Pharmaceuticals (Basel). 2023 Nov 13;16(11):1596. doi: 10.3390/ph16111596.

ABSTRACT

Polymorphisms of genes encoding drug metabolizing enzymes and transporters can significantly modify pharmacokinetics, and this can be associated with significant differences in drug efficacy, safety, and tolerability. Moreover, genetic variants of some components of the immune system can explain clinically relevant drug-related adverse events. However, the implementation of drug dose individualization based on pharmacogenomics remains scarce. In this narrative review, the impact of genetic variations on the disposition, safety, and tolerability of the most commonly prescribed drugs is reported. Moreover, reasons for poor implementation of pharmacogenomics in everyday clinical settings are discussed. The literature analysis showed that knowledge of how genetic variations can modify the effectiveness, safety, and tolerability of a drug can lead to the adjustment of usually recommended drug dosages, improve effectiveness, and reduce drug-related adverse events. Despite some efforts to introduce pharmacogenomics in clinical practice, presently very few centers routinely use genetic tests as a guide for drug prescription. The education of health care professionals seems critical to keep pace with the rapidly evolving field of pharmacogenomics. Moreover, multimodal algorithms that incorporate both clinical and genetic factors in drug prescribing could significantly help in this regard. Obviously, further studies which definitively establish which genetic variations play a role in conditioning drug effectiveness and safety are needed. Many problems must be solved, but the advantages for human health fully justify all the efforts.

PMID:38004461 | DOI:10.3390/ph16111596

Antioxidants (Basel). 2023 Oct 30;12(11):1930. doi: 10.3390/antiox12111930.

ABSTRACT

Aripiprazole has fewer metabolic side effects than other antipsychotics; however, there are some severe ones in the liver, leading to drug-induced liver injury. Repeated treatment with aripiprazole affects cell division. Since this process requires a lot of energy, we decided to investigate the impact of aripiprazole on rat liver cells and mitochondria as the main source of cellular energy production by measuring the mitochondrial membrane potential, respiration, adenosine triphosphate (ATP) production, oxidative stress, antioxidative response, and human blood haemolysis. Here, we report that mitochondrial hyperpolarisation from aripiprazole treatment is accompanied by higher reactive oxygen species (ROS) production and increased antioxidative response. Lower mitochondrial and increased glycolytic ATP synthesis demand more glucose through glycolysis for equal ATP production and may change the partition between the glycolysis and pentose phosphate pathway in the liver. The uniform low amounts of the haemolysis of erythrocytes in the presence of aripiprazole in 25 individuals indicate lower quantities of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH+H+), which is in accordance with a decreased activity of glucose 6-phosphate dehydrogenase and the lower dehydrogenase activity upon aripiprazole treatment. The lower activity of glucose 6-phosphate dehydrogenase supports a shift to glycolysis, thus rescuing the decreased mitochondrial ATP synthesis. The putative reduction in NADPH+H+ did not seem to affect the oxidised-to-reduced glutathione ratio, as it remained equal to that in the untreated cells. The effect of aripiprazole on glutathione reduction is likely through direct binding, thus reducing its total amount. As a consequence, the low haemolysis of human erythrocytes was observed. Aripiprazole causes moderate perturbations in metabolism, possibly with one defect rescuing the other. The result of the increased antioxidant enzyme activity upon treatment with aripiprazole is increased resilience to oxidative stress, which makes it an effective drug for schizophrenia in which oxidative stress is constantly present because of disease and treatment.

PMID:38001783 | DOI:10.3390/antiox12111930

BMJ. 2023 Nov 24;383:2784. doi: 10.1136/bmj.p2784.

NO ABSTRACT

PMID:38000791 | DOI:10.1136/bmj.p2784

Curr Oncol. 2023 Nov 2;30(11):9701-9709. doi: 10.3390/curroncol30110704.

ABSTRACT

Patients with incurable cancers have an increasing number of comorbidities, which can lead to polypharmacy and its associated adverse events (drug-to-drug interaction, prescription of a potentially inappropriate medication, adverse drug event). Deprescribing is a patient-centered process aimed at optimizing patient outcomes by discontinuing medication(s) deemed no longer necessary or potentially inappropriate. Improved patient quality of life, risk reduction of side effects or worse clinical outcomes, and a decrease in healthcare costs are well-documented benefits of deprescribing. Deprescribing and advance care planning both require consideration of patients' values, preferences, and care goals. Here, we provide an overview of comorbidities and associated polypharmacy risks in cancer patients, as well as useful tools and resources for deprescribing in daily practice, and we shed light on how deprescribing can facilitate advance care planning discussions with patients who have advanced cancer or a limited life expectancy.

PMID:37999124 | PMC:PMC10670366 | DOI:10.3390/curroncol30110704

Sci Rep. 2023 Nov 22;13(1):20498. doi: 10.1038/s41598-023-47271-w.

ABSTRACT

Although remimazolam is an ultra-short-acting benzodiazepine with a shorter elimination half-life and faster recovery time than midazolam, studies evaluating its safety and efficacy during bronchoscopy are limited. This study aimed to compare the safety and efficacy of remimazolam with those of midazolam for bronchoscopy. This prospective randomized parallel-group study was conducted at a single institution. The primary outcome was the time from the end of the procedure to full alertness. Other procedural time parameters, satisfaction profiles, and adverse effects were thoroughly evaluated. The time taken to reach peak sedation and the time from the end of the procedure to full alertness was significantly shorter in the remimazolam group than in the midazolam group (median [interquartile range], 2 min [1-4] vs. 3 min [2-5], P = 0.006; and median, 2 min [1-5] vs. 5 min [1-12], P = 0.035, respectively). In patients with non-biopsy procedures (n = 79), participant satisfaction was significantly higher in the remimazolam group than in the midazolam group (median rated scale, 10 vs. 7, P = 0.042). Physician satisfaction and willingness to repeat the procedure were similar between groups. Although the incidence of adverse effects was similar between the groups and there was no significant difference, the midazolam group had a higher antidote administration rate than the remimazolam group (15.7% vs. 4.1%, P = 0.092). Remimazolam is effective and safe for achieving adequate sedation, with a shorter onset time and faster neuropsychiatric recovery than midazolam. It may be a new option for sedation during bronchoscopy.Trial registration: The trial registration number is NCT05994547, and the date of first registration is 16/08/2023.

PMID:37993525 | PMC:PMC10665376 | DOI:10.1038/s41598-023-47271-w

PLoS One. 2023 Nov 22;18(11):e0293306. doi: 10.1371/journal.pone.0293306. eCollection 2023.

ABSTRACT

Cash holding is an important strategic decision of enterprises. As a macro-level factor, economic policy uncertainty causes risks, affecting enterprises' cash holdings. Taking the quarterly financial data of China's A-share non-financial listed firms for 2010-2020 as a sample, this study adopts the OLS and fixed effect models to investigate how corporate cash holdings are affected by economic policy uncertainty. The findings indicate that economic policy uncertainty is directly proportional to the level of cash that listed corporations hold. The higher the uncertainty, the more cash the company holds. Among them, state-owned enterprises and the manufacturing industry are more significantly affected by economic policy uncertainty. Finally, considering the regional marketization level and the differences in financing constraints enterprises face, it is concluded through grouping empirical studies that enterprises located in regions with lower marketization levels are more susceptible to policy uncertainty, while financially constrained enterprises are more susceptible to economic policy uncertainty. The study of economic policy uncertainty is helpful to guide enterprises to realize the importance of coping strategies in advance under the background of intensifying economic policy uncertainty. Therefore, this paper proposes to introduce policies on the premise of fully considering the smoothness of the economy and the differences in the conditions of firms of different natures, as well as some proposals to alleviate financing constraints, reduce the adverse effects of uncertainty on firms, and bolster the marketization process.

PMID:37992087 | PMC:PMC10664914 | DOI:10.1371/journal.pone.0293306

BMC Pharmacol Toxicol. 2023 Nov 21;24(1):64. doi: 10.1186/s40360-023-00708-4.

ABSTRACT

OBJECTIVE: Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.

METHODS: Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.

RESULTS: Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.

CONCLUSION: Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.

PMID:37990344 | DOI:10.1186/s40360-023-00708-4

Sci Transl Med. 2023 Nov 22;15(723):eade8460. doi: 10.1126/scitranslmed.ade8460. Epub 2023 Nov 22.

ABSTRACT

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly to the development of obesity and associated metabolic disorders. By suppressing the rise in leptin through the use of a monoclonal leptin-neutralizing antibody, we effectively prevented weight gain, restored glucose tolerance, and preserved adipose tissue and liver function in antipsychotic drug-treated mice. Mechanistically, suppressing excess leptin resolved local tissue and systemic inflammation typically associated with antipsychotic drug treatment. We conclude that hyperleptinemia is a key contributor to antipsychotic drug-associated weight gain and metabolic deterioration. Leptin suppression may be an effective approach to reducing the undesirable side effects of antipsychotic drugs.

PMID:37992151 | DOI:10.1126/scitranslmed.ade8460

Drug Saf. 2023 Dec;46(12):1363-1379. doi: 10.1007/s40264-023-01355-8. Epub 2023 Nov 21.

ABSTRACT

INTRODUCTION: Adverse drug reactions (ADRs) can be reported by Health Care Professionals (HCPs; e.g., physicians, pharmacists) and non-Health Care Professionals (non-HCPs; e.g., consumers). Previous studies investigating differences between reports from HCPs and non-HCPs rarely considered the completeness of information provided. In addition, they mostly did not distinguish between physicians and pharmacists or were performed years ago. The aim of our study was to analyse and compare the completeness of information provided in reports from physicians, pharmacists and consumers from Germany in a more recent dataset.

MATERIALS AND METHODS: We analysed all spontaneous reports from Germany received between 2018 and 2021 in the ADR database EudraVigilance exclusively reported by physicians (n = 69,976), pharmacists (n = 42,396) or consumers (n = 121,144). Demographical parameters of the patients were analysed descriptively. Completeness of reports was evaluated applying an established score (vigiGrade). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression analysis in order to identify report, patient, drug or ADR-specific information provided more often in reports from physicians, pharmacists or consumers.

RESULTS: Within the study period the number of reports per year by physicians and pharmacists decreased steadily, while an opposite trend was observed for consumer reports. The proportion of female patients was higher in reports from pharmacists (64.4%) and consumers (64.8%) compared to those from physicians (55.3%). On average, patients in reports from pharmacists (58.7) were older compared to those from physicians (53.5) and consumers (52.6). As an example for the presence of specific information, the time to onset of the ADR could be calculated more often in consumer compared to physician (OR 1.9 [1.8-1.9]) and pharmacist reports (OR 1.7 [1.6-1.7]). In contrast, pharmacist (OR 0.5 [0.4-0.5]) and consumer (OR 0.5 [0.5-0.5]) reports included the indication of the suspected drug less often than physician reports. Physician reports on average (mean = 0.5) were slightly more complete according to the vigiGrade score compared to reports from consumers (mean = 0.4) and pharmacists (mean = 0.4).

CONCLUSION: The ADR reports from consumers were comparable with regard to the completeness score with those from physicians and pharmacists underlining their value. Differences in completeness of specific information between the reporter types were found, suggesting that a common reporting of interactions between the three reporters may further improve the completeness of ADR reports. Furthermore, stratified analysis of ADR reports per reporter type may be helpful for certain objectives in scientific research.

PMID:37987966 | DOI:10.1007/s40264-023-01355-8

Am J Nurs. 2023 Dec 1;123(12):54-62. doi: 10.1097/01.NAJ.0000997216.21988.19.

ABSTRACT

There were 36,136 new HIV diagnoses in the United States and dependent areas in 2021, despite a 12% reduction in estimated HIV incidence from 2017 to 2021. The burden of HIV remains disproportionately high among certain populations, including gay and bisexual men, Black/African American individuals, and Hispanic/Latino individuals, and racial and ethnic health care disparities persist. The Ending the HIV Epidemic initiative aims to significantly reduce new infections, with a focus on HIV prevention, particularly the use of preexposure prophylaxis (PrEP). However, challenges remain in achieving equitable PrEP distribution. As frontline health care providers, nurses play a pivotal role in this battle against HIV. This article provides an update on PrEP screening recommendations, the types of PrEP available, dosing, adverse effects, and the role of nurses in patient support and monitoring.

PMID:37988020 | DOI:10.1097/01.NAJ.0000997216.21988.19

J Int Med Res. 2023 Nov;51(11):3000605231211402. doi: 10.1177/03000605231211402.

ABSTRACT

OBJECTIVE: To explore the effects of oral semaglutide on glycaemic parameters, body weight, and satisfaction in the first recipient patients with type 2 diabetes mellitus in Slovenia, in a real-world clinical practice setting.

METHODS: The first consecutive adult patients with type 2 diabetes who were eligible for oral semaglutide treatment were included in this prospective, open-label interventional study. Patients received increasing doses of oral semaglutide and were evaluated at inclusion, at 1 month, then 3-5 months after starting treatment. Fasting blood glucose, glycosylated haemoglobin (HbA1c), body weight, patient satisfaction with oral semaglutide treatment (using the validated Treatment Satisfaction Questionnaire for Medication), and adverse effects, were analysed. Statistical analyses were performed using one-way analysis of variance, and, when significant interactions were found, Bonferroni post-hoc test. A P-value <0.05 was considered statistically significant.

RESULTS: Twenty patients (11 male: 9 female; mean age, 59.9 ± 1.5 years; mean diabetes duration, 8.5 ± 1.4 years) were included. Oral semaglutide (7 and 14 mg) significantly decreased HbA1c (from 9.4 ± 0.3% to 8.2 ± 0.2% and 7.8 ± 0.2%, respectively) and fasting plasma glucose (from 11.2 ± 0.5 mmol/L to 9.2 ± 0.7 mmol/L and 8.9 ± 0.4 mmol/L, respectively). Oral semaglutide (14 mg) significantly decreased body weight (from 100.9 ± 2.7 kg to 92.7 ± 2.4 kg). Patients reported that treatment was easy to use and expressed high global satisfaction. Mild and transient, mostly gastrointestinal, adverse effects were reported in 10 patients.

CONCLUSIONS: Oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, was effective and safe, and associated with high patient satisfaction, in its first recipients in Slovenia. The results are important for daily clinical practice involving patients with type 2 diabetes, however, due to the small study population, lack of placebo control, and short exposure to oral semaglutide, the effectiveness of oral semaglutide in clinical practice requires further investigation.

PMID:37987649 | DOI:10.1177/03000605231211402

Anaesthesiologie. 2023 Dec;72(12):887-893. doi: 10.1007/s00101-023-01355-4. Epub 2023 Nov 17.

ABSTRACT

BACKGROUND: In a large proportion of patients admitted to the emergency department (ED), the initial main symptom is nonspecific. One possible reason for this, especially in older patients, may be adverse drug reactions (ADR) due to their frequent polypharmacy.

AIM: To illustrate the incidence of ADRs, the affected patient population including risk factors, and drug classes with ADRs leading to nonspecific symptoms. To provide practice recommendations for the management of ADRs in the ED.

MATERIAL AND METHODS: Presentation of the pharmacological principles on ADRs, statistics of pharmacovigilance centers as well as original literature including experiences from clinical practice and own projects.

RESULTS: In 10% of patients with nonspecific symptoms an ADR is responsible for presentation in the ED. In 60% of cases these ADRs are not correctly identified in the ED setting. A small number of drug classes are responsible for most of these referrals. Databases, risk stratification, clinical pharmacists, or clinical decision support systems are available to improve ADR identification and management. As these options are partly associated with considerable costs or the validation for German EDs is missing, a widespread application does not take place.

CONCLUSION: Correct identification of ADRs in patients with nonspecific symptoms in the ED is necessary to initiate adequate treatment. These ADRs are often overlooked because processes and tools for identification and management are not applied in the ED, leading to a lack of awareness. For high-risk patients in the ED, the focus should be on drug history, ideally considering patient-specific risk factors and specific drug classes.

PMID:37978070 | DOI:10.1007/s00101-023-01355-4

BMC Med Inform Decis Mak. 2023 Nov 16;23(1):263. doi: 10.1186/s12911-023-02355-5.

ABSTRACT

BACKGROUND: Patient safety is a central healthcare policy worldwide. Adverse drug events (ADE) are among the main threats to patient safety. Children are at a higher risk of ADE in each stage of medication management process. ADE rate is high in the administration stage, as the final stage of preventing medication errors in pediatrics and neonates. The most effective way to reduce ADE rate is using medication administration clinical decision support systems (MACDSSs). The present study reviewed the literature on MACDSS for neonates and pediatrics. It identified and classified the data elements that mapped onto the Fast Healthcare Interoperability Resources (FHIR) standard and the functionalities of these systems to guide future research.

METHODS: PubMed/ MEDLINE, Embase, CINAHL, and ProQuest databases were searched from 1995 to June 31, 2021. Studies that addressed developing or applying medication administration software for neonates and pediatrics were included. Two authors reviewed the titles, abstracts, and full texts. The quality of eligible studies was assessed based on the level of evidence. The extracted data elements were mapped onto the FHIR standard.

RESULTS: In the initial search, 4,856 papers were identified. After removing duplicates, 3,761 titles, and abstracts were screened. Finally, 56 full-text papers remained for evaluation. The full-text review of papers led to the retention of 10 papers which met the eligibility criteria. In addition, two papers from the reference lists were included. A total number of 12 papers were included for analysis. Six papers were categorized as high-level evidence. Only three papers evaluated their systems in a real environment. A variety of data elements and functionalities could be observed. Overall, 84 unique data elements were extracted from the included papers. The analysis of reported functionalities showed that 18 functionalities were implemented in these systems.

CONCLUSION: Identifying the data elements and functionalities as a roadmap by developers can significantly improve MACDSS performance. Though many CDSSs have been developed for different medication processes in neonates and pediatrics, few have actually evaluated MACDSSs in reality. Therefore, further research is needed on the application and evaluation of MACDSSs in the real environment.

PROTOCOL REGISTRATION: (dx.doi.org/10.17504/protocols.io.bwbwpape).

PMID:37974195 | PMC:PMC10652533 | DOI:10.1186/s12911-023-02355-5

Anaesth Rep. 2023 Nov 15;11(2):e12258. doi: 10.1002/anr3.12258. eCollection 2023 Jul-Dec.

ABSTRACT

Ondansetron is a highly selective 5-hydroxytryptamine receptor antagonist and the most commonly used anti-emetic for the prevention of postoperative nausea and vomiting. Ondansetron has a low affinity for dopamine receptors and so extrapyramidal side effects are rare. Here, we present the case of a 14-year-old girl who developed a severe post-operative acute dystonic reaction which included oculogyric crisis. We believe that ondansetron was the most likely cause, although propofol may have been a synergistic or alternative causative agent. The patient had no significant past medical history and had previously undergone two uneventful general anaesthetics which included both ondansetron and propofol. The prolonged duration and severity of the reaction and failure to fully respond to specific treatments resulted in the need for tracheal intubation and transfer to a paediatric intensive care unit. She subsequently recovered uneventfully with no ongoing neurological sequalae. Ondansetron-induced dystonic reactions are rare and unpredictable and can occur in patients who have previously received the drug without complication. They are thought to be caused by an imbalance between inhibitory and excitatory neurotransmitters in the extrapyramidal system. Specific treatments include anticholinergics, antihistamines and benzodiazepines.

PMID:37974908 | PMC:PMC10646813 | DOI:10.1002/anr3.12258

J Natl Cancer Inst. 2023 Nov 16:djad241. doi: 10.1093/jnci/djad241. Online ahead of print.

ABSTRACT

BACKGROUND: Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors, and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering.

METHODS: Using the Surveillance, Epidemiology and End Results Medicare-linked database we identified 15,002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6-months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric or drug-related event(s).

RESULTS: There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not significantly linked to acute events in the 3-month post-taper period (odds ratio 1.02; p = .62), nor at any point in the future (odds ratio 0.96; p = .46).

CONCLUSIONS: Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric or drug-related events, in contrast to prior research in the general population.

PMID:37971959 | DOI:10.1093/jnci/djad241

AAPS PharmSciTech. 2023 Nov 16;24(8):233. doi: 10.1208/s12249-023-02670-0.

ABSTRACT

Blood cancer, also known as hematological malignancy, is one of the devastating types of cancer that has significantly paved its mortality mark globally. It persists as an extremely deadly cancer type and needs utmost attention owing to its negligible overall survival rate. Major challenges in the treatment of blood cancer include difficulties in early diagnosis, as well as severe side effects resulting from chemotherapy. In addition, immunotherapies and targeted therapies can be prohibitively expensive. Over the past two decades, scientists have devised a few nanoparticle-based drug delivery systems aimed at overcoming this challenge. These therapeutic strategies are engineered to augment the cellular uptake, pharmacokinetics, and effectiveness of anticancer drugs. However, there are still numerous types of nanoparticles that could potentially improve the efficacy of blood cancer treatment, while also reducing treatment costs and mitigating drug-related side effects. To the best of our knowledge, there has been limited reviews published on the use of nano-based drug delivery systems for the treatment of hematological malignancies. Therefore, we have made a concerted effort to provide a comprehensive review that draws upon recent literature and patents, with a focus on the most promising results regarding the use of nanoparticle-based approaches for the treatment of hematological malignancies. All these crucial points covered under a common title would significantly help researchers and scientists working in the area.

PMID:37973643 | DOI:10.1208/s12249-023-02670-0

Australas Emerg Care. 2023 Nov 14:S2588-994X(23)00087-8. doi: 10.1016/j.auec.2023.10.005. Online ahead of print.

ABSTRACT

BACKGROUND: Following a national multicentre study, two emergency department (ED) screening tools were developed to determine risk of medication-related problems; one for use at ED presentation and another at ED discharge to the community. This study aimed to determine the inter-rater reliability amongst ED health professionals when applying these screening tools to a series of case scenarios.

METHODS: A prospective, cross-sectional study was undertaken in the ED of a major metropolitan hospital. Twelve case scenarios were developed following ED observation of a range of patients, which were incorporated into a questionnaire and distributed to 50 health professionals. Inter-rater reliabilities of each explanatory variable of the screening tools and overall assessment were calculated using Fleiss' multi-rater kappa.

RESULTS: The questionnaire was completed by 15 doctors, 19 nurses and 16 pharmacists. Fleiss' kappa showed an overall inter-rater reliability for the ED presentation tool of 0.83 (95% CI 0.83-0.84), indicating near perfect agreement. Fleiss' kappa for the ED discharge tool was 0.83 (95% CI 0.83-0.85), which also showed near perfect agreement.

CONCLUSIONS: The screening tools produced favourable inter-rater reliability amongst ED health professionals. These results have important implications for ensuring consistency of ED decision-making in screening patients at risk of developing medication-related problems.

PMID:37973428 | DOI:10.1016/j.auec.2023.10.005

Arterioscler Thromb Vasc Biol. 2023 Nov 16. doi: 10.1161/ATVBAHA.123.319692. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the ubiquitous utilization of central venous catheters in clinical practice, their use commonly provokes thromboembolism. No prophylactic strategy has shown sufficient efficacy to justify routine use. Coagulation factors FXI (factor XI) and FXII (factor XII) represent novel targets for device-associated thrombosis, which may mitigate bleeding risk. Our objective was to evaluate the safety and efficacy of an anti-FXI mAb, gruticibart (AB023), in a prospective, single-arm study of patients with cancer receiving central line placement.

METHODS: We enrolled ambulatory cancer patients undergoing central line placement to receive a single dose of gruticibart (2 mg/kg) administered through the venous catheter within 24 hours of placement and a follow-up surveillance ultrasound at day 14 for evaluation of catheter thrombosis. A parallel, noninterventional study was used as a comparator.

RESULTS: In total, 22 subjects (n=11 per study) were enrolled. The overall incidence of catheter-associated thrombosis was 12.5% in the interventional study and 40.0% in the control study. The anti-FXI mAb, gruticibart, significantly prolonged the activated partial thromboplastin time in all subjects on day 14 compared with baseline (P<0.001). Gruticibart was well tolerated and without infusion reactions, drug-related adverse events, or clinically relevant bleeding. Platelet flow cytometry demonstrated no difference in platelet activation following administration of gruticibart. T (thrombin)-AT (antithrombin) and activated FXI-AT complexes increased following central line placement in the control study, which was not demonstrated in our intervention study. CRP (C-reactive protein) did not significantly increase on day 14 in those who received gruticibart, but it did significantly increase in the noninterventional study.

CONCLUSIONS: FXI inhibition with gruticibart was well tolerated without any significant adverse or bleeding-related events and resulted in a lower incidence of catheter-associated thrombosis on surveillance ultrasound compared with the published literature and our internal control study. These findings suggest that targeting FXI could represent a safe intervention to prevent catheter thrombosis.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465760.

PMID:37970718 | DOI:10.1161/ATVBAHA.123.319692

World J Hepatol. 2023 Oct 27;15(10):1109-1126. doi: 10.4254/wjh.v15.i10.1109.

ABSTRACT

Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q. This leads to copper deposition in various organs, most importantly in the liver and brain. The genetic mutations are vast, well reported in the West but poorly documented in developing countries. Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians. Diagnostic scoring systems are not fool-proof. The availability and affordability of chelators in developing countries impact the drug compliance of patients. While D-penicillamine is a potent drug, its side effects lead to drug discontinuation. Trientine is cost-prohibitive in developing countries. There is no single test to assess the adequacy of chelation. Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool. In the presence of cirrhosis, hypersplenism clouds the assessment of myelosuppression of drugs. Similarly, it may be difficult to distinguish disease tubulopathy from drug-induced glomerulonephritis. Neurological worsening due to chelators may appear similar to disease progression. Presentation as fulminant hepatic failure requires rapid workup. There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices. This review addresses the challenges and clinical dilemmas faced at beside in developing countries.

PMID:37970614 | PMC:PMC10642431 | DOI:10.4254/wjh.v15.i10.1109

ACS Omega. 2023 Oct 26;8(44):41363-41373. doi: 10.1021/acsomega.3c04931. eCollection 2023 Nov 7.

ABSTRACT

This article presents a comprehensive study of the development of a novel nanocomposite comprising core-shell Fe3O4@MCM-41 with superparamagnetic properties and hydroxyapatite (HAp). The nanocomposite serves as a pH-responsive nanocarrier, offering an efficient injectable dosage for teriparatide (PTH (1-34)) delivery. The aim is to address the limitations associated with drug-induced side effects, precautionary measures, and frequent injections. The nanocomposites, as prepared, were characterized using techniques including X-ray diffraction, Fourier transform infrared, zeta potential, dynamic light scattering, VSM, scanning electron microscopy, and transmission electron microscopy. The nanocomposites' average crystallite diameter was determined to be 27 ± 5 nm. The hydrodynamic size of the PTH (1-34)-loaded nanocarrier ranged from 357 to 495 nm, with a surface charge of -33 mV. The entrapment and loading efficiencies were determined to be 73% and 31%, respectively. All of these findings collectively affirm successful fabrication. Additionally, in vivo medication delivery was investigated using the HPLC method, mirroring the in vitro tests. Utilizing the dialysis approach, we demonstrated sustained-release behavior. PTH (1-34) diffusion increased as the pH decreased from 7.4 to 5.6. After 24 h, drug release was higher at acidic pH (88%) compared to normal pH (43%). The biocompatibility of the PTH (1-34)-loaded nanocarrier was assessed using the MTT assay employing the NIH3T3 and HEK-293 cell lines. The results demonstrated that the nanocarrier not only exhibited nontoxicity but also promoted cell proliferation and differentiation. In the in vivo test, the drug concentration reached 505 μg within 30 min of exposure to the magnetic field. Based on these findings, the Fe3O4@MCM-41/HAp/PTH (1-34) nanocomposite, in combination with a magnetic field, offers an efficient and biocompatible approach to enhance the therapeutic effect of osteogenesis and overcome drug limitations.

PMID:37970037 | PMC:PMC10633862 | DOI:10.1021/acsomega.3c04931