Long-term Use Research Articles

12273 Do The First 48 Hours Of Hospitalization Require More Vigilance In Geriatric Patients At Risk Of Hypoglycemia?

Abstract Disclosure: S. Ravi: None. H. Afsana: None. Hypoglycemia (HG; blood glucose <70 mg/dL) is a commonly encountered problem in hospitalized patients and is associated with significant morbidity and mortality as well as increased healthcare costs. Elderly patients are particularly vulnerable to HG as they are more likely to have autonomic dysfunction, resulting in fewer discernible symptoms as well as an impaired counterregulatory response, making it more likely that events go undetected and uncompensated. A survey of the literature identifies a number of risk factors for developing HG, including nephropathy, liver disease, infection, cognitive dysfunction, as well as sulfonylurea and long-term insulin use. Given the significant risks posed by HG, we pose the question: how can we do better to identify geriatric patients at high risk of HG events? In this retrospective chart review, data was collected from charts of patients aged 65-99 years with HG, who presented to the ED and were hospitalized for various reasons at a community hospital. Patients were included if a diagnosis of HG was documented in the EMR during hospitalization regardless of diagnosis of Diabetes Mellitus (DM). In 219 total individuals, potential associated variables were analyzed using descriptive statistics, chi-square tests, and Fisher’s exact tests. When data was not complete for any individual variables, the incomplete data was excluded during respective analysis. Among 219 patients, 128 (58.45%) presented at the time of admission, 33 (15.07%) presented within 24 hours after, 15 (6.85%) presented between 24 - 47 hours after, and 43 (19.63%) presented ≥48 hours after admission. Overall, 80.37% of HG events occurred within the first 48 hours of hospitalization. Interestingly there was no significant relationship identified between severity of HG events and HbA1c. The percent distribution identified delayed or missed meals (33%), insulin use (26%), and infection (8%), as the most common potential causes. These findings suggest that it is beneficial to extend the suspicion of HG events to all geriatric patients, regardless of diagnosis of DM. While validated tools have been proposed to identify diabetic patients at risk for HG, fewer studies have been done to identify potential markers of HG risk in all geriatric patients. It may be that the first 48 hours pose a critical period to identifying and better managing these patients’ blood sugars. While use of continuous glucose monitoring in the inpatient setting has been proposed as a potential solution, other cost-effective methods include ensuring timely delivery of meals and food intake, as well as closer finger stick glucose monitoring in the first 48 hours. Higher powered studies across a wider variety of clinical settings are required to further investigate hypoglycemic events in geriatric patients and to synthesize validated assessment tools. Presentation: 6/2/2024

The role of aryl hydrocarbon receptor agonists in the treatment of vitiligo.

Vitiligo is a chronic autoimmune disorder characterized by progressive skin depigmentation. Vitiligo significantly impacts patients' quality of life, contributing to psychological and social burdens. Despite readily available therapeutic options, many cases remain refractory to treatment, highlighting the critical need for safer and more effective therapies. Currently, ruxolitinib is the only FDA-approved medication for vitiligo; however, it carries a black box warning for serious adverse effects, including infections, malignancy, and major cardiovascular events, limiting its use. Recent studies have identified the aryl hydrocarbon receptor (AhR) as a promising therapeutic target, suggesting that AhR agonists could address the multifaceted pathogenesis of vitiligo. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search to analyze the role of AhR agonists in the treatment of vitiligo on PubMed, Cochrane, Embase, MEDLINE, and Web of Science databases on April 15, 2024. Fourteen studies met the inclusion criteria, comprising two clinical trials, two case reports, and nine basic science studies. Our search revealed that culturing AhR agonists with melanocytes upregulates melanin-synthesizing enzymes, reduces reactive oxygen species, and modulates pro-inflammatory cytokines such as IL-17A and IL-22. Tapinarof, a topical AhR agonist used commonly for the treatment of psoriasis, demonstrated clinical efficacy in repigmentation with a favorable safety profile compared to long-term steroid use. Although limited by the number of clinical studies, this review underscores the potential of using AhR agonists, such as tapinarof, as a transformative approach to vitiligo management. Future clinical trials are necessary to evaluate the safety, efficacy, and long-term outcomes of AhR agonists.

8079 PPI Breaks a Leg! An Unusual Case of Atypical Femur Fracture

Abstract Disclosure: M. Sedghian: None. M. Flanagan: None. D. Pinkhasova: None. K. Selk: None. G. Moloney: None. Background: Atypical femur fractures (AFF) occur along the shaft of the femur extending from the subtrochanteric region proximally to the distal femoral metaphysis. These fractures have an increased incidence in patients taking bisphosphonates and denosumab for osteoporosis and develop as stress reactions in the lateral cortex of the femoral shaft (beaking). However, few cases that meet the characteristics of these fractures have occurred in patients who have never used antiresorptive drugs. We present a case with a history of long-term proton pump inhibitor (PPI) use and possible association with AFF. Clinical Case: The patient is a 68-year-old female with a past medical history of hypothyroidism who presented to the emergency department (ED) after an atraumatic femur fracture and consequently ground level fall. The patient reported experiencing a distinctive cracking sound in her femur while leaning over to wash her feet, resulting in a fall that prompted her to seek immediate care in the ED. Upon initial evaluation, radiographic imaging was significant for displaced left mid-femoral diaphyseal fracture and right femur lateral cortex thickening consistent with AFF. Labs were consistent with elevated PTH to 100.7 [18.4-80.1], Vit D2 1,25 (OH)2 <8 pg/mL, Vit D 25OH 34 ng/ml [30-100], and Calcium level of 9.5. Upon further history taking, the patient stated that she has been taking PPIs intermittently for more than 10 years. She denied a history of bisphosphonate and denosumab exposure, non-Hodgkin's lymphoma, rheumatoid arthritis, and COL1A2 variant mutations as main predisposing factors for atypical femur fractures. She had potential steroid exposure for less than a year before hospitalization as she was on "adrenal complex" from her functional medicine provider. The patient underwent open reduction and internal fixation of the left femur with placement of intramedullary nail and prophylactic fixation with placement of intramedullary nail of the right femur as there was radiographic evidence of beaking. Discussion/Conclusion: Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. Overall, PPIs are positively associated with elevated fracture risk in multiple studies. Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, decreasing bone turnover, impairing calcium absorption, and altering homocysteine levels through impairment of folate and vitamin B12 absorption.This case supports a potential association between long-term PPI use and atypical femur fractures. There have been other case reports that also highlight this potential risk of PPI use. This shows the importance of more comprehensive research on this topic as the number of patients on long-term PPIs is growing in outpatient settings. Presentation: 6/2/2024

7933 Baseline Demographics and Design of the SkybriGHt Registry Study. A US Multi-center, Prospective, Non-interventional, Long-term, Effectiveness and Safety Study of Children and Adolescents with Growth Hormone Deficiency Treated with Lonapegsomatropin

Abstract Disclosure: P.F. Backeljauw: Advisory Board Member; Self; Ascendis Pharma, Inc., Novo Nordisk, BioMarin. Consulting Fee; Self; Ascendis Pharma, Inc., Novo Nordisk, BioMarin, Cavalry, Upsher-Smith. Speaker; Self; Ascendis Pharma, Inc., BioMarin. A.K. Maniatis: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., BioMarin, Novo Nordisk, Pfizer, Inc.. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., OPKO, Novo Nordisk, Pfizer, Inc.. Speaker; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., BioMarin, Novo Nordisk, Pfizer, Inc.. Other; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma, Inc., BioMarin, Novo Nordisk, Pfizer, Inc. M. Abuzzahab: Advisory Board Member; Self; Ascendis Pharma, Inc., Pfizer, Inc.. Consulting Fee; Self; Rhythm. Research Investigator; Self; Ascendis Pharma, Inc., Novo Nordisk, Lumos, Rhythm, Soleno, Medtronic, Inhale. Other; Self; DSMB for LG. S.D. Chernausek: Advisory Board Member; Self; Ascendis Pharma, Inc. T. Lipman: Speaker; Self; Novo Nordisk. A.K. Dewan: Advisory Board Member; Self; Pfizer, Novo Nordisk. Consulting Fee; Self; Novo Nordisk. Research Investigator; Self; Medtronic. Speaker; Self; Ascendis Pharma, Inc., Novo Nordisk. Other; Self; Twistle. G. Prakasam: Advisory Board Member; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Consulting Fee; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Grant Recipient; Self; Mannkind Corporation. Research Investigator; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Speaker; Self; Ascendis Pharma, Inc., Novo Nordisk, AstraZeneca, Johnson &Johnson, Lilly USA, LLC, Medtronic, Mannkind Corporation, Pfizer, Inc., Ultragenyx. Other; Self; Ultragenyx, Pfizer, Inc., Mannkind Corporation, Medtronic, Lilly USA, LLC, Johnson &Johnson, AstraZeneca, Novo Nordisk, Ascendis Pharma, Inc. M.B. Kabbani: Employee; Self; The Pediatric Endocrine & Diabetes Clinic, PC. E. Huang: Employee; Self; Ascendis Pharma, Inc. S. Raveendran: Employee; Self; Ascendis Pharma, Inc. C. Zhao: Employee; Self; Ascendis Pharma, Inc. J.N. Caminis: Employee; Self; Ascendis Pharma, Inc. A.D. Rogol: Advisory Board Member; Self; Ascendis Pharma, Inc., Tolmar. Consulting Fee; Self; Ascendis Pharma, Inc., Tolmar. Other; Self; United States Anti-doping Agency, World Anti-doping agency, Tomlar, Ascendis Pharma, Inc., Up To Date. Objectives: Lonapegsomatropin is a prodrug that delivers unmodified somatropin and is approved by the FDA and EC as a once-weekly treatment for pediatric growth hormone deficiency (pGHD). The overall objectives of the observational SkybriGHt study are to assess safety and effectiveness of lonapegsomatropin in the post-marketing setting. The primary objectives are to describe demographics, clinical characteristics, and treatment patterns. Secondary objectives are to describe clinical outcomes assessments (COAs), long-term outcomes of treatment, treatment adherence and persistence, and outcomes in patients transitioning from childhood to adulthood. Exploratory objectives will examine the impact of adherence on clinical outcomes, and assess all cause and GHD-related resource utilization and costs. A preliminary description of the baseline characteristics and demographics of the first 50 patients enrolled is described here. Methods: In the ongoing SkybriGHt study approximately 900 participants from the US, diagnosed with pGHD and prescribed lonapegsomatropin consistent with routine clinical practice, will be invited to enroll by their HCP. The decision to treat with lonapegsomatropin is made prior to and independently of any potential participation in the study. Participants are enrolled over a 5 year period with the study intended to conclude after 10 years. COAs are collected using questionnaires assessing health-related quality of life in functioning and well-being, treatment satisfaction, and patient preference. Safety is assessed via reporting of adverse events and laboratory test results. Results: Of the first 50 patients enrolled, 11 (22%) had participated in previous trials of lonapegsomatropin, 42 (84%) were male, the median age was 9.9 years (range 3.1, 15.0), and median age at diagnosis was 7.2 years. No participants were previously treated with long-acting GH prior to lonapegsomatropin, and 36 (72.0%) were treated previously with daily GH. Conclusions: The SkybriGHt registry will evaluate the long-term safety, effectiveness, and treatment use patterns (including demographics), with lonapegsomatropin in clinical practice. This preliminary baseline data show that patients were predominantly male, consistent with prior treatment patterns of GHD in the United States. Description of baseline characteristics of additional enrolled patients will be presented. Presentation: 6/3/2024

Safety and Tolerability of Antihypertensive Agents in Long-term: A Literature Review

Hypertension is known to affect more than one billion people globally and is estimated to increase to 1.5 billion by 2025. It is considered one of the leading causes of death and cardiovascular disease worldwide. The safety of long-term antihypertensive use is also a concern. Through a narrative or literature review, this study evaluated antihypertensive agents based on the results of various literature searches. Researchers reviewed the safety and tolerability of five classes of antihypertensive agents such as Diuretics, Angiotensin-Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB), Beta-Blockers, and Calcium Channel Blockers (CCB). The use of ARB antihypertensive drugs like valsartan is well tolerated and safe. Moreover, the mortality rate associated with enalapril was 16% lower (95% CI 0.76-0.93; P < 0.001). Captopril and lisinopril of Angiotensin-converting Enzyme Inhibitors (ACEIs) have significant side effects (SEs) compared to any antihypertensive drug. Therefore, this study recommends using the ACEIs group, especially captopril and lisinopril, due to the minimal side effects produced compared to other antihypertensive drugs. In addition, the CCBs or Ca antagonists class like amlodipine is potentially well tolerated and safe as a first-line drug for hypertension treatment. Keywords: antihypertensive drugs, hypertension, safety, side effect, tolerability

Efficacy of balloon angioplasty and stent placement in the treatment of central venous stenosis in patients with chronic kidney disease on hemodialysis

Background: Central venous stenosis is a common complication in hemodialysis patients, often caused by multiple long-term catheter use. This retrospective observational study evaluated the efficacy of balloon angioplasty and stent placement in treating central venous stenosis secondary to hemodialysis catheter use. Methods: A retrospective observational study was conducted at the Hospital General de México Dr. Eduardo Liceaga, analyzing clinical records of 16 chronic kidney disease patients diagnosed with central venous stenosis who underwent endovascular surgery between January 2022 and August 2024. The study evaluated demographic characteristics, comorbidities, stenosis location, and technical success. Statistical analysis included descriptive measures, Shapiro-Wilk test for normality, and paired Student's t-test (α=0.05) to compare pre- and post-angioplasty venous diameters. Results: The mean age of patients was 44.6±13.5 years, with a slight female predominance. The most common stenosis location was the right subclavian vein (31.2%), followed by the left brachiocephalic trunk (25%). Pre-procedure stenotic vessel diameter averaged 3.86±1.5 mm, increasing to 9.19±2.03 mm post-procedure. Statistical analysis showed a significant 138% increase in vessel diameter (p<0.001). Of the 16 procedures, 11 patients underwent successful angioplasty, with 37.5% requiring stent placement due to recoil greater than 30%. In 5 cases, crossing the occlusive lesion was not possible. Conclusions: The study demonstrated the effectiveness of balloon angioplasty and stent placement in treating central venous stenosis, with a statistically significant improvement in vascular diameter. However, further studies with long-term follow-up are needed to evaluate the durability of these results and optimize management of complex cases.

Clinical and genetic insights into ABCA12 variants in three Chinese families with ichthyosis: Genotype-phenotype correlation.

Autosomal recessive congenital ichthyosis (ARCI) comprises a series of non-syndromic ichthyoses. Pathogenic variants in several genes associated with ARCI have so far been identified. Notably, the variants in ABCA12 play a pivotal role in the pathology of ARCI. In this study, we report three Chinese families with compound heterozygous variants in the ABCA12 gene, including two novel variants and four reported variants. Clinical and genetic analyses were conducted to explore the genotype-phenotype correlation among the patients. Immunohistochemistry and transcriptome sequencing were utilized to assess the impact of pathogenic ABCA12 variants on skin homeostasis, revealing decreased levels of ABCA12 and claudin-1, alongside increased levels of involucrin and S100A8. In conclusion, our findings contribute to updating the genotype-phenotypic correlation and provide additional evidence for the long-term use of retinoic acid drugs in patients with causative ABCA12 variants.

Enhancing the Efficacy of Active Pharmaceutical Ingredients in Medicinal Plants through Nanoformulations: A Promising Field.

This article explores the emerging field of nanomedicine as a drug delivery system, aimed at enhancing the therapeutic efficacy of active pharmaceutical ingredients in medicinal plants. The traditional methods of applying medicinal plants present several limitations, such as low bioavailability, poor solubility, challenges in accurately controlling drug dosage, and inadequate targeting. Nanoformulations represent an innovative approach in drug preparation that employs nanotechnology to produce nanoscale particles or carriers, which are designed to overcome these limitations. Nanoformulations offer distinct advantages, significantly enhancing the solubility and bioavailability of drugs, particularly for the poorly soluble components of medicinal plants. These formulations effectively enhance solubility, thereby facilitating better absorption and utilization by the human body, which in turn improves drug efficacy. Furthermore, nanomedicine enables targeted drug delivery, ensuring precise administration to the lesion site and minimizing side effects on healthy tissues. Additionally, nanoformulations can regulate drug release rates, extend the duration of therapeutic action, and enhance the stability of treatment effects. However, nanoformulations present certain limitations and potential risks; their stability and safety require further investigation, particularly regarding the potential toxicity with long-term use. Nevertheless, nanomaterials demonstrate substantial potential in augmenting the efficacy of active pharmaceutical ingredients in medicinal plants, offering novel approaches and methodologies for their development and application.

B-295 Sensitive and Rapid Homogeneous Immunoassay for the Detection of Zolpidem and its Major Metabolite in Urine

Abstract Background Zolpidem, a schedule IV controlled substance under the Controlled Substances Act, is commonly known as Ambien and Ambien CR, a prescription only treatment for insomnia. Zolpidem is one of the most common prescribed sleep aids in the U.S. due to its rapid sedative effects. The recommended duration of treatment is between two days and four weeks, as long-term use of zolpidem increases the risk of habit formation. Addiction to zolpidem can cause severe side effects, including memory loss, delusion, and in extreme cases, fatal overdose. From 2005-2010, Zolpidem-related emergency room visits doubled, underscoring the need for accurate testing as zolpidem testing plays an important role in cases of misuse, diversion, and forensics. The sole commercially available homogeneous immunoassay for the detection of zolpidem in urine has a relatively high cutoff at 20 ng/mL and poor cross-reactivity (0.02%) to major metabolite zolpidem 4-carboxylic acid. ARK Diagnostics has developed the ARK™ Zolpidem Assay to detect zolpidem at a cutoff concentration of 10 ng/mL with high cross-reactivity to its metabolite, Zolpidem phenyl 4-carboxylic acid and no cross-reactivity to zaleplon and zopiclone at concentrations below 100,000 ng/mL. Methods The ARK™ Zolpidem Assay is a liquid stable homogeneous enzyme immunoassay, consisting of two reagents, with a cutoff concentration of 10 ng/mL and semi-quantitative range up to 40 ng/mL. Preliminary performance characterization for this assay was evaluated on the Beckman Coulter AU680 Automated Clinical Chemistry Analyzer. Precision, analytical recovery, specificity, Histogram Overlap Analysis of ±50% controls and the cutoff, and method comparison with LC-MS/MS were evaluated. Results In semi-quantitative mode, total precision ranged from 2.6 to 3.1% CV. Spiked recovery of zolpidem ranged from 88.6% (2.5 ng/mL) to 96.8% (10 ng/mL). The major metabolite, zolpidem phenyl-4-carboxylic acid, showed an approximate equivalence to the 10 ng/mL zolpidem cutoff at 30 ng/mL (33.3% cross-reactivity). Histogram overlap analysis showed no overlap between cutoff and control levels. Method correlation with LC-MS/MS using authentic urine samples showed an excellent agreement with a specificity of 100% and sensitivity of 100% (15 positives and 100 negatives). Conclusions The ARK™ Zolpidem Assay measures zolpidem and its major metabolite zolpidem phenyl-4-carboxylic acid in human urine with acceptable performance. The assay is sensitive, rapid, and applicable to a wide range of clinical chemistry analyzers.

Corneal endothelial density and morphology in long-term soft contact lens users in Japan: a retrospective cross-sectional study of 17,732 eyes

Purpose There is a lack of long-term and large-scale studies on the adverse effects of soft contact lenses (SCLs) on the corneal endothelia of Asian populations. Here, we aimed to examine the effects of long-term SCL use on corneal endothelial density and morphology. Materials and Methods This retrospective study involved consecutive patients at the Miyata Eye Hospital (Miyazaki, Japan), who had used SCLs for more than 1 year. Patients with ophthalmological disorders without refractive errors were excluded. The period of SCL use, SCL type, corneal endothelial cell density (ECD), appearance rate of hexagonal cells (HEX), and coefficient of variation of cells (CV) were analyzed. Results In total, 17,732 eyes of 8866 patients were included in the analysis (age, 26.0 ± 8.8 years). The mean period of SCL use was 6.3 ± 5.4 years. Multivariate regression analysis revealed that ECD and HEX were significantly negatively correlated with the period of SCL use, age, and sex (p < 0.001 for all). The CV was significantly positively correlated with the period of use (p < 0.001), sex (p = 0.002), and age (p < 0.001). Conclusions Corneal ECD, HEX, and CV were significantly associated with the period of SCL use in long-term users. It is essential to regularly check the corneal endothelium in patients with a history of long-term SCL use.

Mid-term results of popliteal-pedal inframalleolar vein bypasses in CLTI patients after previous failed tibial endovascular recanalization

Inframalleolar bypass still preserves its role in the modern endovascular era. Aim of this study was to evaluate the mid-term outcomes of "short" inframalleolar vein bypasses in patients with chronic limb-threatening ischemia (CLTI) after previous failed tibial endovascular recanalization. Between January 2015 and December 2021 107 CLTI patients in 3 Italian Departments of Vascular Surgery underwent "short" inframalleolar vein bypass after failed tibial endovascular recanalization. Early (30-day) and 3-year outcomes were evaluated in terms of survival, primary patency, primary assisted patency, secondary patency, and amputation-free survival. Univariate analysis of the perioperative factors affecting outcomes were performed by means of log-rank test. Associations of procedure variables were sought based on a multivariate Cox regression analysis. Distal anastomosis (inframalleolar) was mostly performed on dorsal pedis (64, 59.8%). At 30 days bypass occlusion was recorded in 5 cases (4.6%). Mean follow-up period was 20.5 ± 17.9 months. Estimated 3-year overall survival was 66.7%. Three-year estimates of primary patency, primary assisted patency, secondary patency, and amputation-free survival were 68.5%, 70.1%, 70.2%, and 76.7%, respectively. Multivariate analysis showed a negative association of insulin treatment with primary patency (HR 4.3, p = .04), primary assisted patency (HR 5.1, p = .02), and secondary patency (HR 5.1, p = .02). Negative association of long-term corticosteroid use was also found with primary patency (HR 7.8, p = .005), primary assisted patency (HR 8.7, p = .003), secondary patency (HR 8.7, p = .003), and amputation-free survival (HR 3.9, p = .05). "Short" vein bypasses to the foot arteries in CLTI patients yielded good mid-term overall patency, and limb salvage rates after a failed tibial endovascular recanalization. Insulin dependent diabetes mellitus, and long-term corticosteroid use seemed to affect the outcomes.

Biomechanical considerations of chemical structure and biosafety of current ceramic biomaterials for dentistry: review and outlook of the current state of the art.

Biomaterial refers to any material, non-pharmaceutical or combination of substances of synthetic or natural origin used for any period independently or as part of a system for the purpose of healing, assisting the growth or replacement of tissues, organs or functions of the body. It is an unsustainable material that interacts with biological systems. Before being produced a biomaterial goes through a sequence of steps, which includes: 1) the definition of the problem that the material will be called to solve (treatment, replacement of the instrument, aesthetic reasons); 2) design of the device, composition and control of materials (mechanical properties, toxicity, biological response, corrosion resistance, interaction with proteins, cells and tissues), manufacture, sterilization and standardization; 3) control of the device (in experimental animals, in vitro) clinical studies, studies; and 4) monitor its long-term use in vivo, in vitro and in patients. Research for ceramic materials is evolving and because they can be porous or glassy, they find applications in medicine and biotechnology, as they can be used as fillers, covering materials and scaffolds. Therefore, ceramic biomaterials are widely used not only in the field of orthopedic and maxillofacial surgery but also in dentistry as for dental prostheses. Materials monitoring technologies allow us to monitor the three-dimensional development in space, as well as imperfections or micro-cracks in the ceramic.

Continuous Subcutaneous Foslevodopa-Foscarbidopa in Parkinson's Disease: A Mini-Review of Current Scope and Future Outlook.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, primarily because of the impairment of dopaminergic neurons. Long-term use of levodopa, the standard PD treatment, often results in fluctuating therapeutic effects and dyskinesia, necessitating alternative therapies. This review aims to synthesize current insights and clinical experiences with foslevodopa-foscarbidopa, focusing on its pharmacokinetics, efficacy, and safety profile, to evaluate its potential in transforming PD therapy. A systematic literature search was conducted up to November 2023 using databases PubMed, Web of Science, and Cochrane Library. The search yielded eight eligible articles, including pharmacological studies, case reports, observational studies, and controlled trials. No language restrictions were applied. Foslevodopa and foscarbidopa, as prodrugs of levodopa and carbidopa, exhibited excellent chemical stability and solubility, facilitating continuous subcutaneous infusion. Clinical trials demonstrated that these prodrugs maintain stable levodopa levels, thereby addressing the limitations of oral levodopa therapy. Phase 1 and 3 studies indicated significant improvements in motor function and quality of life in advanced PD patients. However, a higher incidence of treatment-emergent adverse events, mainly infusion site reactions, was observed compared to oral therapies. Foslevodopa-foscarbidopa emerges as a promising alternative for advanced PD treatment, offering sustained symptom control. Its efficacy in managing motor fluctuations and dyskinesia makes it a viable option in the PD therapeutic spectrum. Future research should focus on long-term safety, economic impact, and broader accessibility. Foslevodopa-foscarbidopa is now commercially distributed in many countries in Europe and in Japan.

Silver nanoparticle-decorated reduced graphene oxide/ nanocrystalline titanium metal-organic frameworks composite membranes with enhanced nanofiltration performance and photocatalytic ability

Nanofiltration (NF) has garnered significant attention for removing persistent dyes from industrial wastewater. However, limited membrane separation efficiency and performance deterioration due to membrane fouling are the primary challenges hindering the broader application of NF technology. Herein, we developed high-performance silver nanoparticle-coated reduced graphene oxide/nanocrystalline MIL125(Ti) composite NF membranes (nAg-rGO/n-MIL), which feature self-cleaning capabilities through photocatalytic activity. This was achieved by intercalating nanocrystalline MIL-125(Ti) (n-MIL) metal-organic frameworks between graphene oxide (GO) nanosheets, followed by reducing the GO nanosheets and decorating them with silver nanoparticles (nAg) via UV exposure. The nAg-rGO/n-MIL demonstrated high water permeability (21.7 LMH/bar) and achieved excellent removal efficiencies for targeting dyes with relatively small molecular weights ranging from 300 to 500Da. Additionally, when operated in an NF system equipped with a UV side-emitting optical fiber, the nAg-rGO/n-MIL exhibited significantly reduced water flux decline and enhanced removal efficiencies, achieving up to 97.5% for methylene blue. Moreover, the nAg-rGO/n-MIL demonstrated high durability under the tested operating conditions, indicating its potential for long-term use in industrial applications. The GO composite membrane, with nanosized MOF-intercalated nanochannels and photocatalytic activity via nAg decoration and GO reduction, offers a promising solution to performance limitations and fouling issues in current nanofiltration membranes.

Use of Lasers in the Nonsurgical Treatment of Peri-Implantitis: A Systematic Review of the Literature.

Peri-implantitis is an infectious disease that causes inflammation of the tissue surrounding an implant. The aim of this systematic review of the literature is to assess the effect of the use of lasers in the nonsurgical treatment of peri-implantitis in order to estimate its benefits compared with conventional therapies. The review's protocol has been registered on PROSPERO international prospective register. The research strategy was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria were as follows: in vivo studies, written in English, measurements of clinical parameters, minimum follow-up at 6 months and with nonsurgical control group, studies about photodynamic therapy, randomized clinical trial, and clinical trial. Electronic (on PubMed, Cochrane, Latin American and Caribbean Health Sciences Literature, and Report Evidence-based Practice Centers databases) and manual searches (in articles' references) were conducted until July 2021. Risk of bias was assessed for each reference thanks to the Cochrane Collaboration's tool. A total of 12 randomized clinical trials, with a high level of evidence, were selected and investigated in this systematic review. A table summarizes data extracted from these articles. It appears that the parameters improve favorably by using lasers, but without any significant difference. In accordance with the analysis of studies, our results show that laser therapy with specific characteristics allows to obtain beneficial therapeutic effects on wound healing in the short and the medium-term concerning the clinical parameters in the nonsurgical treatment of peri-implantitis. Concerning its long-term usefulness, it has yet to be confirmed. However, its benefits remains limited since the results agree that the effects of the laser are similar to those obtained by using conventional therapy.

Patterns of Corticosteroid Prescriptions among Patients at Community Pharmacies in Lahore, Pakistan

Background: Corticosteroids are a class of steroid hormones produced by the adrenal gland and are used to treat many diseases, including autoimmune diseases and inflammatory diseases. Besides their role in many diseases, long-term use, misuse, and overuse cause side effects including hypertension, diabetes mellitus, and osteoporosis. Objective: The aim of current study is to evaluate the prescription pattern of corticosteroids in different community pharmacies, among patients, in Lahore. Methods: The cross-sectional stratified convenient study performed using a validated questionnaire to analyse the prescription pattern of corticosteroids in patients at different community pharmacies in Lahore. Total 92 patients are participating in this study. Results: A total of 92 patients take part in the study. In this research 67.4% females are participated. The average age of patients is above 30 years. Asthma is the most common reason for corticosteroids administration (19.6%) followed by rheumatoid arthritis (12.0%) whereas in inflammatory bowel disease they are least prescribed (1.1%). Prednisolone is the most prescribed drug (33.7%) and Oral route is the frequently given route. Conclusion: Our data shows that the prescription pattern of corticosteroid must be improved. Health care providers should pay attention to counseling of patients and guide them about dose tapering to avoid adverse effects.

Preparation and Characterization of Isradipine as Surfactant-Free Dry Emulsion

Background: Oral anticoagulation medication, warfarin, and non-vitamin K antagonist oral anticoagulants (NOAC) may require long-term use which may affect patients’ satisfaction with their treatment and their quality of life (QOL). Objective: To compare the quality of life and treatment satisfaction among groups of patients using different anticoagulant therapies (warfarin and NOAC). Methods: A cross-sectional study was performed at Ibn Al-Bitar Hospital for cardiac surgery in Baghdad in the period from December 2022 to May 2023. The study population included a convenient sample of patients receiving either warfarin or non-vitamin k antagonist oral anticoagulants treatment. The Arabic version of the short form 12 (SF-12) questionnaire and the Anti-Coagulant Treatment Satisfaction Scale (ACTS) questionnaire were used to assess the quality of life and satisfaction with treatment respectively. Results: The study included 181 patients in total. The mean physical and mental quality of life scores for study participants were 42.3±9.92 and 52.6±10.36 respectively. There was no significant difference in the QOL between patients taking warfarin and those on non-vitamin k antagonist oral anticoagulant treatment. The mean total satisfaction score was 65.4±6.73. Patients receiving non-vitamin k antagonist oral anticoagulants had significantly higher satisfaction compared to those receiving warfarin. The physical score correlated significantly with gender, educational level, employment status, number of chronic medications, and number of chronic diseases. The total satisfaction score correlated significantly with gender, number of chronic medications, number of side effects, and duration of anticoagulation. There was a significant correlation between the QOL and treatment satisfaction. Conclusion: Treatment with non-vitamin K antagonist oral anticoagulants showed comparable QOL and higher treatment satisfaction than that of warfarin. Better treatment satisfaction can improve patients’ QOL which may ultimately enhance their adherence to treatment.

Preparation and properties of ZTA/alloyed high manganese steel composites

In the long-term use of high manganese steels, it is not desirable to achieve wear resistance by austenite deformation strengthening alone. The wear resistance of high manganese steel is much lower than that of ordinary wear-resistant steel under medium and low stress conditions. Improving the instability of wear resistance caused by defects in high manganese steels is an important problem to be solved in current industrial production. In this study, a new type of high manganese alloy with high hardness and high wear resistance was prepared by multi-alloying with Cr-W-Mo elements on the basis of 20Mn1.2C. ZTA ceramic particles reinforced high manganese steel composites were prepared by selecting high manganese steel materials with excellent mechanical properties as the metal matrix of ceramic reinforced metal matrix composites. The Cr-W-Mo multi-alloyed high manganese alloys are mainly composed of a mixed austenite and ferrite matrix, M3C-type cementite and M6C-type carbides. The Cr2W6Mo6 sample has the best overall mechanical properties. Its hardness reached 49.8 HRC, which is 1.20 times higher than that of the Cr2 sample. The mass loss was 0.2571 g, which is 79.92% of the Cr16 sample (0.3217 g). The ZTA ceramic particles were well composited with the alloyed high manganese steel matrix, and the thickness of the interfacial layer was 20-30 μm, with the formation of Mn2AlO4 and (Fe, Mn)2SiO4, and (Al, Cr)2O3 in the interfacial layer. The best abrasion resistance was obtained at a ZTA content of 40 vol.%. The mass loss was 0.1669 g, which is 51.88% of the Cr16 material (0.3217 g).

The Role of Cardio-Renal Inflammation in Deciding the Fate of the Arteriovenous Fistula in Haemodialysis Therapy.

Vascular access is an indispensable component of haemodialysis therapy for end-stage kidney disease patients. The arteriovenous fistula (AVF) is most common, but importantly, two-year failure rates are greater than fifty percent. AVF failure can occur due to a lack of suitable vascular remodelling, and inappropriate inflammation preventing maturation, or alternatively neointimal hyperplasia and vascular stenosis preventing long-term use. A comprehensive mechanistic understanding of these processes is still lacking, but recent studies highlight an essential role for inflammation from uraemia and the AVF itself. Inflammation affects each cell in the cascade of AVF failure, the endothelium, the infiltrating immune cells, and the vascular smooth muscle cells. This review examines the role of inflammation in each cell step by step and the influence on AVF failure. Inflammation resulting in AVF failure occurs initially via changes in endothelial cell activation, permeability, and vasoprotective chemokine secretion. Resultingly, immune cells can extravasate into the subendothelial space to release inflammatory cytokines and cause other deleterious changes to the microenvironment. Finally, all these changes modify vascular smooth muscle cell function, resulting in excessive and unchecked hyperplasia and proliferation, eventually leading to stenosis and the failure of the AVF. Finally, the emerging therapeutic options based off these findings are discussed, including mesenchymal stem cells, small-molecule inhibitors, and far-infrared therapies. Recent years have clearly demonstrated a vital role for inflammation in deciding the fate of the AVF, and future works must be centred on this to develop therapies for a hitherto unacceptably underserved patient population.

Long-term opioid prescribing and the incidence of opioid-related hospitalizations or emergency department visits among patients with metastatic cancer.

200 Background: Many patients with metastatic cancer experience cancer-related pain which is commonly managed using opioids. Although opioids are an effective tool for cancer pain management, their use can result in adverse effects which may be related to long-term use and are understudied in this population. Therefore, we aimed to describe long-term opioid prescribing (LTOP) practices among patients with metastatic cancer and investigate the incidence of opioid-related hospitalizations and emergency department (ED) visits among recipients of long-term prescribing. Methods: This retrospective cohort study used population-based data from Alberta, Canada to identify patients diagnosed with stage IV cancers between 2004-2017 who had at least 1-year of follow-up and were opioid naïve at diagnosis. LTOP was defined as receipt of a ≥90-day supply of opioids with less than a 30-day gap in supply within a 180-day period. Prescribing practices were characterized according to timing (early vs. end-of-life [EoL] onset), morphine equivalent dose, duration, and concurrent medication use. The EoL phase of disease was defined as the year preceding death. The incidence rate of opioid-related encounters was compared between different characteristics of LTOP. Results: The study included a total of 10927 patients, 2521 (23%) of whom received long-term opioid prescribing after diagnosis. LTOP became more common as patients approached EoL, with most patients (53%) having LTOP initiated only within their last year of life. 85 patients (3.4%) experienced an opioid-related hospitalization or ED visit after initiation of LTOP, with an incidence rate of 2.36 (95% CI 1.92, 2.86) encounters per 100 person-years. Higher opioid dosage and concurrent prescribing of anxiolytics, benzodiazepines, antidepressants, and neuroleptic medications were significantly associated with a higher incidence of opioid-related encounters. Conclusions: Long-term opioid prescribing is commonly experienced by patients living with metastatic cancer as a chronic disease. The concurrent use of psychoactive drugs during LTOP was associated with experiencing opioid-related hospitalizations/ED visits.