the impact of BPH treatments in the real world, this healthcare utilization analysis attempts to compare complications and procedures subsequent to a surgical intervention vs. daily medication. METHODS: Patient-level data on men with BPH who received medical therapy only, MIST or invasive surgery in an outpatient setting from 2015-2021 were analyzed in a representative sample of US Medicare and commercial claims (IBM Watson). Procedures (post-operative following surgery or occurring after initiation of medical therapy) were identified with CPT codes. Overall event rates through 12 months post-treatment were calculated via cumulative incidence curves. RESULTS: 203,504 medical therapy patients were analyzed with average treatment of 716 days [most common medications: tamsulosin (n=75,698), Tadalafil (n=55,129)]. 5.5% of medication patients underwent procedures within the first year of treatment, the most frequent being cystoscopy (n=9,920), catheterization (n=1,792), and bladder irrigation (n=975). Mean time to onset for any event was 121d. Top diagnoses that drove cystoscopies included LUTS symptoms and urinary retention. For the surgical cohort, 24,035 TURP, 11,911 PVP, 84 Aquablation, 8,649 PUL, and 1,944 Rezum comprised the population. Procedural complication rates continued to be lowest after PUL (17%) with mean onset of 55d, highest for Rezum (28%, mean onset 29d), and comparable among the invasive surgeries: 20%, 21%, 22% for Aquablation (mean onset 18d), TURP (mean onset 35d), and PVP (mean onset 38d), respectively. Top complications for MIST and traditional surgeries were cystoscopies, catheterizations, and bladder irrigations. CONCLUSIONS: Surgical intervention delivers treatment in one setting while medical therapy is affected by lack of compliance and discontinuation. We recognize the difficulties in comparing just one aspect of treatment complications between two treatment paradigms. We reveal∼6% of medical therapy patients undergo procedures through 1 year as disease progresses. Procedure complication rates were similar between TURP and PVP yet lowest for PUL. Although the Aquablation data are relatively immature due to the newness of the technology, the 20% rate reflects a safety profile similar to TURP and higher than PUL. Source of Funding: Teleflex © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1091 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Steven Kaplan More articles by this author Ronald Kaufman More articles by this author Daniel Rukstalis More articles by this author Claus Roehrborn More articles by this author Expand All Advertisement PDF downloadLoading ...

Тактика ведения пациентов с экссудативной формой возрастной макулярной дегенерации при резистентности к одному из анти-VEGF препаратов

The exudative form of AMD can develop suddenly, leading within a few weeks or months to the death of photoreceptors, a sharp decrease in BCVA and persistent central scotoma. Despite significant progress in the treatment of neovascular AMD associated with the introduction of anti-VEGF drugs into clinical practice, a number of patients have an insufficient response or its absence with standard administration regimens, and sometimes a decrease in the therapeutic effect after repeated intravitreal injections [1, 2]. Purpose. To development management tactics for patients resistant to one of the anti-VEGF drugs. Material and мethod. This study included 25 patients with a diagnosis of exudative AMD who received Aflibercept in the treat &amp; extend regimen for a year, without a significant effect (persistence of intraretinal, subretinal and/or fluid under RP). Patients were switched to brolucizumab. The mean maximum correctable visual acuity in patients treated with aflibercept before switching drugs was 0.41 ± 0.11. The mean number of injections during the first year in the aflibercept group was 7.1 and 6.8 after switching to brolucizumab. The maximum correctable visual acuity at the end of 1 year of treatment with brolucizumab was 0.47 ± 0.1. Before the start of treatment with aflibercept, the mean CRT was 435.2 ± 119.8, at the end of the first year of treatment 403.3 ± 115.9, before 1 intravitreal injection of brolucizumab 407.2 ± 119.3 and 1 year after the start of therapy 357.6 ± 111.4 (p = 0.042). A statistical difference was found between the preparations and the height of the detachment of the retinal pigment epithelium at the end of the first year of treatment. Changes in the height of detachment of the retinal pigment epithelium in 3 eyes (12 %) were not observed when changing the drug. A positive response to drug switching should be noted, although it cannot be overlooked that there are patients who are resistant to anti-VEGF therapy per se. Keywords: the exudative form of AMD, anti-VEGF drugs, neovascular AMD.

Ovarian Function Suppression in Premenopausal Women With Concurrent Endocrine Therapy Use

IntroductionAlmost 20% of patients receiving ovarian function suppression (OFS) and endocrine therapy (ET) for breast cancer treatment had inadequate OFS within the first year of treatment. Few studies have explored the long-term effectiveness of OFS to maintain estrogen suppression. Patients and MethodsThis retrospective, single institution study examined premenopausal women with early-stage breast cancer undergoing treatment with OFS and ET. The primary endpoint was the percentage of patients with inadequate ovarian suppression (estradiol ≥10 pg/mL) during OFS cycle 2 or later. The secondary endpoint was the percentage of patients with inadequate ovarian suppression within the first cycle after OFS initiation. Differences in age, body mass index (BMI), and previous chemotherapy use were summarized via multivariable logistic regression. ResultsOf the 131 patients included in the analysis, 35 (26.7%) lacked adequate suppression during OFS cycle 2 or later cycles. Patients with adequate suppression throughout treatment were more likely to be older (odds ratio [OR] 1.12 [95% CI, 1.05-1.22], P = .02), have a lower BMI (OR 0.88 [95% CI, 0.82-0.94], P < .001), and have received chemotherapy (OR 6.30 [95% CI, 2.06-20.8], P = .002). A total of 20 of 83 patients (24.1%) had an inadequately suppressed estradiol level within 35 days of OFS initiation. ConclusionThis “real world” cohort demonstrates that estradiol concentrations above the postmenopausal range of the assay are frequently detected, including more than 1 year after the start of OFS. Additional research is needed to establish estradiol monitoring guidelines and optimal degree of ovarian suppression.

Twice-daily injections and multiple daily injections of insulin in toddlers with type 1 diabetes: a retrospective cohort study.

Twice-daily injections and multiple daily injections of insulin in toddlers with type 1 diabetes: a retrospective cohort study.

I am feeling stressed, are you?: Breast cancer patients and caregivers' inter-psychophysiological symptoms during the first year of breast cancer treatment

ObjectiveBreast cancer treatment can be a stressful time for both the patient and their caregiver. Both patients and caregivers can experience increases psychophysiological distress (e.g., pain interference, fatigue, anxiety, depressive symptoms, perceived health); however, it is not clear how psychophysiological distress before treatment is linked to distress during the first year of treatment both interpersonally and intrapersonally. MethodsThe present study recruited 54 patient-caregiver dyads during diagnosis before breast cancer treatment started. Both patients and caregivers complete self-reported surveys at baseline (before treatment), then 6-weeks, 6-months, and 12-months after the start of treatment. Specifically, we examine trajectories of psychophysiological change using Actor-Partner Interdependence Models (APIMs) Growth Curve Models and clinically specific times of psychophysiological influence using APIM path analyses. ResultsResults indicate that patient and caregiver psychophysiological distress before treatment is linked to psychophysiological distress during the first year of treatment both intrapersonally and interpersonally but somewhat differently depending on the symptom. For example, for perceived health there are no interpersonal effects and for fatigue caregivers appear to experience the majority of psychophysiological distress effects. ConclusionOur findings suggest that medical practitioners could evaluate patients and their caregivers for psychophysiological distress prior to breast cancer treatment and consider referrals to therapy or psychoeducation to help with symptom management throughout the first year of treatment.

A203 EARLY PROACTIVE DRUG MONITORING STRATEGY OF INFLIXIMAB AS MONOTHERAPY FOR INFLAMMATORY BOWEL DISEASE IN PAEDIATRIC PATIENTS IS ASSOCIATED WITH GOOD SUSTAINED CLINICAL REMISSION

Abstract Background Monotherapy with Infliximab (IFX) can be as efficient as combotherapy with immunomodulators in the treatment and maintenance of remission for children with inflammatory bowel disease (IBD) if an early proactive therapeutic drug monitoring strategy is adequately performed. This strategy may allow optimization of blood levels of IFX in order to obtain a sustained clinical response. Purpose This study demonstrated that with appropriate early trough levels of IFX before dose #3 and dose #4 , monotherapy was very efficient in inducing remssion at week 52 . Method A retrospective study was conducted at CHU Sainte-Justine, Montréal,Canada .Children with IBD 2 to 18 years old diagnosed between 01/2018 and 06/2020 and treated with IFX less than 30 days after diagnosis were included .IFX blood levels were collected before the 3rd and/or 4th dose of IFX and regularly thereafter. Adjustments were done in IFX dose per infusion according to blood levels and clinical response. The primary outcome was clinical remission at one year after diagnosis.The secondary outcomes included: (1) At 52 weeks, the median (IQR) dose of IFX (mg/kg) and the intervals between IFX infusions ; (2) the median (IQR) number of IFX dose changes and the median (IQR) number of blood trough levels of IFX done. Result(s) 101 patients were included : 56.4% males; 81CD; 18 UC; 2 IBDU. Mean age at diagnosis was 13.2 years (IQR = 11.20 to 15. 20). Median time to IFX initiation after diagnosis was 5 days (IQR :3-14).Median IFX dose #1: was 8.4 mg/kg (IQR = 5. 8 to 10). 90% of patient had an IFX optimisation (increasing dose and/or shortening intervals) after dose 3 or dose 4. At week 52, 36,5% of patients were receiving IFX infusion every 4 weeks and 30,6% every 6 weeks. The median IFX dose per infusion was 8,9mg/kg (IQR = 7.4- 9,8 ). The IFX doses at week 52 varied greatly according to age at diagnosis The median number of IFX blood level dosage was 4 per patient over a year (IQR=3-5).At week 52, 83 patients (84.6%) achieved clinical remission with a median IFX level of 10.96 (7.05-15.59). 74 /83 (89%) were on monotherapy and 9/83(10.8%) on combotherapy Image Conclusion(s) Early treatment for IBD with IFX as monotherapy and an early proactive optimization strategy is associated with a good sustained steroid free clinical remissionAt week 52, 83 patients (84.6%) achieved clinical remission with a median IFX level of 10.96 (7.05-15.59). 74 /83 (89%) were on monotherapy and 9/83(10.8%) on combotherapy.The majority of the patients required IFX optimization during their first year of treatment. We therefore recommend to proactively monitor blood levels of IFX before the third and fourth dose of IFX and thereafter, in order to lower the risk of treatment failure and anti-infliximab antibodies occurrence. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest C. Girard: None Declared, S. Ackhar: None Declared, S. Sassine: None Declared, L. Chapuy: None Declared, P. Jantchou: None Declared, C. Deslandres Speakers bureau of: moderator and speaker Abbvie and Janssen