Average Duration Of Treatment Research Articles

Early Access for Medicines in ITALY: The Case of Ruxolitinib for Patients with Graft-Versus-Host Disease

After European Medicines Agency (EMA) approval, national pricing and reimbursement procedures are necessary to guarantee access to drugs, based on the willingness to pay and the recognition of therapeutic value. These can result in delays in drug availability for patients, even for those with important unfmet needs for whom it may be necessary and ethical to ensure access. The objective of this study was to evaluate the use of ruxolitinib for patients with graft-versus-host disease (GvHD) after EMA approval at the University Hospital of Catania. We analysed data about the use of ruxolitinib in patients with GvHD, describing their basic characteristics, their outcomes and the cost of the treatment. In the reference period, 24 ruxolitinib treatments were started according to the Summary of Product Characteristic. The average treatment duration was 10 months. Twenty patients showed a response, maintained over time, with no adverse reactions. The total expenditure amounts to EUR 963,424. The use of ruxolitinib in a real population confirms its role in an important therapeutic need. The quantification of costs requires a reflection on the sustainability of early access to medicines authorised by the EMA for serious diseases and in the absence of therapeutic alternatives.

Quality of life and tolerability of B-cell directed therapy of multiple sclerosis with ofatumumab in a patient-centered real-world observational study.

Ofatumumab (Kesimpta®) is a subcutaneous CD20-targeting antibody approved in Germany in 2021 for the treatment of relapsing multiple sclerosis (RMS). After careful instruction, patients can administer the treatment themselves. We previously reported data of 101 patients (Klimas et al. in Nervenarzt 94:923-933, 2023). The objective of this longitudinal study is to explore the tolerability and acceptability of ofatumumab from a patient perspective over a follow up period of 6months. In this prospective observational real-world study, we report follow up data of 81 patients. We evaluated sociodemographic data, disease duration, duration and side effects of ofatumumab use, expanded disability status scale (EDSS), Beck Depression Inventory II (BDI-II), Short-Form 36 (SF-36), Fatigue Scale of Motor and Cognitive Functions (FSMC), and modified Multiple Sclerosis Functional Composite Test (MSFC). In addition, we asked for subjective treatment outcomes, such as impact on quality of life, walking distance, concentration, mood, medication adherence, fatigue and the subjective course of MS on a numerical rating scale (1 = very negative; 5 = very positive). Furthermore, treatment discontinuations were recorded. The average duration of ofatumumab treatment was 10months. In comparison to previous published data of our cohort, patients reported a significant increase in headache (10% up to 26%, p = 0.004) and limb pain (5% up to 26%, p < 0.001) as persistent side effects after the injections. More patients reported a very positive effect (p < 0.0001) on quality of life. 4 confirmed relapses occurred but no EDSS worsening, and no treatment discontinuations were documented during the observation period. As previously described, our prospective study indicates that patients have a good tolerability of ofatumumab, precisely because of the mild and few side effects at the first administration. However, the longer the observation period, the more headaches and limb pain occurred after the injections. Despite this, patients' subjective quality of life improved. There were no discontinuations during the follow-up period, with the limitation of a high loss to follow-up.

Effect of long-term betahistine treatment on the clinical outcomes of patients with cochlear Meniere’s disease

Background Many studies have discussed the betahistine treatment for Meniere’s disease (MD). However, regarding cochlear MD, there is no consensus on the long-term betahistine treatment. Aims/objectives This study aims to investigate the relationship between the betahistine treatment duration in patients with cochlear MD and their clinical outcomes. Material and Methods We enrolled 78 patients with 96 ears who were diagnosed with cochlear MD and received the treatment for more than 6 months. Outcomes included the hearing status, frequency of acute hearing loss attack, and whether the disease progressed to MD. Clinical characteristics including age, sex, side of affected ear, treatment duration of betahistine and trichlormethiazide, and pre-treatment hearing level was recorded from medical charts. Results Comparing the clinical characteristics by outcomes, the average betahistine treatment duration was the independent factor for hearing status of four-tone average (p = 0.01) and low-tone average (p = 0.03). Patients with average betahistine treatment duration of at least 277 days per year had higher odds ratio for improvement of the hearing status of four-tone and low-tone average. Conclusions For patients with cochlear MD, regular and long-term betahistine treatment can benefit their hearing outcome in the low- and medium-frequency.

Corticotomy as a stage of complex treatment of orthodontic patients. Review.

In this article, we consider an urgent problem of modern orthodontic dentistry - the acceleration of treatment periods. The average duration of traditional orthodontic treatment is significantly high and is 24-28 months, which requires long-term cooperation of patients and doctors. In particular, in adult patients, this process is more complex and prolonged, which can lead to refusals of treatment. The article also discusses the biological basis of orthodontic tooth movement associated with the restructuring of the alveolar bone and research aimed at accelerating this process. The authors discuss various methods of corticotomy and other innovative approaches to reduce treatment time and improve results. Important attention is paid to the introduction of minimally invasive and predictable surgical methods. The studies of domestic and foreign authors are analyzed for a better understanding of this problem.

Safety and efficacy of anticoagulant treatment in patients with ovarian vein thrombosis: a systematic review and meta-analysis of observational studies

BackgroundThe role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain. ObjectivesWe aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients. MethodsA systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024. Eligible studies included randomized controlled trials and observational studies enrolling at least 10 adult patients with objectively diagnosed OVT and treated with any anticoagulants. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42021270883). ResultsWe included 17 observational studies (621 anticoagulated and 376 nonanticoagulated OVT patients); 9 studies enrolled mainly pregnancy/puerperium-related OVT. Most patients received heparins alone (45.7%) or proceeded to vitamin K antagonists (39.2%). The average treatment duration was ≤3 months in 8 studies (47.1%), >3 to ≤6 months in 6 studies (35.3%), and >6 months in 3 studies (17.6%). In treated patients, mortality rate was 2.43% (95% CI, 0.54%-5.41%; I2 = 53.8%; 12/406 patients; 13 studies), major bleeding was 1.27% (95% CI, 0.48%-2.38%; I2 = 2.5%; 7/583 patients; 15 studies), recurrent venous thromboembolism (VTE) was 3.49% (95% CI, 1.12%-6.95%; I2 = 63.5%; 22/482 patients; 15 studies), and vessel recanalization was 89.4% (95% CI, 74.6%-98.6%; I2 = 80.6%; 163/184 patients; 8 studies). The rate of recurrent VTE in untreated patients was 8.65% (95% CI, 2.61%-17.35%); however, the difference compared with treated patients was not statistically significant (risk ratio, 0.70; 95% CI, 0.36-1.37). At subgroup analyses, the rates of major bleeding and recurrent VTE were 0.80% (95% CI, 0.0-2%.17%) and 3.81% (95% CI, 0.42%-9.63%) in pregnancy/puerperium-related OVT, respectively, and 1.12% (95% CI, 0.32%-2.34%) and 1.78% (95% CI, 0.62%-3.46%), respectively, when analyzing only full-text studies. ConclusionThere is paucity of literature regarding OVT. Our results suggest that anticoagulation is associated with low rates of major bleeding and recurrent VTE.

First metatarsal shortening after hallux valgus surgery: Benefits of treatment with distraction osteogenesis

IntroductionIatrogenic shortening and elevation of the first metatarsal (MT1) is a common complication of hallux valgus surgery, inducing metatarsalgia underneath the lesser rays, a reason for patient dissatisfaction. For resolving this problem, different types of revision surgery are described, of which lengthening MT1 by distraction osteogenesis is underreported and therefore undervalued. Materials and methodsWe present three cases with iatrogenic shortening after hallux valgus surgery treated by distraction osteogenesis of MT1 using a custom-made frame, made of Ilizarov equipment. To evaluate the amount of lengthening, the length of the first and second metatarsal (MT2) and the parabolic distribution of the metatarsal heads were compared before and after distraction. To evaluate correction in the sagittal plane, Meary’s angle was measured pre- and post-lengthening. Pain was noted by a visual analogic score during follow-up. ResultsIn our series of three cases, lengthening of MT1 between 7 mm and 18 mm, resulted in an improved parabolic distribution of the MT heads. The average difference between the second and first MT-head, relative to the SM4 axis (M2–M1) improved from 9.4 mm (± 0.9 mm) to 2.8 mm (± 0.7 mm) resolving corresponding pain in all patients. Meary’s angle was normalized in one case. The average duration of treatment was 116 days (± 9 days). Minimal follow up was 11 years. ConclusionUsing Ilizarov equipment for distraction osteogenesis of MT1 is a low-cost and effective method. Over time, this technique has proven its utility in pronounced iatrogenic shortening of MT1. The possibility to lengthen more than 1 cm, to correct in multiple planes, as well as early mobilization and weight bearing are additional advantages, but one must be careful to avoid overcorrection. The need for strict follow-up with multiple radiographs and rigorous patient selection is mandatory.

Assessment Methods and Intervention Strategies for Cleft-Related Lateral Misarticulation in Chinese-Speaking Children.

The aim of this study was to analyze the characteristics and error speech features of cleft-related lateral misarticulation and provide a basis for clinical evaluation and rational intervention. Participants who were diagnosed with lateral misarticulation after cleft palate repairment were 126 children aged 4, 6 to 16, and 11, and they had complete palatopharyngeal closure, no abnormalities in their speech organs and occlusion, and no hearing or intellectual impairments. The Chinese standard pronunciation clarity word list, the American KAY CSL4500, the Beijing Yangchen YF-16 computer speech analysis workstation, soundproof rooms, Wechsler scales of intelligence-fourth edition, and audiometers were used to evaluate the cleft-related lateral misarticulation. Statistical analysis was performed on the age, gender, error rate, corner of the mouth deviation direction, comorbidity, duration of intervention, period of treatment, and therapeutic effect of concentrated or normal intervention group in different patients. Our results showed that 2 to 3 straight stripes were visible at the onset of consonants /ti:/ /t'i:/, and 3 clear straight lines were visible in /tʂ/, indicating that the lateralized sound had 2 or 3 bursts and lasted for 1 to 2ms. The onset age of lateralized sound was mostly below 12 years old. Chinese lateralized sound mainly occurred in vowel /i:/, and the occurrence rate of consonants with tongue surface /tɕ]/ /tɕ'/ /ɕ/ was the highest. In addition, the corner of the mouth deviation was also an indicator of lateralization sound, and other types of speech disorders mostly accompanied it. There was a significant difference in the improvement of speech clarity between the concentrated intervention group and the normal group before and after treatment. The 2 groups' average duration and course of treatment were not significantly different. Still, the period of concentrated intervention was shortened considerably, and the speech clarity of both groups of children after treatment exceeded 96%, reaching a normal level.

Financial toxicity in the background of free health care: A cross-sectional survey in a tertiary care hospital in India.

e13685 Background: The financial toxicity of cancer treatment is a known fact in low to middle-income countries due to poverty, lack of health insurance and illiteracy. We tried to estimate the financial strain and its contributing factors in an Indian population with access to free cancer treatment. Methods: All government employees and their dependents are eligible to receive free treatment including inpatient management, investigations and medicines at our institute. All cancer patients ≥18 years were invited to participate in a survey. The survey included their demographic, cancer and therapy details, the COST-FACIT questionnaire, and information about increase in expenses since cancer diagnosis and source of additional finances. Results: 300 cancer patients completed the survey. 61.3% of the respondents were females and the mean patient age was 43.14 years. Breast cancer was the most common malignancy and stage IV was the most common stage. 44% were residents of a rural area. The average duration of treatment was 8.03 months. Prior to cancer diagnosis, 37.2% of the patients had average monthly expenses between INR 10-25,000 (USD 120 to 300). The approximate increase in monthly expenditures after cancer diagnosis was between INR 5-10,000 (USD 60 to 120) for 33.4% and between INR 10-25,000 (USD 120 to 300) for 31.4% of the population. The primary income source for 65.7% respondents was the salary of the government employee while 48% had two or more earning members in the family. Cancer treatment negatively affected the earning capacity of the patient alone in 40% of the population, while in 28% it affected the earning capacity of the patient and caregiver. 51% had to utilise their savings, 39% sold fixed assets, and 31% borrowed or took a loan to cope with the additional financial strain. Commonest expenses were travel, accommodation, and food (75.7%). 34.5% spent money on other therapy-related costs (second opinion or alternative therapy). The mean COST-FACIT score was 21.38,(20-24) demonstrating mild financial toxicity. Predictors of high financial toxicity were a single-earning member, familial discord and long duration of treatment (&gt; 6 months). Conclusions: Though all participants had access to free cancer treatment, all experienced mild financial toxicity due to non-therapeutic expenses. Despite desperate financial measures to complete treatment, most participants did not express severe financial toxicity. This may be attributed to the stigma of expected high expenditure associated with cancer treatment in India. COST-FACIT scoring may not have suitably assessed the financial strain experienced by patients with free healthcare. Additional financial information collected by the survey, (monthly expenses, earning members, source of additional funds), helped us to better understand financial impact of cancer treatment and identify gaps in our healthcare.

Evolution of quality of life (QoL) and symptom burden (SB) in patients receiving inpatient palliative care (PC) following one week of care in a specialized palliative care unit (PCU): A comparison of two groups, with one receiving specialized outpatient palliative care prior to admission.

e23160 Background: This study sought to investigate changes in QoL and SB among PC Pt undergoing one week of inpatient care in a specialized PCU. The Pt population was stratified into two groups (Gp), with one Gp pretreated from pre-admission PC provided by an outpatient multidisciplinary PC team, while the other Gp did not receive such support prior to admission. Although the average duration of treatment at a PCU in Germany is 1-2 weeks, the question also arises as to whether a significant improvement in SB/QoL can be expected after just one week of PC in a PCU. Methods: PC Pt with various cancer entities were prospectively included in a non-randomized study. Pt in Gp 1 received outpatient specialized PC prior to admission, while Pt in Gp 2 did not. Over an 8-month period, we gathered data from one academic cancer center, utilizing the EORTC QLQ-C30, one of the most widely used Pt reported outcome (PRO) instruments to assess health-related QoL in cancer Pt. Pt completed the QLQ-C30 at T0 (admission) and T1 (day 7), enabling the assessment of potential changes in their QoL and SB over time. Results: A total of 103 pt (51.5% male) were enrolled (Gr 1: 42%, Gr 2: 58%). At T0, there were no significant differences regarding QLQ-C30 scores between Gp 1 and 2. Over the course of one week several significant and clinically relevant changes in QoL and SB were found: Emotional functioning demonstrated an uplift in both Gp (Gp 1: mean (M) 41.5 IQR 33 vs. 53.1 IQR 50, p 0.014, Gp 2: M 48.2 IQR 46 vs. 56.8 IQR 58, p 0.029), as did the global health status (Gp 1: M 20.7 IQR 17 vs. 36.2 IQR 33, p &lt; 0.001, Gp 2: M 25.6 IQR 25 vs. 35.3 IQR 33, p &lt; 0.001). Nausea and vomiting showed a reduction (Gp 1: M 29.9 IQR 17 vs. 6.8 IQR 0, p &lt; 0.001, Gp 2: M 22.6 IQR 17 vs. 8.2 IQR 0, p &lt; 0.001), along with a notable decline in pain (Gp 1: M 67.4 IQR 67 vs. 25.3 IQR 17, p &lt; 0.001, Gp 2: M 73.1 IQR 83 vs. 29.7 IQR 17, p &lt; 0.001). A decrease was observed in insomnia (Gp 1: M 63.6 IQR 67 vs. 27.6 IQR 33, p &lt; 0.001, Gp 2: M 60.1 IQR 67 vs. 27.6 IQR 33, p &lt; 0.001). There were no significant differences between Gp 1 and 2 in the extent of improvement in the various symptom scales from T0 to T1, except for cognitive functioning, where Gp 1 exhibited an increase while Gp 2 demonstrated a decrease (p 0.044). Conclusions: The findings of our study demonstrate that QoL and several symptoms prevalent in cancer Pt cared for in the PCU experienced significant enhancement over the span of just one week of PCU care. Both Gp, Pt receiving specialized outpatient PC prior to admission and those without, equally benefited from inpatient PC. All mentioned changes from T0 to T1 are considered not only significant, but clinically relevant.

Safety and efficacy of osimertinib plus bevacizumab as first-line treatment in EGFR-mutant NSCLC with brain metastases: A dynamic ctDNA-guided study.

e20606 Background: Non-small cell lung cancer (NSCLC) patients with positive driver genes had a higher incidence of brain metastasis. This study evaluates the efficacy and safety of Osimertinib combined with Bevacizumab as first line treatment in EGFR-mutant NSCLC with brain metastases, utilizing liquid biopsy and dynamic molecular detection to guide treatment strategies. This approach is anticipated to bring progression-free survival (PFS) benefits and shows different resistant mechanisms. Methods: We enrolled EGFR-mutant NSCLC patients with brain metastases receiving Osimertinib and Bevacizumab as first-line therapy. Paired plasma and cerebrospinal fluid (CSF) samples were collected at baseline, during stable disease, and at disease progression for Next-Generation Sequencing (NGS) analysis. The study's primary endpoints were central nervous system (CNS) PFS and objective response rate (ORR). Secondary endpoints included overall PFS, ORR, disease control rate (DCR), and safety. We also investigated resistance mechanisms to the combination therapy. Results: A total of 28 patients from Beijing TianTan Hospital (May 2020 - July 2023) were retrospectively enrolled. The average Bevacizumab treatment duration was 8.21 months (range: 1-27 months). CNS PFS was 26.73 months (95% CI, not reached), and overall PFS was 21.93 months (95% CI, 18.84-25.02 months). The CNS PFS for patients with 19del and L858R mutations were not reached and 26.73 months (95% CI, 15.11-38.35 months), respectively (p = 0.25). Patients undergoing intracranial local treatment showed a CNS PFS not reached, compared to 23.33 months (95% CI, 16.21-30.45 months) for those who did not (p = 0.417). The CNS ORR was 88%, ORR was 76%, and DCR was 100%. At the time of data cutoff (Dec 15th, 2023), 1 patient progressed in both lung and CNS metastases, 8 patients only progressed in lung, 8 patients only progressed in CNS metastases .EGFR C797S mutation was detected in 2 plasma sample, Met amplification in 1 tumor tissue, EGFR C719S mutation in 1 paired plasma-tumor tissue and PIK3CA in 2 plasma sample. Increasing abundance in TP53 and CDKN2A were detected in 2 paired plasma-tumor tissue. Adverse events of grade 3 or higher included one case (3.6%) of severe ulcerative colitis leading to Osimertinib discontinuation and two cases (7.1%) of bevacizumab discontinuation due to bleeding events. Conclusions: Osimertinib combined with Bevacizumab as a first-line treatment significantly prolonged CNS PFS in EGFR-mutant NSCLC patients with brain metastases, offering superior control over intracranial lesions compared to Osimertinib monotherapy (15.2 months, FLAURA study). This study underscores the potential of dynamic ctDNA monitoring in guiding effective treatment strategies for this patient population. Further research is warranted to explore the broader clinical implications of these findings.

Real-world treatment patterns and clinical outcomes in patients with prostate cancer.: A single institution experience in Saudi Arabia.

To describe the current real-world treatment landscape, sequence of therapies, and outcomes in patients with prostate cancer (PC). A retrospective cohort study for PC patients diagnosed at King Abdullah Medical City Cancer Center in Makkah, Saudi Arabia, between January 2011 and December 2021. Data extracted from electronic medical records. A total of 282 patients with PC, with a mean age of 70 years and body mass index of 27. Among them, 274 (99%) had no family history of cancer, while 164 (58%) had hypertension and 125 (44%) had diabetes mellitus. Adenocarcinoma was the most common histology, found in 275 (97%) patients, with 99 (35%) having a Gleason score of 9. Notably, 184 (65%) patients presented with metastatic disease, and 147 (52%) with bone metastasis. While 198 (70%) patients underwent surgery, 184 (65%) did not receive radiotherapy. The most common first-line metastatic therapy was abiraterone in 23 (8%) patients, followed by enzalutamide in 7 (2.5%). During the study period, 167 (59%) patients survived, with an average treatment duration of 2.5 years. This study provides insights into real-world treatment patterns and clinical outcomes in patients with PC. The findings of this study highlight the importance of adhering to treatment standards and making informed clinical decisions.

Case series of 3 Pressure Ulcers Cured with Education through Telemedicine

Objectives: The case series with pressure ulcers who was cured by education through telemedicine will be presented as a model for how a Korean medicine doctor can participate in the telemedicine of pressure ulcers. We also aim to report on the perspectives of medical staff and patients regarding the improved telemedicine services in Korean medicine.Methods: The study included three cases of pressure ulcers in home care, and education on pressure ulcer management was provided to patients, caregivers, and collaborators via telemedicine. Basic training was provided to teach the sealed wet dressing therapy method. After the basic training, feedback on the treatment was provided by taking photos or videos of the patient's treatment process, and the feedback process was repeated until the dressing method was perfected.Results: A combination of telemedicine, home visits, and home care successfully treated pressure ulcers in home care patients using a multidisciplinary approach. The education through telemedicine alone improved the National Pressure Ulcer Advisory Panel (NPUAP) stages and the total score of the Pressure Ulcer Scale for Healing (PUSH) Tool, and all three cases were finally cured with an average treatment duration of 26.7 days. The patient's and clinician's perspectives also showed that telemedicine can effectively engage patients, caregivers, and collaborators, and motivate them to manage pressure ulcers.Conclusions: For patients having trouble visiting the hospital or desiring treatment at home, consideration can be given to telemedicine for traditional Korean medicine education in pressure ulcer management.

Adverse events of patients treated with antibody-drug conjugates in phase 1 clinical trials at the Royal Marsden Drug Development Unit from 2014 to 2024.

e15020 Background: Antibody-drug conjugates (ADCs) are designed to improve therapeutic indices of cytotoxic agents. Nevertheless, they may induce unexpected toxicities not observed with parent payloads. This study aimed to characterize the adverse events (AEs) seen in patients treated with ADCs in Phase 1 trials at The Royal Marsden Drug Development Unit (DDU). Methods: This is a retrospective cohort analysis of consecutive patients who received at least one dose of an ADC in a phase I trial from January 2014 to January 2024 at The Royal Marsden DDU. Descriptive statistics of patient characteristics, ADCs, and treatment-related AEs were performed. Univariate and multivariate logistic regression will be utilized to assess correlations among patient and ADC characteristics and adverse events. P values of &lt; 0.05 will be considered significant. Results: A total of 131 patients who participated in twelve ADC trials were included. The median age of participants was 63 years (range: 31-84) and 61% were females. Patients received a median of three prior lines of systemic treatment. The most common type of ADC target, antibody, linker and payload were receptor tyrosine kinase (51%), humanized IgG monoclonal antibody (69%), valine-citrulline (VC) cleavable linker (85%), and a tubulin-binding payload (59%), respectively. Most patients received an ADC dose of 1-3 mg/kg (76%) with each cycle given once every 3 weeks (64%). The median number of cycles was 3 with an average treatment duration of 63 days. Within the cohort, 89% of patients developed any grade AE and 17% experienced grade 3 or higher AEs. The major treatment-related AEs were fatigue (48%), nausea/vomiting (27%), ocular toxicity (26%), neuropathy (26%), skin rash (20%) and pneumonitis (8%). The median time to first onset of treatment-related adverse events were 37 days for ocular toxicity, 46 days for pneumonitis, and 54 days for neuropathy. ADC-related AEs led to treatment interruptions (51%), dose reductions (13%), and treatment discontinuations (28%). Two treatment-related grade 5 events occurred. The objective response rate was 18%, with 1 complete response and 22 partial responses. Conclusions: Despite being designed to minimize side effects, ADCs were associated with significant toxicities, including unexpected adverse events unrelated to target, antibodies or the payloads, limiting their therapeutic indices. Further analysis of the relationship between different components of the wide range of ADCs and AEs are warranted to better understand the potential mechanisms of ADC toxicity.

Current status of PD-(L)1 inhibitor usage in advanced or metastatic non-small cell lung cancer: A national survey of oncologists in China.

e20559 Background: The aim of the present study conducted by Chinese Society of Clinical Oncology Expert Committee on Immunotherapy was to obtain real-world information on the use of PD-(L)1 inhibitors for non-small cell lung cancer (NSCLC) in different regions of China via a national questionnaire survey for oncologists. Methods: This survey was distributed online to cancer-related medical departments in 202 first-tier to fourth-tier cities of China between March to April 2023. The national survey consisted of four sections regarding oncologists’ concerns about immunotherapy as follows: treatment choice, response assessment, treatment duration, and management of immune-related adverse events (irAEs). Results: A total of 2,018 oncologists completed this survey. For advanced squamous (SQ) and non-squamous (NSQ) NSCLC without targetable genetic alterations, PD-(L)1 inhibitor-based regimens were the most widely used first-line treatment regimen (SQ: 52%, NSQ: 46%), followed by chemotherapy alone (SQ: 37%, NSQ: 37%) and other regimens (SQ: 11%, NSQ: 17%). The average treatment duration of 1L PD-(L)1 inhibitor-based regimens in SQ NSCLC and NSQ NSCLC were 6.4 and 6.2 cycles, respectively. 67% of oncologists may discontinue immunotherapy or change regimens when the first radiographic tumor assessment was SD per RECIST 1.1. Other reasons for early discontinuation of PD-(L)1 inhibitors before PD or unacceptable toxicity included economic reasons (78%) and patients’ low willingness to continue immunotherapy even they reached CR/PR (62%). Oncologists in the second-tier cities and below were more likely to discontinue immunotherapy when the tumors were stable, with shorter treatment duration of 5.7 cycles versus 7.1 cycles in the first-tier cities. The most common irAEs included dermatologic, endocrine, pulmonary, gastrointestinal, and hepatic toxicities. Conclusions: PD-(L)1 inhibitor-based regimens have become the priority choice for advanced NSCLC in China, however, the status of standardized continuous use of immunotherapy is obviously insufficient. There is a gap between clinical practice and clinical trials regarding PD-(L)1 inhibitor usage, which need more attention. [Table: see text]

Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy.

Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered.

#496 Individualized approach in dialysate sodium prescription—safe and effective

Abstract Background and Aims The management of Na+ levels in hemodialysis (HD) patients plays a crucial role in maintaining their overall health and well-being. Na+, an essential electrolyte, is responsible for maintaining fluid balance, nerve function, and muscle contraction. However, in end-stage renal disease (ESRD) patients undergoing HD, Na+ imbalances are common and can have detrimental effects on their cardiovascular health. Furthermore, HD patients have been prescribed a standardized dialysis bath Na+ concentration (dNa+) during their HD sessions. The individualized approach aims to optimize Na+ balance, minimize adverse effects, and improve patient outcomes. Additionally, dietary Na+ intake, fluid status, and interdialytic weight gain (IDWG) also influence Na+ levels and should be considered when determining the appropriate Na+ prescription. The study aimed to assess whether an individualized dNa+ prescription can contribute to lower IDWG, expressed as a percent of prescribed dry weight (IDWG%). Method This retrospective, non-interventional study included all &amp;gt;18-year-old patients undergoing hemodialysis for &amp;gt;90 days at a single center. Patients were followed for a period of 18 months (December 2021–June 2023), during which the dNa+ concentration was gradually changed, as part of routine clinical care, until a gradient between plasma and dialysis bath Na+ of −2 mEq/L was achieved. Plasma Na+ levels were measured once monthly before a dialysis session along with other parameters such as IDWG and blood pressure. Results A total of 79 patients were enrolled in the study. The average age of the patients was 63.33 ± 12.1 years, with 43 (54.4%) being male. At baseline, the average duration of HD treatment was 255 ± 2.36 minutes, and the mean blood pump rate was 384.7 ± 42.81 ml/min. The majority of patients (98.8%) received HD treatments thrice weekly. Starting from January 2022, the mean dNa+ concentration decreased non-significantly from 139.39 ± 0.96 mmol/L to 138.99 ± 3.18 mmol/L, p = 0.13. The mean plasma Na+ concentration increased from 133.25 ± 2.9 to 136.59 ± 3.47 mmol/L, p &amp;lt; 0.00001, and while mean systolic blood pressure increased slightly (118.38 ± 12.25 to 122.87 ± 12.43, p = 0.01), it remained well controlled. The mean IDWG% decreased from 3.53 ± 1.34%, to 2.74 ± 1.35%, p = 0.35 and the proportion of patients with IDWG &amp;gt;5% decreased remarkably by more than half (11.4% to 5.1%), but due to the low patient numbers, the finding did not quite reach significance (p = 0.15, Table 1). Conclusion Our study demonstrates that individualized dNa+ management in HD patients is a beneficial approach, contributing to a decrease in the proportion of patients with severe IDWG increase, thereby addressing a crucial cardiovascular risk factor. Systolic blood pressure before dialysis remained well controlled, despite a slight, but significant increase. Our findings underscore the safety and potential benefits of an individualized approach to dialysate Na+ concentration, encouraging further exploration for enhanced HD patient care and increased overall well-being.

#246 Understanding the impact of antiangiogenic drug-induced proteinuria on kidney function in cancer patients

Abstract Background and Aims Proteinuria is a common adverse event associated with the use of vascular endothelial growth factor (VEGF) inhibitor drugs, which are widely employed in oncology for treating various tumors. The incidence of proteinuria of all degrees ranges from 10% to 90%, with proteinuria in the nephrotic range occurring in 1-5% of cases. VEGF plays a crucial role in maintaining the integrity of the glomerular capillary wall. Podocytes, constitutively express VEGF, and VEGF receptors are present on both the surface of glomerular capillary endothelial cells and podocytes. Any disruption in the podocyte-endothelial VEGF axis can lead to the loss of endothelial fenestrations in glomerular capillaries, proliferation of glomerular endothelial cells, loss of podocytes, and subsequent proteinuria. The most common pathological findings include focal segmental glomerulosclerosis and minimal change nephropathy, typically associated with tyrosine kinase inhibitors (TKIs), as well as thrombotic microangiopathy (TMA), more frequently observed in pts treated with anti VEGF. Proteinuria is a recognized risk factor for progressive renal damage and end-stage renal disease. However, it's worth noting that the average treatment duration for patients on anti-angiogenic therapy is considerably shorter than the time indicated by clinical studies as necessary to induce renal damage from proteinuria in healthy individuals. However, the long-term impact of drug-induced proteinuria on renal function remains uncertain. The aim of the study is to investigate the association between proteinuria induced by anti-VEGF/VEGFR drugs and its long-term effects on renal function in cancer patients. Method A retrospective study was conducted on 124 patients undergoing anti-VEGF/VEGFR therapy for ≥6 months. 45% of the patients enrolled in the study were on TKI monotherapy, 36% received TKI plus immune checkpoint inhibitors (ICIs), 10% received anti- VEGF treatment, 7% received TKI + chemotherapy (CT), and 2% received anti-VEGF + ICIs. Among patients, 51% were undergoing treatment for kidney cancer, 25% for thyroid cancer, 14% for colon cancer, 7% for liver cancer, and 5% for lung cancer. The study assessed the time course of estimated glomerular filtration rate (eGFR), the influence of baseline eGFR on subsequent variations, the association between proteinuria and renal function, and the identification of risk factors for proteinuria or renal failure. Proteinuria was quantified as proteinuria/24 h. Results Among the 124 patients, 53 developed proteinuria &amp;lt;1 g/24 h, 41 between 1-3 g/24 h, and 30 &amp;gt;3 g/24 h. Specific data are outlined in Table 1. A trend toward a reduction in eGFR of −5 ml/min/1.73 m2 was observed in all patients after 2 years of treatment. The high proteinuria group exhibited a greater percentage change in eGFR compared to the other groups (−1.5% vs −8.5% vs −12.3%) as depicted in Fig. 1A, along with a time-dependent decrease in eGFR. There was no significant difference in the development of eGFR &amp;lt;30 ml/min/1.73 m2 between groups, and no patients permanently discontinued treatment due to nephrotoxicity. No differences in eGFR reduction were noted among the three groups categorized by baseline eGFR (Fig. 1B). Importantly, renal function after the end of therapy was found to be reversible. Conclusion The study did not find a correlation between the degree of proteinuria secondary to anti-VEGF/VEGFR and significant reductions in renal function. Therefore, treatment can be continued irrespective of the degree of proteinuria. Clinical decisions regarding the continuation of therapy with these drugs should weigh the benefits in terms of survival against the potential risks of toxicity, including a modest reduction in renal glomerular filtration rate.

Economic aspects of long-term left ventricular assist device treatment for chronic heart failure.

Technological advances and the current shortage of donor organs have contributed to an increase in the number of left ventricular assist device (LVAD) implantations in patients with end-stage heart failure. Demographic change and medical progress might raise the number of these patients, resulting in a further increase in the number of LVAD implantations. The aim of this study was to evaluate the long-term costs of LVAD therapy and identify diagnoses resulting in expensive stays. In this retrospective analysis of prospectively collected data, all patients after implantation of a second- or third-generation LVAD by 31 March 2022 were included. In addition to demographic and survival data, revenues and case mix points were determined for each patient. Of the 163 patients included, 75.5% were male. The mean age at LVAD implantation was 52±14years. The mean survival was 1458±127days. During follow-up, the total inpatient treatment time per patient was 70±87days. The average duration of outpatient treatment was 55.1%, based on the total duration of support. The average revenue per patient for the implant stay was $193192.35±$111801.29, for inpatient readmissions $52068.96±$116630.00, and for outpatient care $53195.94±$62363.53. LVAD implantation in patients with end-stage heart failure leads to improved survival but a significant increase in treatment costs. Further multi-centre studies are necessary in order to be able to assess the effects of long-term LVAD treatment on the healthcare system.

Early Non-Surgical Treatment For Microtia Types 1 and 2.

Esthetic concerns and psychosocial distress often accompany auricular deformities and malformations in both children and their parents. Approximately 30% of newborns are affected by auricular anomalies, with 15% to 20% resulting in permanent defects. While surgical intervention is typically considered the gold standard for malformations, a non-surgical approach, such as splinting, molding, or other non-invasive techniques, can effectively address deformations if promptly administered by a specialist. Microtia, classified into 4 types, presents challenges ranging from fundamental structural anomalies in types 1 and 2 to severe defects in type 3 and complete absence of the external ear in type 4 (anotia). This study introduces a novel non-invasive treatment modality for microtia types 1 and 2. The cohort consisted of 5 newborns treated for microtia types 1 or 2 between 2022 and 2023. Utilizing the EarWell system, treatment was initiated before 3 weeks of age (mean age: 2 weeks), with an average treatment duration of 6.6 weeks, supplemented by molding treatment as needed. Minor adverse effects, such as simple dermatitis, were observed in 2 patients. All parents expressed high satisfaction with the esthetic outcomes, with 60% reporting extreme satisfaction. The prompt initiation of the treatment protocol for microtia types 1 and 2 led to outstanding and timely outcomes in infants, enhancing the quality of life for both parents and their children. Early intervention for subsequent treatment may improve the condition and, in certain cases, serve as a satisfactory alternative for parents hesitant about further surgical intervention for their children.

Safety and Efficacy of Paliperidone Palmitate in Pediatric Patients with Autism and Intellectual Disability.

This retrospective chart review examines the safety, tolerability and effectiveness of long acting injectable paliperidone palmitate (P-LAI) targeting irritability in twenty-six youth and transition-aged individuals with autism spectrum disorder (ASD) and/or intellectual disability (ID) over a 3-year window. Clinical response was evaluated via prospectively assigned Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales as well as number of hospital presentations. P-LAI was well tolerated with only 3 patients stopping P-LAI due to side effects. The average duration of P-LAI treatment was 21.1months. Difficulty with medication compliance was the most common reason for initiating P-LAI. There was a statistically significant improvement in CGI-I, CGI-S and hospital visits and no change in BMI noted. Given the potential difficulty of medication administration in this population, this evidence of safety, tolerability as well as preliminary data supporting effectiveness is an important addition to the literature regarding psychopharmacologic management of irritability in youth with ASD and ID.