Am Fam Physician. 2024 Feb;109(2):143-153.

ABSTRACT

Poisoning is the leading cause of injury-related morbidity and mortality in the United States. The highest rates of exposure to poisons occur in children five years and younger, but opioid overdoses in young adults account for most deaths from poisonings in recent years. Intentional or accidental medication poisoning should be considered when evaluating patients with mental status changes, vital sign abnormalities, seizures, and gastrointestinal or cardiovascular problems. For all poisoned patients, a comprehensive history and physical examination are needed. Knowledge of toxidromes may help identify the cause in unknown ingestions; however, their usefulness may be limited when multiple toxins are ingested. Electrocardiography is indicated in patients reporting chest pain and dyspnea and in overdoses of beta blockers, tricyclic antidepressants, and antidysrhythmics. Measurement of electrolyte, serum creatinine, and serum bicarbonate levels and calculation of the anion gap may be helpful based on the clinical presentation. Treatment of a patient with acute poisoning is based on resuscitation and stabilization with a focus on airway, breathing, and circulation. When poisoning is suspected, the Poison Control provides health care workers and the public with access to a specialist 24 hours a day.

PMID:38393798

Int J Oncol. 2024 Apr;64(4):38. doi: 10.3892/ijo.2024.5626. Epub 2024 Feb 23.

ABSTRACT

Lung cancer represents a marked global public health concern. Despite existing treatment modalities, the average 5‑year survival rate for patients with patients with lung cancer is only ~20%. As there are numerous adverse effects of systemic administration routes, there is an urgent need to develop a novel therapeutic strategy tailored specifically for patients with lung cancer. Non‑invasive aerosol inhalation, as a route of drug administration, holds unique advantages in the context of respiratory diseases. Nanoscale materials have extensive applications in the field of biomedical research in recent years. The present study provides a comprehensive review of the classification, applications summarized according to existing clinical treatment modalities for lung cancer and challenges associated with inhalable micron/nanoparticle drug delivery systems (DDSs) in lung cancer. Achieving localized treatment of lung cancer preclinical models through inhalation is deemed feasible. However, further research is required to substantiate the efficacy and long‑term safety of inhalable micron/nanoparticle DDSs in the clinical management of lung cancer.

PMID:38391039 | DOI:10.3892/ijo.2024.5626

Paediatr Respir Rev. 2024 Feb 12:S1526-0542(24)00014-9. doi: 10.1016/j.prrv.2024.01.004. Online ahead of print.

ABSTRACT

One hurdle in the management of CF, a disease characterized by progressive endobronchial infection, is the presence of hypersensitivity reactions to antimicrobials due to prolonged and repetitive treatment courses. The aim of this review is to compile existing data and provide insight to medical professionals on a long-debated topic for optimum patient care. Clinical studies were inducted from the last 15 years and filtered based on their relativity to drug hypersensitivity reactions (DHRs), antibiotics and CF. After completing the selection process, 10 clinical studies were thoroughly examined. The most frequent antibiotic group related to DHRs were beta-lactams. Frequency of the most common overall type of reaction (immediate or nonimmediate) differed among clinical studies. Although severe reactions seem rare comparatively, they do occur during and even after completion of treatment regimens. The prevalence of true drug allergies should be confirmed using a variety of tests available, however, should not be confused with overall DHR rates. Genetic mutations, gender and lifetime antibiotic dose were not related with an increased risk for DHR development. On the contrary, the most important factor according to most studies was the cumulative antimicrobial dose in a given period of time, especially when delivered parenterally. DHRs are an indisputable problem in the management of CF patients. Understanding possible risk factors and increased awareness is vital in both hospital and outpatient settings as early detection can decrease the severity of the reactions.

PMID:38395639 | DOI:10.1016/j.prrv.2024.01.004

BMJ Case Rep. 2024 Feb 23;17(2):e257772. doi: 10.1136/bcr-2023-257772.

ABSTRACT

We present the case of a patient with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) who received lutetium Lu-177 vipivotide tetraxetan (also known as 177Lu-PSMA-617) due to progressive disease despite chemotherapy, hormonal therapy and radiation, including palliative mediastinal and central nervous system radiation. He was subsequently hospitalised for worsening acute onset dyspnoea despite clinically responding to therapy. Interval imaging revealed progressive multifocal ground-glass opacities superimposed on a background of underlying peribronchovascular fibrosis. Further workup, including an extensive workup to identify a possible infectious aetiology, ruled out most aetiologies leaving radiation pneumonitis (RP), radiation recall pneumonitis (RRP) and drug-induced pneumonitis as possible diagnoses secondary to 177Lu -PSMA-617. The associated imaging findings of ground-glass opacities and consolidation can be like other aetiologies such as acute infection and subsequently may be treated incorrectly. In the use of theragnostics like 177Lu -PSMA-617, it is fundamental to apply the practices of radioprotection learnt from radiotherapy, as well as to consider prior radiotherapy treatments and their possible side effects when used in conjunction.

PMID:38395466 | DOI:10.1136/bcr-2023-257772

Sci Rep. 2024 Feb 22;14(1):4366. doi: 10.1038/s41598-024-54229-z.

ABSTRACT

Attrition rate is higher in developing nations and it leftovers a major obstacle to enhance the benefits of therapy and achieve the 90-90-90 plan targets. Despite this fact, data on the incidence and its predictors of attrition among human immune deficiency virus infected children on antiretroviral therapy are limited in developing countries including Ethiopia especially after the test and treat strategy implemented. This study aimed to assess the incidence and predictors of attrition among human immune deficiency virus infected children on antiretroviral therapy in Amhara Comprehensive Specialized Hospitals, Northwest Ethiopia. A retrospective follow-up study was conducted among 359 children on ART from June 14, 2014, to June 14, 2022. Study participants were selected using simple random sampling method and the data were collected using Kobo Toolbox software and analysis was done by STATA version 14. Both bi-variable and multivariable Cox regression models were fitted to ascertain predictors. Lastly, an AHR with a 95% CI was computed and variables with a p-value of < 0.05 were took an account statistically key predictors of attrition. The overall incidence of attrition rate was 9.8 (95% CI 7.9, 11.9) per 100 PYO. Children having baseline hemoglobin < 10 mg/dl (AHR 3.94; 95% CI 2.32, 6.7), suboptimal adherence (AHR 1.96; 95% CI 1.23, 3.13), baseline opportunistic infection (AHR 1.8; 95% CI 1.17, 2.96), and children who had experienced drug side effects (AHR 8.3; 95% CI 4.93, 13.84) were established to be a significant predictors of attrition. The attrition rate was relatively high. Decreased hemoglobin, suboptimal adherence, presence of drug side effects and baseline opportunistic infection were predictors of attrition. Therefore, it is crucial to detect and give special emphasis to those identified predictors promptly.

PMID:38388643 | PMC:PMC10883953 | DOI:10.1038/s41598-024-54229-z

Drug Saf. 2024 Feb 22. doi: 10.1007/s40264-024-01404-w. Online ahead of print.

ABSTRACT

Medical science has often used adult males as the standard to establish pathological conditions, their transitions, diagnostic methods, and treatment methods. However, it has recently become clear that sex differences exist in how risk factors contribute to the same disease, and these differences also exist in the efficacy of the same drug. Furthermore, the elderly and children have lower metabolic functions than adult males, and the results of clinical trials on adult males cannot be directly applied to these patients. Spontaneous reporting systems have become an important source of information for safety assessment, thereby reflecting drugs' actual use in specific populations and clinical settings. However, spontaneous reporting systems only register drug-related adverse events (AEs); thus, they cannot accurately capture the total number of patients using these drugs. Therefore, although various algorithms have been developed to exploit disproportionality and search for AE signals, there is no systematic literature on how to detect AE signals specific to the elderly and children or sex-specific signals. This review describes signal detection using data mining, considering traditional methods and the latest knowledge, and their limitations.

PMID:38388828 | DOI:10.1007/s40264-024-01404-w

Mult Scler. 2024 Feb 22:13524585241232277. doi: 10.1177/13524585241232277. Online ahead of print.

ABSTRACT

We present a case of a 30-year-old man with relapsing-remitting multiple sclerosis who developed psoriasiform dermatitis following his second course of ocrelizumab. This resolved with topical therapies and discontinuation of treatment. Cases of psoriasiform rashes have been increasingly reported in the use of ocrelizumab and are possibly due to B-cell (CD20) depletion and T-cell overregulation. Nevertheless, skin-related adverse reactions are not yet considered in the risk management plans of anti-CD20 treatments in multiple sclerosis.

PMID:38385208 | DOI:10.1177/13524585241232277

SAGE Open Med Case Rep. 2024 Feb 20;12:2050313X241233432. doi: 10.1177/2050313X241233432. eCollection 2024.

ABSTRACT

Remdesivir is a nucleotide prodrug of an adenosine analog. It binds to the viral Ribonucleic Acid (RNA)-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely. Remdesivir has demonstrated in vitro and in vivo activity against Severe Acute Respiratory Syndrome Coronavirus 2; it also acts in vitro neutralization activity against the Omicron variant and its subvariants. We reported a 54-years-old woman admitted with Coronavirus disease 2019. Considering to require a high fraction of inspired oxygen therapy (⩾0.6) and based on lung high resolution computed tomography, Remdesivir therapy was ordered for 5 days. She experienced palpitations and dizziness 2 days after starting Remdesivir therapy. Her QTc interval was prolonged on the electrocardiogram without any significant electrolyte abnormalities or concomitant use of medications. Although the cardiac side effects of Remdesivir therapy have been well documented, in a few cases reported the association between Remdesivir therapy and QTc interval prolongation. Since, QTc interval prolongation has the potential risk of sudden cardiac death, the clinicians should be aware of mentioned association and check electrocardiogram daily, as well as other laboratory exams.

PMID:38384983 | PMC:PMC10880539 | DOI:10.1177/2050313X241233432

EClinicalMedicine. 2024 Feb 15;69:102495. doi: 10.1016/j.eclinm.2024.102495. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: In April 2023, the antisense oligonucleotide tofersen was approved by the U.S. Food and Drug Administration (FDA) for treatment of SOD1-amyotrophic lateral sclerosis (ALS), after a decrease of neurofilament light chain (NfL) levels had been demonstrated.

METHODS: Between 03/2022 and 04/2023, 24 patients with SOD1-ALS from ten German ALS reference centers were followed-up until the cut-off date for ALS functional rating scale revised (ALSFRS-R), progression rate (loss of ALSFRS-R/month), NfL, phosphorylated neurofilament heavy chain (pNfH) in cerebrospinal fluid (CSF), and adverse events.

FINDINGS: During the observation period, median ALSFRS-R decreased from 38.0 (IQR 32.0-42.0) to 35.0 (IQR 29.0-42.0), corresponding to a median progression rate of 0.11 (IQR -0.09 to 0.32) points of ALSFRS-R lost per month. Median serum NfL declined from 78.0 pg/ml (IQR 37.0-147.0 pg/ml; n = 23) to 36.0 pg/ml (IQR 22.0-65.0 pg/ml; n = 23; p = 0.02), median pNfH in CSF from 2226 pg/ml (IQR 1061-6138 pg/ml; n = 18) to 1151 pg/ml (IQR 521-2360 pg/ml; n = 18; p = 0.02). In the CSF, we detected a pleocytosis in 73% of patients (11 of 15) and an intrathecal immunoglobulin synthesis (IgG, IgM, or IgA) in 9 out of 10 patients. Two drug-related serious adverse events were reported.

INTERPRETATION: Consistent with the VALOR study and its Open Label Extension (OLE), our results confirm a reduction of NfL serum levels, and moreover show a reduction of pNfH in CSF. The therapy was safe, as no persistent symptoms were observed. Pleocytosis and Ig synthesis in CSF with clinical symptoms related to myeloradiculitis in two patients, indicate the potential of an autoimmune reaction.

FUNDING: No funding was received towards this study.

PMID:38384337 | PMC:PMC10878861 | DOI:10.1016/j.eclinm.2024.102495

Front Immunol. 2024 Feb 1;15:1368496. doi: 10.3389/fimmu.2024.1368496. eCollection 2024.

NO ABSTRACT

PMID:38380321 | PMC:PMC10877587 | DOI:10.3389/fimmu.2024.1368496

Eur J Hosp Pharm. 2024 Feb 21:ejhpharm-2023-004028. doi: 10.1136/ejhpharm-2023-004028. Online ahead of print.

ABSTRACT

OBJECTIVES: Biological disease-modifying antirheumatic drugs (bDMARDs) require specific storage temperatures, but are frequently stored outside the recommended range of 2-8°C. As incorrect storage may affect therapy effectiveness and consequently lead to higher disease activity, compliance with recommended storage temperatures should be improved. eHealth interventions can provide insight into storage temperatures and alerts in case of deviations from recommended temperatures. Therefore, this study aims to assess the effect of a smart temperature logger on correctly storing bDMARDs at home by patients with rheumatic diseases.

METHODS: A pre-post study was performed in a hospital in the Netherlands. The baseline period consisted of 12 weeks of storage temperature measurement with a passive temperature logger, and the intervention period consisted of 12 weeks of storage temperature measurement with a smart temperature logger. This smart logger included a smartphone application which provided insight into storage temperatures and real-time alerts when exceeding recommended temperatures. The main outcome measure was the difference in the number of patients who stored their bDMARDs correctly between baseline and intervention. Secondary outcomes were the difference in the proportion of measurement time within 2-8°C between baseline and intervention, the distribution of measurement time among temperature categories, and the patient's acceptance measured using a questionnaire based on the Technology Acceptance Model.

RESULTS: In total, 48 participants (median age 55 years (IQR 47-64), 53% male) were analysed. The proportion of participants correctly storing bDMARDs increased from 18.8% (n=9) during baseline to 39.6% (n=19) during intervention (p=0.004). The median proportion of measurement time between 2-8°C improved by 6% (IQR 0-34%) (p<0.0001). Technology acceptance was scored as moderate.

CONCLUSIONS: Temperature monitoring and real-time feedback with a smart temperature logger shows potential to improve at-home storage of bDMARDs, provided that continuous connection is realised to ensure real-time alerts and data collection.

PMID:38383141 | DOI:10.1136/ejhpharm-2023-004028

Korean J Anesthesiol. 2024 Feb 20. doi: 10.4097/kja.23747. Online ahead of print.

ABSTRACT

BACKGROUND: Posterior spinal fusion (PSF), commonly used for adolescent idiopathic scoliosis (AIS), causes severe postoperative pain. Intravenous (IV) administration of acetaminophen has shown promise for opioid-sparing analgesia; however, its analgesic effect and optimal timing for its standard use remain unclear. Our study aimed to evaluate the analgesic effect and optimal timing of IV acetaminophen administration in pediatric and adolescent patients undergoing PSF and requiring adequate pain control.

METHODS: This prospective, randomized, triple-blind trial was conducted in patients aged 11-20 undergoing PSF. Participants were randomized into three groups: the preemptive group (received IV acetaminophen 15 mg/kg after anesthetic induction/before surgical incision), the preventive group (received IV acetaminophen 15 mg/kg at the end of surgery/before skin closure), and the placebo group. The primary outcome was cumulative opioid consumption during the first 24 h postoperatively.

RESULTS: Among the 99 enrolled patients, the mean ± standard deviation (SD) amount of opioid consumption during the postoperative 24 h was 60.66 ± 23.84, 52.23 ± 22.43, and 66.70 ± 23.01 mg in the preemptive, preventive, and placebo groups, respectively (overall p = 0.043). A post hoc analysis revealed that the preventive group had significantly lower opioid consumption than the placebo group (p = 0.013). However, no significant differences between the groups were observed for the secondary outcomes.

CONCLUSIONS: The preventive administration of scheduled IV acetaminophen reduces cumulative opioid consumption without increasing the incidence of drug-induced adverse events in pediatric and adolescent patients undergoing PSF.

PMID:38383005 | DOI:10.4097/kja.23747

Eur J Drug Metab Pharmacokinet. 2024 Feb 21. doi: 10.1007/s13318-024-00877-5. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative armed with a strong free radical scavenging nitrone moiety. This study aims to evaluate the pharmacokinetics, safety profile, and tolerability of TBN tablets after a single ascending dose (SAD) and multiple ascending doses (MAD) in healthy Chinese volunteers.

METHODS: This phase I, single-center, open-label study was conducted in China. The SAD portion consisted of four cohorts with dose levels of 400-1800 mg. The MAD portion included three cohorts in which subjects received doses of 600-1800 mg twice daily for 7 days (13 consecutive doses). The third portion was a randomized, two-period, crossover design to assess the influence of food with a single dose of TBN tablets (1200 mg). The safety profile was evaluated by monitoring adverse events (AEs), vital signs, electrocardiograms, physical examinations, and laboratory test results.

RESULTS: Fifty-two healthy subjects aged 18 to 45 years with a body mass index between 19.0 and 26.0 kg/m2 were enrolled. After a single dose of TBN, the median time to maximum plasma concentration (Tmax) was 2.48-3.24 h and the mean half-life (t1/2) was 1.28 to 2.10 h across all doses. In the MAD study, the median Tmax was 2.48 to 3.48 h. In the 400-1800 mg dose range, there was a tendency for less than proportional increases in the maximum plasma concentration (Cmax), the area under the concentration-time curve from 0 to time of last measurable concentration (AUC0-t), and the area under the concentration-time curve from 0 to infinity (AUC0-inf) in both single- and multiple-dose periods. A significantly higher TBN exposure was observed in females than males in both a single and multiple doses of the 600 mg and 1200 mg groups, with a geometric mean female-to-male ratio of 138.69-203.18%. Food decreased the Cmax and AUC0-t of TBN to 45.19% and 59.73%, respectively. Each dose group reached a steady state after 4 days. No drug accumulation was observed. Two subjects had drug-related AEs. A decreased neutrophil count and drug eruption in the SAD portion (1200 mg group) and an increased alanine aminotransferase level in the food effect group were found. All AEs were mild and tolerable (CTCAE grade 1) and resolved without any medical intervention.

CONCLUSION: TBN tablets had a good safety profile and were well tolerated in healthy Chinese volunteers. Steady-state concentrations were reached after 4 consecutive days of oral administration. The results of this phase I study will provide guidance for the design of future TBN clinical studies.

CHINESE CLINICAL TRIAL REGISTRY: ChiCTR1900022092.

PMID:38381348 | DOI:10.1007/s13318-024-00877-5

Front Neurol. 2024 Feb 6;15:1342111. doi: 10.3389/fneur.2024.1342111. eCollection 2024.

ABSTRACT

BACKGROUND: Migraine imposes a substantial global burden, impacting patients and society. Pharmacotherapy, as a primary treatment, entails specific adverse reactions. Emphasizing these reactions is pivotal for improving treatment strategies and enhancing patients' well-being. Thus, we conducted a comprehensive bibliometric and visual analysis of relevant literature.

METHODOLOGY: We conducted a comprehensive search on the Science Citation Index Expanded within the Web of Science, restricting the literature for analysis based on criteria such as document type, publication date, and language. Subsequently, we utilized various analytical tools, including VOSviewer, Scimago Graphica, the R package 'bibliometrix', CiteSpace, and Excel programs, for a meticulous examination and systematic organization of data concerning journals, authors, countries/regions, institutions, keywords, and references.

RESULTS: By August 31, 2023, the literature was distributed across 379 journals worldwide, authored by 4,235 individuals from 1726 institutions. It featured 2,363 keywords and 38,412 references. 'HEADACHE' led in publication count, with 'SILBERSTEIN S' as the most prolific author. The United States ranked highest in publication volume, with 'UNIV COPENHAGEN' leading among institutions.

CONCLUSION: Our research findings indicate that researchers in the field continue to maintain a focus on the calcitonin gene-related peptide (CGRP) system and explore diverse mechanisms for drug development through the application of novel biotechnological approaches. Furthermore, it is imperative to enhance the assessment of clinical trial outcomes, consistently monitor the efficacy and safety of prominent drugs such as Erenumab and Fremanezumab. There is a need for further evaluation of acute and preventive treatments tailored to different populations and varying types of migraine.

PMID:38379705 | PMC:PMC10878131 | DOI:10.3389/fneur.2024.1342111

BMC Bioinformatics. 2024 Feb 20;25(1):79. doi: 10.1186/s12859-024-05705-w.

ABSTRACT

BACKGROUND: Identification of potential drug-disease associations is important for both the discovery of new indications for drugs and for the reduction of unknown adverse drug reactions. Exploring the potential links between drugs and diseases is crucial for advancing biomedical research and improving healthcare. While advanced computational techniques play a vital role in revealing the connections between drugs and diseases, current research still faces challenges in the process of mining potential relationships between drugs and diseases using heterogeneous network data.

RESULTS: In this study, we propose a learning framework for fusing Graph Transformer Networks and multi-aggregate graph convolutional network to learn efficient heterogenous information graph representations for drug-disease association prediction, termed WMAGT. This method extensively harnesses the capabilities of a robust graph transformer, effectively modeling the local and global interactions of nodes by integrating a graph convolutional network and a graph transformer with self-attention mechanisms in its encoder. We first integrate drug-drug, drug-disease, and disease-disease networks to construct heterogeneous information graph. Multi-aggregate graph convolutional network and graph transformer are then used in conjunction with neural collaborative filtering module to integrate information from different domains into highly effective feature representation.

CONCLUSIONS: Rigorous cross-validation, ablation studies examined the robustness and effectiveness of the proposed method. Experimental results demonstrate that WMAGT outperforms other state-of-the-art methods in accurate drug-disease association prediction, which is beneficial for drug repositioning and drug safety research.

PMID:38378479 | DOI:10.1186/s12859-024-05705-w

J Child Adolesc Psychopharmacol. 2024 Feb;34(1):28-33. doi: 10.1089/cap.2023.0043.

ABSTRACT

Introduction: Combinatorial pharmacogenetic testing panels are widely available in clinical practice and often separate medications into columns/bins associated with low, medium, or high probability of gene-drug interactions. The objective of the Adolescent Management of Depression (AMOD) study was to determine the clinical utility of combinatorial pharmacogenetic testing in a double-blind, randomized, controlled effectiveness study by comparing patients who had genetic testing results at time of medication initiation to those that did not have results until week 8. The objective of this post hoc analysis was to assess and report additional outcomes with respect to significant gene-drug interactions (i.e., a medication in the high probability gene-drug interaction bin as defined by a proprietary algorithm) compared with patients taking a medication with minimal to moderate gene-drug interactions (i.e., a medication from the low or medium probability gene-drug interaction bin, respectively). Methods: Adolescents 13-18 years (N = 170) with moderate to severe major depressive disorder received pharmacogenetic testing. Symptom improvement and side effects were assessed at baseline, week 4, week 8, and 6 months. Patients were grouped into three categories based on whether the medication they were prescribed was associated with low, medium, or high risk for gene-drug interactions. Patients taking a medication from the low/medium gene-drug interaction bin were compared with patients taking a medication from the high gene-drug interaction bin. Results: Patients taking a medication from the high gene-drug interaction bin were more likely to endorse side effects compared with patients taking a medication in the low/medium gene-drug interaction bin at week 8 (p = 0.001) and 6 months (p < 0.0001). Depressive symptom severity scores did not differ significantly across the medication bins. Conclusions: This study demonstrates the utility of gene-drug interaction testing to guide medication decisions to minimize side effect burden rather than solely prioritizing the search for the most efficacious medication. (Clinical Trials Registration Identifier: NCT02286440).

PMID:38377526 | DOI:10.1089/cap.2023.0043

J Cancer Res Ther. 2023 Oct 1;19(7):2076-2078. doi: 10.4103/jcrt.jcrt_2165_21. Epub 2023 Jan 12.

ABSTRACT

The incidence of 5-Fluorouracil (5FU)- induced leukoencephalopathy is <5% among the patients treated with this agent. It may present with disorientation, confusion, agitation, seizure, and coma. It should be suspected when patients present with any of these symptoms during or immediately after 5FU chemotherapy. Early detection of drug-induced leukoencephalopathy is important as the clinical symptoms can be reversed by early discontinuation of the drug. Therefore, clinicians should be aware of the possibility of this adverse neurologic effect of 5FU. We describe the case of a 35-year-old female with carcinoma esophagus with 5FU-induced leukoencephalopathy.

PMID:38376324 | DOI:10.4103/jcrt.jcrt_2165_21

Antivir Ther. 2024 Feb;29(1):13596535241233128. doi: 10.1177/13596535241233128.

ABSTRACT

BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs.

METHODS: Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods.

RESULTS: During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, p = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs.

CONCLUSIONS: Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.

PMID:38375582 | DOI:10.1177/13596535241233128

Drug Des Devel Ther. 2024 Feb 15;18:453-462. doi: 10.2147/DDDT.S438703. eCollection 2024.

ABSTRACT

INTRODUCTION: Methotrexate (MTX) is one of the most widely used drugs in cancer chemotherapy and treating rheumatoid arthritis. The hepatotoxicity of MTX is one of its major side effects. Roflumilast (ROF) has been recognized to have antioxidant and anti-inflammatory activity in in-vivo and in-vitro models. The present study aimed to explore the potential protective effects of roflumilast against MTX-induced liver toxicity in male Wistar rats.

METHODS: High dose of 5 mg/kg for 4 consecutive days subcutaneous (S.C) injection of methotrexate for induction of acute liver injury. A total of 24 Wistar rats, rats were used in four different groups. The NS injections were given S.C to the control group once a day for 4 consecutive days. SC injections of MTX (5 mg/kg) were given to the MTX group daily for four days. At 5 mg/kg once daily for four days, the roflumilast group was given daily oral roflumilast. An injection of MTX and oral roflumilast were given to the MTX + roflumilast group once daily for four consecutive days.

RESULTS: Administration of high dose MTX (5 mg/kg) today 4 produced a significant decrease in hepatic glutathione (GSH) levels and a significant increase in ALT and AST liver enzymes, hepatic malondialdehyde (MDA), tumor suppressor protein (p53), interleukin 6, interleukin 1 levels compared to the control group. Treatment with roflumilast for 4 days significantly attenuated unfavorable changes in these parameters. According to histopathological findings, Roflumilast significantly reduced MTX-induced inflammation and degeneration in the liver. In conclusion, the findings indicate that roflumilast may have a potential therapeutic benefit in treating rats with MTX-induced liver toxicity by mitigating its effects.

PURPOSE: The aim of this study is to investigate the potential protective effects of roflumilast against MTX-induced liver toxicity in Wistar rats.

PMID:38374827 | PMC:PMC10875972 | DOI:10.2147/DDDT.S438703

Urol Pract. 2024 Mar;11(2):312-323. doi: 10.1097/UPJ.0000000000000497. Epub 2024 Feb 6.

ABSTRACT

INTRODUCTION: Medical misinformation regarding COVID-19 immunization remains rampant and a public concern, and as such, there is a need for national studies evaluating the immunization's safety profile. We sought to quantify and analyze urologic adverse events and symptoms after COVID-19 immunization, compare these events reported between COVID-19 vaccine types, and compare these events reported following COVID-19 immunization relative to those reported following other immunizations.

METHODS: We conducted a retrospective case-control disproportionality analysis by querying the Food and Drug Administration Vaccine Adverse Event Reporting System for all reported symptoms following COVID-19 immunization through December 23, 2022, as well as for all non-COVID immunizations.

RESULTS: Using a total of 704,231 event reports containing 2,982,187 symptoms related to COVID vaccination and a total of 770,975 event reports containing 2,198,993 symptoms related to all vaccinations other than COVID-19 for disproportionality analysis, no urologic symptom produced a positive signal when grouping all vaccinations. When stratifying by manufacturer, some symptoms related to Janssen vaccination were positive, but this may be in part due to overreporting secondary to media attention rather than a strong association between Janssen vaccination and urologic adverse events.

CONCLUSIONS: Although there have been anecdotal reports of adverse events associated with the COVID-19 vaccine, our review of the Vaccine Adverse Event Reporting System database did not produce positive signals across all 4 measures for any potential adverse event. Our findings do not suggest increased scrutiny is required regarding these adverse events potentially related to the COVID-19 immunization. Further evaluation and analysis of the COVID-19 immunization is ongoing.

PMID:38377155 | DOI:10.1097/UPJ.0000000000000497