Drug-related Side Effects Research Articles

P0772 Efficacy and consumption of golimumab is similar with European and American dosing regimens in Ulcerative Colitis: Results of a prospective study

Abstract Background Golimumab is a subcutaneous TNF-alpha inhibitor approved for ulcerative colitis in European Union (EU) and United States of America (US). Interestingly, maintenance dose for patients weighing ≤80 kg is different in EU and US. In EU, golimumab maintenance dose in 50 mg every 4 weeks with an option of reactive dose escalation to 100 mg every 4 weeks in case of inappropriate response. In US, maintenance dose is 100 mg every 4 weeks for all patients, irrespective of body weight and response to induction. Here we compared efficacy, safety and drug consumption of EU and US maintenance dosing of golimumab in patients weighing ≤80 kg. Methods In this investigator initiated prospective study (ClinicalTrials.gov ID: NCT04156984) we recruited 29 patients with active ulcerative colitis. After common induction (golimumab 200 mg at baseline and 100 mg at week 2) all patients received 1 year of maintenance treatment. First 15 patients received US maintenance regimen with 100 mg golimumab monthly and next 14 patients received EU maintenance regimen with 50 mg golimumab monthly. Those in EU regimen with inadequate response to induction or loss of response during maintenance phase (rectal bleeding score (RBS) > 0 or endoscopic Mayo score (eMayo) ≥ 2) increased dose of golimumab from 50 mg to 100 mg. Co-primary endpoints were endoscopic improvement (eMayo ≤ 1) at weeks 14 and 50 and clinical remission (RBS = 0 and stool frequency score (SFS) < 2) at weeks 14, 26, 38, and 50. Statistical analysis included Chi-square and Mann-Whitney tests. Results Patient demographic data are shown in Table 1. Endoscopic improvement and clinical remission rates were similar with EU and US maintenance regimens (Figure 1). 8/14 (57%) of patients in EU regimen needed dose escalation to 100 mg due to inadequate response after a median of 8.6 weeks (interquartile range 6 to 14 weeks). Drug persistence and drug consumption was similar in both maintenance regimens (Figure 1). In the US regimen 3 potentially drug-related side effects occurred (one case each: one-dermatome herpes zoster, labial herpes, skin small vessel vasculitis), but none in the EU regimen. Conclusion In this prospective study, EU and US golimumab maintenance regimens resulted in similar endoscopic improvement and clinical remission rates during the first year of treatment with golimumab in patients with ulcerative colitis weighing ≤80 kg. Due to high dose escalation rates in EU regimen dose consumption was similar in both maintenance regimens.

Exploration of molecular interactions responsible for anti-inflammatory attributes of GI friendly micro-sized formulation of flurbiprofen and clove oil.

Clove oil obtained from Syzygium aromaticum(L.) is traditionally employed to treat inflammation associated with rheumatism, gastric disorders, and as ananalgesic. Chemo-herbal combinations are known to have potent anti-inflammatory and analgesic effects, while mitigating the drug related side effects. The purpose of this study was to evaluate anti-inflammatory, analgesic and antipyretic effects of a combination of flurbiprofen and clove oil in a micro-emulsion (FCM) form using various in vivomodels. Micro-emulsion of flurbiprofen and clove oil (FCM) was prepared following reported protocols and three different dose combinations (25, 12.5 and 6.25mg/kg) were evaluated in carrageenan and histamine-induced acute inflammation, CFA-induced arthritis, yeast-induced pyrexia, and aceticacid-induced writhing models. qPCR studies were conducted to explore the possible mechanism of action. GC-MS of clove oil was performed to explore its chemical composition. FCM 25mg/kg treated group exhibited significantly better (p < 0.05) effects compared to clove oil (CM) and flurbiprofen (FBR) (25mg/kg)treated groups in both acute and chronic models. Histopathological study of joints showed a reduction in infiltration of inflammatory cells, bone erosion, and tissue oedema in FCM (25mg/kg)treatedgroup as compared to other treatment groups. Significant up-regulation in mRNA expressionof anti-inflammatory (IL-4, IL-10) and down-regulation of pro-inflammatory genes(NF-κB, IL-6, TNF-α, IL-1β and COX-2) was observed in all the FCM-treated groups but, 25mg/kg-treated group showed comparatively better results. Gross macroscopic examination of stomach sections also showed relatively less deleterious effects of test treatments(CM and FCM) as compared with FBR treated group. Serum levels of liver enzymes (alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), blood urea nitrogen (BUN) and creatinine were also found to be normal as compared to FBR and tween-water (TW) treated groups.GC-MS of clove oil revealed that it was rich in eugenol contents. This study reveals that a combination of flurbiprofen and clove oil in a micro-emulsion form could be a promising approach to enhance therapeutic actions and to mitigate synthetic drugs related side effects in clinical settings. It might implicate a synergistic action on the modulation of inflammatory genes expression. Further research is warranted to explore the full potential of this combination in treating various inflammatory conditions.

Perception and Identification of Behavioral and Psychological Symptoms of Dementia (BPSD) in China Medical Community.

Behavioral and psychological symptoms of dementia (BPSD), as neuropsychiatric manifestations within dementia, constitute core features of dementia. However, there remains a gap in understanding the recognition of BPSD in China. Our current study was to explore the clinical awareness and treatment approaches for BPSD in China, focusing especially on the perspectives of neurologists and psychiatrists. A multicenter national survey was designed and a semi-structured questionnaire was distributed to healthcare professionals including doctors and nurses across all provinces of China. The questionnaire incorporated either closed (yes/no) and multiple-choice questions. The questions centered on the following areas: the perceived global frequency and relevance of BPSD; the assessment tools employed for evaluating BPSD; pharmacological approaches for addressing psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disorders; drug-related side effects; non-pharmacological treatment strategies. The anonymity of questionnaire responses was maintained to encourage participants to candidly express their viewpoints. The majorities of respondents recognized the importance of BPSD. There were apparent differences in the perception of BPSD between neurologists and psychiatrists, encompassing variances in symptoms recognition, diagnostic approaches, and treatment strategies. A notable high percentage of neurology (27.8%) and psychiatry staff (23.6%) would not choose non-pharmacological interventions. Meanwhile, antipsychotics was overused in China. For aggression and agitation, more than half of neurologist and psychiatrist preferred antipsychotics. For psychosis, more than 80% of doctors chose antipsychotics. Nearly one-third of the medical staff expressed a preference for traditional Chinese medicine including ginkgo biloba extract. In summary, this study in China has shed light on the features related to perception, recognition, management, treatment options, and observed side effects associated with BPSD. Our findings have the potential to significantly enhance the understanding of BPSD characteristics among medical practitioners and offering valuable insights into improved management and treatment strategies of neuropsychic symptoms of dementia in China.

Oral Targeted Delivery of Codonopsis Radix Polysaccharide via Succinyl -DHA Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic intestinal disease characterized by spleen-lung qi deficiency and dampness-pathogenic obstruction. Although there are various treatment options available, patients frequently encounter significant drug-related side effects. Previous studies have shown the potential of Codonopsis Radix polysaccharides A (CPA) in treating UC, but their limited bioavailability has restricted their clinical use. Therefore, the objective of this study was to develop a novel formulation that can address the aforementioned limitations and assess its potential advantages. We synthesized a negatively charged amphipathic prodrug called CPA-SA-DHA (CSD), which consists of CPA as the hydrophilic component, and succinic anhydride and docosahexaenoic acid as the hydrophobic segments. The CSD nanoparticles obtained had a particle size of 180.0 ± 3.2 nm, a negative zeta potential of -29.8 ± 5.3 mV, and a uniform shape with a PDI index of 0.230 ± 0.003. The interaction between positive and negative charges significantly increased the retention time of CSD nanoparticles in the colonic microenvironment. Furthermore, CSD nanoparticles demonstrated enhanced bioavailability in UC mice compared to CPA. Additionally, we observed that CSD nanoparticles exhibited therapeutic effects on DSS-induced UC mice by regulating the diversity and abundance of gut microbiota. This effect may be mediated by the inhibition of pro-inflammatory signaling pathways TLR4/NF-κB. These findings confirm the potential of CSD nanoparticles as a promising treatment option for UC.

Heterogeneity in Reported Side Effects Following Initiation of Elexacaftor-Tezacaftor-Ivacaftor: Experiences at a Quaternary CF Care Center.

The benefits of Elexecaftor-Tezacaftor-Ivacaftor (ETI) therapy on the health and wellbeing of people with CF (pwCF) are well documented. Since approval, however, a growing number of potential side effects have emerged in reports from clinical practice. With current understanding of ETI tolerability limited to data from clinical trials, the prevalence of side effects and their impact on care decision making remains poorly categorized. A 10-question survey was developed and distributed to patients 18 years or older who were treated at the Massachusetts General Hospital CF centers. Reports of side effects were measured across 12 distinct categories, and dose adjustments and discontinuation due to side effects were collected. If a patient reported no side effects, they did not have to complete the entire survey. Among 92 respondents initiated on ETI, 51 respondents (55.4%) reported potential side effects and 41 (44.5%) respondents reported no adverse events. The most commonly reported side effects were mental health, changes in appearance, and gastrointestinal complaints, which were reported by 22.8%, 30.4%, and 21.7% of patients, respectively. Eighteen (19.6%) respondents modified their dosing in response to side effects, and six discontinued treatment permanently (6.52%) due to persistent side effects. Responses demonstrated marked heterogeneity, with most respondents reporting at least one side effect following initiation. Dose modification was commonly utilized to mitigate adverse effects, however few respondents had to discontinue treatment. These findings demonstrate the importance of monitoring for potential drug-related side effects of ETI in clinical settings.

Paracetamol is both a friend and a foe: What should a pediatrician know? A clinical case

One of the most common drug-related side effects is hepatotoxicity. The most common cause of severe drug-induced liver injury is acetaminophen (paracetamol), as it is an over-the-counter drug. Paracetamol is safe and effective in children and adolescents at therapeutic doses; however, it is the leading cause of acute liver failure in children (21% of cases) and adults (40%) with overdose. The clinical presentation of toxic liver damage depends on the time elapsed after taking paracetamol and its dose. Symptoms of liver damage are not always obvious but can develop rapidly from day 2 to day 5 after poisoning. The article presents a clinical case of an unintentional overdose of paracetamol in a teenage girl due to non-compliance with the dose and regimen.

The Superiority of Compressed Colchicine Tablets over Coated Colchicine Tablets for Familial Mediterranean Fever.

Background and Objectives: Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease characterized by recurrent febrile attacks and serosal inflammation. The goals of FMF treatment are to prevent acute attacks and the development of amyloidosis. This study aimed to investigate the benefit of switching to compressed colchicine tablets in patients with FMF who are resistant or intolerant to the pharmaceutical preparation of coated colchicine tablets in terms of attack frequency and side effects. Materials and Methods: Patients who developed resistance and intolerance under coated colchicine tablet treatment and, therefore, switched to compressed colchicine tablets were identified. The attack frequencies and drug-related side effects in patients using the two different pharmaceutical colchicine preparations were compared. Results: The mean age of the 172 patients treated with compressed tablets alone following coated tablets was 36.3 ± 11.4 years, and 75 (43.6%) were male. The most common genetic mutation was detected as M694V in 111 (64.5%) patients, and 36 (20.9%) of them were homozygous. A decrease in the daily colchicine dose was found after switching to compressed colchicine tablets in patients followed for 7 years (2.1 ± 0.7 mg vs. 1.7 ± 0.5 mg; p < 0.001). Episodes lasted for one to three days and then resolved spontaneously. After treatment with the compressed tablet form of colchicine, 129 (75%), 33 (19%), and 10 (6%) patients had 0-3, 4-6, and more than 7 attacks, respectively (p < 0.001). Diarrhea and aminotransferase elevation, the most common side effects in patients using coated colchicine tablets, decreased after using compressed colchicine tablets (p < 0.001). Conclusions: Compressed colchicine tablets were shown to be effective in patients who did not respond to coated colchicine therapy and those with pre-treatment intolerance to biological agents.

Sedation with Chloral Hydrate and Melatonin in Childhood Electroencephalography

Objective: Recording an electroencephalography (EEG) in children is challenging due to their restlessness during the procedure and inability to follow the required instructions. Sleep deprivation and the use of sedative agents are necessary to perform the recording. This study aims to compare the success of sedation with chloral hydrate and melatonin. Methods: Patients who underwent EEG recording between December 2023 and March 2024 were retrospectively evaluated. The chloral hydrate and melatonin groups were formed for the patients requiring sedation. According to the protocol applied in our clinic, chloral hydrate was administered orally at a dose range of 30-50 mg/kg (max 1500 mg), while melatonin was given orally at a dose of 1-3 mg. The sociodemographic information of the patients was recorded from hospital charts, sleeping rates and EEG recording duration were compared. Results: Of the 471 patients EEG performed, 240 (51%) were female and 231 (49%) were male. The mean age was 9.1±5.1 years, with a median age of 9.5 years. Sleep deprivation was appropriately carried out in 434 patients (92.3%), while 37 patients did not achieved sleep deprivation. Among the 76 patients who received sedation, chloral hydrate was used in 45 (59.2%) and melatonin in 31 (40.8%). Sleeping ratio were 82.2% and 80.6% in the chloral hydrate and melatonin groups respectively; there was no statistically significant difference in sleeping rates (p: 0.86). No serious drug-related side effects were observed in either group. Rare gastric complaints, such as gastric discomfort and nausea/vomiting were noted in the chloral hydrate group. Conclusion: Melatonin and chloral hydrate provided similar rates of sedation. This study showed either drug can be choosen for the sedation in pediatric EEG recordings.

Atomoxetine and spironolactone combine to reduce obstructive sleep apnea severity and blood pressure in hypertensive patients.

Norepinephrine reuptake inhibitors such as atomoxetine (ato) can improve OSA by increasing pharyngeal muscle activity. Mineralocorticoid antagonists such as spironolactone, may potentiate the reduction of OSA severity and reduce blood pressure. We evaluated whether adding spironolactone to atomoxetine (ato-spiro) improved responses in hypertensive OSA patients. Twenty-one patients with an apnea-hypopnea index (AHI) between 10 and 50 events/h and a history of hypertension were recruited and crossed-over in random order to ato 80mg and ato-spiro 80/50mg for 1 week after a 3-day low dose run-in period. Two dropped out due to drug related side effects. Polysomnography and 24-hour blood pressure (BP) monitoring were performed at baseline and after each treatment period. AHI decreased on both ato and ato-spiro from a baseline median(IQR) of 20.3(18.8 to 28.5) to 8.2(7 to 13.1) and 6.2(5.7 to 14.1), respectively (p < 0.001 for both). Systolic BP (mmHg) fell by mean(95%CI) -4.5(-13.8 to 4.8, p = 0.33) on ato and - 10.3(-19.2 to -1.5, p = 0.02) on ato-spiro, and diastolic BP dropped by -3.0(-8.0 to 2.0, p = 0.23) on ato and - 5.0(-9.1 to -0.9; p = 0.02) on ato-spiro. Both ato and ato-spiro led to a significant shift from apnea to hypopnea predominance (p < 0.001), and significant reductions in hypoxic burden (p ≤ 0.001) and REM sleep (p ≤ 0.001). Both ato-spiro and ato alone decreased OSA severity similarly, but ato-spiro led to even greater, statistically significant and clinically meaningful falls in systolic and diastolic BP. BP reductions were likely due to ato-related improvements in upper airway patency and hypoxemia, and to spiro-related reduced fluid retention. These findings show promise for ato-spiro as an oral treatment for hypertensive OSA patients. REGISTERED AT CLINICALTRIALS.GOV: NCT04905979.

Impact of Vanessa's Law on the Reporting of Serious Adverse Events: A Retrospective Study Among Antiplatelet Users in a Tertiary-Care Cardiology Centre

BackgroundAntiplatelet drugs, such as clopidogrel, ticagrelor, prasugrel, and acetylsalicylic acid, may be associated with a risk of adverse events (AEs). Vanessa's Law was enacted to strengthen regulations to protect Canadians from drug-related side effects (with mandatory reporting of serious adverse events [SAEs]). ObjectiveTo determine whether Vanessa's Law has led to an increase in SAE reporting among antiplatelet users. MethodsThis descriptive retrospective study was conducted from January, 2018-December, 2021. Included are 260 adult antiplatelet users (cohorts: 2018 [n = 64]; 2019 [n = 79]; 2020 [n = 73]; 2021 [n = 44]) hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval. The main diagnostic of hospitalization was coded using the International Classification of Diseases,10th revision, Canadian version, and data related to demographic characteristics, hospitalization length-of-stay, drugs administered, and AEs were extracted. ResultsThe 260 antiplatelet users were hospitalized mainly for diseases of the circulatory system (codes [I00-I99]; 2018, 75 %; 2019, 71 %; 2020, 71 %; 2021, 77 %) or diseases of the respiratory system (codes [J00-J99]; 2018, 6 %; 2019, 8 %; 2020, 4 %; 2021, 7 %). The median age was 70 years. The median duration of hospital stay was 3 days. Among the 1395 AEs recorded during the study, 12 % were SAEs. None of the SAEs (or AEs) was reported to Health Canada, either before or after Vanessa’s Law implementation. ConclusionsThese results provide the first picture of reporting trends for SAEs among antiplatelet users in Canada. Investigation of the underreporting of SAEs is needed, as the implementation of a mandatory policy does not seem to have had a favourable impact. Clinical Trial Registration135263.

Comparison of Transforaminal Magnesium Sulfate with Steroid Injection in the Management of ‎Radicular Back Pain: A Randomized Double-Blinded Clinical Trial Study

Background: This study compares the effects of transforaminal magnesium sulfate injection versus other methods for managing radicular back pain, highlighting its potential for improved pain relief and functional outcomes. Methods: This randomized, double-blind clinical trial involved 30 patients with radicular back pain who were randomly assigned to receive either transforaminal magnesium sulfate or triamcinolone injection. Primary outcomes were pain intensity and functional disability, assessed using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI), respectively. These were evaluated at five time points: Before the injection, 2 weeks, 1 month, 3 months, and 6 months after the injection. Secondary outcomes included drug-related adverse events within the six-month follow-up period. Results: Baseline characteristics were not significantly different between the two study groups. Compared to pre-injection measures, post-injection pain intensity and functional disability were significantly reduced in both groups at all time points (P &lt; 0.001). At all postoperative evaluations, pain intensity and functional disability were lower in the magnesium sulfate group compared to the steroid group (P &lt; 0.001). No drug-related side effects were recorded in either group. Conclusions: For patients with radicular back pain, transforaminal magnesium sulfate injection appears to be an effective and safe alternative to transforaminal steroid injection.

Clinical and molecular response to alpha1-oleate treatment in patients with bladder cancer.

The tumoricidal complex alpha1-oleate targets bladder cancer cells, triggering rapid, apoptosis-like tumor cell death. Clinical effects of alpha1-oleate were recently observed in patients with non-muscle invasive bladder cancer (NMIBC), using a randomized, placebo-controlled study protocol. To investigate if there are dose-dependent effects of alpha1-oleate. Here, patients with NMIBC were treated by intravesical instillation of increasing concentrations of alpha1-oleate (1.7, 8.5, or 17 mM) and the treatment response was defined relative to a placebo group. Strong, dose-dependent anti-tumor effects were detected in alpha1-oleate treated patients for a combination of molecular and clinical indicators; a complete or partial response was detected in 88% of tumors treated with 8.5 mM compared to 47% of tumors treated with 1.7 mM of alpha1-oleate. Uptake of alpha1-oleate by the tumor triggered rapid shedding of tumor cells into the urine and cell death by an apoptosis-like mechanism. RNA sequencing of tissue biopsies confirmed the activation of apoptotic cell death and strong inhibition of cancer gene networks, including bladder cancer related genes. Drug-related side effects were not recorded, except for local irritation at the site of instillation. These dose-dependent anti-tumor effects of alpha1-oleate are promising and support the potential of alpha1-oleate treatment in patients with NMIBC.

Machine Learning Techniques for Predicting Drug-Related Side Effects: A Scoping Review.

Drug safety relies on advanced methods for timely and accurate prediction of side effects. To tackle this requirement, this scoping review examines machine-learning approaches for predicting drug-related side effects with a particular focus on chemical, biological, and phenotypical features. This was a scoping review in which a comprehensive search was conducted in various databases from 1 January 2013 to 31 December 2023. The results showed the widespread use of Random Forest, k-nearest neighbor, and support vector machine algorithms. Ensemble methods, particularly random forest, emphasized the significance of integrating chemical and biological features in predicting drug-related side effects. This review article emphasized the significance of considering a variety of features, datasets, and machine learning algorithms for predicting drug-related side effects. Ensemble methods and Random Forest showed the best performance and combining chemical and biological features improved prediction. The results suggested that machine learning techniques have some potential to improve drug development and trials. Future work should focus on specific feature types, selection techniques, and graph-based methods for even better prediction.

Cartilage decellularized matrix hydrogel loaded with protocatechualdehyde for targeted epiphycan treatment of osteoarthritis

Osteoarthritis (OA) is a prevalent chronic disease, characterized by chronic inflammation and cartilage degradation. This study aims to deepen the understanding of OA's pathophysiology and to develop novel therapeutic strategies. Our study underscores the pivotal role of Epiphycan (EPYC) and the IL-17 signaling pathway in OA. EPYC, an essential extracellular matrix constituent, has been found to exhibit a positive correlation with the severity of OA. We have discovered that EPYC modulates the activation of the IL-17 signaling pathway within chondrocytes by regulating the interaction between IL-17A and its receptor, IL-17RA. This regulatory mechanism underscores the intricate interplay between the extracellular matrix and immune signaling in the pathogenesis of OA Another finding of our study is the therapeutic effectiveness of protocatechualdehyde (PAH) in OA. PAH significantly reduces chondrocyte hypertrophy and supports cartilage tissue recovery.by targets EPYC. To reduce the side effects of orally administered PAH and maintain its effective drug concentration, we have developed a decellularized matrix hydrogel loaded with PAH for intra-articular injection. This novel drug delivery system is advantageous in minimizing drug-related side effects and ensuring sustained release PAH within the joint cavity.

Promoting dental patient safety toward judicious medication usage: a review

Objective: This critical review aimed to review strategies for health promotion and patient safety regarding the usage of drugs prescribed by dental practitioners. Methods: Manual searches were conducted on PubMed, Embase, and in the Cochrane database of systematic reviews using the keywords “dentistry”, “medication error”, “drug-related side effects and adverse reactions”, and “patient safety”. Publications by the World Health Organization, and the World Dental Federation were also searched to organize this review. Results: Several approaches have been identified to promote patient safety, including continuum education and training of practitioners, interdisciplinary work with clinical pharmacists, and electronic tools to aid practitioners in prescribing the adequate therapeutic regimen avoiding dosage errors and checking for potential drug interactions. Conclusion: Medication errors are common in dentistry, as such, it is fundamental that health professionals, patients, governments, and communities commit to advancing improvements and medication safety.

The Promise of MDMA in the Future Treatment of Severe Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is an often debilitating condition caused by a person’s exposure to traumatic events. Symptoms of PTSD include intrusive thoughts, suicidal ideation, and highly negative and distressing emotional states. Current treatments for PTSD such as cognitive behavioral therapy, EMDR, and SSRIs and SNRIs are ineffective for a large chunk of patients who seek out treatment. A majority of patients with PTSD do not respond to talking therapy, and the remission rate for patients on SSRIs and SNRIs is low. The ineffectiveness of recommended treatments has led to experimentation with drugs like MDMA. MDMA increases levels of chemicals in the brain that induce happy and calm states. This drug also decreases fear states in patients, allowing them to more comfortably discuss traumatic events without the possible side effects of extreme emotional numbness or high levels of anxiety. Research conducted in the last decade on MDMA in addition to psychotherapy in a clinical setting has yielded impressive results. A majority of patients in all three conducted trials experienced a long-term reduction in PTSD symptoms. MDMA in a clinical setting was also proven to be safe, with no serious drug-related side effects on patients. With such high rates of symptom reduction, these studies provide hope for the future of effective and safe PTSD treatment.

Understanding patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, Uganda, a qualitative study.

In 2016, Uganda added Hydroxyurea (HU) to the list of essential drugs to treat sickle cell disease SCD. However, Hydroxyurea utilization has been low for several countries in sub-Saharan Africa. This study examined patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, in Uganda. To understand the patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease, we conducted a parallel convergent mixed methods study at outpatient departments of two national referral hospitals in Uganda from October 2022 to January 2023. The cross-sectional mixed-methods study employed both quantitative and qualitative methods. We collected survey data from a systematic sample of 259 participants and conducted individual interviews with a purposive sample of 40 participants (20 adolescents or their caregivers and 20 adult patients with SCD) and interviewed them individually on their knowledge, perceptions, barriers, and facilitators of HU utilization. Descriptive data were analyzed using Stata 16, whereas qualitative data were analyzed thematically using an inductive approach supported by NVivo 12 software. We triangulated data to determine the concordance of qualitative and quantitative data. The study enrolled 40 participants for qualitative interviews and 259 patients for quantitative, with an average age of 16, over half being female, 46% having secondary education, and 96% unmarried. The prevalence of HU use was 78%. The study identified three themes as follows: Patient barriers at the individual including Inadequate knowledge about HU, Persistent pain, Poor adherence to HU, Poor communication with health care workers, and Psychosocial and emotional challenges. At the facility level, long queues and poor quality of care, drug-related side effects that affect HU, and drug stock-outs were reported. Myths, rumors, and misconceptions about HU, and gender-related barriers were reported to affect HU utilization at a community level. Facilitators for the use of HU and recommendations for improvement. Facilitators included perceived benefits, long duration on HU, information sharing by healthcare workers, availability of complementary drugs, confirmation of diagnosis, and availability of medication at public health facilities or private pharmacies. Patients suggested continuous adherence support, encouragement from healthcare workers, sensitization about benefits and risks, a peer-to-peer approach, and financial support for adolescents and women to start businesses to resolve financial problems. Implementing the use of HU has been challenging in Uganda and needs improvement. Facilitators to hydroxyurea use have been highlighted, though Patient-identified barriers at individual, facility, and community levels that need to be resolved. The experiences and insights shared by our participants provide invaluable guidance for increasing the uptake of HU. Further studies are needed to establish validated instruments to assess patients' pain communication and adherence to the HU regimen.

#2231 The efficacy of anti-viral therapies for hepatitis B in kidney transplant recipients

Abstract Background and Aims The efficacy and long-term outcomes of anti-viral therapies used for hepatitis B treatment or prevention continue to be a challenging area in kidney transplantation practice. This study aimed to determine the effectiveness of anti-viral treatment in a hepatitis B kidney transplant cohort and its effect on long-term graft and overall survival. Method We reviewed the data of 589 patients who were followed up on at our clinic between January 1, 2002, and December 31, 2023. Recipients who were AntiHbc IgG positive and received Rituximab and HbsAg negative recipients whose donor was HbsAg positive were included in the prophylaxis group, and recipients who were HbsAg positive were included in the treatment group. Age- and gender-matched recipients who did not use anti-viral treatment constituted the control group. HBV-DNA positivity in the prophylaxis group and an increase in HBV-DNA titers in the treatment group were indicators of treatment ineffectiveness. Anti-viral treatment-related side effects were noted. Graft functions, graft, and overall survival rates were examined at the beginning of treatment and at the last visit. Results A total of 30 patients receiving anti-viral therapy (prophylaxis n = 15, treatment n = 15) were included and compared with 32 control patients. The median age of the prophylaxis group was 49 (13–60) years, the median age of the treatment group was 46 (15–63) years, and the median age of the control group was 44 (22–71) years (p = 0.846). No difference was detected between the groups in terms of gender distribution. Entecavir was used in 17 patients, tenofovir in 7, and lamivudine in 6 patients. Hepatitis B activation was not observed in any patient in the prophylaxis group. An increase in HBV-DNA level was observed in 2 of 5 patients (40%) in the treatment group, followed by lamivudine. No treatment unresponsiveness was observed with other agents. No anti-viral drug-related side effects were reported in any patient. While there was no graft loss in the anti-viral treatment groups during follow-up, overall survival was determined as 100% in the prophylaxis group, 80% in the treatment group, and 90.6% in the control group (log rank p = 0.404). No hepatitis B-related mortality was reported. The findings are summarized in Tables 1 and 2. Conclusion Kidney transplant recipients using anti-viral medications for Hepatitis B, either for treatment or prophylaxis, showed similar graft and patient survival compared to the control group. Entecavir is the most commonly used anti-viral agent. Our findings support that it is advisable to consider alternative anti-viral medications instead of lamivudine, as there is a potential risk of non-response.

Cationic liposomes as a drug-free system for efficient anticancer therapy by intracytoplasmic delivery of sodium bicarbonate

Developing the delivery systems with high therapeutic efficacy and low side effects is of great interest and significance for anticancer therapy. Compared to the high cost in synthesizing new chemotherapeutic drugs, exploring the anticancer potentials of existing chemicals is more convenient and efficient. Sodium bicarbonate (BC), a simple inorganic salt, has shown its tumor inhibition capacity via regulating the acidity of tumor microenvironment. However, the effects of intracytoplasmic BC on tumor growth and the potentials of BC to serve as an anticancer agent are still unknown. Herein, we developed a BC-loaded cationic liposome system (BC-CLP) to deliver BC into the cytosol of cancer cells. The in vitro studies showed that the BC-CLP containing 1% BC (w/v) had a size of 112.9 nm and a zeta potential of 19.1 mV, which reduced the viability of the model cancer cells (human oral squamous cell carcinoma HSC-3 cells) to 13.7%. In contrast, the neutral BC-LP caused less than 50% viability reduction. We further found that BC-CLP released BC directly into cytoplasm via membrane fusion pathway rather than endocytosis, leading to the remarkable increase of cytosolic pH, which may contribute to the anticancer effect of BC-CLP. Our findings indicate that BC-CLP is a potential system for high-efficiency cancer therapy without causing drug-related side effects or resistance.

HMMF: a hybrid multi-modal fusion framework for predicting drug side effect frequencies

BackgroundThe identification of drug side effects plays a critical role in drug repositioning and drug screening. While clinical experiments yield accurate and reliable information about drug-related side effects, they are costly and time-consuming. Computational models have emerged as a promising alternative to predict the frequency of drug-side effects. However, earlier research has primarily centered on extracting and utilizing representations of drugs, like molecular structure or interaction graphs, often neglecting the inherent biomedical semantics of drugs and side effects.ResultsTo address the previously mentioned issue, we introduce a hybrid multi-modal fusion framework (HMMF) for predicting drug side effect frequencies. Considering the wealth of biological and chemical semantic information related to drugs and side effects, incorporating multi-modal information offers additional, complementary semantics. HMMF utilizes various encoders to understand molecular structures, biomedical textual representations, and attribute similarities of both drugs and side effects. It then models drug-side effect interactions using both coarse and fine-grained fusion strategies, effectively integrating these multi-modal features.ConclusionsHMMF exhibits the ability to successfully detect previously unrecognized potential side effects, demonstrating superior performance over existing state-of-the-art methods across various evaluation metrics, including root mean squared error and area under receiver operating characteristic curve, and shows remarkable performance in cold-start scenarios.