Adjunctive Medications Research Articles

Mental Health Polypharmacy in "Non-Coded" Primary Care Patients: The Effect of Deprescribing.

Background: Mental health (MH) polypharmacy, defined as prescribing multiple mental health medications for the same condition, presents significant challenges in clinical practice. With varying prevalence rates and an increasing trend, particularly in the UK, this deprescribing prospective quality improvement project aimed to address the complexities and risks associated with MH polypharmacy. Patients and Methods: A large primary care centre in London was selected for this project. Electronic records of 667 patients (non-coded in mental health lists) were analysed as a result of the absence of a Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) for mental health. Seventy-two non-coded patients exhibiting "same-class" as well as "adjunctive" and "augmentation" polypharmacy were identified. Their demographic and health data, including MH diagnoses, physical status, and lifestyle habits, were evaluated. This deprescribing prospective project included 68 patients and employed a model inspired by the Plan-Do-Study-Act (PDSA) cycle, focusing on reducing psychotropic, adjunctive, and augmentative medications while monitoring mental health control through face-to-face consultations using the Patient Health Questionnaire-9 (PHQ-9) and Generalised Anxiety Disorder Assessment-7 (GAD-7) scores, alongside physical health parameters. Results: The project revealed a significant decrease in the average number of psychotropic and adjunct medications from initial consultations to the end of the 18-month period. Additionally, a marked reduction in reported side effects and drug interactions was observed. Improvements in mental health control, as evidenced by PHQ-9 and GAD-7 scores, were noted. Physical health parameters, including BMI, blood pressure, heart rate, HbA1c, and cholesterol levels, also showed significant improvements. Educational initiatives for patients and clinicians were successfully implemented, contributing to these positive outcomes. Discussion: The project faced challenges like balancing medication reduction with mental health stability, patient apprehension, and the absence of standardised protocols. However, the successful reduction in medication numbers and the improvement in health outcomes highlight the effectiveness of the model. This project underscores the necessity of a tailored approach to MH polypharmacy, emphasising continuous education, clinical titration, and adherence to guidelines. Future research is needed to develop clear guidelines for medication combination in mental health care and to understand the long-term effects of polypharmacy in mental health populations. Conclusions: This project demonstrates the potential for significant improvements in the management of MH polypharmacy. By carefully managing medication reductions and employing a comprehensive care approach, including patient education and clinician training, the project achieved improvements in both mental and physical health outcomes. These findings suggest a promising direction for future practices in MH polypharmacy management.

Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer’s disease

ABSTRACT Background Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties. Objective This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients. Methods This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester. Results The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalasebefore silymarin = 9.29 ± 7.02 vs Catalaseafter silymarin = 5.32 ± 2.97, p = 0.007 and MDAbefore silymarin = 4.29 ± 1.90 vs MDAafter silymarin = 1.66 ± 0.84, p < 0.001) while MMSE increased notably (MMSEbefore silymarin = 10.39 ± 6.42 vs MMSEafter silymarin = 13.37 ± 6.81, p < 0.001). Conclusion Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD.

Low dose lofexidine for medically directed outpatient opioid tapering in adults with chronic pain: a prospective case series

BackgroundIn adults with chronic pain, mild-to-moderate withdrawal symptoms during medically directed opioid tapering in the outpatient setting may not be accompanied by hypertension or tachycardia. This clinical scenario could limit the use of lofexidine at dosages reported in clinical trials of opioid withdrawal precipitated by abrupt opioid discontinuation. Thus, the primary aim of this prospective case series is to describe the use of low dose lofexidine for opioid withdrawal in patients with chronic pain undergoing medically directed opioid tapering in an outpatient setting.MethodsSix patients (white 5, Latino 1) admitted to an outpatient interdisciplinary pain rehabilitation program met inclusion and exclusion criteria. Patients self-selected to undergo medically directed opioid tapering, and the medication the patients were prescribed upon admission was used in the taper schedule. Upon initiation of the opioid taper, patients received 0.18 mg of lofexidine every 6 hours. ResultsFive of the six patients were women, and the median morphine milligram equivalents at baseline were 36.9. The median taper duration was 15 days, and the median duration of lofexidine administration was 14 days. Withdrawal scores were mild throughout the taper in four patients, and two patients with fibromyalgia experienced single episodes of moderately severe withdrawal symptoms at the median morphine milligram equivalent midpoint of the taper. No hypotension or sustained bradycardia were observed, and no adverse effects related to lofexidine were reported.ConclusionThe observations from this prospective case series suggest that low-dose lofexidine may be a feasible adjunct medication to attenuate withdrawal symptoms in adults with chronic pain undergoing outpatient opioid tapering.

Edaravone alleviated allergic airway inflammation by inhibiting oxidative stress and endoplasmic reticulum stress

Oxidative stress and endoplasmic reticulum stress (ERS) was associated with the development of asthma. Edaravone (EDA) plays a classical role to prevent the occurrence and development of oxidative stress-related diseases. Herein, we investigated the involvement and signaling pathway of EDA in asthma, with particular emphasis on its impact on type 2 innate lymphoid cells (ILC2) and CD4+T cells, and then further elucidated whether EDA could inhibit house dust mite (HDM)-induced allergic asthma by affecting oxidative stress and ERS. Mice received intraperitoneally injection of EDA (10 mg/kg, 30 mg/kg), dexamethasone (DEX) and N-acetylcysteine (NAC), with the latter two used as positive control drugs. DEX and high dose of EDA showed better therapeutic effects in alleviating airway inflammation and mucus secretion in mice, along with decreasing eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) than NAC. Further, the protein levels of IL-33 in lung tissues were inhibited by EDA, leading to reduced activation of ILC2s in the lung. EDA treatment alleviated the activation of CD4+ T cells in lung tissues of HDM-induced asthmatic mice and reduced Th2 cytokine secretion in BALF. ERS-related markers (p-eIF2α, IRE1α, CHOP, GRP78) were decreased after treatment of EDA compared to HDM group. Malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), and superoxide dismutase (SOD) were detected to evaluate the oxidant stress in lung tissues. EDA showed a protective effect against oxidant stress. In conclusion, our findings demonstrated that EDA could suppress allergic airway inflammation by inhibiting oxidative stress and ERS, suggesting to serve as an adjunct medication for asthma in the future.

Opioid crisis in the USA: what are implications for Switzerland?

Warnings in Europe signal a rise in illicitly-manufactured fentanyl and other high potency synthetic opioids which could destabilize drug markets, strain health systems, and escalate harms of substance use and death. Here, we provide an overview of fentanyl in North America, drawing implications for Switzerland. Fentanyl withdrawal starts sooner, is more severe, and has worse anxiety and pain. Clinical care includes aggressive use of full agonist opioids, opioid agonist therapies (OAT) and adjunctive medications for acute withdrawal, and a need for low-threshold, readily accessible OAT to engage patients and mitigate harms. The US experience suggests the importance of widespread naloxone distribution, peer-based initiatives, early warning systems, and partnerships across patient-groups, healthcare systems, and public health.

A Prospective Post-Marketing Observational Study of Brivaracetam in People With Focal Epilepsy.

We evaluated the effectiveness and tolerability of brivaracetam (BRV), an adjunctive antiseizure medication, as a treatment for focal epilepsy in adults. In this prospective study, we enrolled 51 participants from 3 sites across Canada. At 6 months, 68% (26/38) of participants were still taking BRV, among whom 35% (8/23) attained seizure freedom and 48% (11/23) saw their seizure frequency reduced by over 50%. We did not measure any significant change in irritability, quality of life, depression, and anxiety while treated with BRV. Our findings suggest BRV is effective in reducing seizure frequency among adults with focal epilepsy.

Novel Techniques for Musculoskeletal Pain Management after Orthopedic Surgical Procedures: A Systematic Review.

Effective postoperative pain management is critical for recovery after orthopedic surgery, but often remains inadequate despite multimodal analgesia. This systematic review synthesizes evidence on innovative modalities for enhancing pain control following major orthopedic procedures. Fifteen randomized controlled trials and comparative studies evaluating peripheral nerve blocks, local anesthetic infiltration, cryotherapy, transcutaneous electrical stimulation, adjunct medications, and other techniques are included. Thematic analysis reveals that peripheral nerve blocks and local anesthetic infiltration consistently demonstrate reduced pain scores, opioid consumption, and side effects versus conventional analgesia alone. Oral multimodal medications also show promise as part of opioid-sparing regimens. Adjunctive approaches like cryotherapy, music, and dexmedetomidine require further research to optimize protocols. Despite promising innovations, critical knowledge gaps persist regarding comparative effectiveness, optimal interventions and dosing, combination strategies, cost-effectiveness, and implementation. High-quality randomized controlled trials using standardized protocols are essential to guide the translation of enhanced multimodal regimens into clinical practice. This review provides a framework for pursuing research priorities and advancing evidence-based postoperative pain management across orthopedic surgeries.

A Retrospective Evaluation of Adjunctive Phenobarbital vs. Benzodiazepine Alone for the Treatment of Moderate Alcohol Withdrawal in the Emergency Department

BackgroundPhenobarbital has been used in the emergency department (ED) as both a primary and adjunctive medication for alcohol withdrawal, but previous studies evaluating its impact on patient outcomes are limited by heterogenous symptom severity. ObjectivesWe compared the clinical outcomes of ED patients with moderate alcohol withdrawal who received phenobarbital, with or without benzodiazepines, with patients who received benzodiazepine treatment alone. MethodsThis is a retrospective cohort study conducted at a single academic medical center utilizing chart review of ED patients with moderate alcohol withdrawal between 2015 and 2020. Patient encounters were classified into two treatment categories based on medication treatment: phenobarbital alone or in combination with benzodiazepines vs. benzodiazepines alone. Chi-square test or Fisher's exact was used to analyze categorical variables and the Student's t-test for continuous data. ResultsAmong the 287 encounters that met inclusion criteria, 100 received phenobarbital, compared with 187 that received benzodiazepines alone. Patients who received phenobarbital were provided significantly more lorazepam equivalents. There was a significant difference in the percentage of patient encounters that required admission to the hospital in the phenobarbital cohort compared with the benzodiazepine cohort (75% vs. 43.3%, p < 0.001). However, there was no difference in admission level of care to the floor (51.2% vs. 52.0%), stepdown (33.8% vs. 28%), or intensive care unit (15% vs. 20%), respectively. ConclusionsPatients who received phenobarbital for moderate alcohol withdrawal were more likely to be admitted to the hospital, but there was no difference in admission level of care when compared with patients who received benzodiazepines alone. Patients who received phenobarbital were provided greater lorazepam equivalents in the ED.

Exploring Indigenous Medicinal Plants for Managing Diabetes Mellitus in Uganda: Ethnobotanical Insights, Pharmacotherapeutic Strategies, and National Development Alignment

Diabetes Mellitus (DM) stands as a pressing global health concern, particularly in Uganda, where its prevalence mirrors global trends driven by urbanization, lifestyle changes, and genetic predispositions. This study delves into Uganda's rich heritage of medicinal plants, investigating their use in managing DM within local communities. A comprehensive review was conducted, exploring the epidemiology and pathophysiology of DM in Uganda, emphasizing genetic predispositions, lifestyle factors, and the healthcare landscape. The study unveils indigenous medicinal plants employed for DM management, detailing their usage, preparation, and potential therapeutic properties. Additionally, the pharmacotherapeutic landscape for DM management, encompassing oral hypoglycemic agents, injectable therapies, and adjunctive medications, is scrutinized in alignment with Uganda's healthcare policies. Moreover, the study aligns strategies for DM management with Uganda's National Development Plan (NDP), outlining an integrative approach for healthcare infrastructure, primary care strengthening, sustainable financing, health information systems, and collaborative partnerships. Keywords: Diabetes Mellitus, Medicinal Plants, Uganda, Ethnobotany, Pharmacological Evaluation, National Development Plan, Integrated Healthcare Strategies

Exploring Indigenous Medicinal Plants for Managing Diabetes Mellitus in Uganda: Ethnobotanical Insights, Pharmacotherapeutic Strategies, and National Development Alignment

Diabetes Mellitus (DM) stands as a pressing global health concern, particularly in Uganda, where its prevalence mirrors global trends driven by urbanization, lifestyle changes, and genetic predispositions. This study delves into Uganda's rich heritage of medicinal plants, investigating their use in managing DM within local communities. A comprehensive review was conducted, exploring the epidemiology and pathophysiology of DM in Uganda, emphasizing genetic predispositions, lifestyle factors, and the healthcare landscape. The study unveils indigenous medicinal plants employed for DM management, detailing their usage, preparation, and potential therapeutic properties. Additionally, the pharmacotherapeutic landscape for DM management, encompassing oral hypoglycemic agents, injectable therapies, and adjunctive medications, is scrutinized in alignment with Uganda's healthcare policies. Moreover, the study aligns strategies for DM management with Uganda's National Development Plan (NDP), outlining an integrative approach for healthcare infrastructure, primary care strengthening, sustainable financing, health information systems, and collaborative partnerships. Keywords: Diabetes Mellitus, Medicinal Plants, Uganda, Ethnobotany, Pharmacological Evaluation, National Development Plan, Integrated Healthcare Strategies

OR01-01 Oral, Once-daily, Paltusotine (Non-peptide Selective Somatostatin Receptor Subtype 2 Agonist) Therapy In Patients With Acromegaly Is Associated With Long-term Biochemical And Symptom Control And Is Preferred Over Injectable Somatostatin-Receptor Ligands

Abstract Disclosure: M.R. Gadelha: Advisory Board Member; Self; Crinetics Pharmaceuticals, Ipsen, Novo Nordisk, and Recordati Rare Diseases. Research Investigator; Self; Crinetics Pharmaceuticals and Recordati Rare Diseases. Speaker; Self; Crinetics Pharmaceuticals, Ipsen, Novo Nordisk, and Recordati Rare Diseases. H.S. Randeva: None. M.B. Gordon: Consulting Fee; Self; Crinetics Pharmaceuticals, HRA Pharma, Novo Nordisk, and Recordati Rare Diseases. Grant Recipient; Self; Ascendis, Camurus, Chiasma, Corcept, Crinetics, Ipsen, Novartis, Novo Nordisk, Opko, Pfizer, and Strongbridge. M. Doknic: Advisory Board Member; Self; Pfizer in CEE region. Research Investigator; Self; Crinetics Pharmaceuticals, Pfizer, Camurus, Ascendis, Opko, Ipsen, and Teva. Speaker; Self; Pfizer, Novartis, Novo Nordisk, Sandoz, and Merck. E. Mezosi: Research Investigator; Self; Crinetics Pharmaceuticals. M. Toth: Consulting Fee; Self; Ipsen, Novartis, Pfizer, and Recordati Rare Diseases. Research Investigator; Self; Crinetics Pharmaceuticals. C.L. Boguszewski: Consulting Fee; Self; Novo Nordisk. Research Investigator; Self; Crinetics Pharmaceuticals and Recordati Rare Diseases. Speaker; Self; Ipsen and Recordati Rare Diseases. C.T. Ferrara-Cook: Employee; Self; Crinetics Pharmaceuticals. A. Casagrande: Employee; Self; Crinetics Pharmaceuticals. A. Krasner: Employee; Self; Crinetics Pharmaceuticals. Paltusotine is an investigational oral, once-daily, non-peptide, SST2 agonist in development for the treatment of acromegaly and neuroendocrine tumors. Interim analysis results from patients with acromegaly treated with paltusotine for up to 2 years in ACROBAT Advance (NCT04261712), an ongoing, 4-year, single-arm, open-label extension study, are reported here. Patients who completed ACROBAT Edge (NCT03789656) or Evolve (NCT03792555) phase 2 parent studies were eligible to enroll in Advance. In Edge, patients were either sub-optimally controlled on injectable somatostatin-receptor ligand (iSRL; octreotide or lanreotide) therapy alone or in combination with cabergoline; or required combination therapy or pasireotide to achieve normal IGF-I levels at baseline. Evolve enrolled patients who had normal IGF-I levels on iSRL monotherapy at baseline. In Advance, adjunctive medication with cabergoline or pegvisomant was allowed in patients who had not achieved normal IGF-1 levels on maximum dose of paltusotine (40 mg). Serum IGF-I levels were measured using Immunodiagnostic Systems iSYS immunoassay. Symptoms were assessed using the Acromegaly Symptom Diary (ASD; score range, 0-70; higher numbers indicate greater symptom burden), which was developed based on FDA recommendations for patient-reported outcome tools. Patient treatment preference was also evaluated. Forty-three patients were enrolled in Advance (Edge, n=32; Evolve, n=11; 88% of eligible patients). At baseline on iSRL, mean (SD) age was 53.0 (11.6) years, 56% were females, 86% had previous pituitary surgery, and none had radiotherapy. Median (IQR) IGF-I levels remained stable: baseline on iSRL, 1.15x ULN (0.84, 1.46; n=43); in Advance, Week 51 1.08x ULN (0.87, 1.26; n=37), Week 77 1.01x ULN (0.85, 1.28; n=27), and Week 103 1.10x ULN (0.96, 1.45; n=10). Among patients receiving adjunctive medication in Advance, 94% were from the Edge study. Acromegaly symptoms were stably controlled: median (IQR) ASD scores at baseline on iSRL, 8.57 (3.57, 20.14; n=21) and, in Advance at Week 77, 8.0 (5.0, 18.0; n=14). At Week 52, 32 (88.9%) of the 36 respondents preferred once-daily oral paltusotine, 2 (5.6%) preferred previous injections, and 2 (5.6%) had no preference. The most common treatment-emergent adverse events (TEAEs) reported were headache (30.2%), arthralgia (25.6%), and fatigue (18.6%). No serious drug-related TEAEs were reported. Of the 6 patients who discontinued the study, 1 (2.3%) was due to a TEAE (headache). Glycemic control, as measured by HbA1c, was stable during paltusotine treatment. In conclusion, with up to 2 years of follow-up in patients with acromegaly, once-daily oral paltusotine treatment was well-tolerated, associated with stable IGF-I and symptom control relative to that achieved by iSRLs, and was preferred over injected therapy. Support: Crinetics Pharmaceuticals. Presentation: Thursday, June 15, 2023

Dexmedetomidine use for patients in palliative care with intractable pain and delirium: A retrospective study.

Patients seen by the palliative care team often have difficult and intractable symptoms. The current standard of practice to manage these symptoms is the deeply sedating midazolam continuous subcutaneous infusion for patients who are expected to expire within hours to days. Dexmedetomidine provides sedation but lacks evidence in palliative care use. This study describes continuous subcutaneous infusion of dexmedetomidine's effect on refractory pain and delirium. Retrospective, observational chart review and conducted in accordance with SQUIRE (quality improvement study). Twenty adult patients (18 years of age or older) with metastatic cancer disease admitted to three palliative complex care units of Fraser Health who received continuous subcutaneous infusion of dexmedetomidine between January 2017 to August 31, 2019. Average length of dexmedetomidine use was 9 days (1/3 length of stay). Eight of the 13 patients with pain symptoms exhibited an overall decline in pain. Four of the 6 patients with delirium had an initial decrease in delirium, but it did not last beyond the first day. Despite progressive clinical deterioration, adjunctive medications decreased or remained the same for 53% of as needed medications and 65% for regularly scheduled medications. Forty-five percent of patients had ≥50% days of rousable sedation. Hypotension occurred in 85% of patients. Dexmedetomidine provided benefit in managing intractable pain while allowing patients to remain rousable, but only had a short effect on delirium symptoms.

Improving Outcomes in Infants With Neonatal Abstinence Syndrome With the Eat, Sleep, Console Method.

Neonatal abstinence syndrome (NAS) is a significant public health concern. A quality improvement project was executed in a neonatal intensive care unit at a large urban hospital. The aim was to address the prolonged hospitalization of infants and exposure to medications to treat NAS. The goal was to determine whether the eat, sleep, console (ESC) method decreases the length of stay (LOS) and morphine usage when compared with the Finnegan Neonatal Abstinence Scoring System (FNASS). The inclusion criteria were 36 weeks' or longer gestation and exposure to opiates in utero. The FNASS method was replaced by the ESC method with a refocus on nonpharmacologic care. Data were collected for 6 months during implementation of the ESC method and compared with the 6 months prior to implementation. The results of the project include: the average LOS decreased from 25.9 days to 13.7 days, a 47% reduction; the rate of scheduled morphine initiation decreased from 58% to 7%, an 88% reduction; as-needed morphine initiation decreased from 33% to 7%, a 79% reduction; and the rate of adjunctive medication initiation decreased from 17% to 0%, a 100% reduction. The outcomes of LOS and rate of morphine usage were significantly improved when using the ESC method when compared with the FNASS at this facility. The results support future implications including expanding the ESC program to the well newborn population at this facility and other similar units. Further research needs to be done on long-term neurodevelopmental outcomes.

Patients' Preferences for Adjunctive Parkinson's Disease Treatments: A Discrete-Choice Experiment.

Several adjunctive medications are available to reduce OFF time between levodopa/carbidopa (LD/CD) doses for people with Parkinson's disease (PD). To explore how individuals with PD balance benefits and burdens when considering adjunctive medications. US adults (30-83 years) with self-reported PD, currently treated with LD/CD, who experienced OFF episodes were recruited through the Fox Insight study to complete a discrete-choice experiment survey. Respondents selected among experimentally designed profiles for hypothetical adjunctive PD treatments that varied in efficacy (additional ON time), potential adverse effects (troublesome dyskinesia, risk of diarrhea, risk of change in bodily fluid color), and dosing frequency or the option "No additional medicine". Data were analyzed with random-parameters logit models. Respondents (N=480) would require ≥60 additional minutes of daily ON time to accept either a 40% risk of change in bodily fluid color or 10 additional minutes with troublesome dyskinesia daily. Respondents would require 40 additional minutes of daily ON time to accept a 10% risk of diarrhea and 22 additional minutes of daily ON time to switch from 1 additional pill each day to 1 pill with each LD/CD dose. On average, respondents preferred adjunctive PD medication over no additional medication. Results predicted that 59.1% of respondents would select a hypothetical treatment profile similar to opicapone, followed by no additional medication (27.5%) and a hypothetical treatment profile similar to entacapone (13.4%). The data collected were based on responses to hypothetical choice profiles in the survey questions. The attributes and levels selected for this study were intended to reflect the characteristics of opicapone and entacapone; attributes associated with other adjunctive therapies were not evaluated. Patients with PD expressed interest in adjunctive treatment to increase ON time and would accept reduced ON time to avoid adverse effects.

Are anxiety and depression risk factors for poor medication adherence in patients with an implantable cardioverter defibrillator?

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): TrygFonden The Lundbeck Foundation Patient@Home Background The implantable cardioverter defibrillator (ICD) is the preferred treatment for prevention of sudden cardiac death. Most patients with an ICD receive adjunctive medication to manage their heart disease. Poor medication adherence is a prognostic risk factor for cardiac patients and is linked to psychological factors, such as anxiety and depression. To our knowledge, no studies have examined if anxiety and/or depression at the time of ICD implantation is associated with medication adherence during the first year post-implantation. This information is important as it could help health care professionals identify and prevent poor medication adherence in ICD patients. Purpose To examine if anxiety and/or depression at ICD implantation are associated with medication adherence one-year post-implantation in ICD patients. Methods Secondary outcome analysis of the ACQUIRE-ICD, multisite, randomised controlled trial. Out of 478 patients with a first-time ICD or cardiac resynchronization therapy defibrillator (CRT-D) included in the trial, 433 patients (90.6%) took heart medication. Of these 433 patients, 322 patients (74.4%) were included in the analyses as they completed assessments at both baseline (implantation) and at 12 months post-implantation. Medication adherence was measured with the 8-item Morisky Medication Adherence Scale (MMAS), anxiety with Generalized Anxiety Disorder scale (GAD-7), and depression with Patient Health Questionnaire-9 (PHQ-9). Results The mean age of the participants was 60.2 ± 11.2, mainly male (83.9%). Medication adherence was generally medium to high at baseline [6.8% low adherence, 40.1% medium adherence, 53.1% high adherence, mean MMAS score: 7.31 ± 0.94), and at 12-months follow-up (8.1% low adherence, 37.3% medium adherence, 54.6% high adherence, mean MMAS score: 7.33 ± 0.93). In univariate analyses, depression scores at baseline were significantly negatively associated with medication adherence at 12-months post-implantation while adjusting for baseline MMAS scores (B = -0.02, 95% CI [- 0.04, -0.00], p = .04). This association remained statistically significant in the multivariate analysis also adjusting for gender, intervention group, heart failure severity (NYHA class I-II versus III-IV), and implantation center (B = -0.03, 95% CI [- 0.05, -0.00], p = .02). Anxiety scores at baseline were not significantly associated with medication adherence at 12-months post-implantation in neither the univariate (B = -0.02, 95% CI [- 0.04, 0.01], p = .14) nor adjusted analyses (B = -0.02, 95% CI [- 0.04, 0.00], p = .09). Conclusion Depression symptoms at the time of ICD implantation were associated with medication adherence at 12 months post-implantation with higher depression symptoms being associated with lower medication adherence. Anxiety symptoms were not predictive of medication adherence. Patients presenting with depressive symptoms at ICD implantation might be at risk for poor medication adherence.

Probiotics and autoprobiotics for treatment of Helicobacter pylori infection.

The article discusses various approaches for probiotic treatment of Helicobacter pylori (H. pylori) infection: Probiotics as an adjuvant treatment in the standard eradication therapy; probiotic strains as a monotherapy; and autoprobiotics as a monotherapy. Autoprobiotics refer to indigenous bifidobacteria, lactobacilli, or enterococci isolated from a specific individual, intended to restore his/her microbiota and improve his/her health. The potential mechanisms of probiotic action against H. pylori include correction of the gut microbiota, immunological effects (enhancement of humoral and cellular immunity, and reduction of oxidative stress), direct antagonistic effects against H. pylori (such as colonization resistance and bacteriocin synthesis), and stimulation of local immunological protection (strengthening of the mucous protective barrier and reduction of gastric mucosa inflammation). The incorporation of probiotics into comprehensive eradication therapy shows promise in optimizing the treatment of H. pylori infection. Probiotics can enhance the eradication rates of H. pylori, reduce the occurrence and severity of side effects, and improve patient compliance. Probiotic or autoprobiotic monotherapy can be considered as an alternative treatment approach in cases of allergic reactions and insufficient effectiveness of antibiotics. We recommend including probiotics as adjunctive medications in anti-H. pylori regimens. However, further randomized multicenter studies are necessary to investigate the effects of probiotics and autoprobiotics against H. pylori, in order to gain a better understanding of their mechanisms of action.

P-610 Lipid metabolism mediated the effect of glucose homeostasis and insulin resistance on IVF/ICSI outcomes in PCOS women

Abstract Study question To investigate the potential mediation role of lipid metabolism on the effect of glucose metabolism on IVF/ICSI outcomes in PCOS women. Summary answer Lipid metabolism indicators were possible mediators of the effect of glucose metabolism indicators on IVF/ICSI early reproductive outcomes in PCOS women. What is known already Women with PCOS have high incidences of dyslipidemia, obesity, impaired glucose tolerance (IGT), diabetes, and insulin resistance (IR) and are fragile to female infertility. The causality between dyslipidemia, glucose homeostasis dysregulation, and IR has been widely discussed. Dyslipidemia may be an intermediate biological mechanism for the associations between abnormal glucose metabolism and potential disorders of oocytogenesis and embryogenesis in PCOS women. Study design, size, duration We retrospectively analyzed 917 PCOS women aged between 20 – 45 years old who underwent their first fresh IVF/ICSI cycle with autologous oocytes during 2018 – 2020 at a reproductive center. Participants/materials, setting, methods Data on baseline reproductive and cycle characteristics were collected from the internal database derived from the electronic medical records. The pregnancy outcomes were collected by well-trained follow-up staff from telephone interviews. Associations between glucose and lipid metabolism indicators and IVF/ICSI outcomes were explored using multivariable generalized linear regressions. Mediation analyses were conducted to examine the role of lipid metabolism on the association between glucose metabolism and IVF/ICSI outcomes. Main results and the role of chance Significant dose-dependent relationships were found between glucose metabolism indicators and IVF/ICSI early reproductive outcomes, as well as between glucose metabolism indicators and lipid metabolism indicators (all P &amp;lt; 0.05). Also, we found significant dose-dependent relationships between lipid metabolism indicators and IVF/ICSI early reproductive outcomes (all P &amp;lt; 0.05). The mediation analysis indicated that elevated FPG, 2hPG, FPI, 2hPI, HbA1c, and HOMA2-IR were significantly associated with decreased retrieved oocyte count, MII oocyte count, normal fertilization count, normal cleavage count, high-quality embryo count, or blastocyst formation count after controlling for lipid metabolism indicators. Serum TG mediated 6.0 – 31.0% of the associations; serum TC mediated 6.1 – 10.8% of the associations; serum HDL-C mediated 9.4 – 43.6% of the associations; serum LDL-C mediated 4.2 – 18.2% of the associations; and BMI mediated 26.7 – 97.7% of the associations. Limitations, reasons for caution Given the retrospective nature, bias in data collection cannot be excluded. Besides, we did not consider any adjunctive therapy, including diet, exercise, or medication (i.e., metformin) before or during IVF treatment. The possible random errors in single measurements may also lead to certain imprecise estimates of association. Wider implications of the findings Our study emphasizes a mediation role of lipid metabolism in the impact of glucose metabolism on oocytogenesis and embryogenesis in PCOS women, suggesting that the monitoring and management of preconception lipid metabolism, glucose homeostasis, and IR are essential for improving the IVF/ICSI outcomes of PCOS women. Trial registration number Not Applicable

Opioid Utilization After Scoliosis Surgery is Greater in Marfan Syndrome Than Adolescent Idiopathic Scoliosis.

Retrospective matched case cohort. Compare postoperative opioid utilization and prescribing behaviors between patients with Marfan syndrome (MFS) and adolescent idiopathic scoliosis (AIS) after posterior spinal fusion (PSF). Opioids are an essential component of pain management after PSF. However, due to the potential for opioid use disorder and dependence, current analgesic strategies aim to minimize their use, especially in younger patients. Limited information exists on opioid utilization after PSF for syndromic scoliosis. Twenty adolescents undergoing PSF with MFS were matched with patients with AIS (ratio, 1:2) by age, sex, degree of spinal deformity, and the number of vertebral levels fused. Inpatient and outpatient pharmaceutical data were reviewed for the quantity and duration of opioid and adjunct medications. Prescriptions were converted to morphine milligram equivalents (MMEs) using CDC's standard conversion factor. Compared with patients with AIS, patients with MFS had significantly greater total inpatient MME use (4.9 vs . 2.1 mg/kg, P ≤ 0.001) and longer duration of intravenous patient-controlled anesthesia (3.4 vs . 2.5 d, P = 0.001). Within the first 2 postop days, MFS patients had more patient-controlled anesthesia boluses (91 vs . 52 boluses, P = 0.01) despite similar pain scores and greater use of adjunct medications. After accounting for prior opioid use, MFS was the only significant predictor of requesting an opioid prescription after discharge (odds ratio: 4.1, 95% CI: 1.1-14.9, P = 0.03). Patients with MFS were also more likely to be discharged with a more potent prescription (1.0 vs . 0.72 MME per day/kg, P ≤ 0.001) and to receive a longer-duration prescription (13 vs . 8 d, P = 0.005) with a greater MME/kg (11.6 vs . 5.6 mg/kg, P ≤ 0.001) as outpatients. Despite a similar intervention, patients with MFS and AIS seem to differ in their postoperative opioid usage after PSF, presenting an opportunity for further research to assist clinicians in better anticipating the analgesic needs of individual patients, particularly in light of the ongoing opioid epidemic.

ANRIL promotes the regulation of colorectal cancer on lymphatic endothelial cells via VEGF-C and is the key target for Pien Tze Huang to inhibit cancer metastasis

lncRNA ANRIL is an oncogene, however the role of ANRIL in the regulation of colorectal cancer on human lymphatic endothelial cells (HLECs) is remain elusive. Pien Tze Huang (PZH, PTH) a Tradition Chinese Medicine (TCM) as an adjunctive medication could inhibit the cancer metastasis, however the mechanism still uncovering. We used network pharmacology, subcutaneous and orthotopic transplanted colorectal tumors models to determine the effect of PZH on tumor metastasis. Differential expressions of ANRIL in colorectal cancer cells, and stimulating the regulation of cancer cells on HLECs by culturing HLECs with cancer cells’ supernatants. Network pharmacology, transcriptomics, and rescue experiments were carried out to verify key targets of PZH. We found PZH interfered with 32.2% of disease genes and 76.7% of pathways, and inhibited the growth of colorectal tumors, liver metastasis, and the expression of ANRIL. The overexpression of ANRIL promoted the regulation of cancer cells on HLECs, leading to lymphangiogenesis, via upregulated VEGF-C secretion, and alleviated the effect of PZH on inhibiting the regulation of cancer cells on HLECs. Transcriptomic, network pharmacology and rescue experiments show that PI3K/AKT pathway is the most important pathway for PZH to affect tumor metastasis via ANRIL. In conclusion, PZH inhibits the regulation of colorectal cancer on HLECs to alleviate tumor lymphangiogenesis and metastasis by downregulating ANRIL dependent PI3K/AKT/VEGF-C pathway.

Ultrasound-guided stellate ganglion block for the treatment of migraine in elderly patients: A retrospective and observational study.

This study aimed to assess the effectiveness and safety of ultrasound-guided stellate ganglion block (SGB) in the prophylactic treatment of migraine in the elderly. Treatment of migraine in the elderly is often difficult and troublesome due to multiple comorbidities, drug interactions, and adverse effects (AEs). SGB may be an effective treatment approach for migraine in the elderly as its clinical use is rarely limited by concomitant diseases and age-related physiological changes; however, no studies have evaluated the effectiveness of SGB in the treatment of migraine in the elderly population. This is a retrospective observational case series study. We retrospectively analyzed patients with migraine aged ≥65 years, who underwent ultrasound-guided SGB for headache management between January 2018 and November 2022. Pain intensity using the numerical rating scale (NRS, 0-10), number of days with headache per month, duration of headache, and the consumptions of acute medications were recorded before SGB treatment, and at 1, 2, and 3 months after the last SGB. Safety assessment included thorough documentation of serious and minor AEs related to SGB. Of 71 patients, 52 were analyzed in this study. After the final SGB, the NRS scores decreased significantly from a mean (± standard deviation [SD]) of 7.3 (1.2) at baseline to 3.3 (1.4), 3.1 (1.6), and 3.6 (1.6) at 1, 2, and 3 months, respectively (vs. baseline, p < 0.001). The mean (SD) number of headache days per month significantly reduced from 23.1 (5.5) to 10.9 (7.1) (p < 0.001), 12.7 (6.5) (p = 0.001), and 14.0 (6.8) days (p = 0.001) at the 1-, 2-, and 3-month follow-ups, respectively. The values of headache duration were also significantly lower at the 1-month (mean [SD] 12.5 [15.8] h, p = 0.001), 2-month (mean [SD] 11.3 [15.9] h, p = 0.001), and 3-month follow-ups (mean [SD] 14.3 [16.0] h, p = 0.001) compared to pre-treatment baseline (mean [SD] 22.7 [17.1] h). There were 33/52 (64%) patients experiencing at least a 50% reduction in acute medications consumption 3 months after the final SGB treatment. The overall AEs rate associated with ultrasound-guided SGB was 9.0% (26/290 SGBs). There were no serious AEs; all reported AEs were minor and transient. Stellate ganglion block treatment could reduce pain intensity, headache frequency, and duration of migraine, thereby reducing the need for adjunctive medications in elderly patients. Ultrasound-guided SGB might be a safe and effective intervention for the treatment of migraine in elderly patients.