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Recently, we have proposed simple methodology to derive clearance and rate constant equations, independent of differential equations, based on Kirchhoff's Laws, a common methodology from physics used to describe rate-defining processes either in series or parallel. Our approach has been challenged in three recent publications, two published in this journal, but notably what is lacking is that none evaluate experimental pharmacokinetic data. As reviewed here, manuscripts from our laboratory have evaluated published experimental data, demonstrating that the Kirchhoff's Laws approach explains (1) why all of the experimental perfused liver clearance data appear to fit the equation that was previously believed to be the well-stirred model, (2) why linear pharmacokinetic systemic bioavailability determinations can be greater than 1, (3) why renal clearance can be a function of drug input processes, and (4) why statistically different bioavailability measures may be found for urinary excretion versus systemic concentration measurements. Our most recent paper demonstrates (5) how the universally accepted steady-state clearance approach used by the field for the past 50 years leads to unrealistic outcomes concerning the relationship between liver-to-blood Kpuu and hepatic availability FH , highlighting the potential for errors in pharmacokinetic evaluations based on differential equations. The Kirchhoff's Laws approach is applicable to all pharmacokinetic analyses of quality experimental data, those that were previously adequately explained with present pharmacokinetic theory, and those that were not. The publications that have attempted to rebut our position do not address unexplained experimental data, and we show here why their analyses are not valid. SIGNIFICANCE STATEMENT: The Kirchhoff's Laws approach to deriving clearance equations for linear systems in parallel or in series, independent of differential equations, successfully describes published pharmacokinetic data that has previously been unexplained. Three recent publications claim to refute our proposed methodology; these publications only make theoretical arguments, do not evaluate experimental data, and never demonstrate that the Kirchhoff methodology provides incorrect interpretations of experimental pharmacokinetic data, including statistically significant data not explained by present pharmacokinetic theory. We demonstrate why these analyses are invalid.

BACKGROUND: Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion. METHODS: This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance. RESULTS: Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P

BackgroundPersons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations.MethodsHPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization.DiscussionThis trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care.Trial registrationClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

It is generally believed that bioavailability (F) calculated based on systemic concentration area under the curve (AUC) measurements cannot exceed 1.0, yet some published studies report this inconsistency. We teach and believe, based on differential equation derivations, that rate of absorption has no influence on measured systemic clearance following an oral dose, i.e., determined as available dose divided by AUC. Previously, it was thought that any difference in calculating F from urine data versus that from systemic concentration AUC data was due to the inability to accurately measure urine data. A PubMed literature search for drugs exhibiting F > 1.0 and studies for which F was measured using both AUC and urinary excretion dose-corrected analyses yielded data for 35 drugs. We show and explain, using Kirchhoff's Laws, that these universally held concepts concerning bioavailability may not be valid in all situations. Bioavailability, determined using systemic concentration measurements, for many drugs may be overestimated since AUC reflects not only systemic elimination but also absorption rate characteristics, which is most easily seen for renal clearance measures. Clearance of drug from the absorption site must be significantly greater than clearance following an iv bolus dose for F(AUC) to correctly correspond with F(urine). The primary purpose of this paper is to demonstrate that studies resulting in F > 1.0 and/or greater systemic vs urine bioavailability predictions may be accurate. Importantly, these explications have no significant impact on current regulatory guidance for bioequivalence testing, nor on the use of exposure (AUC) measures in making drug dosing decisions.

BackgroundPeople who use drugs (PWUD) experience elevated HIV risk and numerous barriers to facility-based HIV testing. HIV self-testing (HIVST) could circumvent many of those barriers and is acceptable among PWUD, yet HIVST implementation for PWUD is limited. Service providers' perspectives on specific HIVST delivery strategies could help increase availability for PWUD.MethodsFrom April-November 2021, we interviewed 16 health, harm reduction, and social service providers working with PWUD in San Diego, CA. Interviews and rapid thematic analysis explored perspectives on HIVST's utility and appropriateness, as well as the feasibility of and anticipated challenges with specific HIVST delivery strategies, including peer or secondary distribution.ResultsParticipants viewed HIV as a significant threat to PWUD health and confirmed the presence of numerous barriers to local facility-based HIV testing. Participants viewed HIVST as a promising and potentially empowering solution. Based on community familiarity with secondary distribution of harm reduction supplies (i.e., naloxone) and information, participants viewed secondary distribution of HIVST kits as an appropriate and feasible strategy for increasing the reach of HIVST, but also described potential barriers (e.g., engaging socially disconnected individuals, ensuring linkages to services following HIVST) and provided suggestions for alternative HIVST kit delivery models (e.g., harm reduction vending machines).ConclusionsService providers viewed secondary distribution of HIVST kits among PWUD as promising, appropriate, and feasible, yet specialized efforts may be needed to reach the most marginalized individuals and ensure consistent provision of educational information and referral supports that maximize the impact of this approach.

This review addresses current changes in the approach to treating patients with multiple sclerosis (MS). The widely practiced approach of utilizing agents with lower treatment efficacy (LETA) at onset with subsequent escalation has been challenged by new data suggesting that MS patients derive greater benefit when therapy is initiated with high-efficacy treatment agents (HETA). Several recent studies compared treatment efficacy and safety of early administration of HETA versus LETA. The results of randomized, double blind, phase III studies with LETA as a control arm and population-based larger and longer studies using propensity scoring, marginal structural modeling and weighted cumulative exposure analysis support the benefit of early treatment with HETA. Patients initiating their treatment with HETA, regardless of prognostic factors and MRI burden at baseline, showed significantly lower annualized relapse rate (ARR) and reduced disability progression in follow-up periods of up to 10-15 years. Moreover, the safety profile of recently approved HETA ameliorates concerns about off-target effects associated with a number of earlier high-efficacy drugs. Patient perception has also changed with an increasing preference for medication profiles that both improve symptoms and prevent disease progression. Accumulating data from randomized studies and the results of large population-based studies demonstrating short-term and longer-term patient benefits support the view that HETA should be more widely used. The adoption of early treatment with HETA capitalizes on a window of opportunity for anti-inflammatory drugs to maximally impact disease pathology and heralds a sea change in clinical practice toward pro-active management and away from a philosophy routed in generating clinical benefit as a consequence of treatment failure.

Background Methods Results Conclusions To evaluate and compare the long‐term efficacy of medical treatments for normal tension glaucoma (NTG) in controlling intraocular pressure (IOP), and establish a hierarchical ranking based on their effectiveness. ‘Long‐term’ is defined as a treatment duration of over 12 weeks in randomised controlled trials (RCTs).This systematic review and model‐based network meta‐analysis (MBNMA) collected data of 795 patients with 997 eyes from RCTs. Patients with NTG were selected based on strict inclusion/exclusion criteria, with randomsation procedures and masking as reported in the individual trials. Eight different medications were compared, including prostaglandin analogues, beta‐blockers, brimonidine, unoprostone isopropyl, brovincamine, and palmitoylethanolamide (PEA). Notably, PEA is an oral medication, while other drugs are topical agents.Primary outcome is the long‐term efficacy of IOP control across medications with different follow‐up durations. Among the eight medications, PEA demonstrates the highest efficacy (Surface under the cumulative ranking, SUCRA = 7.46%), followed by two prostaglandin analogues: travoprost (SUCRA = 6.86%) and latanoprost (SUCRA = 6.76%), then two beta‐blockers: nipradilol (SUCRA = 4.90%) and timolol (SUCRA = 4.89%). Both brimonidine and unoprostone isopropyl have SUCRA scores below 4.0%, indicating modest but limited efficacy. Brovincamine has the lowest SUCRA score (1.32%), reflecting minimal effectiveness.This study revealed PEA as a promising agent for long‐term IOP control in NTG patients, suggesting potential use as primary or adjunctive therapy. The outcomes call for PEA's consideration in clinical practice and highlight the need for further research into its long‐term efficacy and safety for NTG. [ABSTRACT FROM AUTHOR]

As effective treatment of glioblastoma is still an unmet need, targeted delivery systems for efficient treatment are of utmost interest. Therefore, in this paper, surface modifications with a small peptide c(RGD) or physiological protein (ApoE3) were investigated. Cellular uptake in murine endothelial cells (bEnd.3) and different glioma cells (human U-87 MG, rat F98) was tested to elucidate possible differences and to correlate the uptake to the receptor expression. Different liposomal formulations were measured at 1 and 3 h for three lipid incubation concentrations. We calculated the liposomal uptake saturation S and the saturation half-time t1/2. An up to 9.6-fold increased uptake for ApoE3-modified liposomes, primarily in tumor cells, was found. Contrarily, c(RGD) liposomes showed a stronger increase in uptake in endothelial cells (up to 40.5-fold). The uptake of modified liposomes revealed enormous differences in S and t1/2 when comparing different tumor cell lines. However, for ApoE3-modified liposomes, we proved comparable saturation values (~25,000) for F98 cells and U-87 MG cells despite a 6-fold lower expression of LRP1 in F98 cells and a 5-fold slower uptake rate. Our findings suggest that cellular uptake of surface-modified liposomes depends more on the target structure than the ligand type, with significant differences between cell types of different origins. [ABSTRACT FROM AUTHOR]

A spectrophotometric approach that is straightforward, efficient, highly sensitive, and precise has been devised for quantifying biotin in both its pure state and pharmaceutical samples. Analysis of biotin in biological and pharmaceutical samples is essential for therapeutic evaluation and patient follow-up bioavailability. Several methods for determining this drug have drawbacks including specialized equipment that many quality control laboratories and universities in developing countries lack. The methodology relies on the inhibitory approach of biotin on the Pd(II) promoted ligand substitution (LS) reaction involving phenylhydrazine (PHZ) and hexacyanoferrate(II). The process entails replacing cyanide in [Fe(CN)6]4- with PHZ, triggering the development of a complex [Fe(CN)5PHZ]3-. The complex demonstrates a significant level of absorption at a specific wavelength of 488 nm. The established limit of detection for biotin is 0.117 μg mL−1. Experiments on recovery are conducted to confirm the precision and accuracy of biotin quantification. The suggested approach has been effectively utilized for the examination of biotin in pristine samples and various medications, demonstrating remarkable levels of precision and accuracy. The outcomes show good agreement when compared to the findings of the official analytical method. The excipients typically employed in medicines do not exhibit any interference with the suggested methodology. This methodology is highly effective for accurately determining trace levels of different drugs and biological molecules that can significantly impede the catalytic efficiency of Pd(II). [ABSTRACT FROM AUTHOR]

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OBJECTIVES: The objective of this study was to evaluate the frequency of long QT syndrome (LQTS) in the electrocardiographic tracing of elderly people and the concomitant use of drugs that can aggravate this condition. METHODS: This is a crosssectional, observational study of elderly patients in outpatient services at Hospital Santa Casa de Misericórdia de Vitória, over a six-month period. RESULTS: A total of 163 patients with 75 ± 8 (60–94) years of age, 60.7% (n = 99) of whom were female, participated in the study. Of the total number of patients, 33.1% (n = 54) were regularly taking at least one pharmaceutical that increased the risk of QTc prolongation; 34 patients (20.9%) had prolonged QTc and 15 (9,2%) had at-risk QTc. Of these patients with at-risk QTc, 4 (23.4%) were using at least 1 1 pharmaceutical that increases the risk of QT prolongation (p = 0.07). CONCLUSION: In this sample, a high frequency of LQTS was observed, as well as the use of pharmaceuticals that potentially cause LQTS and arrhythmias.

Prescribing medications involves complex cognitive processes, and mistakes in prescription can cause serious adverse events. Deprescribing is one of the last opportunities to prevent patient harm from the use of drugs that should be avoided, especially among older patients. This viewpoint article aims to discuss the prescription process and some essential concepts, such as polypharmacy, prescription of potentially inappropriate medications, and, particularly, the relevance of deprescribing and its relationship with the appropriate prescription of medications in older people.

Introduction. The data on the wide clinical use of low-molecular-weight heparin (LMWH) preparations are presented, necessitating the need for efficient and high-quality production of appropriate pharmaceuticals. The revealed variability of anticoagulant activity of LMWH preparations implies the provision of production with validated methods of control and certification. The aim of the work is to study the possibility of control of anticoagulant activity and assessment of functional compatibility of LMWH preparations when using domestic test systems.Text. The data on analytical characteristics of chromogenic and coagulometric methods performed with the help of domestic test systems are presented. Their parameters correspond with the existing international requirements. The possibility of the mentioned methods to certify LMWH preparations correctly and reproducibly is shown. The given research results testify to the possibility of clotting methods to determine the bioequivalence of the studied preparations of LMWH.Conclusion. The presented data prove the expediency of production control and certification of LMWH preparations by domestic test systems.

Introduction: self-medication is an effort made by an individual to obtain medication and use it without diagnosis, prescription, supervision, or consultation with a doctor to treat certain minor illnesses. Self-medication is self-medication without a doctor's prescription. In disease treatment, risks such as misdiagnosis, use of excessive drug doses, and long-term use can cause adverse effects on patients. Objective: to determine the description of the public's use of self-medicated pharmaceutical preparations. Methods: This type of research uses a descriptive method, namely research that includes surveys with data collection in the form of questionnaires with a total of 81 respondents. The sampling method uses Non-Probability Sampling with Purposive Sampling techniques using an open-ended questionnaire format in collecting data and recording reports. Result: results of research data collection that the description of the use of pharmaceutical preparations by self-medication in the Bung Permai Housing Community is that 81 respondents (100.00%) carry out self-medication, the source of drug information is from print and electronic media, namely 36 respondents (44.45%), the place of purchase of medicine was at the pharmacy/clinic, namely 43 respondents (53.02%), the disease suffered was fever, 23 respondents (28.40%), and the pharmaceutical preparation used was paracetamol, 27 respondents (33.33%). Conclusion: the description of self-help's use of pharmaceutical preparations in the Permai Community Housing is mostly self-medication. Therefore, there is a need for better education and supervision of using pharmaceutical preparations independently to increase understanding and safety in self-medication. It is hoped that in the future, there will be research on public knowledge and behavior regarding self-medication of pharmaceutical preparations so that changes in respondents' knowledge and behavior can be seen after being given good and correct information.

Introduction: Pharmacists are critical in providing safe and accurate education to patients on disease states and medications. Artificial intelligence (AI) has the capacity to generate patient education materials at a rapid rate, potentially saving healthcare resources. However, overall accuracy and comfort with these materials by pharmacists need to be assessed. Objective: The purpose of this study was to assess the accuracy, readability, and likelihood of using AI‐generated patient education materials for ten common medications and disease states. Method s : AI (Chat Generative Pre‐Trained Transformer [ChatGPT] v3.5) was used to create patient education materials for the following medications or disease states: apixaban, Continuous Glucose Monitoring (CGM), the Dietary Approaches to Stop Hypertension (DASH) Diet, enoxaparin, hypertension, hypoglycemia, myocardial infarction, naloxone, semaglutide, and warfarin. The following prompt, "Write a patient education material for..." with these medications or disease states being at the end of the prompt, was entered into the ChatGPT (OpenAI, San Francisco, CA) software. A similar prompt, "Write a patient education material for...at a 6th‐grade reading level or lower" using the same medications and disease states, was then completed. Ten clinical pharmacists were asked to review and assess the time it took them to review each educational material, make clinical and grammatical edits, their confidence in the clinical accuracy of the materials, and the likelihood that they would use them with their patients. These education materials were assessed for readability using the Flesh‐Kincaid readability score. Results: A total of 8 pharmacists completed both sets of reviews for a total of 16 patient education materials assessed. There was no statistical difference in any pharmacist assessment completed between the two prompts. The overall confidence in accuracy was fair, and the overall readability score of the AI‐generated materials decreased from 11.65 to 5.87 after reviewing the 6th‐grade prompt (p <.001). Conclusion: AI‐generated patient education materials show promise in clinical practice, however further validation of their clinical accuracy continues to be a burden. It is important to ensure that overall readability for patient education materials is at an appropriate level to increase the likelihood of patient understanding. [ABSTRACT FROM AUTHOR]

Abstract Background Providing primary care for people with frailty can be challenging due to an increased risk of adverse outcomes and use of potentially inappropriate medications which may exacerbate characteristics of frailty. eConsult is a service where primary care providers can receive timely specialist advice for their patients through a secure web-based application. We aimed to develop a classification system to characterize medication-focused eConsult questions for older adults with frailty and assess its usability. Methods A classification system was developed and refined over three cycles of improvement through a cross-sectional study of 35 cases categorized as medication-focused from cases submitted in 2019 for patients aged 65 or older with frailty through the Champlain BASE eConsult service (Ontario, Canada). The final classification system was then applied to each case. Results The classification system contains 5 sections: (1) case descriptives; (2) intent and type of question; (3) medication recommendations and additional information in the response; (4) medication classification; and (5) potentially inappropriate medications. Among the 35 medication-focused cases, the most common specialties consulted were endocrinology (9 cases, 26%) and cardiology (5 cases, 14%). Medication histories were available for 29 cases (83%). Many patients were prescribed potentially inappropriate medications based on explicit tools (AGS Beers Criteria®, STOPPFall, Anticholinergic Cognitive Burden Scale, ThinkCascades) yet few consults inquired about these medications. Conclusion A classification system to describe medication-related eConsult cases for patients experiencing frailty was developed and applied to 35 eConsult cases. It can be applied to more cases to identify professional development opportunities and enhancements for eConsult services.

Copyright of Revista ADM is the property of Asociacion Dental Mexicana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Some medications could affect driving ability in traffic accidents and increase accident rates. Objective: To describe the pharmacological consumption profile of patients treated for traffic accidents in Bogotá, Colombia. Method: A cross-sectional study was implemented based on the medical records of patients admitted to an emergency department due to traffic accidents in 2019. Sociodemographic variables and pharmacological history were described. The Mann-Whitney U test compared age and hospital stay between patients consuming and not consuming medications. Results: 1037 records were reviewed; 67% were men. 9.6% of patients were taking drugs; antihypertensives were the most common. The age of patients who consumed medication was significantly older than those who denied such consumption (p<0.001). Conclusions: Medication consumption is low among people in traffic injured in Bogotá, Colombia. More studies are needed in this area. [ABSTRACT FROM AUTHOR]

Background: Providing primary care for people with frailty can be challenging due to an increased risk of adverse outcomes and use of potentially inappropriate medications which may exacerbate characteristics of frailty. eConsult is a service where primary care providers can receive timely specialist advice for their patients through a secure web-based application. We aimed to develop a classification system to characterize medication-focused eConsult questions for older adults with frailty and assess its usability. Methods: A classification system was developed and refined over three cycles of improvement through a cross-sectional study of 35 cases categorized as medication-focused from cases submitted in 2019 for patients aged 65 or older with frailty through the Champlain BASE eConsult service (Ontario, Canada). The final classification system was then applied to each case. Results: The classification system contains 5 sections: (1) case descriptives; (2) intent and type of question; (3) medication recommendations and additional information in the response; (4) medication classification; and (5) potentially inappropriate medications. Among the 35 medication-focused cases, the most common specialties consulted were endocrinology (9 cases, 26%) and cardiology (5 cases, 14%). Medication histories were available for 29 cases (83%). Many patients were prescribed potentially inappropriate medications based on explicit tools (AGS Beers Criteria®, STOPPFall, Anticholinergic Cognitive Burden Scale, ThinkCascades) yet few consults inquired about these medications. Conclusion: A classification system to describe medication-related eConsult cases for patients experiencing frailty was developed and applied to 35 eConsult cases. It can be applied to more cases to identify professional development opportunities and enhancements for eConsult services. [ABSTRACT FROM AUTHOR]

Aim: To appraise and synthesize research investigating optimizing the administration of solid oral dosage forms (SODFs) to adults with swallowing difficulties. Design: An integrative review. Methods: An electronic search was conducted on Medical Literature Analysis and Retrieval System Online (Public Medline interface), Elsevier SciVerse Scopus and Scientific Electronic Library Online (updated February 2023). Restriction regarding the publication date was not considered for the inclusion of records. Studies addressing risks, general aspects, recommendations about patient postural adjustments, swallowing techniques, swallowing aids and aspects of concealment of SODFs were included. Results: Fifty-three records published between 2002 and 2021 were included. The main administration risks were aspiration, asphyxia and solid oral dosage form-induced oral/oesophageal mucosal lesions. The most frequent general aspect reported was administering one oral dosage form at a time. The sitting position was the most patient postural adjustment mentioned. The most frequently reported solid oral dosage form swallowing technique was the lean-forward method for capsules. Solid oral dosage form swallowing aids cited: tongue and throat lubricant and solid oral dosage form coating device, swallowing cup and swallowing straw. Conclusion: The literature data on administering SODFs for adults with swallowing difficulties were appraised and synthesized. Some aspects, for example, not administering SODFs simultaneously, can make swallowing safer. Postural adjustments and solid oral dosage form swallowing aids are important to avoid administration risks. Swallowing SODFs can be easier if learned by techniques. Liquid and food are helpful as vehicles, and several of these have been listed. Implications for the Profession and/or Patient Care: By optimizing the contributing factors of administering oral pharmacotherapy, the nurse can use appropriate practices to improve patient safety. Additionally, knowing and establishing the administration aspects are reasonable steps for standardizing care for patients with swallowing oral dosage form difficulties. Impact: • This study addressed administering SODFs to adult patients with swallowing difficulties. • The administration of SODFs to adult patients with swallowing difficulties can be optimized if only one oral dosage form at a time is administrated and if patient postural adjustments, swallowing techniques and swallowing aids are used. • This investigation will impact the care of patients with swallowing difficulties. Reporting Method: The authors declare they adhered to the relevant EQUATOR guidelines and report following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. [ABSTRACT FROM AUTHOR]

A novel, repeatable, and swift kinetic approach for determining alpha-lipoic acid (ALA) in sodium lauryl sulfate (SLS) micellar medium has been presented, and it has been connected to ALA determination in drug formulations. The approach is based on ALA inhibitory property. ALA (containing two sulfur atoms) forms a chelate with Pd2+, lowering the effective [Pd(II)], and ultimately, the Pd2+ catalyzed cyanide substitution rate from [Ru(CN)6]4- by pyrazine (Pz). Fixed times of 5 and 10 minutes were chosen under optimal reaction conditions with [Pyrazine] = 3.0 × 10-4 mole L-1, pH = 4.0 ± 0.02, Temp = 318 ± 0.2 K, I = 0.1 mole L-1 (NaClO4), [Ru(CN)64-] = 2.75 × 10-5 mole L-1, [Pd+2] = 6.0 × 10-5 mole L-1, and [SLS] = 8.5 × 10-3 mole L-1 to calculate the absorbance at 370 nm associated with the final substitution product [Ru(CN)5 Pz]3-. ALA's inhibiting influence on the Pd2+ catalyzed cyanide substitution with pyrazine from [Ru(CN)6]4-, has been represented by a modified mechanistic approach. The concentration of ALA in various water specimens can be measured at the micro-level down to 1.25 × 10-6 mole L-1 using the established kinetic spectrophotometric approach. The suggested method is highly reproducible and has been effectively applied to accurately quantify the ALA in pharmaceutical samples. Even as much as 1000 with [ALA], typical additives used in medications do not significantly hinder the determination of ALA. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric liquid medications (PLM) are frequently administered to children, yet their usage may contribute to the onset of dental caries. Despite its prevalence, there is a notable scarcity of scientific research regarding caregivers’ knowledge of this potential cariogenic risk. Objective: This study aims to assess the knowledge of the main caregivers of children aged 5 to 12 years concerning the cariogenic potential associated with the use of PLM. Materials and Methods: A cross-sectional analytical obser-vational study involving 152 primary caregivers of children aged 5 to 12 was conducted. Data were collected on caregivers’ perceptions of the cariogenic risk associated with PLMs and their consumption habits. The study also assessed oral hygiene routines and evaluated the level of information provided by healthcare professionals. Results: Research findings indicated a significant lack of awa-reness among primary caregivers regarding the cariogenic risks of PLMs, with 78.95% being unaware of these risks and 47.37% unaware of the sugars present in such medications. Additionally, a high rate of PLM consumption was observed, with 63% of caregivers using them in the last year. The study underscored a notable absence of guidance from healthcare professionals, as 91.45% of the caregivers stated that they had not received instructions on tooth brushing after the administration of the PLM. Conclusions: The study highlights a significant lack of awa-reness among primary caregivers regarding the cariogenic risks associated with the ingestion of pediatric liquid medications. This deficit in information and preventive measures presents a substantial obstacle to children’s oral health. To address this issue, it is crucial for healthcare professionals to offer comprehensive guidance and promote preventive measures.

A rapid, novel and cost‐effective spectrofluorimetric method developed to determine moxifloxacin (MFX) in pharmaceutical preparations because MFX in a pH 10 medium could reduce the fluorescence intensity of l‐tryptophan. The maximum fluorescence excitation and emission wavelengths were found to be 280 and 363 nm respectively. A range of factors affecting fluorescence quenching and the effect of co‐existing substances were investigated. Fluorescence quenching values (ΔF = FL‐tryptophan − FMoxi‐L‐tryptophan) displayed a strong linear relationship with the MFX concentration ranging from 0.2 to 8.0 μg/ml under optimum conditions. The limit of detection was found to be 6.1 × 10−4 μg/ml. The proposed method was shown to be suitable for MFX determination in pharmaceutical tablets and biological fluids by the linearity, recovery and limit of detection. The spectrofluorimetric approach that has been developed is extremely eco‐friendly, as evidenced by the fact that all the experimental components and solvents were safe for the environment. [ABSTRACT FROM AUTHOR]

The drug phenobarbital (PHB) was determined in bulk and tablet dosage form by a simple and sensitive spectrophotometric method. This method is based on calculating the area under the curve in the region between 230-246 nm. The Linearity of the method was 10-45 ppm and R2 was 0.9998. The percentage recovery rate was 100.10204% and the relative standard deviation coefficient was in the range of 0.19140-0.12386%. Limit detection was 0.15746 ppm, limit quantification was 0.52489 ppm, the Molar absorption coefficient was 18.66888 × 103 l mol-1 cm-1, and the Sandell's index was 0.01243 µg/cm2. The method was successfully applied to determination of PHB in its pharmaceutical preparations. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present the case of a 20‐month‐old girl with Schimmelpenning‐Feuerstein‐Mims (SFM) syndrome with extensive head, neck, and torso skin involvement successfully managed with topical trametinib. Trametinib interferes downstream of KRAS and HRAS in the MAPK signaling pathway, of which KRAS was implicated in our child's pathogenic variant. Although other dermatologic conditions have shown benefit from oral trametinib, its topical use has not been well reported. Our patient showed benefit from the use of twice‐daily topical trametinib, applied to the epidermal and sebaceous nevi over a 16‐month period, leading to decreased pruritus and thinning of the plaques. [ABSTRACT FROM AUTHOR]

As effective treatment of glioblastoma is still an unmet need, targeted delivery systems for efficient treatment are of utmost interest. Therefore, in this paper, surface modifications with a small peptide c(RGD) or physiological protein (ApoE3) were investigated. Cellular uptake in murine endothelial cells (bEnd.3) and different glioma cells (human U-87 MG, rat F98) was tested to elucidate possible differences and to correlate the uptake to the receptor expression. Different liposomal formulations were measured at 1 and 3 h for three lipid incubation concentrations. We calculated the liposomal uptake saturation S and the saturation half-time t1/2. An up to 9.6-fold increased uptake for ApoE3-modified liposomes, primarily in tumor cells, was found. Contrarily, c(RGD) liposomes showed a stronger increase in uptake in endothelial cells (up to 40.5-fold). The uptake of modified liposomes revealed enormous differences in S and t1/2 when comparing different tumor cell lines. However, for ApoE3-modified liposomes, we proved comparable saturation values (~25,000) for F98 cells and U-87 MG cells despite a 6-fold lower expression of LRP1 in F98 cells and a 5-fold slower uptake rate. Our findings suggest that cellular uptake of surface-modified liposomes depends more on the target structure than the ligand type, with significant differences between cell types of different origins.

Despite the benefits derived from the use of pharmaceuticals, these compounds are currently considered contaminants of emerging concern because of their presence and persistence in the environment. This study aimed to determine the toxicity of 27 pharmaceuticals and the interaction effects of binary mixtures of selected compounds towards two model organisms: the microcrustacean Daphnia magna and the bacterium Aliivibrio fischeri (Microtox test). Six compounds, namely polymyxin B, polymyxin E, fluoxetine, diphenhydramine, clenbuterol and ketoprofen exhibited moderate toxicity towards D. magna. Additionally, three compounds (cefotaxime, polymyxin B, polymyxin E) also showed a moderate toxic effect on A. fischeri. The comparison of such results with model estimations showed inaccuracy in the predicted data, highlighting the relevance of experimental ecotoxicological assays. The assayed mixtures contained four selected drugs of high-hazard according to their reported concentrations in wastewater and surface water (diphenhydramine, trimethoprim, ketoprofen, and fluoxetine); data revealed interactions only in the fluoxetine-containing mixtures for D. magna, while all mixtures showed interactions (mostly synergistic) for Microtox. Chronic effects on the reproduction of D. magna were observed after exposure to fluoxetine and diphenhydramine, although higher sensitivity was determined for the latter, while the mixture of these compounds (which showed acute synergy in both models) also affected the reproduction patterns. Nonetheless, all the effects described at the acute or chronic level (for individual compounds or mixtures) were determined at concentrations higher than commonly reported at environmental levels. This work provides valuable ecotoxicological information for the risk assessment of pharmaceuticals and their mixtures in the environment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In Brazil, ethnic-racial inequalities exist in all fields, obstructing access to goods, services, and opportunities, including healthcare services. However, there are no apparent studies that assess, at a national level, ethnic-racial disparities in poisoning cases, emphasizing skin color as a determining factor. The study aimed to examine the relationship between race/ethnicity and general poisoning cases, by medications, pesticides, and drug of abuse in Brazilian states. Poisoning cases data were extracted for the years 2017, 2018, and 2019. Notification data for general poisoning cases and toxic agents were collected: medications, pesticides, and drugs of abuse. Data were categorized between whites and non-whites (blacks, browns, and indigenous) and without information on skin color/ethnicity. Rates of poisonings amongst ethnic-racial groups and cases of not declared skin color as well as relative risk (RR) of poisoning among non-whites were calculated. All states in the North, Northeast (states with the worst Human Development Index), Midwest, and 2 states in the Southeast exhibited higher rates of poisoning cases per 100,000 inhabitants among non-whites. The RR values for nonwhite individuals were higher in the North and Northeast regions for all types of poisonings. The type of poisoning cases that presented the highest RR for non-whites over the 3 years was drugs of abuse (2-2.44), when compared to other types of poisonings from pesticides (2-2.33) and medications (1.5-1.91). The spatial distribution of poisoning cases rates and RR of nonwhite population support public policies to reduce socioeconomic and environmental inequalities.

This article aims to contribute to the discussion about medication literacy, by focussing on the social contextuality of the information mobilised in the use of medicines. We aim to explore the social construction processes of medication literacy, as an essential dimension for a more layperson-centred approach in the promotion of literacy in this field. This approach is justified by the growing social and cultural dissemination of medication use, the diversification of its uses beyond health and illness, and the increasing degree of lay autonomy in managing its use. The article is organised in two main sections. In the first section, we review the social history of medication literacy, including a discussion of the social contextuality of literacy phenomena. In the second section, the analysis of social contextuality is operationalised with a focus on information, covering: (i) ways of relating to institutional information and sources of information about medication; (ii) contexts of sociability in which information is shared and validated. This analysis is empirically supported by selected results from two research projects, conducted in Portugal, on the consumption of medicines and dietary supplements for performance purposes - that is, for the management and/or improvement of cognitive, bodily or relational performance., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The aim of the study was to investigate the physicochemical stability of mitomycin-containing medicinal products for bladder instillation, formulated with urea as excipient (mito-medac®, Mitomycin medac). For comparison, the stability of reconstituted Urocin® and Mitem® bladder instillation was studied., Methods: Mitomycin-containing medicinal products were either reconstituted with the prepackaged 0.9% NaCl solution, nominal volume 20 mL (mito-medac®, Mitem®, Urocin®) or with 20 mL water for injection (Mitomycin medac, Mitem®, Urocin®) to a nominal concentration of 1 mg/mL and stored at room temperature (20-25°C). Samples were taken immediately after reconstitution and after 24 hours. Physicochemical stability was determined by reverse-phase high performance liquid chromatography with photodiode array detection, measurement of pH and osmolarity, and inspection for visible particles or colour changes., Results: The initial pH values of the test solutions reconstituted with prepackaged 0.9% NaCl (5.2-5.6) were significantly lower than those reconstituted with water for injection (6.6-7.4). Solutions reconstituted with 0.9% NaCl solutions rapidly degraded and concentrations fell below the 90% limit after 24 hours of storage. When reconstituted with water for injection, degradation was less rapid. Concentrations of Mitomycin medac and Urocin remained above the 90% limit after 24 hours., Conclusions: The physicochemical stability of mitomycin 1 mg/mL bladder instillation prepared with prepackaged 0.9% NaCl in prefilled PVC bags is less than 24 hours at room temperature. Unfavourable pH values of the solvents cause rapid degradation of mitomycin. Mitomycin solutions reconstituted at the point of care should be administered immediately to avoid degradation and loss of efficacy. Urea added as excipient did not accelerate degradation., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

We present the case of a patient with failed desensitisation to paclitaxel that was ultimately successful with omalizumab treatment. Our patient, a female aged between 20-25 and diagnosed with a triple negative breast cancer, received first-line treatment with carboplatin and paclitaxel. During the second cycle of paclitaxel, she experienced heat, dyspnoea, facial angioedema and vomiting. Skin tests for allergic reactions returned negative results, and drug provocation tests showed a positive result (anaphylaxis). Rapid drug desensitisation (RDD) was carried out with two bags of dilutions but at the beginning of the infusion, the patient experienced symptoms again, so the infusion was stopped. Therefore, the use of omalizumab, already reported as a successful adjuvant in desensitisation to other drugs, was considered. The anti-immunoglobulin E (IgE) monoclonal antibody was administered off-label before the first programmed desensitisation with success: total dose of paclitaxel was infused without any reaction. The patient was able to receive the complete chemotherapy treatment., Competing Interests: Competing interests: JLA acknowledges payments from Lilly, Roche, Novartis and that he is a member of the Safety Monitoring Board of his institution., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the physical compatibility of 10% calcium chloride and 10% calcium gluconate in combination with injectable solutions, administered in the paediatric and adult intensive care unit setting during toxicological resuscitation involving calcium channel blockers and beta-blockers., Methods: Forty-eight combinations were prepared at room temperature, including the following products: calcium chloride, calcium gluconate, insulin, epinephrine, norepinephrine, highly concentrated dextrose solution, sodium chloride, Plasma-Lyte A and Ringer's lactate. A visual evaluation at times 0, 1, 4, 24, 48 and 72 hours and a particle count test with the LS-20 particle counter at times 0, 4, 24 and 72 hours were performed. The admixtures were considered incompatible if there was a precipitate, a colour change, turbidity, viscosity or a gas formation. The stability of calcium salts was also tested in empty IV bags and syringes by the particle count test., Results: All drug mixtures were found to be compatible by visual evaluation and using the particle counter based on United States Pharmacopoeia chapter 788 (USP<788>) specifications. Calcium salts were compatible with insulin and vasopressors in the tested combinations. The stability of 10% calcium salts in empty IV bags and polypropylene syringes was demonstrated for up to 48 hours at room temperature., Conclusion: All the combinations tested were physically compatible for up to 72 hours at room temperature. Clinical use of calcium salt infusions, at an undiluted concentration, in combination with these injectable solutions in a toxicological resuscitation context is considered clinically acceptable., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Anticancer drug preparation control is essential to ensure quality and patient safety. Drugcam (Eurekam Company) is a digital video-assisted control system based on artificial intelligence methods to identify vials used and volumes withdrawn. As for any control system, qualification is required before use in a chemotherapy compounding unit (CCU)., Methods: We conducted an operational qualification (sensitivity, specificity and accuracy assessment of vials and volumes recognition and quantitative analysis of measured volumes) and a performance qualification (comparison with visual control) of Drugcam in our CCU, as well as an impact study on compounding time and compound supply time., Results: Sensitivity, specificity and accuracy of vials (94%, 98% and 96%, respectively) and volumes (86%, 96% and 91%, respectively) recognition are satisfactory. It depends on both the object presented and the camera tested. False positives, which could lead to release of non-compliant preparation, were detected. Volume reading errors may exceed the tolerance threshold of ±5% for small volumes. Drugcam did not significantly lengthen compounding time and compound supply time., Conclusions: No recommendations for a qualification method of this new type of control equipment exist. However, a qualification process is essential to understand tool limitations and integrate them into the CCU risk management system. Drugcam enables anticancer drug preparation to be secure and is also useful for initial and continuous staff training., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Prefilled syringes (PFS) may offer clinical and economic advantages over conventional parenteral medication delivery methods (vials and ampoules). The benefits of converting from vials and ampoules to PFS have been explained in previous drug-specific economic models; however, these models have limited generalisability to different drugs, healthcare settings and other countries. Our study aims to (1) present a comprehensive economic model to assess the impact of switching from vials to PFS delivery; and (2) illustrate through two case studies the model's utility by highlighting important features of shifting from vials to PFS., Methods: The economic model estimates the potential benefit of switching to PFS associated with four key outcomes: preventable adverse drug events (pADE), preparation time, unused drugs, and cost of supplies. Model reference values were derived from existing peer-reviewed literature sources. The user inputs specific information related to the department, drug, and dose of interest and can change reference values. Two hypothetical case studies are presented to showcase model utility. The first concerns a cardiac intensive care unit in the United Kingdom administering 30 doses of 1 mg/10 mL atropine/day. The second concerns a coronavirus (COVID-19) intensive care unit in France that administers 30 doses of 10 mg/25 mL ephedrine/day., Results: Total cost savings per hospital per year, associated with reductions in pADEs, unused drugs, drug cost and cost of supplies were £34 829 for the atropine example and €104 570 for the ephedrine example. Annual preparation time decreased by 371 and 234 hours in the atropine and ephedrine examples, respectively., Conclusions: The model provides a generalisable framework with customisable inputs, giving hospitals a comprehensive view of the clinical and economic value of adopting PFS. Despite increased costs per dose with PFS, the hypothetical case studies showed notable reductions in medication preparation time and a net budget savings owing to fewer pADEs and reduced drug wastage., Competing Interests: Competing interests: MW, HG, AT, and TE were employees of BD at the time this study was developed and conducted. MP received consultancy fees from BD for providing analytical support. Alkemi LLC (BJL and KAC) received consultancy fees from BD for providing analytical medical writing support. Alkemi LLC did not receive budget for publication writing. JFHE does not have any conflicts of interest to declare., (© European Association of Hospital Pharmacists 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Providing a better understanding of what makes a compound a successful drug candidate is crucial for reducing the high attrition rates in drug discovery. Analyses of the differences between active compounds, clinical candidates and drugs require high-quality datasets. However, most datasets of drug discovery programs are not openly available. This work introduces a dataset of compound-target pairs extracted from the open-source bioactivity database ChEMBL (release 32). Compound-target pairs in the dataset either have at least one measured activity or are part of the manually curated set of known interactions in ChEMBL. Known interactions between drugs or clinical candidates and targets are specifically annotated to facilitate analyses of differences between drugs, clinical candidates, and other active compounds. In total, the dataset comprises 614,594 compound-target pairs, 5,109 (3,932) of which are known interactions between drugs (clinical candidates) and targets. The extraction is performed in an automated manner and fully reproducible. We are providing not only the datasets but also the code to rerun the analyses with other ChEMBL releases., (© 2024. European Molecular Biology Laboratory, Max Planck Institute of Molecular Physiology, Paul D. Leeson, Robert J. Young.)

Parenteral artificial nutrition (PAN) is a lifesaving medical treatment for many patients worldwide. Administration of the wrong PAN drug can lead to severe consequences on patients' health, including death in the worst cases. Thus, their correct identification, just before injection, is of crucial importance. Since most of these drugs appear as turbid liquids, they cannot be easily discriminated simply by means of basic optical analyses. To overcome this limitation, in this work, we demonstrate that the combination of speckle pattern (SP) imaging and artificial intelligence can provide precise classifications of commercial pharmaceutical suspensions for PAN. Towards this aim, we acquired SP images of each sample and extracted several statistical parameters from them. By training two machine learning algorithms (a Random Forest and a Multi-Layer Perceptron Network), we were able to identify the drugs with accurate performances. The novelty of this work lies in the smart combination of SP imaging and machine learning for realizing an optical sensing platform. For the first time, to our knowledge, this approach is exploited to identify PAN drugs.

Micropollutants, especially pharmaceutical compounds, are of significant concern owing to their ngL - 1 to µgL - 1 concentration, making them difficult for conventional treatment plants to remove from wastewater. Despite municipal wastewater treatment plant being a primary source of these compounds to be released into the wastewater, on comparison little attention has been given to hospital wastewater. The major focus of studies addressing pharmaceutical compounds is based on synthetic wastewater. This study addresses this research gap by treating wastewater to remove micropollutants (Fluvastatin, ketoprofen, paracetamol, ciprofloxacin, carbamazepine, sulfamethoxazole, and lorazepam) by employing a fluidized aerobic bioreactor. Tubesettler was attached to a fluidized-bed bioreactor to see if it could be used as a polishing unit rather than a secondary clarifier. The environmental risk from the effluent discharge into the environment was assessed regarding the hazard quotient. The paracetamol and ketoprofen were removed at an efficiency of 51% and 60%, respectively, followed by carbamazepine at 50%, ciprofloxacin at 40%, fluvastatin at 47%, sulfamethoxazole at 31%, and lorazepam at 20%. The influent posed moderate environmental risk with (Hazard Quotient) HQ > 0.5, while in effluent the risk was reduced with HQ value 0.4. For effluent from fluidized bed bioreactors (HQ 0.13) and tube setters (HQ 0.15). The associated tube settler was found suitable for polishing units with additional removal efficiencies of 15-43% for all the targeted pharmaceutical compounds. Further studies are required to explore disinfectants' effect on the reactor's biodegradation efficiency. Also, further modification and a hybrid version of the fluidized bed bioreactor can be used., (© 2024. The Author(s).)

The global focus on wastewater treatment has intensified in the contemporary era due to its significant environmental and human health impacts. Pharmaceutical compounds (PCs) have become an emerging concern among various pollutants, as they resist conventional treatment methods and pose a severe environmental threat. Advanced oxidation processes (AOPs) emerge as a potent and environmentally benign approach for treating recalcitrant pharmaceuticals. To address the shortcomings of traditional treatment methods, a technology known as the electro-Fenton (EF) method has been developed more recently as an electrochemical advanced oxidation process (EAOP) that connects electrochemistry to the chemical Fenton process. It has shown effective in treating a variety of pharmaceutically active compounds and actual wastewaters. By producing H 2 O 2 in situ through a two-electron reduction of dissolved O 2 on an appropriate cathode, the EF process maximizes the benefits of electrochemistry. Herein, we have critically reviewed the application of the EF process, encompassing diverse reactor types and configurations, the underlying mechanisms involved in the degradation of pharmaceuticals and other emerging contaminants (ECs), and the impact of electrode materials on the process. The review also addresses the factors influencing the efficiency of the EF process, such as (i) pH, (ii) current density, (iii) H 2 O 2 concentration, (iv) and others, while providing insight into the scalability potential of EF technology and its commercialization on a global scale. The review delves into future perspectives and implications concerning the ongoing challenges encountered in the operation of the electro-Fenton process for the treatment of PCs and other ECs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The healthcare sector is a major contributor of greenhouse gas emissions, and reduction and proper sorting of healthcare waste is essential to achieve sustainable healthcare. This study aimed to characterize the quantity and composition of pharmaceutical waste from a major Danish hospital. Pharmaceutical waste was collected from Odense University Hospital, including departments located in both Odense and Svendborg. The average daily production of pharmaceutical waste was 1150 g/day in Odense and 5967 g/day in Svendborg, with the operating rooms in Svendborg contributing 3143 g/day. The amount and composition of pharmaceutical waste varied greatly between departments, but some common patterns were identified. Propofol accounted for about one third of the pharmaceutical waste obtained from operating rooms. Antibiotics for systemic use constituted a significant proportion of the pharmaceutical waste from several departments and were the therapeutic group from which most different drugs were identified. Paracetamol accounted for 33.5% of the discarded tablets/capsules in Odense and 12.6% in Svendborg. Medications dispensed by automated dose dispensing accounted for a significant proportion of the discarded tablets/capsules in departments using this service. This study highlights some key areas for reduction and management of pharmaceutical waste and contributes to the currently limited evidence within this area., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Introduction: The COVID-19 pandemic has led to unforeseen and novel manifestations, as illustrated by the management of drug shortages through the development of hospital production of sterile pharmaceutical preparations (P2S). Visual inspection of P2S is a release control whose methods are described in monographs of the European Pharmacopoeia (2.9.20) and the United States Pharmacopeia (1790). However, these non-automated visual methods require training and proficiency testing of personnel. The main objective of this work was to compare the reliability and speed of analysis of two visual methods and an automated method for detecting visible particles by image analysis in P2S. Furthermore, these methods were used to evaluate sources of particulate contamination during pre-production processes (washing, disinfection, depyrogenation) and production (filling, capping)., Materials and Methods: Three pharmacy technicians examined 41 clear glass vials of type I, 10 and/or 50 mL through manual visual inspection (MVI), semi-automated (SAVI), and automated (AVI) inspection. The vials were distributed as follows: (i) 16 vials of water for injection containing either glass particles (224 µm or 600 µm), stopper fragments, or textile fibres; (ii) five sterile injectable specialties; (iii) 20 vials of water for injection prepared under different pre-production conditions., Results and Discussion: MVI and SAVI detected 100% of visible particles compared with 28% for AVI, which showed a deficiency in detecting textile fibres. All three methods correctly analysed P2S that did not contain visible particles. The three methods detected particles in vials maintained under International Organization for Standardization (ISO) 9 pre-production conditions. However, detections by (i) MVI and SAVI, and by (ii) AVI of particles contained in vials maintained under ISO 8 pre-production conditions were deemed satisfactory and unsatisfactory, respectively., Conclusion: The importance of visual inspection of P2S requires rapid, sensitive, and reliable detection methods. In this context, MVI and SAVI have proven to be more effective than AVI for a more competitive financial, training, and implementation investment., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. Re-use permitted under CC BY. Published by BMJ.)

The human microbiome plays a key role in drug development and precision medicine, but understanding its complex interactions with drugs remains a challenge. Identifying microbe-drug associations not only enhances our understanding of their mechanisms but also aids in drug discovery and repurposing. Traditional experiments are expensive and time-consuming, making computational methods for predicting microbe-drug associations a new trend. Currently, computational methods specifically designed for this task are still scarce. Therefore, to address the shortcomings of traditional experimental methods in predicting potential microbe-drug associations, this paper proposes a new prediction model named GCNATMDA. The model combines two deep learning models, Graph Convolutional Network and Graph Attention Network, and aims to reveal potential relationships between microbes and drugs by learning related features. Thus improve the efficiency and accuracy of prediction. We first integrated the microbe-drug association matrix from the existing dataset, and then combined the calculated microbe-drug characteristic matrix as the model input. The GCN module is used to dig deeper into the potential characterization of microbes and drugs, while the GAT module further learns the more complex interactions between them and generates the corresponding score matrix. The experimental results show that the GCNATMDA model achieves 96.59% and 93.01% in AUC and AUPR evaluation indexes, respectively, which is significantly better than the existing prediction models. In addition, the reliability of the prediction results is verified by a series of experiments., (© 2024. The Author(s).)

Recycled wastewater effluent irrigation and implementing limited irrigation rates are two promising strategies for water conservation in agriculture. However, one major challenge is the accumulation and translocation of Pharmaceutical and Personal Care Products (PPCPs) from recycled water to crops. This study investigated the effects of UV persulfate (UV/PS) treatment of recycled water and limited irrigation rate on PPCPs accumulation and physiological responses of St. Augustine turfgrass via a 14-week field trial. Carbamazepine (CBZ), sulfamethoxazole (SMX), triclosan (TCS), fluoxetine (FLX) and diclofenac (DCF) were spiked at 0.1-1.5 µg/L into recycled water and two limited irrigation rates corresponding to 60 % and 80 % of reference Evapotranspiration (ET o ) were applied. Results showed that UV/PS removed 60 % of CBZ and > 99 % of other PPCPs from recycled water. Irrigation with UV/PS treated recycled water resulted in approximately a 60 % reduction in CBZ accumulation and complete removal of SMX, DCF, FLX and TCS in both turfgrass leaves and roots. A more limited irrigation rate at 60 % ET o resulted in a higher accumulation of CBZ accumulation compared to 80 % ET o . Similarly, the canopy temperature increased under 60 % ET o irrigation rate compared to 80 % ET o , suggesting that turfgrass under 60 % ET o was more prone to water stress. Applying a 60 % ET o irrigation rate was not sufficient to maintain the turfgrass quality in the acceptable range. A negative correlation between the visual quality and cumulative mass of PPCPs in turfgrass leaves at different irrigation rates was observed, yet irrigation rate was the major driver of turfgrass overall quality and health. Insights from this study will help to integrate recycled water with treatment and limited irrigation, thereby enhancing agricultural water reuse practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Accurately predicting ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties early in drug development is essential for selecting compounds with optimal pharmacokinetics and minimal toxicity. Existing ADMET-related benchmark sets are limited in utility due to their small dataset sizes and the lack of representation of compounds used in drug discovery projects. These shortcomings hinder their application in model building for drug discovery. To address this issue, we propose a multi-agent data mining system based on Large Language Models that effectively identifies experimental conditions within 14,401 bioassays. This approach facilitates merging entries from different sources, culminating in the creation of PharmaBench. Additionally, we have developed a data processing workflow to integrate data from various sources, resulting in 156,618 raw entries. Through this workflow, we constructed PharmaBench, a comprehensive benchmark set for ADMET properties, which comprises eleven ADMET datasets and 52,482 entries. This benchmark set is designed to serve as an open-source dataset for the development of AI models relevant to drug discovery projects., (© 2024. The Author(s).)

Microbes have been demonstrated to be closely linked to diseases that pose a major threat to human health. Computing technologies can help researchers find potential microbe-drug associations more quickly and precisely. In this study, we introduced a novel computational prediction model called GLNNMDA based on global and local features of microbes and drugs to infer possible microbe-drug correlations. In GLNNMDA, we first constructed a heterogeneous network based on known microbe-drug relationships by integrating multiple similarity metrics of drugs and microbes. Subsequently, low-dimensional features will be extracted for nodes in the heterogeneous network by adopting the graph attention encoder. Next, based on combining these low-dimensional features with multiple properties of microbes and drugs to form a new comprehensive feature matrix, we would utilize the GLF module to extract the global and local features for microbes and drugs respectively, and then, we would further fuse these global and local features to come up with predictions of possible microbe-drug associations. Moreover, in order to evaluate the prediction performance of GLNNMDA, under the framework of fivefold cross-validation, intensive comparative experiments and case studies were done on different well-known public databases. The results showed that GLNNMDA obtained the highest AUC values as well as AUPR values of 0.9802 ± 0.0011, 0.9773 ± 0.0021 and 0.8586 ± 0.0004, 0.8008 ± 0.0031 in the two databases, MDAD and aBiofilm, respectively, compared to the state-of-the-art competing prediction methods. In addition, case studies of well-known microorganisms and drugs have demonstrated the effectiveness of GLNNMDA in inferring potential microbial drug associations, which implies that GLNNMDA may be a useful tool for microbe-drug association prediction in the future. The source code is available at: " https://github.com/KuangHaiYue/GLNNMDA.git "., (© 2024. The Author(s).)