Safety Of Long-term Use Research Articles

Comprehensive Biosafety Profile of Carbomer-Based Hydrogel Formulations Incorporating Phosphorus Derivatives.

Determining the safety of a newly developed experimental product is a crucial condition for its medical use, especially for clinical trials. In this regard, four hydrogel-type formulations were manufactured, all of which were based on carbomer (Blank-CP940) and encapsulated with caffeine (CAF-CP940), phosphorus derivatives (phenyl phosphinic (CAF-S1-CP940) and 2-carboxyethyl phenyl phosphinic acids (CAF-S2-CP940)). The main aim of this research was to provide a comprehensive outline of the biosafety profile of the above-mentioned hydrogels. The complex in vitro screening (cell viability, cytotoxicity, morphological changes in response to exposure, and changes in nuclei morphology) on two types of healthy skin cell lines (HaCaT-human keratinocytes and JB6 Cl 41-5a-murine epidermal cells) exhibited a good biosafety profile when both cell lines were treated for 24 h with 150 μg/mL of each hydrogel. A comprehensive analysis of the hydrogel's impact on the genetic profile of HaCaT cells sustains the in vitro experiments. The biosafety profile was completed with the in vivo and in ovo assays. The outcome revealed that the developed hydrogels exerted good biocompatibility after topical application on BALB/c nude mice's skin. It also revealed a lack of toxicity after exposure to the hen's chicken embryo. Further investigations are needed, regarding the in vitro and in vivo therapeutic efficacy and safety for long-term use and potential clinical translatability.

Knowledge, attitudes, and current practices toward lung cancer palliative care management in China: A national survey.

11143 Background: To demonstrate the status and differences in knowledge, attitudes, and practices (KAP) of lung cancer palliative care (LCPC) management, and to measure patient controlled analgesia (PCA) in cancer pain management in of China. Methods: A questionnaire on LCPC management was used in this study, which involved a total of 2093 participants from 706 hospitals in China. Seven major components make up the questionnaire, including chi-square tests or Fisher exact probabilities to measure the differences in KAP between hospitals grades. Comparing distributions of ordered data between groups was done using the Kruskal-Wallis H test or the Mann-Whitney U test. Multiple choice questions use multiple response cross analysis. Correlation was evaluated by the Spearman correlation coefficient. Results: 84.2% participants believed that anti-tumor therapy is equally important as palliative care. The satisfaction rate of participants from grade 3 hospitals, which was significantly higher than that of grade 2 and grade 1 hospitals (χ²=27.402, P=0.002). The most common symptoms requiring LCPC was pain. The major barriers toward to LCPC were “Patients and families are concerned about the safety of long-term use of palliative care related drugs”. The most common reasons for the use of PCA treatment were 31.1% participants thought “Patients with systemic application of large doses of opioids or adverse reactions to opioids that cannot be tolerated”. The top three barriers toward PCA treatment of cancer pain were (i) worry about adverse reactions of drug overdose, (ii) worry about opioid addiction, and (iii) increase of patients' economic burden. In the past 24 months, 33.9% of the participants had not participated in online or offline training related to palliative care of lung cancer. Conclusions: Chinese healthcare workers are in need of training for lung cancer palliative care and, in particular, for controlling cancer pain symptoms.

Bio-distribution and toxicity potential of human umbilical cord mesenchymal stem cells in cynomolgus monkeys

Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine.

A Revolution in Cellular Aging: A Narrative Review of the Promising Role of Nanorobots in Diagnosis, Treatment, and Regenerative Medicine

Nanorobots, also known as nanobots, are promising medical structures with significant potential for revolutionizing medical treatments and preventing their onset. Nanorobotics shows promise for diagnosing, treating, and regenerating age-related diseases. These tiny machines can repair cellular damage, deliver drugs, stimulate tissue regeneration, and monitor treatments. However, their application in controlling cellular aging is in its early stages, requiring more research to fully understand their potential and address safety concerns. Despite this, the benefits of nanorobots in age-related disease management justify further investigation. This narrative review article provides an overview of recent developments in nanorobotics, specifically focusing on its medical applications. PubMed and Google Scholar were utilized to conduct a comprehensive search using relevant keywords including "nanorobots", "cellular aging", "drug delivery systems", "cellular repair", "therapeutics", and "diagnosis". Only articles published between 2005-2023 were selected to support the arguments with up-to-date evidence. The extracted information includes nanorobot design, fabrication methods, applications, and key findings. A quality assessment was performed, and the data were categorized thematically to identify patterns and trends. The article concludes with an examination of the current state and future prospects of nanorobotics in different fields. Our research showed that nanorobots have significant potential in the diagnosis, treatment, and regenerative medicine of age-related diseases. They can detect and repair cellular damage caused by aging, targeting DNA damage and cellular protein misfolding. Nanorobots can also deliver drugs directly to affected areas, reducing side effects. Furthermore, they stimulate tissue regeneration and the growth of new blood vessels by delivering growth factors. Nanorobots can also monitor treatment effectiveness by measuring drug concentration in tumor cells. However, there are concerns about their safety in long-term use that require further research. Overall, nanorobots present an innovative approach to addressing cellular changes in aging, but more research is needed to understand their full potential and address safety concerns. The use of nanorobots in treating cellular aging has opened new possibilities in diagnosing and treating age-related diseases and it is a rapidly evolving field with the potential to revolutionize age-related disease treatment and improve the quality of life globally.

Update on Antioxidant Therapy with Edaravone: Expanding Applications in Neurodegenerative Diseases.

The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis.

Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long-term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.

Topical Treatment for Dry Eye Disease Related to Sjögren's Syndrome: A Systematic Review

Abstract
 Introduction & Objectives : Sjögren’s syndrome (SS) is a systemic autoimmune disorder characterized by dry eyes and dry mouth caused by inflammation in exocrine glands. Dry eye with SS is often more severe than non-SS dry eye and can greatly affect patients’ quality of life, thus treatment modalities must be selected carefully. This study aims to evaluate the recent studies on topical treatment for dry eye disease related to SS and provide evidence based recommendation for clinical practice.
 Methods : Electronic literature search was performed through the PubMed and Cochrane database from the last 10 years. We only included studies with prospective clinical trial design, a follow-up period of at least 4 weeks, and had outcome parameters among the following: Ocular Surface Disease Index, Schirmer test, tear break up time, tear meniscus height, and corneal fluorescein staining.
 Results : Fifteen studies were selected from 125 articles retrieved. We identified clinical trials using tacrolimus, cyclosporine, cortisol phosphate, diquafosol, rebamipide, fluorometholone, hydrocortisone, clobetasone butyrate, autologous serum, autologous platelet lysate, artificial tear, and various type of vehicles including hyaluronic acid, sodium hyaluronate, almond oil, ceftazidime,or saline solution.
 Conclusion : Cyclosporine has comparably equal efficacy to corticosteroid eye drops in improving signs and symptoms of dry eye in SS, but with a better safety for long-term use. Autologous serum is also an effective therapy with the best concentration being 100% serum (no dilution). Diquafosol is a promising therapy but more research is needed to confirm its efficacy and safety.

Long-term efficacy and safety of divozilimab during 2-year treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS

To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg every 24 weeks during 100 weeks for the treatment of patients with multiple sclerosis (MS), including relapsing-remitting multiple sclerosis (RRMS) and secondary progressive MS (SPMS) with relapses. The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS (NCT05385744) included 338 adult patients with MS distributed in a 1:1 ratio into two groups: DIV 500 mg and teriflunomide (TRF) 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks, then entered an additional period from weeks 49 to 100, which included three cycles of therapy. The efficacy was assessed based on the results of brain MRI and registration of data on relapses. 308 subjects completed 5 therapy cycles according to the study protocol. An analysis of the effectiveness of DIV therapy over 2 years showed a persistent suppression of MRI and clinical activity of the disease in comparison with TRF, which was confirmed by all the studied MRI indicators (including CUA; total number of gadolinium-enhancing (GdE) lesions on T1-weighted scans ; number of new or enlarged lesions on T2-weighted scans; lesions volume change on T2-weighted scans; change in the volume of hypointense lesions on T1-weighted scans). The use of DIV was associated with a statistically significant decrease in ARR compared to TRF (p=0.0001). The ARR in the DIV group was 0.057, in the TRF group - 0.164 with 95% confidential interval for the frequency ratio [0.202; 0.593]. The incidence of GdE lesions on T1-weighted scans in the DIV group was significantly lower than in the TRF group. The average number of such lesions was 0.0±0.08 and 1.0±4.46 in the DIV and TRF groups, respectively (p<0.0001). Progression of EDSS was detected in 18 (10.7%) and 36 (21.3%) patients in the DIV and TRF groups, respectively (p=0.0075). The proportion of patients with relapses was 11.2% (n=19) in the DIV group and 23.1% (n=39) in the TRF group (p=0.0039). In the subpopulation of patients with SPMS, no cases of increase in EDSS were detected, and not a single case of exacerbation was recorded over 2 years of using DIV. Also, DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and laboratory abnormalities, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. The results of the BCD-132-4/MIRANTIBUS CT indicate a high sustained efficacy and safety of long-term use of DIV in comparison with TRF during 2 years of therapy.

Безопасность долгосрочного применения ритуксимаба у пациентов с ювенильным идиопатическим артритом: результаты когортного ретроспективного исследования

Juvenile idiopathic arthritis (JIA) is the most frequent rheumatic disease of childhood. The goal of juvenile arthritis therapy is to achieve durable clinical and laboratory remission and a good quality of life. Various groups of drugs are used in the treatment of JIA, one of which is the anti-CD20 drug rituximab. Rituximab causes B-cell depletion, which may lead to decreased immunoglobulin levels, decreased antigen-presenting function of B-lymphocytes and impaired T-cell response. The main side effects of rituximab administration are infusion reactions, hypogammaglobulinaemia, neutropenia and infectious complications. Safety studies of rituximab use have been conducted mainly in adult patients with rheumatoid arthritis, in paediatric patients with oncological diseases and diffuse connective tissue diseases. There have been no long-term safety studies of rituximab in children with JIA. Objective. To evaluate the safety of long-term use of rituximab in patients with juvenile idiopathic arthritis. Patients and methods. A cohort retrospective study of patients with JIA aged from 2 to 17 years with evaluation of adverse events on the background of rituximab therapy was carried out; the maximum duration of follow-up was 165 months. Rituximab was administered by intravenous drip at a dose of 375 mg/m2 body surface area by 4 weekly injections (61% of all courses given) or 2 injections of 1000 mg 2 weeks apart (29%). 4% had 1 administration per course; 6% had 3 consecutive weekly administrations. The indication for repeat rituximab administration and the number of administrations were determined on an individual basis. Safety was assessed by registration of adverse events (AEs) according to medical records; AEs registered during the patient's hospitalisation and anamnestic data on AEs during the interhospital period were taken into account; infectious, infusion and other AEs were considered separately. Results. Rituximab demonstrated a sufficiently high safety profile: 88/102 (86%) patients did not report any serious AEs (grade ≥3); life-threatening AEs (grade 4-5) were reported in 7/102 (7%) patients, included 4 episodes of severe pneumonia, 3 episodes of sepsis; their incidence was 2.5 cases per 100 PY. The incidence of infectious AEs was 57.4/100 patient-years; 85% of them corresponded to mild severity; most often infectious AEs were registered in the first year of rituximab therapy; pneumonia (16/100 PY) and ENT infections (11.3/100 PY) prevailed in the structure. Infusion reactions developed with an incidence of 34.8/100 PY, most frequently registered at the first rituximab administration and manifested as influenza-like syndrome (18.4/100 PY) and rash (10.3/100 PY). The incidence of neutropenia was 17/100 PY, erythropenia 0.7/100 patient-years; decreased blood immunoglobulin levels (IgA – 5.3 episodes, IgM – 6.7, IgG – 3.4/100 patient-years), increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity – 3.9/100 PY, 1 episode of increased serum urea levels. Conclusion. The use of rituximab in patients with JIA may be accompanied by the development of AEs, which include infusion reactions, infectious complications, cytopenias, decreased level of immunoglobulins in blood, increased activity of ALT and AST. Implementation of the algorithm for the management of patients with JIA under rituximab treatment into clinical practice will allow to ensure monitoring of AEs, their detection at early stages, timely initiation of adequate therapy to prevent the development of severe complications. Key words: juvenile idiopathic arthritis, safety of therapy, rituximab, adverse events, infusion reactions, infectious complications

КОНСЕРВАТИВНОЕ ЛЕЧЕНИЕ КИСТ МОЛОЧНЫХ ЖЕЛЕЗ: ВОЗМОЖНОСТИ ПРИМЕНЕНИЯ ПРЕПАРАТА ИНДИНОЛ ФОРТО

Among the drugs used in the conservative therapy of breast cysts and fibrocystic mastopathy, phytopreparations are mainly used in clinical practice. &#x0D; The drug Indinol Forto, obtained from plants of the cruciferous family, contains indolecarbinol, the effect of which is associated with the regulation of estrogen metabolism, inhibition of pathological proliferation, blockade of the formation of inflammatory cytokines, activation of apoptosis of transformed cells, reduction of breast cysts. The paper presents the results of a study of the pharmacological effect of the drug Indinol Forto on cystic formations of the breast. A comparative study of the use of the drug Indinol Forto showed its high effectiveness in the treatment of breast cysts, which consists in reducing the number and size of cystic formations of the breast. The drug Indinol Forto in the conservative treatment of breast cysts showed its effectiveness after 3 months of use: there was a decrease in the number of cysts (complete regression) by 3±0,5 in 13 (28,9%) patients and a partial regression of cysts with a decrease in their size by 28,7±5,8% in 16 (35,6%) patients. The optimal effect of Indinol Forto manifested itself after 6 months of use: the number of cysts decreased by 5±1,1 in 19 (42,2%) patients, and in 22 (48,9%) patients, a partial regression was noted with their reduction in size by almost half – by 49,0±7,2%. The results of the conducted studies have shown that Indinol Forto is the optimal drug that positively affects the dynamics of cystic formations of the breast. The drug Indinol Forto is well tolerated when taken orally, has no clinically identified side effects, which justifies the safety of long-term use.

Применение склеральных линз для коррекции посткератопластической аметропии

Purpose. Analysis of clinical and functional results of correction of postkeratoplastic ametropia with rigid gas-permeable scleral lenses. Material and methods. Clinical and functional results of the correction of postkeratoplastic ametropia (PA) with rigid gas-permeable scleral lenses (RGSL) were analyzed based on a comprehensive examination of 25 eyes (25 patients). Of these, there were 16 men and 9 women. The mean age of the patients was 40±9 years. Uncorrected visual acuity (UCVA) was 0.14±0.16, best corrected visual acuity (BCVA) with glasses was 0.44±0.25, the spherical refractive component was 1.37±2.58 D, the cylindrical refractive component was –4,75±1.68 D. The follow-up period was about 5 years. Results. After application of RGSL, all patients noted a significant improvement in visual acuity due to the correction of PA and an increase in the regularity of the corneal graft. There was a statistically significant increase in BCVA in RGSL up to 0.66±0.13 (p=0.0022), which remained stable throughout the entire observation period. BCVA in RGSL 0.5 and above was noted in 93% of the eyes. In all patients, after the selection of RGSL, a significant decrease in total corneal aberrations, including higher order ones, was noted. When calculating the cell density of the epithelium of the corneal graft on HRT III Cornea after 5 years of wearing RGSL, a decrease in the cell density of all layers of the epithelium was noted. The absence of endothelial cell density loss, clinically significant corneal graft edema, and reduction in the biomechanical properties of the corneal graft indicate the safety of long-term use of RGSL in patients after keratoplasty. Conclusion. Clinical and functional analysis of the correction of postkeratoplastic ametropia with rigid gas-permeable scleral lenses during 5 years of observation showed: higher rates of best corrected visual acuity compared to spectacle correction by an average of 0.22±0.05, a significant decrease in corneal aberrations, a decrease in the density of cells of all corneal graft epithelium layers, high optical efficiency, and safety of their use during the entire observation period. Key words: postkeratoplastic ametropia, rigid gas-permeable scleral lens, corneal graft

Efficacy of tofacitinib in psoriatic arthritis: literature review and case report

The article presents the results of a search in the PubMed and Google Scholar databases (meta-analyses, systematic reviews, clinical trials and case studies) evaluating the treatment of PsA with tofacitinib (TOFA). The review contains the most up-to-date information about the efficacy and safety of TOFA, a drug from the group of janus kinase inhibitors (JAKi), a brief description of the mechanism of action of TOFA is given, with mention of blocked signaling intracellular pathways. The spectrum of “key” clinical manifestations of psoriatic arthritis (PsA) is described, in which the therapeutic potential of TOFA (peripheral arthritis, psoriasis, enthesitis and dactylitis) is most fully revealed. The results of the main randomized controlled trials (OPAL Broaden and OPAL Beyond), postmarketing trials, descriptive studies and clinical observations are considered, and the high efficacy of TOFA for the treatment of PsA patients who did not respond to therapy with synthetic disease-modifying drugs and/ or Tumor Necrosis Factor inhibitors (TNFi) is demonstrated. The results (and their interpretation) of studying the safety of long-term use of different doses of TOFA – 5 mg 2 times a day and 10 mg 2 times a day and retention (“survival”) are presented therapy, with an emphasis on adverse events of special interest (“large” cardiological events (MACE), oncologics, infections). The results of treatment with tofacitinib in patients with PsA according to the All-Russian register of patients are presented. The pronounced positive effect of TOFA on the parameters that are defined as “patient-reported outcome – PRO” is particularly emphasized: indicators of fatigue, self-assessment, patient’s assessment of his condition according to VAS, assessment by HAQ-DI (Health Assessment Questionnaire), SF-36 (non-specific questionnaire for quality assessment patient’s life), etc. A clinical observation is presented that demonstrates a vivid therapeutic effect on arthritis, enteritis, dactylitis, clinical signs of spondylitis, sacroiliitis, as well as the skin process in a patient with active PsA.

Efficacy and safety of long-term use of tedizolid in disseminated nocardiosis after heart transplantation.

Efficacy and safety of long-term use of tedizolid in disseminated nocardiosis after heart transplantation.

Efficacy and safety of long-term use of low molecular weight heparins in patients with systemic lupus erythematosus and antiphospholipid syndrome

To date, the management of patients with antiphospholipid syndrome (APS) with ineffectiveness and/or intolerance to vitamin K antagonists and direct oral anticoagulants remains controversial. One of the treatment strategies is the administration of low molecular weight heparins (LMWH) over a long period of time. Objective: to evaluate the efefficacy and safety of long-term treatment with LMWH in patients with APS. Material and methods. The study included 15 patients (13 women and 2 men) with APS. In 2 of them APS was isolated, in 12 it was combined with systemic lupus erythematosus (SLE), and in 1 – with SLE and psoriatic arthritis. The mean age of patients was 44 ± 12 years, and the mean duration of disease was 12 [6; 18] years. All patients were repeatedly examined in the V. A. Nasonova Research Institute of Rheumatology during hospitalizations and continued outpatient care in the clinical diagnostic center of the Institute. Results and discussion. Ten (67 %) patients received nadroparin, 5 (33 %) patients received enoxaparin. The median duration of therapy was 4 [1; 10] years. Indications for the use of LMWH were inefficacy and intolerance of oral anticoagulants (n = 12, 100 %) and vascular involvement such as thromboangiitis obliterans with the development of chronic arterial insufficiency, ulcers and necrosis of the toes (n = 6, 40 %). During therapy, 13 (86 %) of 15 patients showed clinical improvement: healing of ulcers and necrosis, reduction in the stage of arterial insufficiency, recanalization of venous blood clots. During the entire treatment period with LMWH, one patient experienced a relapse of thrombosis due to an insufficient dose of the drug. No hemorrhagic complications occurred in any case. Other adverse events, including elevated liver aminotransferases, osteoporosis, and thrombocytopenia, were also not observed. Conclusion. The results obtained suggest that long-term therapy with LMWH may be safe and effective in patients with APS.

SAT093 Closed-Loop Insulin Delivery Versus Standard Care In Type 1 Diabetic Pediatric Patients: A Meta-analysis Of Randomized Controlled Trials

Abstract Disclosure: L.C. Hespanhol: None. V.C. Moreira: None. A.C. Silva: None. I.R. Marques: None. A. Godoi: None. A. Mahesh: None. C. Oommen: None. C.H. Silva: None. C. Gomes: None. I.A. Souza: None. I.A. Miyawaki: None. J.E. Loyola Júnior: None. J. De Sa: None. E.M. Padrao: None. Background: Treatment of Type I Diabetes Mellitus (T1DM) in the pediatric population is a clinical challenge. The first closed-loop system (CL) was approved for pediatric use in 2020 with the aim of improving therapeutic and safety outcomes for patients. Since then, many randomized clinical trials have been performed, yet, to our knowledge no meta-analysis evaluating the effect of long-term CL on glycemia in children and adolescents with T1DM was performed. Purpose: To compare the therapeutic efficacy and safety of long-term use of CL insulin delivery systems to standard care (SC) in pediatric patients with T1DM. Methods: PubMed, Cochrane and EMBASE were systematically searched in October 2022 to include randomized controlled studies (RCTs) comparing CL systems (automated pancreas, hybrid CL and advanced hybrid CL) versus SC (daily insulin injections, sensor augmented pump and continuous glucose monitoring) with at least 12 weeks of duration. Outcomes assessed were percentage time in range (% TIR) 70-180mg/dL, change in HbA1c and percentage time with hypoglycemia (glucose &amp;lt; 70mg/dL). Statistical analysis were performed with RevMan 5.4.1 and R software. Heterogeneity was assessed with I² statistics and random-risk effect was used if I2 &amp;gt; 50%. The protocol was registered in PROSPERO (ID: CRD42022366710). Results: A total of 7 randomized studies with 827 patients with T1DM were included, of whom 471 (56.7%) used automated devices and 356 (43.3%) continued their usual care. The %TIR was significantly higher in the CL systems when compared to SC (MD 8.70%; 95% CI 7.08 to 10.31; p &amp;lt; 0.001; I² = 0%). Similarly, CL systems showed a significantly higher HbA1c mean difference when compared to SC (MD -0.38; 95% CI -0.59 to -0.16; p &amp;lt; 0.001; I² = 0%). When evaluating percentage time with hypoglycemia, the time was non-significantly lower in the CL system group when compared to SC (MD -0.47%; 95% CI -1.06 to 0.13; p = 0.12; I² = 55%). Conclusion: In this meta-analysis of randomized trials in pediatric population with T1DM, the use of CL insulin devices was associated with a higher proportion of time in the optimal glucose range and greater decrease of HbA1c relative to standard care, regardless of CL system type. However, the use of CL insulin delivery was not associated with less time in hypoglycemia range. Therefore, CL systems seem to be safe and superior to standard care regarding glycemic control. Presentation: Saturday, June 17, 2023

Ophthalmic Self-Medication Practices and Associated Factors of Using Steroid Eye Drops Among Adult Ophthalmic Patients.

Self-medication is defined as the selection of medicines by individuals to treat self-diagnosed ophthalmic symptoms without consultation of healthcare professionals. Topical steroids can produce severe eye-threatening complications, including the elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage. In recent times, many over-the-counter (OTC) ophthalmic preparations are possible without a prescription. There are a lot of concerns about the safety of long-term use of nonprescription ophthalmic drugs, which may lead to a variety of serious ocular complications. To determine the prevalence of self-medication ocular topical steroid practices and associated factors among adult ophthalmic patients attending ophthalmology clinics at King Saud Medical City (KSMC) in Riyadh. A cross-sectional study targeted adults aged 18 or older who had used topical steroids eye drops. The data were collected through interviews, and an online questionnaire was distributed among patients who attended ophthalmology clinics between December 2022 and February 2023. From a total of 308 responses, 92 (29.8%) were using ocular topical, 58 (18.8%) with a prescription, five (1.6%) without a prescription, and 29 (9.4%) with and without a prescription, while 216 (70.1%) did not use it. The frequency of using ocular topical steroids without a prescription among participants was 11 (12%) once and 33 (35%) many times. Additionally, 26 (28.3%) were having complications, mostly eye infections (11, 12.4%), glaucoma (8, 9%), and cataracts (6, 6.7%). The reasons for practicing self-medication ofsteroid eye drops among participants were 14 (15.2%) repeated symptoms, 11 (15.2%) had heard advice from friends, and 11 (15.2%) think they had enough knowledge. The study reported the use of self-medication with steroids in ophthalmology clinics at KSMC, even though detecting a high level of perception and acceptable practices among participants. This practice is mainly due to participants having repeated symptoms and thinking they have enough knowledge. Educating the patients would help in reducing the incidence of self-medication steroid eye drops and its associated complications.

Long-term safety of macitentan in patients with pulmonary hypertension: A meta-analysis of randomised controlled trials.

Macitentan has demonstrated its effectiveness in patients with pulmonary hypertension (PH), but its safety, especially for long-term use, needs to be further explored. This systematic review and meta-analysis aimed to determine the safety of long-term use of macitentan in patients with PH. A systematic search was made of PubMed, Embase, Cochrane Library and clinicaltrials.gov, without language restrictions. Randomised controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo, were reviewed. Estimated effects of included studies were pooled as risk ratios (RRs), with 95% confidence intervals (CIs). Six RCTs (enrolling 1003 participants) met the inclusion criteria. Anaemia (RR 3.86, 95% CI 2.05-7.30), headache (RR 1.52, 95% CI 1.02-2.26) and bronchitis (RR 2.24, 95% CI 1.30-3.87) were more frequent in the macitentan groups. There was no statistically significant difference in the proportion of patients with at least one adverse event (AE) or serious adverse event (SAE), AEs leading to discontinuation of study treatment, all-cause death, right ventricular failure (RVF) and peripheral oedema between the two groups. The long-term use of macitentan is safe for patients with PH, although with a higher risk of anaemia, headache and bronchitis.

Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study

Prior studies have suggested that proton pump inhibitor (PPI) use is associated with increased risk of dementia; however, these have been limited by incomplete assessment of medication use and failure to account for confounders. Furthermore, prior studies have relied on claims-based diagnoses for dementia, which can lead to misclassification. We investigated the associations of PPI and histamine-2 receptor antagonist (H2RA) use with dementia and cognitive decline. We conducted a post hoc analysis of ASPirin in Reducing Events in the Elderly (ASPREE), a randomized trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities. Baseline and recent PPI and H2RA use were determined according to review of medications during annual in-person study visits. Incident dementia was defined according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, criteria. Secondary endpoints include cognitive impairment, no dementia (CIND) and changes in cognition. Associations of medication use with dementia and CIND outcomes were examined using Cox proportional hazards models. Changes in cognitive test scores were examined using linear mixed-effects models. Baseline PPI use vs nonuse was not associated with incident dementia (multivariable hazard ratio, 0.88; 95% confidence interval, 0.72-1.08), CIND (multivariable hazard ratio, 1.00; 95% confidence interval, 0.92-1.09), or with changes in overall cognitive test scores over time (multivariable B,-0.002; standard error, 0.01; P= .85). Similarly, no associations were observed between H2RA use and all cognitive endpoints. In adults ≥65 years of age, PPI and H2RA use were not associated with incident dementia, CIND, or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.

A Real-World Prognosis in Idiopathic Pulmonary Fibrosis: A Special Reference to the Role of Antifibrotic Agents for the Elderly.

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia, and its prevalence increases with age. In the era of pre-antifibrotic agents, the median survival time of Japanese patients with IPF is 35 months, with a 5-year survival rate in western countries ranging from 20% to 40%. The prevalence of IPF is highest in elderly patients aged ≥75 years; however, the efficacy and safety of long-term use of pirfenidone and/or nintedanib are not fully understood. This study aimed to determine the efficacy and safety of the sole use of antifibrotic agents (pirfenidone or nintendanib) for IPF in the elderly. We retrospectively reviewed patients with IPF who were diagnosed and treated with either pirfenidone or nintedanib in our hospital between 2008 and 2019. We excluded patients with the subsequent use of both antifibrotic agents. We examined the survival probability and frequency of acute exacerbation, with focus on long-term use (≥1 year), elderly patients (≥75 years of age), and disease severity. We identified 91 patients with IPF (male to female ratio: 63 to 28, age 42 to 90 years). The numbers of patients with disease severity classified by JRS (I/II/III/IV) and GAP stage (I/II/III) were (38/6/17/20) and (39/36/6), respectively. The survival probabilities were comparable between the elderly (n = 46) and non-elderly groups (n = 45, p = 0.877). After the initiation of antifibrotic agents, the cumulative incidence ratio of acute exacerbation of IPF was significantly lower in the early stage (GAP stage I, n = 20) than in the progressive stage of disease (GAP stages II and III, n = 20, p = 0.028). A similar trend was noted in the JRS disease severity classification (I, II vs. III, IV) (n = 27 vs. n = 13, p = 0.072). In the long-term treatment (≥1 year) group (n = 40), the survival probabilities at 2 and 5 years after treatment initiation were 89.0% and 52.4%, respectively, which did not reach the median survival rate. Even in elderly patients (≥75 years of age), antifibrotic agents demonstrated positive effects on survival probability and the frequency of acute exacerbation. These positive effects would be improved for earlier JRS/GAP stages or long-term use.

How to Make the Right Choice of Proton Pump Inhibitor for Patients with Gastroesophageal Reflux Disease?

Аim: to analyze the main pharmacokinetic properties of proton pump inhibitors (PPIs) and their significance in the treatment of gastroesophageal reflux disease (GERD).Key points. Pantoprazole has a high bioavailability, the absolute bioavailability of pantoprazole at a dose of 40 mg is 77 % from the first dose and does not change with repeated use. Pantoprazole shows a faster onset of action than omeprazole. Simultaneous food intake does not change the bioavailability of pantoprazole. Suppression of hydrochloric acid production while taking pantoprazole accompanies by the achievement of endoscopic remission of GERD by day 28 in 91 % of patients with reflux esophagitis and by day 56 in all patients in the PANSTAR studies. Pantoprazole has little effect on CYP2C19 compared to other PPIs, minimizing the risk of drug-drug interactions. Pantoprazole is the most pH-selective PPI, which determines the specificity of action only in the parietal cells of the stomach and the greatest safety of long-term use in patients with comorbid pathology.Conclusion. PPIs form the basis of the therapy of acid-dependent diseases, and, in particular, gastroesophageal reflux disease. Pantoprazole is distinguished from other PPIs by its persistent high bioavailability, long-term antisecretory effect, and very low affinity for cytochrome P450.