Drug Categories Research Articles

Evaluating the Protective Effect of Melatonin on Atorvastatin-induced Mitochondrial Toxicity in Pancreatic Beta Cells.

Atorvastatin and other statins belong to a category of cholesterollowering drugs, which may cause some damage to pancreatic cells despite their effectiveness. The present study investigated the effects of melatonin against atorvastatin-induced toxicity on islets of Langerhans and CRI-D2 cells. The MTT assay was used to determine cell viability. The effect of various concentrations of melatonin (0,10, 50, 100, 250, 500 and 1000 μM) on CRI-D2 cell viability was evaluated for 24 hours to determine the non-cytotoxic concentrations of melatonin. Additionally, cells were treated with different concentrations of atorvastatin (10, 100, and 150 ng/mL) for 24 hours to determine a concentration that could induce the maximum cell death. After selecting the appropriate concentrations for melatonin, cells were treated with atorvastatin (10, 100, and 150 ng/ml) and melatonin (10 and 100 μM) simultaneously for a period of 24 hours. Malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, catalase, and glutathione peroxidase activity were assessed as indicators of oxidative stress. To assess mitochondrial function, the ratio of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) were measured. Atorvastatin markedly raised ROS and MDA levels. This result was associated with a decrease in MMP, an increase in the ADP/ATP ratio, and a change in the activity of antioxidant enzymes. Atorvastatin (150 ng/mL)-induced mitochondrial damage was alleviated by concurrent melatonin and atorvastatin therapy. These results suggest that melatonin has a protective effect against atorvastatininduced toxicity in the mitochondria of pancreatic cells.

Enhancing drug-target interaction predictions in context of neurodegenerative diseases using bidirectional long short-term memory in male Swiss albino mice pharmaco-EEG analysis

Background and ObjectiveEmerging diseases like Parkinson or Alzheimer's, which are not curable, endanger human mental health and are challenging to research. Drug target interactions (DTI) are pivotal in the screening of candidate drugs and focus on a small pool of drug targets. Electroencephalogram shows the responses to psychotropic medicines in the brain bioelectric activity. Synaptic activity can be analyzed by using Local Field Potential recordings obtained from micro-electrodes implanted in the brain. The aim is to evaluate the effects of drug on brain bioelectric activity and increase the drug classification accuracy. The ultimate goal is to advance our understanding of how drugs affect synaptic activity and open the door to more focused treatment for neurodegenerative diseases. MethodsIn this study, Pharmaco-EEG recordings are processed using Advanced neural network models, particularly Convolutional Neural Networks, to assess the effects of medications. The five different medicines used in this study are Ephedrine, Fluoxetine, Kratom, Morphine, and Saline. The signals observed are local field potential signals. To overcome some limits of DTI prediction, we propose Bidirectional Long Short-Term Memory (LSTM) for the categorization of intracranial EEG (i-EEG) data, departing from standard approaches. Similar EEG patterns are presumably caused by drugs that work by homologous pharmacological pathways, producing similar psychotropic effects. To improve accuracy and reduce training loss, our study introduces a bidirectional LSTM model for classification along with Bayesian optimization ResultsHigh recall, precision, and F1-Scores, particularly a 95% F1-Score for morphine, ephedrine, fluoxetine, and saline, suggest good performance in predicting these drug classes. Kratom produces a somewhat lower recall of 94%, but a high F1-Score of 97% and perfect precision of 1.00. The weighted average F1-Score, macro average, and overall accuracy are all consistently high (around 97%), indicating that the model works well throughout the spectrum of drugs. ConclusionsImproved model performance was demonstrated by using a diversified dataset with five drug categories and bidirectional LSTM boosted with Bayesian optimization for hyperparameter tuning. From earlier limited-category models, it represents a substantial advancement.

A drug repurposing screen reveals dopamine signaling as a critical pathway underlying potential therapeutics for the rare disease DPAGT1-CDG.

DPAGT1-CDG is a Congenital Disorder of Glycosylation (CDG) that lacks effective therapies. It is caused by mutations in the gene DPAGT1 which encodes the first enzyme in N-linked glycosylation. We used a Drosophila rough eye model of DPAGT1-CDG with an improperly developed, small eye phenotype. We performed a drug repurposing screen on this model using 1,520 small molecules that are 98% FDA/EMA-approved to find drugs that improved its eye. We identified 42 candidate drugs that improved the DPAGT1-CDG model. Notably from this screen, we found that pharmacological and genetic inhibition of the dopamine D2 receptor partially rescued the DPAGT1-CDG model. Loss of both dopamine synthesis and recycling partially rescued the model, suggesting that dopaminergic flux and subsequent binding to D2 receptors is detrimental under DPAGT1 deficiency. This links dopamine signaling to N-glycosylation and represents a new potential therapeutic target for treating DPAGT1-CDG. We also genetically validate other top drug categories including acetylcholine-related drugs, COX inhibitors, and an inhibitor of NKCC1. These drugs and subsequent analyses reveal novel biology in DPAGT1 mechanisms, and they may represent new therapeutic options for DPAGT1-CDG.

Measurement Uncertainty and Validation for Quantification of Marijuana Metabolite: (−)-11-nor-9-Carboxy-Δ9-THC in Human Urine by GC-MS/MS

Background: Since the International Olympic Committee (IOC) was established, sports doping control analyses have revealed a high rate of positive cases for cannabinoids. Cannabinoids were banned in all sports where they were used in competition as per the Prohibited List published annually. Further, it was also included in the threshold drug category. Consequently, developing a reliable method for urine Cannabinoids metabolite quantification plays a pivotal role in sports dope testing. Objective: This work aimed to develop and validate a reliable, cost-effective, robust gas chromatography-tandem mass spectrometry method for detecting (−)-11-nor-9-Carboxy-Δ9- THC component in human urine samples, in compliance with ICH and WADA guidelines. Method: The sample preparation was done by enzymatic hydrolysis for deconjugation, further proceeded with solid phase extraction (SPE), liquid-liquid extraction (LLE), and using an XAD2 column, and N-methyl trimethylsilyl trifluoroacetamide (MSTFA) for derivatization. Results: The linearity was obtained in a range of 50–300 ng/mL, and the correlation coefficient was found to be higher than 0.99. Throughout the entire validation study, the difference in Retention Time (RT) for the analyte, including the Internal Standard (IS), was shown to be less than 1.0%. The quantification limit (LOQ) was calculated at a level of 50 ng/mL in human urine samples for the 3 most abundant ion transitions. The detection limit (LOD) was established at 4 ng/mL. Conclusion: The accuracy, precision, linearity, recovery, quantification limit, and selectivity by GC-MS/MS technique were found acceptable and well satisfactory while following the ICH guidelines. The developed method has been proven to be fit for purpose in accordance with the enforced Guidelines of WADA.

Monitoring and modulating respiratory drive in mechanically ventilated patients.

Respiratory drive is frequently deranged in the ICU, being associated with adverse clinical outcomes. Monitoring and modulating respiratory drive to prevent potentially injurious consequences merits attention. This review gives a general overview of the available monitoring tools and interventions to modulate drive. Airway occlusion pressure (P0.1) is an excellent measure of drive and is displayed on ventilators. Respiratory drive can also be estimated based on the electrical activity of respiratory muscles and measures of respiratory effort; however, high respiratory drive might be present in the context of low effort with neuromuscular weakness. Modulating a deranged drive requires a multifaceted intervention, prioritizing treatment of the underlying cause and adjusting ventilator settings for comfort. Additional tools include changes in PEEP, peak inspiratory flow, fraction of inspired oxygen, and sweep gas flow (in patients receiving extracorporeal life-support). Sedatives and opioids have differential effects on drive according to drug category. Monitoring response to any intervention is warranted and modulating drive should not preclude readiness to wean assessment or delay ventilation liberation. Monitoring and modulating respiratory drive are feasible based on physiological principles presented in this review. However, evidence arising from clinical trials will help determine precise thresholds and optimal interventions.

Anaplastic thyroid carcinoma: a genome-based search for new targeted therapy options

Abstract Introduction/Objective Anaplastic thyroid carcinoma (ATC) is a rare, aggressive thyroid cancer. Precision medicine, particularly gene-targeted therapy has emerged as a promising avenue in cancer treatment. However, few targeted therapies have been approved for ATC. Here, we present a genome-based search for new targeted therapy options using next-generation sequencing (NGS) data of 727 ATC cases. Methods/Case Report Deidentified NGS results in 727 ATC cases were obtained from Foundation Medicine. A search of the literature and genomic databases (TCGA, My Cancer Genome, and DGIdb) was performed to analyzed frequency of gene mutations and corresponding gene targeted drugs. Results (if a Case Study enter NA) Remarkably, 99.17% of the 727 ATC cases had at least one targeted drug option available. Among the 254 unique genes identified with pathogenic mutations, 150 (59.06%) were found to have at least 1 corresponding targeted drug. Among the top 35 most frequently mutated genes (frequency > 2.0%), 27 (80.00%) had available targeted therapies. Notably, most drug categories (70.83%) exhibited multi-gene targeting capabilities. The drug categories based on the percentage of genes targeted from highest to lowest are Serine/Threonine and Tryosine kinase inhibitors, therapeutic antibodies, MEK inhibitors, CDK inhibitors, AKT inhibitors, PI3K inhibitors and immunotherapies. There are an additional 16 drug categories that target 1 to 5 of the 35 frequently mutated genes identified. Of particular interest is MTAP, a previously unreported frequently mutated gene which is most often deleted (14.77%). Several drugs are undergoing phase 1 and/or phase 2 clinical trials for MTAP-deleted solid tumors. MTAP loss holds promise for identifying expanding therapeutic options in ATC. Conclusion Our genome-based analysis indicates that 99.17% of the 727 ATC cases have targeted drug options, targeting 59.06% of identified gene mutations. Among the 24 categories of targeted drugs 17 (70.83%) target more than one gene. The 2018 FDA approval of combination BRAF/MEK inhibitor therapy for management of BRAF V600E-positive ATC was a major first step in gene targeted therapies. Besides that, Tyrosine kinase inhibitors, mTOR inhibitor, PPAR-γ agonist, ALK inhibitor, VEGF inhibitor and several combined treatment and immunotherapeutic agents are currently being tested in ATC clinical trials. These promising findings highlight the expanding repertoire of gene-targeted therapy options in ATC and emphasizes the importance of combined strategies and identifying driver mutations.

Analysis of prescriptive monitoring regarding the current therapeutic landscape of rheumatoid arthritis: the experience of an Italian local health authority

ABSTRACT Introduction Rheumatoid Arthritis (RA) is among the most prevalent chronic inflammatory diseases affecting millions of people with a significant expenditure of resources by National Healthcare Systems. This study aimed to analyze all available treatments exclusively for RA to highlight the costs of each treatment type and raise awareness of the use of biosimilar drugs. Methods In an Italian healthcare authority, all prescriptions made for the diagnosis of RA were extracted to verify consumption expressed in Defined Daily Dose (DDD) and the expenditure incurred expressed in euros. Consequently, a grouping into three major drug categories has been performed: anti – tumor necrosis factor alpha agents (TNFα), other injectable formulations, and novel oral formulations. Results Prescriptions for the second half-year 2022 and 2023 have been analyzed, with a total cost of almost 7 million euros in the sample considered. All pharmaceutical categories showed an increase in consumption, but only anti- TNFα recorded a decrease in costs from 25% in 2022 to 22% in 2023, thanks to the lower cost of the biosimilar drug. Conclusion The costs of RA may represent a significant spending commitment for central governments. As a result, actions are needed to encourage the preferential use of biosimilar drugs.

Molecular Docking of Natural Alkaloids with Bcl-xL Protein in The Apoptosis Process

Background: The anti-apoptotic protein Bcl-xL is a viable target for cancer therapy due to its critical role in cancer formation and resistance to chemotherapy. Insights into Bcl-xL’s role have spurred the development of a new category of cancer drugs called Bcl-xL inhibitors, which mimic the BH3-only protein to cause apoptosis. It could be initiated using alkaloids, owing to their remarkable biological characteristics. Alkaloids, among the biggest obtainable from plants, possess a distinctive structure characterized by the presence of a nitrogen atom in various positions within the molecule. Objective: In the current study, the potential of various alkaloids as Bcl-xL inhibitors was investigated through a molecular docking study. Methods: AutoDock Vina software was used to perform docking simulations of the alkaloids. Results: Ten alkaloids/Bcl-xL protein complexes demonstrated strong binding affinities less than -8.0 kcal/mol-1. These complexes include phaenthine (26), 4,5-Dioxoaporphine (1), anonaine (2), atherospermidine (4), limacine (14), liriodenine (16), monomargine (18), ouregidione (24), oxostephanine (25), and taliscanine (29) as the ligand of Bcl-xL protein. Notably, the complexes of Bcl-xL/dicentrinone (10), ouregidione (24), stepharine (28), and taliscanine (29) displayed three to four hydrogen bonds along with hydrophobic contacts. Conclusion: These results suggest that certain alkaloids could act as potential Bcl-xL inhibitors, mimicking BH3-only proteins and thereby potentially triggering apoptosis during cancer treatment.

Comparison of the effect of different doses of phenylephrine infusion on the prevention of hypotension in the elderly under spinal anaesthesia in orthopaedic surgery.

Considering the vasopressor drug categories and doses that can be used for elderly patients following hypotension are few, the present trial aimed to compare the effect of different doses of phenylephrine infusion on the prevention of hypotension in elderly patients undergoing orthopaedic lower extremities surgery. This randomised, double-blind prospective clinical trial was conducted by including 60 elderly patients older than 60 years and classified as American Society of Anesthesiology class I and II who were candidates for femur fracture fixation surgery. White and black cards randomly allocated patients to: group A (25µg/kg/h phenylephrine) or group B (35µg/kg/h phenylephrine). At the T3-T7 time points, group A's systolic and diastolic blood pressure was significantly higher than in group B's (p < 0.05). However, after 27 minutes (T0-T7) of phenylephrine infusion, statistical analysis showed no significant difference between the two groups regarding blood pressure (T8-Tend). The frequency of bradycardia and reactive hypertension in group B were significantly higher than in group A (p = 0.02) and (p = 0.03), respectively. There was no significant difference between the bleeding loss, blood transfusion and crystalloid volume in both groups (p > 0.05). Our trial illustrated that high-dose phenylephrine infusion could not assure haemodynamic stability and may cause some side effects.

Treatment patterns and clinical outcomes in HER2-low metastatic breast cancer, 2018–2023: A retrospective observational study.

398 Background: Current treatment options for patients (pts) with hormone receptor–positive (HR+) human epidermal growth factor receptor 2–low (HER2-low) (immunohistochemistry [IHC] 1+, IHC 2+/in situ hybridization–negative) metastatic breast cancer (mBC) who progress after endocrine therapy (ET) with or without targeted therapy, including CDK4/6 inhibitors (CDK4/6i) or inhibitors of the PIK3CA/AKT/mTOR pathway, have been limited to chemotherapy (CT).In this study, we assessed recent treatment patterns and clinical outcomes in US pts with HR+/HER2-low mBC. Methods: This was a retrospective observational study using the nationwide Flatiron Health electronic health record-derived de-identified database. Pts aged ≥18 years with no prior cancer (excluding non-melanoma skin cancer), de-novo or recurrent HR+/HER2-low mBC diagnosed between January 2018 and December 2022, and who received any line of treatment (LOT) for mBC (excluding clinical trials) were included. Demographic and clinical characteristics were captured prior to and at the index date (date of mBC diagnosis). Pts were followed up from index date to death, last activity date, or end of the study (September 30, 2023). Real-world overall survival (rwOS) from mBC diagnosis and real-world progression-free survival (rwPFS) from the start of each LOT was calculated using the Kaplan-Meier method. Results: A total of 2692 pts were eligible. Median follow up from mBC diagnosis was 38.3 months (interquartile range [IQR] 24.4, 53.4) and median age at mBC diagnosis was 65.0 years (IQR 56.0, 73.0); 45.3% of pts had de-novo mBC. Median LOT was 2.0 (IQR 1.0, 3.0) up to the end of the study (55.1% of pts received second-line [2L], 28.9% third-line [3L], 15.2% fourth-line [4L], and 7.2% fifth-line [5L] therapy). Serial ET cycles accounted for 65.7% of 2L, 45.2% of 3L, 27.9% of 4L, and 18.5% of 5L therapy. The most common drug categories by LOT are shown in the Table. Median rwOS was 43.0 months (95% confidence interval [CI] 40.0, 46.0). rwPFS was 20.5 months (95% CI 19.0, 22.3) in first-line [1L] therapy, 15.6 months (95% CI 14.0, 18.9) in 2L, 17.1 months (95% CI 13.5, 22.8) in 3L, and 13.4 months (95% CI 9.9, not estimable) in 4L. Conclusions: Treatment of HR+/HER2-low mBC has been heterogenous by LOT and mainly characterized by initial use of ET-based therapy followed by higher CT use in later lines. This is associated with diminishing effectiveness, highlighting a need for new treatments. Top five drug categories by LOT, n (%). 1L (n=2692) 2L (n=1484) 3L (n=778) 4L (n=408) 5L (n=195) ET + CDK4/6i 1537 (57.1) 694 (46.8) 217 (27.9) 76 (18.6) 25 (12.8) Endocrine monotherapy 684 (25.4) 202 (13.6) 126 (16.2) 52 (12.8) 21 (10.8) ET + mTORi 9* 61 (4.1) 55 (7.1) 25 (6.1) 17 (8.7) ET + CT 50 (1.9) 74 (5.0) 45 (5.8) 29 (7.1) 22 (11.3) CT alone 269 (10.0) 270 (18.2) 210 (27.0) 161 (39.5) 82 (42.1) CDK4/6i alone 69 (2.6) 29* 8* 3* 3* *Not a top five drug category in the specified LOT.

Forty-two Percent of Patients Undergoing Arthroscopic Shoulder Surgery are Using Psychotropic Medications

PurposeThe purposes of this study were to determine the prevalence of psychotropic medication use in patients undergoing shoulder arthroscopy at a single institution, and to identify the most common medications and classes of drugs being taken in this specific patient population. We hypothesized a large portion of patients undergoing shoulder arthroscopy are concomitantly taking prescription psychotropic medications. MethodsA retrospective chart review was conducted on patients treated by three fellowship trained orthopaedic sports medicine and shoulder surgeons between 2019-2021. All patients who underwent shoulder arthroscopy during this time period were included. The following data was collected: age, sex, laterality for surgery, prior surgeries on operated shoulder, specific surgery performed, and use of psychotropic medications. Drug categories included anticonvulsants, antidepressant/ anxiolytics, sedative hypnotics, stimulants, antipsychotics, and multiple psychotropic drugs. Psychotropic medications were included if they were listed as ‘taking’ at any point in time in the patient’s chart within a 6-month window prior to surgery. ResultsOf the 1,279 (828 males; 451females) patient charts that were reviewed, 534 (41.8%) were prescribed at least one psychotropic. In 2021, 201 (44.4%) of the 453 patients were taking at least one psychotropic. Similarly in 2020, 152 (38.2% of the 453 patients) and 2019, 181 (42.2% of the 429 patients) were found to be on at least one psychotropic. Of the 1,279 patients included, 282 (34.1%) of 828 males were prescribed psychotropic drugs, as compared to 252 (55.9%) of 451 females (p=0.001). From 2019-2021, 137 (25%) of the patients using psychotropic drugs, were prescribed anticonvulsant/mood stabilizers, 105 (19%) antidepressants, 75 (14%) sedative hypnotics, 23 (4%) stimulants, 4 (1%) antipsychotics, 190 (35%) were prescribed multiple psychotropics. From 2019-2021 the rate of antidepressant/ anxiolytic and or sedative hypnotic prescription psychotropic drug use increased from 28% to 30.5% (p=.42). ConclusionThis study demonstrated that a large portion of patients undergoing shoulder arthroscopy were taking psychotropic medication. Further, it was found that female patients had significantly higher utilization of these medications, as compared to males. Clinical RelevanceUnderstanding the prevalence of these medications in orthopaedic patients is essential for surgeons to take into consideration, in order to limit pre-, intra-, and post-operative complications, as well as optimize patient outcomes.

Clinical drug interactions between voriconazole and 38 other drugs: a retrospective analysis of adverse events.

Voriconazole (VRZ) is involved in a variety of drug‒drug interactions (DDIs), but few studies have reported adverse events (AEs) associated with the DDIs of VRZ. The primary goal of this study was to analyse the potential risk factors for AEs caused by DDIs between VRZ and other drugs via the OpenVigil FDA platform and to provide a reference for preventing VRZ DDIs and monitoring clinically related adverse drug events. A retrospective pharmacovigilance study was conducted to investigate the AEs related to DDIs between VRZ and four categories of drugs: proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants, and other antibacterial drugs. AE information for the target drugs from the first quarter of 2004 to the third quarter of 2022 was downloaded from the OpenVigil FDA data platform. Four frequency statistical models-the reporting ratio method, Ω shrinkage measure model, combination risk ratio model, and the chi-square statistics model-were used to analyse the AEs related to DDIs and evaluate the correlation and influence of sex and age between the drug(s) and the target AEs detected. A total of 38 drugs were included, with 262 AEs detected by at least one of the four models and 48 AEs detected by all four models. Some 77 detected AEs were significantly positively correlated with DDIs and were related to higher reporting rates of AEs than when used alone. Graft-versus-host disease was the AE that had the strongest correlation with the drug interaction between VRZ and immunosuppressants (tacrolimus, mycophenolate mofetil, cyclophosphamide, and cyclosporine), and multiple organ dysfunction syndrome was correlated with VRZ in combination with other antibacterial drugs (linezolid, meropenem, cefepime, and vancomycin). Significant sex and age differences in the target AEs were detected for five and nine target drugs, respectively. For VRZ in combination with linezolid, aggravated conditions and respiratory failure should be given more attention in male patients, and mycophenolate mofetil and respiratory failure in female patients. When conditions are aggravated, febrile neutropenia and septic shock should be of particular concern in patients over 18years of age who use VRZ in combination with ceftazidime, ciprofloxacin, or cytarabine. In patients aged under 18, septic shock should be considered when VRZ is used in combination with meropenem and dexamethasone. AEs related to DDIs should receive more attention when VRZ is used in combination with PPIs (renal impairment), NSAIDs (constipation and renal failure), immunosuppressants (graft versus host disease, septic shock) and other antibacterial drugs (multiple organ dysfunction syndrome, febrile neutropenia, and respiratory failure). Considering the influence of sex and age differences in VRZ DDIs, these factors need to be considered when assessing the risk of AEs in patients receiving VRZ and other drugs.

Bariatric surgery decreases prescription drug costs for metabolic syndrome: a Canadian population-based cohort study.

Obesity is a chronic disease that is significantly linked to metabolic syndrome. Bariatric surgery is considered the most effective treatment for obesity resulting in long-term weight loss and comorbidity resolution. Prior studies have demonstrated the overall cost effectiveness of bariatric surgery; however, there is little data regarding direct pharmaceutical costs. The objective of this population-based study is to compare the cost of dispensed common prescription medications for metabolic syndrome before and after bariatric surgery. All patients that were enrolled in the Center for Metabolic and Bariatric Surgery who underwent gastric bypass or sleeve gastrectomy between 2013 and 2019 in Manitoba were included. Basic demographic information and outpatient prescription dispensation data were obtained from the Manitoba Population Research Data Repository, which is housed at the Manitoba Centre for Health Policy. Specific drug categories that were reviewed for costs 5years before and after surgery included Antihypertensives, Lipid Lowering Agents, Insulin and Non-insulin Diabetic Drugs. One thousand one hundred and eighty four patients were included in this review. Comparing the 5-yearpre- and post-surgery, there was a decrease in the overall amount of drug dispensed and the overall cost for all drug categories in the 5years following surgery. These categories included Antihypertensives ($506,268.8), Lipid Lowering Agents ($173,866.48), Insulin ($549,305.92), and Other Diabetes Drugs ($513,371.1). Additionally, older patients experienced a larger proportion of cost savings compared to younger patients, with the exception of non-insulin diabetic medications which trended to have more cost savings in the 30-49year old grouping. This is the first Canadian study to use accurate dispensing data from a provincial administrative prescription database to capture long-term cost savings for metabolic prescriptions after bariatric surgery. The results are consistent with the existing literature for prescriptions post-bariatric surgery. Future study will include subgroup analysis by patient age, gender, income quintile, and geography.

Drug-induced Acute Lung Injury: A Comprehensive Radiologic Review.

Drug-induced acute lung injury is a significant yet often underrecognized clinical challenge, associated with a wide range of therapeutic agents, including chemotherapy drugs, antibiotics, anti-inflammatory drugs, and immunotherapies. This comprehensive review examines the pathophysiology, clinical manifestations, and radiologic findings of drug-induced acute lung injury across different drug categories. Common imaging findings are highlighted to aid radiologists and clinicians in early recognition and diagnosis. The review emphasizes the importance of immediate cessation of the offending drug and supportive care, which may include corticosteroids. Understanding these patterns is crucial for prompt diagnosis and management, potentially improving patient outcomes.

Cerebrospinal Fluid Homovanillic and 5-Hydroxyindoleacetic Acids in a Large Pediatric Population; Establishment of Reference Intervals and Impact of Disease and Medication.

Cerebrospinal fluid (CSF) homovanillic (HVA), and 5-hydroxyindoleacetic acids (5-HIAA) are biomarkers of neurological diseases affecting the dopaminergic and serotoninergic pathways. Establishing reference intervals for these metabolites faces the challenges of a lack of healthy controls and a negative correlation with age, making stratified intervals unrealistic. We propose a pipeline to determine continuous reference intervals for HVA and 5-HIAA using an indirect method. We also studied the confounding effects of different variables and explored the impact of antiepileptic and neuroleptic treatments on HVA and 5-HIAA values. The study used least squares regression to fit age-concentration curves from a cohort of pediatric patients (n = 1533), where the residuals represent metabolite values excluding age effect. Presuming that HVA and 5-HIAA primary deficiencies characterize a distinct subpopulation, we fitted a two-component finite mixture model in age-normalized data and set reference intervals at the central 95% of the nondeficient population. Patients with primary genetic deficiencies of HVA and/or 5-HIAA consistently fall outside the proposed continuous reference intervals. Using the new continuous reference intervals reduces the number of secondary deficiencies detected compared with using stratified values. No correlations were observed between CSF HVA and 5-HIAA values across the studied drug categories (antiseizure and neuroleptic medications). In addition, biopterin values positively influenced both metabolite concentrations. The proposed continuous reference intervals caused a substantial reduction in the number of secondary deficiencies detected, most of which demonstrated no conclusive correlations between the diseases and altered HVA and 5-HIAA values.

Development of an innovative clinical pharmacy service in a urology surgical unit: a new initiative from Qatar.

To provide an insight into the role of a clinical pharmacy initiative in a surgical urology unit through evaluating the nature, significance, associated medications, and acceptance rate of pharmacist interventions. A cross-sectional study was carried out at the Ambulatory Care Center (ACC), Doha, Qatar. Data related to clinical pharmacist interventions and associated rationale were classified according to the nature of the intervention using an adapted classification system. The assessment of the severity followed the National Patient Safety Agency (NPSA) Risk Matrix. Linear regression, Kruskal-Wallis, and post-hoc analyses were performed to determine the association between patient-related and medication-related characteristics on pharmacist interventions. A total of 3284 interventions (on 1486 patients) were analysed. Most patients (n = 1105; 74.4%) had 1-2 interventions. Age and gender showed a positive linear correlation with the number of interventions per patient (p < 0.01). Majority of interventions were related to pharmacological strategy (n = 1858; 56.6%) and quantity of drug (n = 821; 25%). Additional drug therapy (n = 748; 22.78%) was the most common subcategory followed by optimum dose/frequency (n = 691; 21.04%) and discontinuation of medications (n = 352, 10.72%). Anti-infectives were the most identified drug category (n = 798, 55.1%). Most interventions (59.4%) were of moderate significance; patients with moderate interventions were found to be older compared to patients with minor interventions (p = 0.032). Prescribers' acceptance rate was high (>90%), with a notable increase of 6.6% from 2021 to 2023. This study showed that the clinical pharmacy service in the urology surgical field was a fruitful initiative. The clinical pharmacist's role has expanded to include not only therapeutic optimisation while ensuring medication safety across the continuum of perioperative care but also the identification and management of untreated health problems. The dynamic and complexity of the urology patient population challenge clinical pharmacists; however, the practice concepts remain the same as in any other clinical setting.

The application of cell products for the treatment of critical limb ischemia in patients with diabetes mellitus: a review of the literature

The number of patients with diabetes mellitus (DM) has been progressively increasing worldwide over the past decades, and many international organizations consider DM as a public health emergency of the 21st century.Critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease (PAD) in DM and is characterized by a high risk of limb loss without revascularization. Traditional treatment tactics include open and endovascular revascularization surgical techniques. However, in patients not eligible for revascularization and in cases where performed surgical treatment performed has been ineffective, there are almost no therapeutic alternatives, often leading to amputations and death. As of today, one of the newest non-surgical treatment options is cell therapy. Among different cells, mesenchymal stromal cells (MSCs) are potentially one of the most prospective for use in this patient population.This article provides an overview of clinical trials using cell therapy in patients with CLI.To analyze publications, electronic databases PubMed, SCOPUS, ClinicalTrials, and ScienceDirect were searched to identify published data from clinical trials, research studies, and review articles on cell therapy for critical lower extremity ischemia. After the search, 489 results were received.As a result of systematic selection, 22 clinical trials were analyzed.According to the analyzed literature data, the use of cell products in this category of patients is effective and safe. Cell therapy can stimulate the formation of new vessels and enhances collateral circulation; it is also reported improved distal perfusion, increased pain-free walking distance, decreased amputation rates, and increased survival rates.Nevertheless, further study of the potential use of this category of drugs is needed.

Prevalence of substance use among inpatients in two tertiary care hospitals in Tehran

ABSTRACT Background Non-medical use of substances among hospitalized patients is a significant medical challenge, disrupting effective patient care particularly in chronic disease conditions. Therefore, this study looked at how often patients admitted to two hospitals in Tehran might use substances. Methods The present study is a descriptive, cross-sectional research. 286 patients admitted to 12 departments of Rasoul Akram and Firoozgar hospitals in Tehran, were selected by simple random sampling. The WHO ASSIST tool was utilized to quantify the frequency of substance use across different categories. Results Our data revealed a lifetime, and recent (past three months) substance use frequency of 87.4% and 83.6% respectively. The most common substances among men were tobacco (81%), opioids (58%), and alcohol (48%), while sedatives (66%), tobacco (48%), and opioids (46%) were the most common substances among women. Young patients (18–39 years) had a history of substance use across all measured drug categories. The highest frequency of drug use was observed in psychiatry, neurology, orthopedics, and surgery departments. Conclusion Our research revealed a relatively high prevalence of drug use among hospitalized patients. These findings underscore the importance of integrating assessments for non-medical drug use and addiction disorders alongside patients’ existing illnesses to ensure comprehensive patient care.

Biological Barriers for Drug Delivery and Development of Innovative Therapeutic Approaches in HIV, Pancreatic Cancer, and Hemophilia A/B.

Biological barriers remain a major obstacle for the development of innovative therapeutics. Depending on a disease's pathophysiology, the involved tissues, cell populations, and cellular components, drugs often have to overcome several biological barriers to reach their target cells and become effective in a specific cellular compartment. Human biological barriers are incredibly diverse and include multiple layers of protection and obstruction. Importantly, biological barriers are not only found at the organ/tissue level, but also include cellular structures such as the outer plasma membrane, the endolysosomal machinery, and the nuclear envelope. Nowadays, clinicians have access to a broad arsenal of therapeutics ranging from chemically synthesized small molecules, biologicals including recombinant proteins (such as monoclonal antibodies and hormones), nucleic-acid-based therapeutics, and antibody-drug conjugates (ADCs), to modern viral-vector-mediated gene therapy. In the past decade, the therapeutic landscape has been changing rapidly, giving rise to a multitude of innovative therapy approaches. In 2018, the FDA approval of patisiran paved the way for small interfering RNAs (siRNAs) to become a novel class of nucleic-acid-based therapeutics, which-upon effective drug delivery to their target cells-allow to elegantly regulate the post-transcriptional gene expression. The recent approvals of valoctocogene roxaparvovec and etranacogene dezaparvovec for the treatment of hemophilia A and B, respectively, mark the breakthrough of viral-vector-based gene therapy as a new tool to cure disease. A multitude of highly innovative medicines and drug delivery methods including mRNA-based cancer vaccines and exosome-targeted therapy is on the verge of entering the market and changing the treatment landscape for a broad range of conditions. In this review, we provide insights into three different disease entities, which are clinically, scientifically, and socioeconomically impactful and have given rise to many technological advancements: acquired immunodeficiency syndrome (AIDS) as a predominant infectious disease, pancreatic carcinoma as one of the most lethal solid cancers, and hemophilia A/B as a hereditary genetic disorder. Our primary objective is to highlight the overarching principles of biological barriers that can be identified across different disease areas. Our second goal is to showcase which therapeutic approaches designed to cross disease-specific biological barriers have been promising in effectively treating disease. In this context, we will exemplify how the right selection of the drug category and delivery vehicle, mode of administration, and therapeutic target(s) can help overcome various biological barriers to prevent, treat, and cure disease.

A new strategy in bioreactor scale-up and process transfer using a dynamic initial vvm according to different aeration pore size.

Monoclonal antibody drugs have grown into a drug category with a market size of over $100 billion since the first product was launched on the market, which naturally creates a large demand for production. At the same time, the $100 billion market is distributed among more than 200 listed drugs, which indicates that the production demand for monoclonal antibody drugs is diverse. To meet this demand, major suppliers offer single-use bioreactors of all sizes. These single-use bioreactors with different specifications, especially the inconsistency of aeration pore sizes, pose great challenges for technology transfer and scale-up production, and the conventional scale-up strategies of constant Power input/volume ratio (P/V) and constant vessel volume per minute (vvm) can no longer meet the needs. This study simplified the selection of technical parameters in bioreactors based on the differences in aeration pore size. Innovatively combined the aeration pore sizes with initial aeration vvm, and comprehensively investigated the relationship between P/V, vvm and aeration pore size by designing experiments (DoE) using the orthogonal test method. The results showed a quantitative relationship between the aeration pore size and the initial aeration vvm in the P/V range of 20 ± 5W/m3. The appropriate initial aeration was between 0.01 and 0.005m3/min for aeration pore size ranging from 1 to 0.3mm, which was the optimal incubation condition in the bioreactors. The choice of initial ventilation was most related to the final expression. Follow-up studies validated these findings in a 15L glass bioreactor and a 500L single-use bioreactor, and the results were consistent with expectations.