Interruption Of Therapy Research Articles

THU038 Osilodrostat Dosing In Cushing’s Disease: A Pooled Analysis Of The LINC Program

Abstract Disclosure: J. Newell-Price: Consulting Fee; Self; HRA Pharmaceuticals, Diurnal, Novartis Pharmaceuticals, Recordati Rare Diseases, Crinetics. Grant Recipient; Self; Crinetics, Diurnal, HRA Pharmaceuticals, Novartis Pharmaceuticals, Recordati Rare Diseases. R. Pivonello: Consulting Fee; Self; Novartis Pharmaceuticals, Recordati, Corcept Therapeutics, Pfizer, Inc., Bresmed Health Solutions, Damor farmaceutici, S&R Farmaceutici SpA, Organon Italia Srl, Siunergos Pharma, Biohealth Italia Srl. Grant Recipient; Self; Novartis Pharmaceuticals, Recordati, Xeris Pharmaceuticals (Strongbridge), Corcept Therapeutics, Takeda, Neurocrine Biosciences, Camurus AB, Pfizer, Inc., Merk Serono, Ibsa. A. Lacroix: Consulting Fee; Self; Novartis Pharmaceuticals, Recordati, Corcept Therapeutics, Ipsen, Novo Nordisk. Grant Recipient; Self; Novartis Pharmaceuticals, Recordati, Corcept Therapeutics, Ipsen, Novo Nordisk. B.M. Biller: Consulting Fee; Self; HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Research Investigator; Self; served on the LINC 3 steering committee. R. Feelders: Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; Corcept Therapeutics. M. Gadelha: Advisory Board Member; Self; Novo Nordisk, Recordati, Crinetics Pharmaceuticals. Speaker; Self; Recordati, Ipsen, Crinetics, Novo Nordisk. J. Bertherat: Consulting Fee; Self; Atterocor, Shire, HRA Pharmaceuticals, Novartis Pharmaceuticals, Corcept Therapeutics, Recordati. Grant Recipient; Self; Novartis Pharmaceuticals, Pfizer, Inc., HRA Pharmaceuticals. Z. Belaya: None. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. M. Fleseriu: Consulting Fee; Self; HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Research Investigator; Self; served on the LINC 3 steering committee. Introduction: Phase II (LINC 2, NCT01331239) and Phase III (LINC 3, NCT02180217; LINC 4, NCT02697734) studies showed that osilodrostat, a potent oral 11β-hydroxylase inhibitor, was an effective long-term therapy for Cushing’s disease (CD) patients (pts). Objective: This pooled analysis of the LINC program examined how dosing, including dose uptitration and adjustments during long-term maintenance, can provide rapid, sustained mUFC control, minimize AEs and improve treatment outcomes. Methods: Individual pt data from LINC 2, LINC 3 and LINC 4 were pooled and analyzed. Given differences in study designs across trials, placebo treatment periods were excluded. Pts with mUFC >1.5 times the upper limit of normal (ULN) (LINC 2 and LINC 3) or mUFC >1.3 x ULN (LINC 4) were enrolled. In LINC 2, pts started open-label osilodrostat 2 mg twice daily (bid), with dose increases every 2 weeks (W) if mUFC >ULN. In LINC 3, pts started open-label osilodrostat 2 mg bid, with dose increases every 2W until W12 if mUFC >ULN, then every 4W after W12. In LINC 4, pts were randomized to osilodrostat 2 mg bid or placebo for the first 12W. Dose was increased every 3W until W12 if mUFC >ULN and every 3W after W12. Maximum dose was 30 mg bid in all studies (reduced from 50 mg bid in LINC 2 core phase). Dose adjustments were permitted during the extensions based on efficacy and tolerability. Results: This analysis included 229 pts. Median (min-max) osilodrostat exposure was 100.1 weeks (1–351). Median (min–max) daily osilodrostat dose was 6.8 mg/day (1–47); dose needed to achieve mUFC control varied widely between pts. Median time to first mUFC control was 35 days (D; 95% confidence interval [CI] 34–41) in all pts; according to baseline (BL) mUFC severity: mUFC <2 x ULN, 28D (95% CI 17–34); mUFC 2–5 x ULN, 40D (95% CI 34–42); mUFC >5 x ULN, 52D (95% CI 41–56). Median time to first AE of special interest (AESI) was 12W (95% CI 10–15); AESIs occurred at different osilodrostat doses. AEs related to hypocortisolism (BL to W12, 23%; W12–48, 24%; W48–72, 8%; W72 onwards, 20%) and accumulation of adrenal hormone precursors (BL to W12, 36%; W12–48, 37%; W48–72, 14%; W72 onwards, 18%) were less frequent during long-term maintenance than dose titration. AESIs were mostly manageable with dose interruption and/or additional therapy; few patients discontinued treatment as a result (hypocortisolism-related AEs, n=8; adrenal hormone precursor accumulation-related AEs, n=3). Conclusions: Osilodrostat led to sustained mUFC control in all 3 studies; time to control was shorter in pts with lower BL mUFC values. Median daily osilodrostat dose was low but varied widely. Dose titration regimens differed for each study, but AESIs were less frequent during long-term treatment than dose uptitration and were manageable in most pts without stopping treatment. Personalized therapy during dose titration and lifelong monitoring are needed to optimize clinical outcomes in CD pts. Presentation: Thursday, June 15, 2023

A case–control study to assess association of factors with treatment interruption of antiretroviral therapy (ART) among people living with HIV at ART center of tertiary care hospital in Himachal Pradesh, India

Abstract Background: Treatment interruption affects virologic suppression during antiretroviral therapy (ART) among people living with HIV (PLHIV). The present study was planned to explore factors associated with Loss to follow-up (LFU) among PLHIVs receiving ART from 2017 to 2021 at ART center of tertiary care hospital in Himachal Pradesh. Materials and Methods: A case–control study where selected PLHIVs registered with ART center of a tertiary care hospital from 2017 to 2021 were assessed with logistic regression for baseline characteristics and possible reasons for treatment interruption among 120 cases (regular) and 124 controls (missed and LFU). Results: Record-based analysis of a total of 703 PLHIV registered at ART center from 2017 to 2021 observed 18.3% LFU of which 70.5% died over 5 years. Adjusted association showed that mean duration of treatment interruption was significantly positively associated with missed (adjusted odds ratio [aOR]: 1.1; 95% confidence interval [CI]: 0.9–1.1), LFU (aOR: 1.1; 95% CI: 1.0–1.2), and combined (missed + LFU) (aOR: 1.1; 95% CI: 1.01–1.2) as compared to regular category. Effect of adverse effects showed a negative significant association with missed (aOR: 0.1; 95% CI: 0.0–0.2) and combined (missed and LFU) (aOR: 0.1; 95% CI: 0.0–0.1) in comparison to regular category. Conclusions: ART services need to be made available further down to health care delivery system and closer to place of residence of PLHIV.

AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques

The main barrier to HIV cure is a persistent reservoir of latently infected CD4+ T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involves agents that reactivate latent HIV proviruses followed by direct clearance of cells expressing induced viral antigens by immune effector cells and immunotherapeutics. We previously showed that AZD5582, an antagonist of inhibitor of apoptosis proteins and mimetic of the second mitochondrial-derived activator of caspases (IAPi/SMACm), induces systemic reversal of HIV/SIV latency but with no reduction in size of the viral reservoir. In this study, we investigated the effects of AZD5582 in combination with four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) in SIV-infected, ART-suppressed rhesus macaques. Here we confirm the efficacy of AZD5582 in inducing SIV reactivation, demonstrate enhancement of latency reversal when AZD5582 is used in combination with N-803 and show a reduction in total and replication-competent SIV-DNA in lymph-node-derived CD4+ T cells in macaques treated with AZD5582 + RhmAbs. Further exploration of this therapeutic approach may contribute to the goal of achieving an HIV cure.

First multi-center retrospective study assessed the compliance with and persistence of biological therapies in Bulgarian population with rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory joint disease that causes progressive joint damage, leading to severe disability. Early diagnosis, optimal therapy, and strict adherence to the prescribed medication are key factors that allow for the cessation of the disease progression and the preserving of the patient's quality of life. The objective of this study was to estimate the compliance to and persistence of biologic disease-modifying anti-rheumatic drugs (bDMARDs) among the Bulgarian population with RA. This retrospective observational cohort study included 179 patients, who were tracked over a 36-month period. During baseline and subsequent follow-up visits (at months 6, 12, 24, and 36), we monitored the disease activity, side effects, medication tolerability and effectiveness, compliance, and persistence to the prescribed biologic agent. The compliance with bDMARDs among Bulgarian patients with RA was 85.5% in the first year, 76.0% in the second year, and 63.7% in the third year. The Infliximab cohort showed the lowest compliance rate (50%), with the other subgroups bDMARDs having similar results (64-70%) during the period of observation. The median therapy duration across all patient cohorts is 61.9months (IQR 55.7-67.6). Our study did not establish any significant impact of gender, age and disease duration, concomitant treatment with methotrexate, type of biologic agent and previous exposure to biological agents on the treatment adherence. The compliance with and persistence of the prescribed bDMARD among the Bulgarian population with RA is unsatisfactory. Therapy interruption and nonadherence to recommended therapy are associated with disease progression and patient disability. The consequences include not only financial burdens but also psychosocial and physical impacts.

Over forty percent of women living with HIV report interruption in antiretroviral therapy during intrapartum and early postpartum inpatient stay: findings from five hospitals in Ghana

ABSTRACT Antiretroviral therapy (ART) adherence during and after pregnancy is essential to reduce perinatal transmission of HIV. However, little is known about adherence during the intrapartum and early postpartum inpatient hospital stay. Using secondary data from a hospital-based cohort study focused on the relationship between birthweight and engagement in HIV care, we examined the magnitude of, reasons for, and factors associated with incomplete intrapartum and early postpartum ART adherence among adult women (18 years or older) living with HIV who delivered within the previous two weeks at one of five hospitals in Accra, Ghana. Of the 142 enrolled participants who had complete adherence data and reported being on ART at the time of hospital admission, 43% (61/142) reported missing at least one ART dose during labor, delivery, and postpartum, including almost 20% (28/142) missing 2 or more consecutive doses. Women who reported frequently missing ART doses during pregnancy had higher odds of reporting missed doses during their intrapartum and postpartum hospital stays. Among those with inpatient ART interruption, the most frequently cited reasons were: forgetting medication at home (42%) and challenges of being in or recovering from labor (29%). Maternal perception of infant health at birth, hospital level of care, and frequency of missing HIV medications during pregnancy were associated with incomplete ART adherence during the intrapartum and early postpartum inpatient stay. An enabling clinical environment to facilitate access to ART during inpatient stays may have positive implications for ART adherence.

The Use of Questionnaires in Pain Assessment during Orthodontic Treatments: A Narrative Review.

Pain is a complex multidimensional feeling combined with sensorial and emotional features. The majority of patients undergoing orthodontic treatment report various degrees of pain, which is perceived as widely variable between individuals, even when the stimulus is the same. Orthodontic pain is considered the main cause of poor-quality outcomes, patients' dissatisfaction, and lack of collaboration up to the interruption of therapy. A deep understanding of pain and how it influences a patient's daily life is fundamental to establishing proper therapeutic procedures and obtaining the correct collaboration. Because of its multifaced and subjective nature, pain is a difficult dimension to measure. The use of questionnaires and their relative rating scales is actually considered the gold standard for pain assessment. Choosing the most appropriate instrument for recording self-reported pain depends on a patient's age and cognitive abilities. Although several such scales have been proposed, and a lot of them are applied, it remains uncertain which of these tools represents the standard and performs the most precise, universal, and predictable task. This review aims to give an overview of the aspects which describe pain, specifically the pain experienced during orthodontic treatment, the main tool to assess self-perceived pain in a better and more efficient way, the different indications for each of them, and their correlated advantages or disadvantages.

Midline Compared With Peripheral Intravenous Catheters for Therapy of 4 Days or Longer in Pediatric Patients

Peripheral intravenous catheters (PIVCs) frequently fail during treatment causing therapy interruption, pain, recatheterization, and additional health care costs. Midline catheters (MCs) may improve functional dwell time and reduce failure compared with traditional PIVCs. To compare device failure of MCs with PIVCs. This was a pragmatic, randomized clinical superiority trial with an embedded internal pilot study conducted from July 2020 to May 2022. The study took place in a quaternary pediatric hospital in Brisbane, Queensland, Australia. Inclusion criteria were patients aged 1 to 18 years requiring peripherally compatible intravenous therapy for 4 days or longer. Patients were randomly assigned 1:1 to receive a PIVC or MC, stratified by age (≤5 years, >5 years). One catheter was studied per patient. The primary outcome was all-cause device failure, defined as premature cessation of device function. Secondary outcomes included number of insertion attempts, insertion failure, pain (on insertion), procedural time, patient/parent satisfaction (with insertion), device dwell time, device complications during dwell time, additional vascular access devices required to complete treatment, clinician satisfaction (at removal), and health care costs. Of the 128 patients randomly assigned to study groups, 127 patients (median [IQR] age, 7 [2-13] years; 71 male [56%]) had a device inserted, with 65 (51.2%) in the PIVC group and 62 (48.8%) in the MC group. All patients were included in the intention-to-treat analysis. Device failure was lower in patients in the MC group (10 [16.1%]) compared with those in the PIVC group (30 [46.2%]; odds ratio [OR], 0.22; 95% CI, 0.10-0.52; P <.001). MCs were associated with fewer insertion attempts (mean difference [MD], -0.3; 95% CI, -0.5 to 0; P = .04), increased dwell time (MD, 66.9 hours; 95% CI, 36.2-97.5 hours; P <.001), and fewer patients required additional vascular access devices to complete treatment in the MC group (4 [6.5%]) and PIVC group (19 [29.2%]; OR, 0.17; 95% CI, 0.05-0.52; P = .002). Compared with PIVCs, use of MCs was associated with greater patient (9.0 vs 7.1 of 10; P = .002) and parent (9.1 vs 8.2 of 10; P = .02) satisfaction and lower health care costs (AUS -$151.67 [US -$101.13] per person; 95% credible interval, AUS -$171.45 to -$131.90 [US -$114.20 to -$87.95]). Findings suggest that MC insertion for patients requiring peripherally compatible intravenous therapy for 4 days or longer should be prioritized to reduce the resource intensive, expensive, and burdensome sequelae of device failure. Australia New Zealand Clinical Trials Registry, ACTRN12620000724976.

Hemorrhagic Safety of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Tremor without Interruption of Antiplatelet or Anticoagulant Therapy

Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson’s disease (PD) without interrupting anticoagulant or antiplatelet therapies. Methods: This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging. Results: The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure. Conclusion: The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.

Awareness and Perception of Dentists in Kuwait Regarding the Dental Management of Patients on Oral Antithrombotic Medications

Abstract Objective It is crucial that dentists are up to date on the most recent recommendations for managing patients on oral antithrombotic medications (OAMs). The current study aims to analyze dental practitioners' knowledge and practice of perioperative treatment of patients on OAM in Kuwait. Materials and Methods The study was performed among dentists in Kuwait utilizing a structured questionnaire. The questionnaire tested their knowledge about common OAMs and their indications, the bleeding risk of specific dental procedures, as well as the dangers of stopping antithrombotic therapy. Questions regarding the practice of obtaining relevant blood investigations as well as consultations with health professionals and their current course of management pertaining to specific dental procedures were included. Statistical Analysis The collected data were analyzed by SPSS statistical software for Windows, version 28.0 (Chicago, Illinois, United States). The Student's t-test was used to compare mean percentage knowledge scores. Association between independent variables (predictors) and knowledge was assessed by employing univariate and multivariate logistic regression. A p-value of ≤ 0.05 was considered statistically significant. Results A majority of the dentists (60.9%) demonstrated fair knowledge. Gender, practice type, and years of experience were significantly associated with knowledge. Very few dentists knew about direct oral anticoagulants. Eighty-two (33.1%) would rely on international normalized ratio tests done within 72 hours. Sixty-six (26.6%) dentists would interrupt aspirin therapy before extensive dental scaling without a medical consult and 45 (18.1%) would ask the patient to stop warfarin 3 days before extraction of one to three teeth. For patients on aspirin or warfarin, 35.1 and 47.2% of the dentists perceived the postoperative bleeding risk after a simple extraction to be high, and 14.4 and 11.2% of the dentists considered the rethrombosis risk to be low if aspirin and warfarin were interrupted. Conclusion In this study, the dentists demonstrate a lack of knowledge and are not clear regarding practice recommendations. Every dental care provider therefore needs to update their knowledge with the latest antithrombotic medications and their indications, when to order blood investigations and medical consult, bleeding risk associated with each dental procedure, interruption of therapy, and risk of bleeding versus rethrombosis risk.

The Impact of Frailty on Adjuvant Therapies Not Offered to or Declined by Breast Cancer Surgery Patients.

The impact of frailty on adjuvant therapies not offered to or declined by elderly breast cancer surgery patients has been understudied. This is a retrospective review of a prospectively managed single-center database including all breast cancer patients >65years undergoing surgery in 2021. Frailty was determined using an electronic frailty index (eFI) derived from electronic health data. Patients were categorized as Fit (eFI ≤ .10), Pre-frail (.10 < eFI ≤.21), or Frail (eFI > .21). Chart review was performed to collect data on adjuvant therapies not offered or declined. Descriptive statistics and logistic regression were performed. Of 133 patients, 16.5% were frail, 46.6% were pre-frail, and 36.8% were fit. Demographics were similar among groups except age and comorbidities. Of those with adjuvant therapy indicated (n = 123), 15.4% were not offered at least one indicated therapy. Of those offered therapy, some therapy was declined in 22.7%. Frail patients more often were not offered or declined some therapy (frail: 63.2%, pre-frail 36.2%, fit: 28.2%, P = .03). Frailty was associated with having some therapy not offered or declined on univariate modeling (OR 4.4 95% CI 1.4-13.5, P = .01) but not on multivariate. Being frail was associated with higher odds of readmission at 6months on multivariate analysis (OR 9.5, 95% CI: 1.7-54.2. P = .01). Over half of frail patients are not offered or decline some adjuvant therapy. The impact of this requires further study. Given their higher odds of readmission, frail patients require close postoperative monitoring to prevent the interruption of adjuvant therapies.

Influence of interruptions in radiation therapy on long-term results of treatment of stage I-III head and neck cancers in the absence of surgical and chemoradiotherapy

Despite the fact that head and neck tumors are very sensitive to radiation treatment, patients who have completed a course of radiation therapy have a high rate of recurrence and mortality from the underlying disease.The aim of the study was to analyze the event-free survival of patients who completed a course of radiation therapy for stage I-III head and neck cancer according to a radical program under the influence of a number of independent factors such as age, gender, total focal dose, disease stage, duration of a break in a split course of radiation therapy.The effect of the duration of interruption on survival was assessed by analyzing the treatment regimens for patients who received radiation treatment for stage I-III head and neck cancer according to a radical program from 2016 to 2018 at the Brest Regional Oncological Dispensary. Statistical processing of the obtained data included the analysis by the Cox regression method. Data were analyzed using the Kaplan-Meier method to evaluate the outcome.In the multivariate analysis, it was found that the disease stage has the greatest relationship with event-free survival (p &lt; 0.01). The same trend is observed for the duration of interruption in radiotherapy (p &lt; 0.05). The cumulative survival was significantly higher in the group of patients with treatment interruption of less than 3 weeks compared to the group of patients who completed treatment more than 3 weeks apart (80.00 % vs 49.06 %). If the duration of the break is less than 3 weeks, the clinical stage (T1-T3) is not a factor influencing patient survival.Accounting for the effect of interruptions in the course of radiotherapy and the understanding the influence of controllable factors is essential for optimal treatment strategies.

Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India.

Although many drug regimens have been used in the treatment of human immunodeficiency virus (HIV) infection, the National AIDS Control Organization (NACO) of India recommends the use of a fixed-dose combination of tenofovir/lamivudine/dolutegravir (TLD) as a first-line regimen since 2020. In spite of much global data on the use of this combination, experience in the Indian population is still limited. We aim to find out the efficacy and tolerability of this novel regimen, in a tertiary care center of Eastern India. A descriptive observational study, longitudinal in design performed in the antiretroviral therapy (ART) center of a tertiary care hospital in Kolkata, West Bengal, India. All patients who attended the ART center from April 2021 to October 2022 were enrolled in the study following inclusion and exclusion criteria. A detailed history, clinical examination, necessary biochemical tests, and CD4 count of all patients were done at baseline. Subsequently, they were followed up for 6 months with monthly visits when they were enquired about any adverse effects requiring therapy interruptions. At the end of 6 months, CD4 count and viral load were measured. Out of a total sample of 249 patients, the TLD regimen was efficacious in 99.2% (n = 247) in whom viral load was suppressed to <1,000 copies/mL after 6 months of treatment. The regimen had to be temporarily discontinued in 6% of patients (n = 15). The most common cause of treatment interruption was hepatic dysfunction (3.2%) followed by cutaneous manifestation (2.4%). In 14 out of 15 patients, the regimen could be reintroduced and was safely tolerated afterward. Only one patient had to be shifted to an alternative regimen due to tenofovir-induced nephrotoxicity. Thus TLD was tolerated in 99.6% (n = 248) patients. The fixed-dose combination of TLD is a highly efficacious and well-tolerated first-line regimen for ART naïve patients with HIV infection having >95% adherence. How to cite this article: Sengupta D, Ghosh S, Pain S, et al. Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India. J Assoc Physicians India 2023;71(9):72-74.

Efficacy and safety of epigallocatechin-3-gallate in treatment acute severe dermatitis in patients with cancer receiving radiotherapy: a phase I clinical trial

To evaluate the safety and effectiveness of epigallocatechin-3-gallate (EGCG) solution treating the acute severe dermatitis in patients receiving radiotherapy. This phase I research enrolled patients with thoracic cancer receiving radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China. EGCG solution was sprayed to the radiation field when grade III radiation-induced dermatitis (RID) first appearance. EGCG concentration escalated from 660 to 2574 μmol/L using modified-Fibonacci dose-escalation. RID and related symptoms were followed up every day. Between March 2021 and November 2021, 19 patients were enrolled in this phase I research. The median dose of grade III RID first observation was 44 Gy (30.6–52 Gy). As the EGCG treatment was performed continuously, all these grade III RID reactions were significantly decreased to grade I or grade II RID at three days after use of EGCG (p < 0.001). Significant relief can be observed in burning sensation (p < 0.001), tractive sensation (p < 0.001), tenderness (p < 0.001), erythema (p < 0.001), itching (p < 0.001) and pain (p < 0.001) after 15 days of EGCG treatment. No radiation therapy delay or interruption for all 19 patients. No adverse events were observed and reported associated with EGCG. The highest dose of this Phase I trial (2574 μmol/L) was recommended for continuous Phase II trial for further evaluation. In this phase I clinical research, use of EGCG solution is safe and can significantly relief grade III RID in patients receiving radiotherapy. Thus, EGCG might be a new choice for acute sever RID.Trial Registration: ClinicalTrials.gov Identifier: NCT02580279 (Full date of first registration: 12/2014).

The contributionof genotype-guided selection of P2Y12 inhibitor on prognosis in ACS /CCS patients undergoing percutaneous coronary intervention: aretrospective cohort study.

We aimed to explore the contribution of genotype-guided selection of P2Y12 inhibitors on prognosis in Chinese patients with acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Totally, 2063 patients were included. They were divided into empiric treatment group (n = 1025) and individualized treatment group (n = 1038) depending on whether taken CYP2C19 genetic testing. The incidences of clinical endpoint events were compared in two groups at 1-year follow-up. The effective endpoint events were major adverse cardiovascular events (MACEs), including all-cause mortality, in-stent restenosis, nonfatal myocardial infarction, nonfatal stroke and severe recurrent ischemia. Meanwhile, the safe endpoint was bleeding events defined by the Bleeding Academic Research Consortium (BARC) criteria. Finally, 66.83% patients were diagnosed with ACS and 33.17% patients were diagnosed with CCS in empiric group. 68.11% patients were diagnosed with ACS and 31.89% patients were diagnosed with CCS in individualized group. At 1-year follow-up, individualized group showed lower MACEs rate than empiric group (19.61% vs. 10.69%, HR: 1.915; 95% CI: 1.534 to 2.392; P < 0.0001, log-rank test; adjusted HR: 1.983; 95% CI: 1.573 to 2.501; P = 0.000, cox proportional hazards regression models), while bleeding events were significantly less common in empiric group than in individualized group (7.32% vs. 10.40%, HR: 0.693; 95% CI: 0.519 to 0.926; P = 0.0132, log-rank test; adjusted HR: 0.695; 95% CI: 0.518 to 0.933; P = 0.016, cox proportional hazards regression models). It was mainly manifested in BARC class 1 bleeding, which did not warrant the interruption of antiplatelet therapy (ITA). Further, subgroup analyses illustrated that no significant difference existed in cumulative MACEs-free survival rate between all treatment arms of individualized group (P = 0.6579 by log-rank test), and CYP2C19 intermediate metabolizer (IM) genetype appeared to be significantly associated with bleeding events for patients treated with ticagrelor (clopidogrel vs. ticagrelor: 6.80% vs. 14.88%; adjusted HR:0.440; 95% CI: 0.246 to 0.787; adjusted P = 0.006). Genotype-guided selection of P2Y12 inhibitor made a very positive contribution on the prognosis in Chinese ACS/CCS patients undergoing PCI. Instead of intensifying antiplatelet strategies, conventional-dose clopidogrel could be recommended as P2Y12 inhibitor after weighing MACEs and bleeding events in CYP2C19 IM patients.

Impacts of early therapy response, interval to therapy interruption, and cumulative therapy interruption duration on outcome of ibrutinib therapy in relapsed/refractory chronic lymphocytic leukemia.

To investigate the impact of early response and treatment interruption on the survival of patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (r/r CLL/SLL) treated with ibrutinib.This post hoc analysis used data of patients received ibrutinib treatment from an open-label, multicenter phase 3 study comparing ibrutinib with rituximab in patients with r/r CLL/SLL. The association of complete or partial response at 6months, interruption within the first 6months, cumulative interruption durations during the ibrutinib-treated period with progression-free survival (PFS) and overall survival (OS) were evaluated using the adjusted Cox hazard proportional model.The study included 87 patients treated with ibrutinib, of which 74 patients had at least 6months of ibrutinib treatment and were analyzed. The response at 6months did not affect PFS (HR = 0.58, 95%CI: 0.22-1.49) or OS (HR = 0.86, 95%CI: 0.22-3.31). The onset of interruption before or after 6months was not associated with PFS (HR = 0.88, 95%CI: 0.34-2.30) or OS (HR = 0.75, 95%CI: 0.23-2.52). However, a cumulative interruption of more than 35days was independently associated with worse PFS (HR = 2.4, 95%CI: 0.99-5.74) and OS (HR = 2.6, 95%CI: 0.88-7.44). Continuous interruption for more than 14days was associated with a numerically lower 3-year PFS rate (> 14 vs. ≤ 14days: 42% vs. 73%) and 3-year OS rate (> 14 vs. ≤ 14days: 58% vs. 84%, both P > 0.05).Response status at 6months or early therapy interruptions did not affect survival in patients with r/r CLL/SLL treated with ibrutinib. However, a cumulative temporary interruption of more than 35days could potentially impact patient outcomes.

Impact of Abrupt Interruption of Home Psychotropic Medications at ICU Admission.

Background: Abrupt discontinuation of home psychotropic medications is common among critically ill patients but may precipitate clinically significant withdrawal. Objective: To determine the percent of patients with interruptions in home psychotropic medications upon intensive care unit (ICU) admission and to identify outcomes associated with these interruptions. Methods: This was an institutional review board-approved, single-center, retrospective study of critically ill patients with a history of mental illness taking an antipsychotic or antidepressant medication. The primary outcome was the percent of patients with interruption in at least one home psychotropic medication for ≥24 hours upon ICU admission. Secondary outcomes included time to psychotropic re-initiation, percent of home psychotropic medications restarted in the ICU, ICU length of stay (LOS), delirium, withdrawal-related complications, need for acute antipsychotics or benzodiazepines, and reasons for psychotropic interruption. Results: Among 183 patients, 93 (50.8%) had interruptions in home psychotropic therapy for ≥24 hours upon ICU admission. Mean time to reinitiation of at least one psychotropic agent was 1.4 days, and 16.4% of patients did not have any home psychotropics restarted. Patients with psychotropic interruption had a longer ICU LOS (P = 0.01) and greater incidence of ICU delirium (P < 0.01). Withdrawal-related complications were similar between groups. Acute antipsychotic use was greater in patients with psychotropic interruption (P < 0.01). Acute benzodiazepine use was not different between groups (P = 0.87). Most patients did not have a documented reason for therapy interruption. Conclusion and Relevance: Unless contraindicated, clinicians should attempt to restart home psychotropic medications as soon as possible in critically ill patients.

Efficacy of a shorter chemotherapy regimen in a patient with drug-resistant tuberculosis with early surgical intervention

Introduction. Treatment for multidrug-resistant tuberculosis lasts 18 to 24 months, so there is a high rate of therapy interruptions, including patient-initiated interruptions. In recent years, the use of shorter regimens for the treatment of multidrug-resistant tuberculosis has been actively discussed around the world. The first use of shorter chemotherapy regimens was conducted in three regions of the Russian Federation in 2019. However, the prevalence of the use of shorter chemotherapy regimens in our country remains low.The purpose of the study was to demonstrate the high efficacy of a shortened chemotherapy regimen with surgical intervention.Materials and methods. In the conditions of the Central Research Institute of Tuberculosis, the patient underwent a comprehensive examination, including mandatory, additional and optional methods of investigation. Based on the findings of the comprehensive examination and established broad drug resistance of Mycobacterium tuberculosis, a shorter course of chemotherapy was prescribed and surgical treatment was performed after 2 months of therapy.Results and Discussion It was decided to carry out anti-tuberculosis therapy according to a shortened scheme in the amounts: Linezolid, Bedaquiline, Cycloserine, Levofloxacin, Pyrazinamide. Taking into account positive radiological dynamics after two months of treatment and absence of contraindications, early surgery intervention was performed. At the end of a nine-month course of chemotherapy the patient had a stable radiological picture, “fresh” focal and infiltrative changes in the lungs were not detected. Early surgical treatment with a shorter chemotherapy regimen may become a highly effective method in the cure of drug-resistant tuberculosis in the Russian Federation.Conclusion. A shorter chemotherapy regimen with optimal timing of surgical intervention is highly effective and safe to use.

Role of Underlying Liver Pathology in the Development of Immune-Related Hepatitis: A Case-Control Study.

Immune-related hepatitis (irH) is a serious immune-related adverse event (IRAE) that may result in morbidity, immune checkpoint inhibitor (ICI) therapy interruption and, rarely, mortality. The impact of underlying liver pathology, including liver metastasis, on the incidence of irH remains poorly understood. We hypothesized that the presence of underlying liver pathology increased the risk of irH in patients with cancer treated with ICI. We conducted a retrospective case-control study of irH in patients with cancer receiving first ICI treatment from 2016-2020. Provider documented cases of ≥ grade 2 irH were identified and control matched in a 2:1 ratio based on age, sex, time of ICI initiation, and follow-up time. Conditional logistic regression was used to estimate the relationship between irH and liver metastasis at ICI initiation. Ninety-seven cases of irH were identified, 29% of which had liver metastases at time of ICI initiation. Thirty-eight percent of patients developed grade 2, 47% grade 3, and 14% grade 4 irH. When adjusted for covariates/confounders, the presence of liver metastasis was associated with increased odds of irH (aOR 2.79 95% CI 1.37-5.66, p = 0.005). The presence of liver metastases did not correlate with irH grade or rate of irH recurrence after ICI rechallenge. Presence of liver metastases increased the odds of irH in patients with first-time ICI therapy. Limitations include the retrospective nature, moderate sample size, possible selection bias and confounding. Our findings are hypothesis-generating and warrant external validation as well as tissue and circulating biomarker exploration.

Futibatinib (Lytgobi®)

Futibatinib (Lytgobi®)

Acute effects of interruption of cardiac resynchronization therapy on left ventricular morpho-functional parameters as assessed by cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) has become a standard treatment for patients with heart failure with reduced ejection fraction (HFrEF) and left ventricular (LV) dyssynchrony. Both immediate and long-term clinical and functional improvement have been reported after CRT implementation, as well as a decrease in the mortality and hospitalization rates. Recently, it has been questioned whether, once LV function has improved and reverse LV remodeling has occurred, ongoing biventricular pacing is still necessary. Purpose To assess by cardiac magnetic resonance (CMR) the acute effect on LV systolic function and dimensions of discontinuing CRT in patients with HFrEF. Methods The study prospectively included a small cohort of patients with HFrEF (7 males and 1 female; mean age 63.7 ± 2.5 years; ischemic etiology in 50%) receiving an MR-conditional CRT device in accordance with the existing guidelines. CMR examinations have been performed before (pre-CRT) and after 6 months after CRT implantation (post-CRT). Each follow-up CMR study included two full sets of cine images for the evaluation of LV systolic function and volumes obtained, respectively, before (post-CRTON) and after (post-CRTOFF) disabling the CRT function on the device. To warrant patient safety, each post-CRT CMR study was performed following institutional protocols based on specific guidelines for patients with MR-conditional cardiac implantable electronic devices (CIEDs). Results No adverse events or significant changes in the CIEDs parameters (including pacing and sensing thresholds and battery level) were recorded during the follow-up CMR studies. At post-CRT evaluation, CMR image quality was judged to be at least sufficient for analysis in all patients. As compared with the basal pre-CRT study, a significant increase in LVEF was detected at the post-CRTON CMR evaluation (28,1 vs 35,0%; p &amp;lt;0,05) (Figure 1), together with a clear trend towards a decrease in LV end-diastolic volume [LVEDV] (118.72 ± 11.00 mL vs. 107.5 ± 13.86 mL; p = n.s) and LV end-systolic volume [LVESV] (87.12 ± 9.40 mL vs. 71.125 ± 11.26 mL; p = n.s.) (Figure 2). No relevant changes were detected when re-assessing the same LV parameters by CMR immediately after switching off the CRT function (post-CRTOFF study), with persisting increase in LVEF (37.9 ± 4.5%; p &amp;lt;0,05 vs. pre-CRT) and tendency towards decreased LVEDV (97.3 ± 12.3 mL; p = n.s. vs. pre-CRT) and LVESV (63.0 ± 11.4 mL; p = n.s. vs. pre-CRT). Conclusion These preliminary findings show that favorable changes induced on LV function and remodeling by prolonged CRT in HFrEF patients are not promptly lost after the interruption of the electrical therapy. Whether a longer CRT interruption would determine more pronounced variations in the LV parameters or if the effects of CTR discontinuation may be related to the effective length of the period of time between implantation and cessation of the therapy deserve further investigation.