Systemic Adverse Drug Reactions Research Articles

Analysis of systemic serum vancomycin levels following intraarticular application in primary total joint arthroplasty

IntroductionPeriprosthetic joint infection (PJI) is a serious complication following primary total joint arthroplasty (TJA). PJI accounts for 15–25% of revision surgeries, therefore it is associated with PJI is associated with substantial patient morbidity and mortality as well as increased healthcare expenditures due to complex treatment strategies.Recently, intraoperative local application of vancomycin powder is increasingly being used in primary total hip and knee arthroplasty (THA, TKA) as an additive strategy for PJI prevention. Whereas local vancomycin concentrations have already been investigated in prior studies, evidence on systemic vancomycin levels and potential adverse drug reactions (ADR) is limited. Purpose of this study was to investigate systemic vancomycin levels following intraarticular application in primary TJA.Materials and methodsThis pilot study is a prospective analysis of patients undergoing primary THA and TKA between April and July 2023. One gram of vancomycin powder was applied to the prosthesis prior to wound closure. Serum vancomycin levels were measured at two standardised time points, 24 and 48 h postoperatively.ResultsIn total, 103 patients were included, and the patient collective was further stratified by surgical procedure into a THA subgroup (n = 52) and a TKA subgroup (n = 51). Mean serum vancomycin levels showed a significant group difference at both time points (24 h: p < 0.001; 48 h: p = 0.044) with higher serum vancomycin concentrations in the THA cohort. Mean serum vancomycin levels in THA patients were 1.25 μg/ml (range 0.00–7.00 μg/ml) after 24 h and 0.34 μg/ml (range 0.00–4.80 μg/ml) 48 h postoperatively. In TKA, no systemic vancomycin levels were detected. Vancomycin concentrations did not reach therapeutic levels in any patient. No ADR was detected in the whole study collective.ConclusionFollowing intraarticular administration of vancomycin powder, no systemic vancomycin levels within the therapeutic range were detected, thus it may serve as a safe and cost-effective adjunct to strategies for prevention of PJI.

Characteristics of isoniazid-induced psychosis: a systematic review of case reports and case series

PurposeIsoniazid, a first-line antitubercular drug, is associated with nervous system adverse drug reactions such as seizures, peripheral neuropathy, and psychosis. This systematic review of case reports and case series aimed to characterize the demographic, social, and clinical factors associated with isoniazid-induced psychosis in patients with active tuberculosis (TB) and those who received isoniazid for latent TB infection (LTBI).MethodsWe comprehensively searched the Embase, PubMed, and Scopus databases to identify relevant studies published between the date of inception of the database and June 2024.ResultsA total of 28 studies, including 21 case reports and 7 case series involved 37 patients who developed isoniazid-induced psychosis. A higher frequency of isoniazid-induced psychosis was observed during the first 2 months of treatment, with a relatively early onset observed among patients aged 18 years or less. Delusions and/or hallucinations are the common symptoms of isoniazid-induced psychosis. Psychomotor disturbances, disorganized speech or formal thought disorder, disorganized or abnormal behaviour, and neuropsychiatric symptoms (sleep disturbances, hostility or aggression, confusion, affective symptoms, anxiety symptoms, and cognitive difficulties) were the other symptoms observed in the included studies. More than 80% of cases rechallenged with isoniazid resulted in the recurrence of psychotic symptoms.ConclusionPatients with TB and LTBI should be assessed for psychotic and neuropsychiatric symptoms during isoniazid therapy, mainly in the first 2 months. Further research is required to understand the impact of underlying risk factors, such as genetic predisposition and isoniazid pharmacokinetics, as well as the clinical utility and dosage recommendations of pyridoxine for managing isoniazid-induced psychosis.

Insights into Patient Experiences with Facilitated Subcutaneous Immunoglobulin Therapy in Primary Immune Deficiency: A Prospective Observational Cohort

BackgroundImmunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC.MethodIn an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL).ResultsWe enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min–max: 2–40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys.ConclusionfSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients’ drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions.

Retrospective analysis of adverse drug reaction enquiries to a hospital drug information service: lessons to be learned to increase in-hospital drug safety.

Adverse drug reactions (ADRs) are a major drug safety concern and a frequent topic of enquiries to hospital drug information services. Our goal was to analyse these enquiries regarding background, complexity, nature of ADR, and involved drug classes to improve in-hospital drug safety. Retrospectively, ADR enquiries to a German university hospital pharmacy drug information 2018-2022 were analysed regarding enquirer (profession, medical specialty) and enquiry details (drugs, suspected ADR/enquiry prior to drug initiation, ADR system organ class, probable cause identified, and enquiry complexity). Of 543 enquiries, 516 (95%) were asked by physicians, 493 (91%) patient-specific, 390 (71%) on suspected ADRs, and 153 (28%) prior to drug initiation. Enquiries originated frequently from internal medicine (74/13.6%), paediatrics (71/13.1%), neurology (70/12.9%), and haemato-oncology (62/11.4%). Most frequent ADRs were haematologic (94/17%) and hepatic (72/13%). The median number of drugs per enquiry was three (range 0-37), 209 (38%) enquiries referred to one specific drug, 165 (30%) concerned ≥11 drugs. A probable cause for suspected ADRs was identified in 75 (36%) enquiries concerning one drug and 155 (94%) with ≥11 drugs. Most frequent drugs were antineoplastic (54/25.8%), nervous-system-drugs (42/20.1%), and anti-infective (40/19.1%). Most enquiries (342/63%) were complex (multiple/specialist resources). Enquiries were usually asked by physicians referring to suspected ADRs in specific clinical situations. A probable cause was identified in many cases pointing to a direct positive impact on patient care. Enquiries prior to drug initiation should be encouraged to increase drug safety. Information on main ADR effects and drug classes helps with targeted counselling.

Spectrum of psychiatric adverse reactions to cyclin-dependent kinases 4/6 inhibitors: A pharmacovigilance analysis of the FDA adverse event reporting system.

The emergence of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) represented a major breakthrough in the treatment of breast cancer over the past decade. In both clinical trials and real-world settings, it was observed that patients using CDK4/6i might experience psychiatric adverse events (PAEs). Herein, we conducted a pharmacovigilance study to comprehensively assess the correlation between CDK4/6i and PAEs. We obtained individual case safety reports submitted to the FDA Adverse Events Reporting System (FAERS) during the period from January 2015 to December 2023. In disproportionality analysis, the reporting odds ratio (ROR) and information component (IC) values were calculated for each adverse event-drug combination. Univariate logistic regression analysis was utilized to explore factors associated with PAEs following CDK4/6i treatment. A total of 95,591 reports related to CDK4/6i were identified, with 6.72% reporting PAEs, and this proportion exhibited an annual upward trend. Based on the ROR and IC values, 17 categories of PAEs were defined as CDK4/6i-related PAEs. Among these PAEs, insomnia, stress, eating disorder, depressed mood, and sleep disorder were very common, each accounting for over 10% of CDK4/6i reports. Ribociclib showed the highest risk signal of CDK4/6i-related PAEs (ROR = 1.89[1.75-2.04], IC025 = 0.79), followed by palbociclib (ROR = 1.47[1.41-1.53], IC025 = 0.49), while abemaciclib did not exhibit a significant signal (ROR = 0.52[0.44-0.62], IC025 = -1.13). Female sex, younger age and weight exceeding 80 kg were significant risk factors for the incidence of CDK4/6i-related PAEs. Using data from a real-world, large-scale spontaneous reporting system for adverse drug reactions, our study delineated the spectrum of PAEs to CDK4/6i. This potentially offered valuable insights for healthcare professionals to manage the risk of PAEs in patients receiving CDK4/6i treatment, particularly those with psychiatric disorders.

Different therapeutic approaches in melasma: advances and limitations.

Melasma is a chronic hyperpigmentation skin disorder that is more common in the female gender. Although melasma is a multifactorial skin disorder, however, sun-exposure and genetic predisposition are considered as the main etiologic factors in melasma occurrence. Although numerous topical and systemic therapeutic agents and also non-pharmacologic procedural treatments have been considered in melasma management, however, the commonly available therapeutic options have several limitations including the lack of sufficient clinical effectiveness, risk of relapse, and high rate of unwanted adverse drug reactions. Recruitment of nanotechnology for topical drug delivery in melasma management can lead to enhanced skin penetration, targeted drug delivery to the site of action, longer deposition at the targeted area, and limit systemic absorption and therefore systemic availability and adverse drug reactions. In the current review, first of all, the etiology, pathophysiology, and severity classification of melasma have been considered. Then, various pharmacologic and procedural therapeutic options in melasma treatment have been discussed. Afterward, the usage of various types of nanoparticles for the purpose of topical drug delivery for melasma management was considered. In the end, numerous clinical studies and controlled clinical trials on the assessment of the effectiveness of these novel topical formulations in melasma management are summarized.

Knowledge, Attitude and Practice on Adverse Drug Reactions Reporting among Pharmacists in Aden

Introduction: Once a medicine is registered and marketed, healthcare systems rely heavily on spontaneous reporting of adverse drug reactions (ADRs) to monitor the safety of drugs. ADRs reporting is considered a cornerstone of pharmacovigilance (PV) system. Underreporting has been a major obstacle and poses a great challenge to PV activities that negatively influence public health. Therefore, this study aimed to assess pharmacists' knowledge, attitude and practice toward ADRs reporting in Aden City - Yemen. Methods: A comparative cross-sectional study was conducted during November and December 2022 in Aden city. A self-administered, pretested questionnaire- comprised of sections on pharmacists’ characteristics, knowledge of PV concepts and ADR reporting process, attitudes towards ADR reporting and practice of ADR reporting- was administered to selected community and hospital pharmacists. Data were summarized using descriptive statistics and the Pearson’s Chi-square test was used to examine the differences between both groups of pharmacists. Results: Four hundred pharmacists participated in the study. Three quarters of them were males. About half of them correctly identified PV definition and purposes as well as ADR definition, but 38.5% and 37.8% were heard about national ADR scheme/guideline and aware of the existence of an ADR system in Yemen respectively. Only 29.3% and 10.8% showed adequate knowledge of PV concepts and ADRs reporting process respectively. The majority showed positive attitude towards PV and ADR reporting, 97.8% agreed that reporting process can benefit the public health, 94.3% contributes to drug safety and 87.3% agreed that PV should be taught in detail to health care professionals. However, in practice, 48.3% and 41.5% of pharmacists had ever diagnosed an ADR and encountered one or more ADRs in their daily practice respectively and only 12.3% of them had ever reported an ADR. The differences between community and hospital pharmacists by their overall knowledge, attitude scores and in ADR reporting practice were statistically insignificant. Conclusion: The majority of community and hospital pharmacists had inadequate knowledge and poor practice, with a positive attitude towards ADRs reporting. Therefore, strategies to improve knowledge and practices regarding ADR reporting should be implemented. Regular mandatory education and continuous in job training should be provided to all pharmacists and others health care professionals.

Through Indian Eyes: A Case Series on Steroid-induced Secondary Cataract

Lichen planus, a chronic autoimmune dermatological disorder, often necessitates the use of topical corticosteroids for symptom management. However, this case series highlights the emergence of topical steroid-induced secondary cataracts in two patients, emphasizing a previously underrecognized complication. Both patients, females aged 36 and 43, presented with gradual vision loss in their left eyes, attributed to prolonged corticosteroid use for lichen planus and skin allergies, respectively. Ophthalmological examinations confirmed the diagnosis, leading to cataract surgeries. The pathogenesis involves complex cellular and molecular mechanisms, emphasizing the need for vigilant monitoring during corticosteroid therapy. Moreover, the lack of stringent reporting systems for adverse drug reactions in India underscores the necessity for comprehensive monitoring to mitigate economic and quality of life burdens. The study emphasizes the importance of judicious corticosteroid use, tapering regimens, and patient education to minimize complications while effectively managing dermatological conditions. This underscores the critical need for heightened awareness, surveillance, and patient-centred approaches to mitigate the risk of corticosteroid-induced secondary cataracts, ensuring optimal therapeutic outcomes and long-term ocular health.

IMPACT OF AN EDUCATIONAL INTERVENTION ON AWARENESS OF PHARMACOVIGILANCE AND ADR REPORTING AMONGST AYURVEDIC POST-GRADUATE STUDENTS

Objective: Adverse drug reactions (ADR) are one of the major causes of morbidity and mortality. Ayurveda is one of the oldest healthcare systems, widely practiced in India and there is a misconception that AYU and H drugs are free from ADRs. Post-graduate (PG) students are fresh pass-out medical graduates and are major contributors in providing health care at tertiary care centres. The present study was planned with the aim of evaluation of knowledge, attitude and practice of pharmacovigilance amongst PG students and impact of an educational intervention on their knowledge and attitude.&#x0D; Methods: A pre-test, post-test questionnaire based cross-sectional study was conducted. 41 postgraduate students from different branches were included. An educational intervention in the form of sensitization programme, including basic knowledge of pharmacovigilance, monitoring system for pharmacovigilance andcase-based ADR reporting was conducted. A validated questionnaire consisting of questions regarding knowledge, attitude and practice of pharmacovigilance was provided as a pre-test and post-test and the results were statistically evaluated.&#x0D; Results: Scores of pre-test reveals that the participants were aware of basic knowledge of pharmacovigilance but knowledge about reporting procedure and the monitoring system was lacking. The difference in mean scores of pre and post-test was statistically significant. Most of the participants agreed that reporting ADR improves drug safety and frequent sensitization programmes should be conducted but practically, they had not undergone any training/sensitization programme.&#x0D; Conclusion: The study reveals that even with the favorable attitude towards drug safety and ADR reporting, the unawareness of PG students about the monitoring system and deficient ADR reporting indicatesa strong need for the conduction of repeated training/sensitization programmes and other suitable methods for encouraging ADR reporting.

Evaluation of Analgesic Effect of Lidocaine Patch 5% in Post-herpetic Neuralgia: An Interventional Study

Introduction: Herpes Zoster (HZ) is a very painful and debilitating condition caused by the reactivation of the Varicella Zoster Virus (VZV). HZ is characterised by a maculopapular or vesicular rash, usually accompanied by pain that is unilateral and restricted to dermatomes. Post-herpatic Neuralgia (PHN) is defined as pain that persists for more than 90 days after the onset of the HZ rash. Aim: To evaluate the analgesic efficacy of a lidocaine patch in PHN. Materials and Methods: This prospective interventional study conducted at the Department of Anaesthesiology and Critical Care, Pt. BD Sharma, PGIMS, Rohtak, Haryana, India, from February 2020 to March 2021. The study included a total of 24 patients (single group), with a male-to-female ratio of 11:13, aged between 18 and 75 years, all with a Visual Analogue Scale (VAS) score greater than 4. An evaluation of patient pain scores using the VAS and the total number of lidocaine patches used per week for four weeks or until the VAS declined to four was conducted. After obtaining informed and written consent, a medicated 5% lidocaine patch was applied to cover the appropriate area for a minimum period of 12 hours, followed by removal for the next 12 hours. This application continued until the VAS declined to four or up to a maximum of four weeks. The level of significance was set at p≤0.05. Results: In the present study, a total of 24 patients were included. The mean age was 59.5±12.85 years, with 54.2% being female and 45.8% male. The VAS scores at baseline were 8.71±0.999, which reduced to 7.08±1.349 at the end of one week, 5.67±0.007 at the end of two weeks, 4.25±0.442 at the end of three weeks and 3.58±0.830 at the end of four weeks. The VAS scores were significantly lower in all patients over the four weeks (p=0.001). The total number of patches used was 1.88±0.338 at one week, 1.46±0.509 at two weeks, 1.04±0.204 at three weeks and 1.00 at four weeks. The total amount of patches used was significantly reduced over the four weeks (p=0.001). No side-effects related to the lidocaine patch were noted. Conclusion: The 5% lidocaine patch demonstrated good tolerability with a minimal risk of systemic adverse drug reactions and is an effective modality for relieving moderate to severe pain. It is concluded that the 5% lidocaine patch is very effective in the treatment of PHN.

Contemporary Intravenous Iron Usage and Safety Patterns

Introduction: Intravenous (IV) iron is routinely used throughout various medical specialties in addition to hematology, including nephrology, cardiology, obstetrics, gastroenterology, and neurology. While all formulations are considered safe, those with iron dextran (ID) are reported to have a relatively higher incidence of anaphylaxis, often prompting a test-dose prior to full administration. Recently, there has been an ongoing national shortage of ID, leading to higher usage of alternate formulations and need for further characterization of usage and safety. Methods: The Epic electronic health record was searched using the Slicer Dicer function to obtain information regarding intravenous iron administrations from 01/01/2021 to 08/31/2022 at the various Mayo Clinic sites throughout the United States. Adverse events were evaluated through the internal patient safety reporting system for adverse drug reactions. Serious adverse events (SAEs) were defined as those events requiring epinephrine administration, anaphylaxis, hypotension, tachycardia, or an allergic reaction (hives, rash, chest tightness, eye swelling) within 24 hours of IV iron infusion. Non-serious adverse events (NSAEs) were defined as those events requiring administration of an antihistamine, steroid, or reported gastrointestinal disturbance within 24 hours of IV iron infusion. Results: A total of 49,310 infusions were administered during the analyzed period and included the use of five formulations: ID, iron sucrose (IS), ferumoxytol (FM), ferric carboxymaltose (FC), and ferric gluconate (FG). Infusions were distributed amongst Rochester (n=23,899; 16%ID, 77%IS, 5%FM, 2%FC, 0%FG), Florida (n=5,755; 6%ID, 43%IS, 34%FM, 9%FC, 8%FG), Arizona (n=5,123; 4%ID, 81%IS, 3%FM, 11%FC, 1%FG), and the Health System (n=14,533; 3%ID, 85%IS, 9%FM, 2%FC, 1%FG). A total of 49 AEs were reported (59% SAEs; 41% NSAEs), representing 0.099% of all infusions. Most AEs were from IS (n=20; 41%), with ID (19; 39%), FM (9; 18%), and FC (1; 2%) accounting for the remainder. Both SAEs (n=13) and NSAEs (n=7) were reported with IS, with most SAEs occurring on the first dose (85%) and classified as hypotension (39%), allergic (31%), anaphylaxis requiring epinephrine (15%), and tachycardia (15%); no pre-medications were given. These IS AEs were dose independent (Table 1). The incidence of AEs for all IV iron formulations was less than 0.01% (Table 2). Conclusions: While ID was found to have a relatively higher incidence of AEs, all IV iron formulations were found to be safe. The most frequently used formulation was IS, which had a low incidence of AEs even at higher doses, suggesting feasibility for minimizing the number of infusions required to achieve therapeutic levels. Although all formulations demonstrated safety, each institution will likely individualize formulary preferences based upon location of administration (inpatient vs. outpatient), input from the various medical specialties, patient comorbidities, reimbursement patterns, and logistical constraints such as infusion chair time.

Corticosteroid injections for non-spinal musculoskeletal conditions: Consideration of local and systemic adverse drug reactions and side effects

Following specialist training, physiotherapists in some countries, such as the United Kingdom and Norway perform landmark, and ultrasound guided, soft tissue and joint injections for a wide range of musculoskeletal conditions. Whether they inject or not, physiotherapists may wish to recommend injections, and people requiring care commonly seek physiotherapist’s opinions on injection therapy. Globally, there has been a substantial increase in the use of corticosteroid injections to treat musculoskeletal conditions. Those performing injections or providing advice need be cognisant of the possible harms of the procedures and communicate this information sensitively to those considering the procedures. This review synthesises evidence for local and systemic adverse reactions and side effects related to corticosteroid injections in the treatment of non-spinal musculoskeletal conditions. Multiple databases including PubMed, Medline, PEDro, Cinahl were searched, and all levels of evidence were included if they added to the review. Serious adverse events appear to be rare, possibly in part, due to under-reporting of side effects. Where available, suggestions for minimising risk and aftercare have been made. As substantial gaps in the evidence were found, areas for further research are suggested and a decision-making tool is included to facilitate whether to proceed to injection, proceed with precaution or no injection.

Optimization, characterization, and follicular targeting assessment of tretinoin and bicalutamide loaded niosomes

Acne vulgaris, a prevalent skin disorder among teenagers and young adults, can have numerous psychological consequences. Topical treatment of acne would be advantageous by reducing the risk of systemic adverse drug reactions. However, the major challenge would be skin penetration through the stratum corneum. Therefore, during this study, tretinoin (TRT) and bicalutamide (BCT) loaded niosomes with follicular targeting potential were fabricated through the thin film hydration technique. Formulation optimization was performed using the Design-Expert software and optimum formulation was characterized in terms of particle size, zeta potential, transmission electron microscopy, drug loading, and differential scanning calorimetry. In vivo follicular targeting was assessed using rhodamine B-loaded niosomes to follow the skin penetration pathways. The results showed that, the optimum formulation was spherical in shape and had an average diameter of 319.20 ± 18.50 nm and a zeta potential of − 29.70 ± 0.36 mV. Furthermore, entrapment efficiencies were 94.63 ± 0.50% and > 99% and loading capacities were 1.40 ± 0.01% and 1.48 ± 0.00% for BCT and TRT, respectively. According to the animal study results, the prepared niosomes with an average diameter of about 300 nm showed significant accumulation in hair follicles. It seems that the designed niosomal BCT-TRT co-delivery system would be promising in acne management with follicular targeting potential.

Antibiotic-induced neurological adverse drug reactions

Antibiotics are drugs widely used all around the world. Central nervous system adverse drug reactions (CNS ADRs) are mostly under-suspected with antibiotics. Nevertheless, these ADRs could lead to severe complications such as encephalopathy. To illustrate the clinical patterns of these off-target ADRs, we here present data from pharmacovigilance system, through different populations and points of view (worldwide, French population, vulnerable population and individual). These data could help clinicians to better know about CNS ADRs with antibiotics, to better identify risk factors and vulnerable patients and to highlight the importance to set up the right diagnostic explorations in the best timing to avoid complications. Clinicians should request a pharmacological opinion from pharmacologist (biologists and pharmacovigilance clinicians) in front of vulnerable population before or during antibiotics. Pharmacovigilance advice could help clinicians in the diagnosis and the management of an ADR. Therapeutic drug monitoring is particularly contributive to adjust doses of antibiotics administered in vulnerable patients. Pharmacovigilance advice and TDM are essential to perform personalized medicine, and contribute to the proper use of drugs.

Retrospective Analysis of the Efficacy and Safety of Omidenepag Isopropyl 0.002% Ophthalmic Solution in Korean Patients

Purpose: This study aimed to analyze the clinical efficacy and safety of omidenepag isopropyl (OMDI) 0.002% in Korean patients.Methods: A retrospective study was conducted involving 306 patients diagnosed with glaucoma or ocular hypertension, who were administered OMDI 0.002% from May 2021 to June 2022. The primary outcomes were the change in intraocular pressure (IOP) at months 1, 3, and 6 compared to the baseline IOP, and the reactions to the OMDI drug.Results: Out of 235 patients who met the study inclusion criteria, the mean IOP was 16.5 ± 3.4 mmHg at baseline, 14.5 ± 3.0 mmHg at month 1, 14.3 ± 2.7 mmHg at month 3, and 14.7 ± 3.1 mmHg at month 6. The mean IOP reduction at month 6 was -1.6 ± 2.8 mmHg (p &lt; 0.001). On analyzing the IOP by types of glaucoma, the mean IOP change at the 6-month point showed statistically significant results in all types, including normal tension glaucoma, primary open-angle glaucoma, and ocular hypertension (p &lt; 0.05). The frequency of side effects in all patients was 29.8%, with the most commonly reported adverse drug reaction being hyperemia in 18.7% of the total patients. There was one case (0.4%) of uveitis after OMDI administration, but no other systemic adverse drug reactions were reported.Conclusions: Omidenepag isopropyl demonstrated a statistically significant IOP-lowering effect in Korean patients with various types of glaucoma. This suggests that OMDI could potentially serve as a first-line treatment for glaucoma.

Adverse Drug Reactions to Opioids: A Study in a National Pharmacovigilance Database.

Opioids are commonly used as analgesics; however, like any medicine, they can produce adverse drug reactions (ADRs), including nausea, constipation, dependence, and respiratory depression, that result in harmful and fatal events. Therefore, it is essential to monitor the safety of these drugs in clinical practice. This study aimed to characterize the safety profile of opioids by conducting a descriptive study based on a spontaneous reporting system (SRS) for ADRs in The Netherlands, focusing on abuse, misuse, medication errors, and differences between sexes. Reports submitted to the Netherlands Pharmacovigilance Centre Lareb from January 2003 to December 2021 with an opioid drug as the suspected/interacting medicine were analyzed. Reporting odds ratios (RORs) for drug-ADR combinations were calculated, analyzed, and corrected for sex and drug utilization (expenditure) for the Dutch population. A total of 8769 reports were analyzed. Tramadol was the opioid with the most reports during the period (n=2746), while oxycodone or tramadol had the highest number of reports per year in the study period. The most reported ADRs from opioid use were nausea, followed by dizziness and vomiting, independent of sex, and all of them were more often reported in women. Vomiting associated with tramadol (ROR females/males=2.17) was significantly higher in women. Buprenorphine was responsible for most ADRs when corrected for expenditure, with high RORs observed with application site hypersensitivity, application site reaction, and application site rash. Fentanyl gave rise to most of the reports of ADRs concerning abuse, misuse, and medication errors. Patients treated with opioids experienced ADRs, primarily nausea, dizziness, and vomiting. For those groups of drugs, no significant differences were found between the sexes, except for the vomiting associated with tramadol. In general, ADRs related to opioids presented higher RORs when uncorrected and corrected for sexes and expenditure than other drugs. There was more disproportionate reporting for ADRs concerning abuse, misuse, and medication errors for opioids than other drugs in the Dutch SRS.

Deep-Learning-Based Drug Recommendation and ADR Detection Healthcare Model on Social Media

The rapid rise of healthcare social media websites captures a significant amount of healthcare information, leading to mining medical content for pharmacovigilance, medication repositioning, and the healthcare industry. Paramedical advertisers gather health information from social media to propose suitable therapy. Social media makes patients aware of the revolution in clinical care and medical services. The researcher created a centralized social-media-based pharmacovigilance virtual podium to extract relevant medical services. And simultaneously built a virtual community of homogeneous e-patients for informational and emotional support. This article presents a new research-based review of the clinical recommendation system and possible medication repository and adverse drug reaction (ADR) research gaps. This article also explores ADR categorization with SVM, naive Bayes, linear regression, random forest, and deep neural networks. Subsequently, this article presents a preprocessing and clinical feature extraction approach described for drug recommendation and ADR classification. This methodology analyzed preprocessed clinical tweets for language diversity and clinical characteristics. This system also does multilayer content and collaborative filtering for patient-to-disease and disease-to-drug similarity indexing. It reveals the scope and collaborative filtering’s strengths and weaknesses. The collaborative association for filtering comparable clinical entities improves ADR detection and medicine recommendation. DNN comes out with the best result for ADR detection and classification and naive Bayes and SVM gain the comparatively biased result. In contrast, SVM achieves the highest improvement after preprocessing and with the amalgamation of clinical vector space. However, with the amalgamation of clinical vector space, the performance of ADR classification increased by approximately 12% and gained 86% accurate classification with the SIDER dataset.

Advances and Prospects for Hydrogel-Forming Microneedles in Transdermal Drug Delivery.

Transdermal drug delivery (TDD) is one of the key approaches for treating diseases, avoiding first-pass effects, reducing systemic adverse drug reactions and improving patient compliance. Microneedling, iontophoresis, electroporation, laser ablation and ultrasound facilitation are often used to improve the efficiency of TDD. Among them, microneedling is a relatively simple and efficient means of drug delivery. Microneedles usually consist of micron-sized needles (50-900 μm in length) in arrays that can successfully penetrate the stratum corneum and deliver drugs in a minimally invasive manner below the stratum corneum without touching the blood vessels and nerves in the dermis, improving patient compliance. Hydrogel-forming microneedles (HFMs) are safe and non-toxic, with no residual matrix material, high drug loading capacity, and controlled drug release, and they are suitable for long-term, multiple drug delivery. This work reviewed the characteristics of the skin structure and TDD, introduced TDD strategies based on HFMs, and summarized the characteristics of HFM TDD systems and the evaluation methods of HFMs as well as the application of HFM drug delivery systems in disease treatment. The HFM drug delivery system has a wide scope for development, but the translation to clinical application still has more challenges.

A tumor-specific ROS self-supply enhanced cascade-responsive prodrug activation nanosystem for amplified chemotherapy against multidrug-resistant tumors.

Chemotherapy remains the mainstay of cancer treatment, and doxorubicin (DOX) is recommended as a first-line chemotherapy drug against cancer. However, systemic adverse drug reactions and multidrug resistance limit its clinical applications. Here, a tumor-specific reactive oxygen species (ROS) self-supply enhanced cascade responsive prodrug activation nanosystem (denoted as PPHI@B/L) was developed to optimize multidrug resistance tumor chemotherapy efficacy while minimizing the side effects. PPHI@B/L was constructed by encapsulating the ROS-generating agent β-lapachone (Lap) and the ROS-responsive doxorubicin prodrug (BDOX) in acidic pH-sensitive heterogeneous nanomicelles. PPHI@B/L exhibited particle size decrease and charge increase when it reached the tumor microenvironment due to acid-triggered PEG detachment, to favor its endocytosis efficiency and deep tumor penetration. Furthermore, after PPHI@B/L internalization, rapidly released Lap was catalyzed by the overexpressed quinone oxidoreductase-1 (NQO1) enzyme NAD(P)H in tumor cells to selectively raise intracellular ROS levels. Subsequently, ROS generation further promoted the specific cascade activation of the prodrug BDOX to exert the chemotherapy effects. Simultaneously, Lap-induced ATP depletion reduced drug efflux, synergizing with increased intracellular DOX concentrations to assist in overcoming multidrug resistance. This tumor microenvironment-triggered cascade responsive prodrug activation nanosystem potentiates antitumor effects with satisfactory biosafety, breaking the chemotherapy limitation of multidrug resistance and significantly improving therapy efficiency. STATEMENT OF SIGNIFICANCE: Chemotherapy remains the mainstay of cancer treatment, and doxorubicin (DOX) is recommended as a first-line chemotherapy drug against cancer. However, systemic adverse drug reactions and multidrug resistance limit its clinical applications. Here, a tumor-specific reactive oxygen species (ROS) self-supply enhanced cascade responsive prodrug activation nanosystem (denoted as PPHI@B/L) was developed to optimize multidrug resistance tumor chemotherapy efficacy while minimizing the side effects. The work provides a new sight for simultaneously addressing the molecular mechanisms and physio-pathological disorders to overcome MDR in cancer treatment.

Safety and immunogenicity of IMVAMUNE®, a third-generation vaccine based on the modified vaccinia Ankara (MVA) strain

In 1980, the World Health Assembly officially declared smallpox eradicated in the world, which allowed developed countries to stop preventive vaccination against this disease. However, circulating and emerging orthopoxviruses along with the lack of herd immunity prompt the need for emergency smallpox vaccines meeting the current requirements for biologicals.The aim of the study was to analyse the safety and efficacy of third-generation smallpox vaccines based on the MVA strain of vaccinia virus compliant with the current (stricter) immunogenicity and safety requirements in healthy subjects and especially in patients with underlying health conditions, considering the lack of herd immunity to orthopoxviruses.The authors analysed the existing experience with smallpox vaccines. The vaccines based on the modified vaccinia Ankara (MVA) strain hold a special place amongst other third-generation vaccines, as this strain is safe and can be used for creating vector vaccines. Bavarian Nordic produces the MVA-based vaccine under three brand names (Imvanex in the EU, Jynneos™ in the USA, and IMVAMUNE® in Canada). According to the results of MVA-based vaccine clinical trials in healthy volunteers and patients with various underlying conditions, the main mild adverse drug reactions (erythema, pain, pruritus, and swelling) were mostly registered at the injection site. The systemic adverse drug reactions included fatigue, headache, myalgia, and chills; several subjects developed upper respiratory tract infections, nausea, and gastroenteritis, which resolved spontaneously within a day. MVA-based vaccines did not cause any cardiac abnormalities, including myo- or pericarditis. Thus, the vaccines may be used in patients with eczema, atopic dermatitis, inflammatory skin conditions, HIV, tuberculosis, cardiac abnormalities, as well as in children, adolescents, and pregnant women. The optimal intradermal immunisation dose was 1×108 TCID50. Two injections at this dose induced a pronounced humoral and cell-mediated immune response comparable to that induced by one administration of a first-generation smallpox vaccine. At this dose, the study vaccine also boosted pre-existing immunity conferred by a first-generation vaccine. The US Centers for Disease Control and Prevention recommend Jynneos™ for preventing monkeypox in adults (18 years of age and older).