Medicina (Kaunas). 2023 Aug 31;59(9):1585. doi: 10.3390/medicina59091585.

ABSTRACT

Background and Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs), which have anti-inflammatory and analgesic properties, are commonly used in the treatment of various, particularly frequent, as well as chronic, conditions in older patients. Due to common polypragmasia in these patients and a high risk of adverse drug reactions (ADRs) and drug interactions, pain management poses a therapeutic challenge. This study describes the importance of ADR reports in the identification of polypharmacy and the ensuing interactions. Materials and Methods: Both healthcare professionals (HPs) and non-healthcare professionals (non-HPs) reports collected in the EudraVigilance database of NSAIDs, including most commonly co-reported medications and reported reactions, were analysed and differences between HPs and non-HPs reports were identified. Results: In the analysed period and group, non-HPs reported more reactions but indicated fewer drugs as suspect or concomitant. The outcomes of our analysis indicate more HP engagement and more detailed reports of serious ADRs when compared to non-serious individual case safety reports (ICSRs) by non-HPs, which appeared more detailed. Such reactions as kidney failure and increased risk of bleeding are known adverse reactions to NSAIDs and common symptoms of their interactions, which were described in the available literature. They were much more frequently reported by HPs than by non-HPs. Non-HPs more frequently reported reactions that may have been considered less significant by HPs. Conclusions: The differences between healthcare professionals' (HPs) and non-healthcare professionals' (non-HPs) reports may result from the fact that the reports from patients and their caregivers require a professional medical diagnosis based on symptoms described by the patient or additional diagnostic tests. This means that when appropriately classified, medically verified, and statistically analysed, the data may provide new evidence for the risks of medication use or drug interactions.

PMID:37763704 | PMC:PMC10535283 | DOI:10.3390/medicina59091585

Int J Mol Sci. 2023 Sep 12;24(18):13985. doi: 10.3390/ijms241813985.

ABSTRACT

Cancer is one of the major diseases that seriously threaten human life. Traditional anticancer therapies have achieved remarkable efficacy but have also some unavoidable side effects. Therefore, more and more research focuses on highly effective and less-toxic anticancer substances of natural origin. Amphibian skin is rich in active substances such as biogenic amines, alkaloids, alcohols, esters, peptides, and proteins, which play a role in various aspects such as anti-inflammatory, immunomodulatory, and anticancer functions, and are one of the critical sources of anticancer substances. Currently, a range of natural anticancer substances are known from various amphibians. This paper aims to review the physicochemical properties, anticancer mechanisms, and potential applications of these peptides and proteins to advance the identification and therapeutic use of natural anticancer agents.

PMID:37762285 | DOI:10.3390/ijms241813985

Int J Mol Sci. 2023 Sep 12;24(18):13966. doi: 10.3390/ijms241813966.

ABSTRACT

(1) Carfilzomib (Cfz) is an antineoplastic agent indicated for the treatment of multiple myeloma. However, its beneficial action is attenuated by the occurrence of cardiotoxicity and nephrotoxicity as the most common adverse effects. Presently, there is well-established knowledge on the pathomechanisms related to these side effects; however, the research on the metabolic alterations provoked by the drug is limited. (2) An in vivo simulation of Cfz-induced toxicity was developed in (i) Cfz-treated and (ii) control mice. An RP-HRMS-based protocol and an advanced statistical treatment were used to investigate the impact of Cfz on the non-polar metabolome. (3) The differential analysis classified the Cfz-treated and control mice and resulted in a significant number of identified biomarkers with AUC > 0.9. The drug impaired the biosynthesis and degradation of aromatic amino acids (AAA) and led to alterations of uremic toxins in the renal and urine levels. Furthermore, the renal degradation of tryptophan was affected, inducing its degradation via the kynurenine pathway. (4) The renal levels of metabolites showed impaired excretion and degradation of AAAs. Cfz was, finally, correlated with the biosynthesis of renal dopamine, explaining the biochemical causes of water and ion retention and the increase in systolic pressure.

PMID:37762269 | DOI:10.3390/ijms241813966

Int J Mol Sci. 2023 Sep 7;24(18):13827. doi: 10.3390/ijms241813827.

ABSTRACT

Autophagy, the process that enables the recycling and degradation of cellular components, is essential for homeostasis, which occurs in response to various types of stress. Autophagy plays an important role in the genesis and evolution of osteosarcoma (OS). The conventional treatment of OS has limitations and is not always effective at controlling the disease. Therefore, numerous researchers have analyzed how controlling autophagy could be used as a treatment or strategy to reverse resistance to therapy in OS. They highlight how the inhibition of autophagy improves the efficacy of chemotherapeutic treatments and how the promotion of autophagy could prove positive in OS therapy. The modulation of autophagy can also be directed against OS stem cells, improving treatment efficacy and preventing cancer recurrence. Despite promising findings, future studies are needed to elucidate the molecular mechanisms of autophagy and its relationship to OS, as well as the mechanisms underlying the functioning of autophagic modulators. Careful evaluation is required as autophagy modulation may have adverse effects on normal cells, and the optimization of autophagic modulators for use as drugs in OS is imperative.

PMID:37762129 | DOI:10.3390/ijms241813827

Seizure. 2023 Sep 13;112:62-67. doi: 10.1016/j.seizure.2023.09.011. Online ahead of print.

ABSTRACT

PURPOSE: Temporal lobe epilepsy (TLE) is often associated with drug-resistant seizures. We evaluated the efficacy and tolerability of lacosamide (LCM) versus controlled-release carbamazepine (CBZ-CR) monotherapy in adults with newly diagnosed TLE.

METHODS: Exploratory post hoc analysis of patients with temporal focus of localization (indicated as the only localization focus) in a double-blind, noninferiority, phase 3 trial (SP0993; NCT01243177) in patients aged ≥ 16 years with newly diagnosed epilepsy randomized 1:1 to LCM or CBZ-CR monotherapy.

RESULTS: Of 886 treated patients in this trial, temporal lobe focus of localization (TLE) was reported as the single focus for 287 (32.4%) patients (LCM 134, CBZ-CR 153). A similar proportion of patients with TLE on LCM (82 [61.2%]) and CBZ-CR (99 [64.7%]) completed the trial. Kaplan-Meier estimates for 6- and 12-month seizure freedom at the last evaluated dose level (stratified by number of seizures in the 3 months before screening [≤2 or >2 seizures]) were similar with LCM and CBZ-CR (6 months overall: 88.7% and 89.7%; 12 months overall: 78.3% and 81.7%). Treatment-emergent adverse events (TEAEs) were reported by fewer patients on LCM (73.9%) than CBZ-CR (81.0%). Drug-related TEAEs (assessed by the investigator) were reported in 41.8% of patients on LCM and 52.3% of patients on CBZ-CR; 11.2% of patients on LCM and 15.0% on CBZ-CR discontinued due to TEAEs.

CONCLUSION: Lacosamide was efficacious and generally well tolerated as monotherapy in patients with TLE with efficacy outcomes comparable with CBZ-CR, and fewer patients on LCM reported any TEAEs, drug-related TEAEs, or discontinued due to TEAEs.

PMID:37769545 | DOI:10.1016/j.seizure.2023.09.011

BMC Pediatr. 2023 Sep 28;23(1):492. doi: 10.1186/s12887-023-04097-9.

ABSTRACT

BACKGROUND: Evidence of drug-induced liver injury is abundant in adults but is lacking in children. Our aim was to identify suspected drug signals associated with pediatric liver injury.

METHODS: Hepatic adverse events (HAEs) among children reported in the Food and Drug Administration Adverse Event Reporting System were analyzed. A descriptive analysis was performed to summarize pediatric HAEs, and a disproportionality analysis was conducted by evaluating reporting odds ratios (RORs) and proportional reporting ratios to detect suspected drugs.

RESULTS: Here, 14,143 pediatric cases were reported, specifically 49.6% in males, 45.1% in females, and 5.2% unknown. Most patients (68.8%) were 6-18 years old. Hospitalization ranked first among definite outcomes (7,207 cases, 37.2%). In total, 264 disproportionate drug signals were identified. The top 10 drugs by the number of reports were paracetamol (1,365; ROR, 3.6; 95% confidence interval (CI), 3.4-3.8), methotrexate (878; ROR, 2.5; 95% CI, 2.3-2.7), vincristine (649; ROR, 3.0; 95% CI, 2.8-3.3), valproic acid (511; ROR, 3.2; 95% CI, 2.9-3.6), cyclophosphamide (490; ROR, 2.4; 95% CI, 2.2-2.6), tacrolimus (427; ROR, 2.4; 95% CI, 2.2-2.7), prednisone (416; ROR, 2.1; 95% CI, 1.9-2.3), prednisolone (401; ROR, 2.3; 95% CI, 2.1-2.5), etoposide (378; ROR, 2.3; 95% CI, 2.1-2.6), and cytarabine (344; ROR, 2.8; 95% CI, 2.5-3.2). After excluding validated hepatotoxic drugs, six were newly detected, specifically acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine.

CONCLUSIONS: The hepatotoxic risk associated with 264 signals needs to be noted in practice. The causality of hepatotoxicity and mechanism among new signals should be verified with preclinical and clinical studies.

PMID:37770847 | DOI:10.1186/s12887-023-04097-9

Pharmaceutics. 2023 Aug 25;15(9):2199. doi: 10.3390/pharmaceutics15092199.

ABSTRACT

Nitrofurantoin (NFT) is a commonly used antibiotic for the treatment of urinary tract infections that can cause liver toxicity. Despite reports of hepatic adverse events associated with NFT exposure, there is still limited understanding of the interplay between NFT exposure, its disposition, and the risk of developing liver toxicity. In this study, we aim to develop a physiologically based pharmacokinetic (PBPK) model for NFT in three different species (rabbits, rats, and humans) that can be used as a standard tool for predicting drug-induced liver injury (DILI). We created several versions of the PBPK model using previously published kinetics data from rabbits, and integrated enterohepatic recirculation (EHR) using rat data. Our model showed that active tubular secretion and reabsorption in the kidney are critical in explaining the non-linear renal clearance and urine kinetics of NFT. We subsequently extrapolated the PBPK model to humans. Adapting the physiology to humans led to predictions consistent with human kinetics data, considering a low amount of NFT to be excreted into bile. Model simulations predicted that the liver of individuals with a moderate-to-severe glomerular filtration rate (GFR) is exposed to two-to-three-fold higher concentrations of NFT than individuals with a normal GFR, which coincided with a substantial reduction in the NFT urinary concentration. In conclusion, people with renal insufficiency may be at a higher risk of developing DILI due to NFT exposure, while at the same time having a suboptimal therapeutic effect with a high risk of drug resistance. Our PBPK model can in the future be used to predict NFT kinetics in individual patients on the basis of characteristics like age and GFR.

PMID:37765169 | DOI:10.3390/pharmaceutics15092199

Pharmaceutics. 2023 Aug 23;15(9):2181. doi: 10.3390/pharmaceutics15092181.

ABSTRACT

Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations. TDM can be used to determine treatment efficacy and to prevent the occurrence or reduce the risk of drug-induced side effects, being, thus, a tool of personalized medicine. Drugs for which TDM is applied should have a narrow therapeutic range and exhibit both significant pharmacokinetic variability and a predefined target concentration range. The aim of our study was to assess the current status of TDM in Greek public hospitals and estimate its progress over the last 20 years. All Greek public hospitals were contacted to provide data and details on the clinical uptake of TDM in Greece for the years 2003 and 2021 through a structured questionnaire. Data from 113 out of 132 Greek hospitals were collected in 2003, whereas for 2021, we have collected data from 98 out of 122 hospitals. Among these, in 2003 and 2021, 64 and 51 hospitals, respectively, performed TDM. Antiepileptics and antibiotics were the most common drug categories monitored in both years. The total number of drug measurement assays decreased from 2003 to 2021 (153,313 ± 7794 vs. 90,065 ± 5698; p = 0.043). In direct comparisons between hospitals where TDM was performed both in 2003 and 2021 (n = 35), the mean number of measurements was found to decrease for most drugs, including carbamazepine (198.8 ± 46.6 vs. 46.6 ± 10.1, p < 0.001), phenytoin (253.6 ± 59 vs. 120 ± 34.3; p = 0.001), amikacin (147.3 ± 65.2 vs. 91.1 ± 71.4; p = 0.033), digoxin (783.2 ± 226.70 vs. 165.9 ± 28.9; p < 0.001), and theophylline (71.5 ± 28.7 vs. 11.9 ± 6.4; p = 0.004). Only for vancomycin, a significant increase in measurements was recorded (206.1 ± 96.1 vs. 789.1 ± 282.8; p = 0.012). In conclusion, our findings show that TDM clinical implementation is losing ground in Greek hospitals. Efforts and initiatives to reverse this trend are urgently needed.

PMID:37765152 | DOI:10.3390/pharmaceutics15092181

Molecules. 2023 Sep 9;28(18):6544. doi: 10.3390/molecules28186544.

ABSTRACT

Since side-effects of drugs are one of the primary reasons for their failure in clinical trials, predicting their side-effects can help reduce drug development costs. We proposed a method based on heterogeneous graph transformer and capsule networks for side-effect-drug-association prediction (TCSD). The method encodes and integrates attributes from multiple types of neighbor nodes, connection semantics, and multi-view pairwise information. In each drug-side-effect heterogeneous graph, a target node has two types of neighbor nodes, the drug nodes and the side-effect ones. We proposed a new heterogeneous graph transformer-based context representation learning module. The module is able to encode specific topology and the contextual relations among multiple kinds of nodes. There are similarity and association connections between the target node and its various types of neighbor nodes, and these connections imply semantic diversity. Therefore, we designed a new strategy to measure the importance of a neighboring node to the target node and incorporate different semantics of the connections between the target node and its multi-type neighbors. Furthermore, we designed attentions at the neighbor node type level and at the graph level, respectively, to obtain enhanced informative neighbor node features and multi-graph features. Finally, a pairwise multi-view feature learning module based on capsule networks was built to learn the pairwise attributes from the heterogeneous graphs. Our prediction model was evaluated using a public dataset, and the cross-validation results showed it achieved superior performance to several state-of-the-art methods. Ablation experiments undertaken demonstrated the effectiveness of heterogeneous graph transformer-based context encoding, the position enhanced pairwise attribute learning, and the neighborhood node category-level attention. Case studies on five drugs further showed TCSD's ability in retrieving potential drug-related side-effect candidates, and TCSD inferred the candidate side-effects for 708 drugs.

PMID:37764319 | DOI:10.3390/molecules28186544

Medicina (Kaunas). 2023 Sep 11;59(9):1645. doi: 10.3390/medicina59091645.

ABSTRACT

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by antigen-specific T cells and antiplatelet autoantibodies that inhibit platelet production in the bone marrow or destroy platelets in the spleen. ITP is a form of autoimmunity and is closely associated with inflammation. Corticosteroids are the first-line therapy for ITP, with a total response rate of 53-80%. However, corticosteroid therapy is associated with significant side effects and is often ineffective in patients with corticosteroid-resistant or -intolerant disease. Eltrombopag has been validated as a second-line option in ITP therapy. Despite several studies demonstrating the efficacy and safety of Eltrombopag in immune thrombocytopenia patients, the prevalence of Eltrombopag-induced acute kidney injury has been observed. This case report describes a patient who experienced acute kidney injury during Eltrombopag therapy. A sudden increase in serum creatinine to 6.7 mg/dL and metabolic acidosis occurred after eight weeks of Eltrombopag. The patient's renal failure had worsened, proteinuria was detected, and emergency hemodialysis was initiated. With vigilant kidney function screening and prompt treatment, the patient's renal function improved remarkably following cessation of Eltrombopag and initiation of hemodialysis. This case highlights the importance of comprehensive medication history-taking and vigilant kidney function screening in patients receiving Eltrombopag.

PMID:37763764 | DOI:10.3390/medicina59091645

Biomedicines. 2023 Aug 25;11(9):2385. doi: 10.3390/biomedicines11092385.

ABSTRACT

RESEARCH OBJECTIVE: To identify the frequency of opioid use in a group of patients diagnosed with migraine in Colombia.

METHODS: Study of a retrospective cohort of patients with a diagnosis of migraine and a first prescription of antimigraine drugs from emergency services and a priority outpatient clinic. Sociodemographic, clinical, and pharmacological variables were identified; a 12-month follow-up was carried out to identify the use of a new opioid.

RESULTS: A total of 6309 patients with a diagnosis of migraine were identified, with a mean age of 35.5 ± 12.3 years, of which 81.3% were women. Nonsteroidal anti-inflammatory drugs (51.1%) were the most frequently prescribed medications, followed by ergotamine + caffeine (31.3%), acetaminophen (15.05%), and acetaminophen + codeine (14.4%). At the time of the index, 1300 (20.6%) patients received some opioid. During the follow-up, a total of 1437 (22.8%) patients received a new opioid, of which 31.8% belonged to the group that received an initial opioid and 20.4% to the group that did not receive one, which was statistically significant (OR:1.81; 95%CI:1.58-2.07; p < 0.001).

CONCLUSIONS: The frequent use of opioids in the management of migraines is potentially inappropriate and can lead to problems of tolerance, abuse and dependence. This combined with the low prescription of triptans, offers an opportunity for improvements in medical practice.

PMID:37760827 | DOI:10.3390/biomedicines11092385

BMC Complement Med Ther. 2023 Sep 27;23(1):343. doi: 10.1186/s12906-023-04179-2.

ABSTRACT

BACKGROUND: Status epilepticus (SE) is a type of epileptic activity characterized by a failure of the inhibitory mechanisms that limit seizures, which are mainly regulated by the GABAergic system. This imbalance increases glutamatergic neurotransmission and consequently produces epileptic activity. It is also associated with oxidative stress due to an imbalance between reactive oxygen species (ROS) and antioxidant defences. Unfortunately, long-term treatment with anti-epileptic drugs (AEDs) may produce hepatotoxicity, nephrotoxicity, and haematological alterations. In this way, some secondary metabolites of plants have been used to ameliorate the deterioration of nervous system disorders through their antioxidant properties, in addition to their anticonvulsant effects. An example is Centella asiatica, a plant noted to have a reputed neuroprotective effect related to its antioxidant activity. However, similar to conventional drugs, natural molecules may produce side effects when consumed in high doses, which could occur with Centella asiatica. Therefore, we aimed to evaluate the effect of a standardized extract of Centella asiatica L. Urb with tested anticonvulsant activity on biochemical and haematological parameters in rats subjected to lithium/pilocarpine-induced seizures.

METHODS: Twenty-eight adult male Wistar rats were randomly divided into four groups (n = 7 each): vehicle (purified water), Centella asiatica (200 and 400 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as a pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 h for 35 consecutive days. On Day 36, SE was induced using the lithium/pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg s.c., respectively), and the behavioural and biochemical effects were evaluated.

RESULTS: Centella asiatica 400 mg/kg increased the latency to the first generalized seizure and SE onset and significantly reduced the time to the first generalized seizure compared to values in the vehicle group. Biochemical parameters, i.e., haematic cytometry, blood chemistry, and liver function tests, showed no significant differences among the different treatments.

CONCLUSION: The dose of Centella asiatica that produces anticonvulsant activity in the lithium/pilocarpine model devoid of hepatotoxicity, nephrotoxicity, and alterations in haematological parameters suggests that the standardized extract of this plant could be of utility in the development of new safe therapies for the treatment of convulsions associated with epilepsy.

PMID:37759286 | PMC:PMC10523769 | DOI:10.1186/s12906-023-04179-2

BMC Cancer. 2023 Sep 28;23(1):910. doi: 10.1186/s12885-023-11422-z.

ABSTRACT

BACKGROUND: The goal of therapy for many patients with advanced stage malignancies, including those with metastatic gastric and esophageal cancers, is to extend overall survival while also maintaining quality of life. After weighing the risks and benefits of treatment with palliative chemotherapy (PC) with non-curative intent, many patients decide to pursue treatment. It is known that a subset of patients who are treated with PC experience significant side effects without clinically significant survival benefits from PC.

METHODS: We use data from 150 patients with stage-IV gastric and esophageal cancers to train machine learning models that predict whether a patient with stage-IV gastric or esophageal cancers would benefit from PC, in terms of increased survival duration, at very early stages of the treatment.

RESULTS: Our findings show that machine learning can predict with high accuracy whether a patient will benefit from PC at the time of diagnosis. More accurate predictions can be obtained after only two cycles of PC (i.e., about 4 weeks after diagnosis). The results from this study are promising with regard to potential improvements in quality of life for patients near the end of life and a potential overall survival benefit by optimizing systemic therapy earlier in the treatment course of patients.

PMID:37759332 | PMC:PMC10536729 | DOI:10.1186/s12885-023-11422-z

Sci Rep. 2023 Sep 27;13(1):16176. doi: 10.1038/s41598-023-43539-3.

ABSTRACT

Plant growth-promoting bacteria (PGPBs) play a crucial role in mitigating the oxidative damage caused by water stress in different plant species. The aim of this study was to determine the effects of PGPBs and mycorrhiza-like fungi (Piriformospora indica) on improving drought tolerance in moldavian balm (Dracocephalum moldavica L.), a medicinal and aromatic plant. For this purpose, a greenhouse study was conducted in a factorial experiment based on a randomized complete design with three replications. Results indicate that water stress reduces the membrane stability index (MSI), total chlorophyll content (Chlt), carotenoids, and maximum photochemical efficiency of photosystem II (Fv'/Fm') in moldavian balm plants, while increasing superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and hydrogen peroxide (H2O2) content compared to the control (no water stress). Inoculation with PGPBs and Piriformospora indica helped alleviate the negative effects of water stress. The highest MSI (48%) and Fv'/Fm' value (0.82) were observed when inoculated with Enterobacter and Piriformospora, respectively, under non-water-stressed conditions. Inoculation with Agrobacterium, Piriformospora, and Enterobacter improved the Chlt and leaf proline contents, as well as the SOD activity under high water stress, compared to the non-inoculated control values. Furthermore, inoculation with Pseudomonas under high water deficit stress levels increased the MDA content (0.51 mmol g-1 FW) and H2O2 levels (0.40 mmol g-1 FW). The highest yield of flowering branches (2.414 g pot-1) in moldavian balm was obtained with Enterobacter. Based on the enhanced physiological and biochemical responses, as well as increased antioxidant enzyme activity that improve water tolerance in this plant, it is recommended to use PGPBs and Piriformospora indica fertilization.

PMID:37759070 | PMC:PMC10533844 | DOI:10.1038/s41598-023-43539-3

Sci Rep. 2023 Sep 27;13(1):16229. doi: 10.1038/s41598-023-42820-9.

ABSTRACT

If a mammography screening program (MS) is to be expanded, the benefit must be demonstrated for each additional age cohort. For the age interval between 40 and 80 years, the association between tumor-related and tumor-independent mortality of 21 2-year cohorts is modeled using up-to-date, valid data to determine MS outcome. Disease trajectories with and without biennial MS are extrapolated for each age cohort using the available data and knowledge on MS. The competing mortality is randomly generated for each age cohort with and without MS for a follow-up period of 20 years. Analyses of the modeled cohorts describe incremental change for each year, quantifying the changing benefits of MS. With increasing age, the proportion of tumor-independent mortality before and with metastatic disease increases and the benefit decreases. The simulations with 21 studies on the age interval 40-80 years provide four parameters to determine the benefits and costs of MS: The number of prevented deaths, required mammography screening exams (MSE) and their costs, life-years gained, and the required MSEs. If one additional MSE is offered for age groups 48/70 years, this will result in 311/320 prevented breast cancer (BC) deaths with 1742/1494 required MSEs or 8784/4168 life-years gained with 64/140 required MSEs. A rational cutoff cannot be quantified. The mortality effect of MS between 40 and 80 years is quantified in 21 steps using two metrics, number of MSEs per tumor-related mortality prevented and per life-year gained. This provides a decision support for stepwise expansions. Given this real-world evidence no rational age cutoffs for MS becomes evident. A society has to decide which MS costs, including side effects of MS for women who remain BC-free, it is willing and able to accept in order to reduce breast cancer mortality.

PMID:37758770 | PMC:PMC10533880 | DOI:10.1038/s41598-023-42820-9

Pol Merkur Lekarski. 2023;51(4):430-432. doi: 10.36740/Merkur202304119.

ABSTRACT

Modern treatment of glioblastoma multiforme (GBM) is based on neurosurgical methods combined with radiotherapy and chemotherapy. The prognosis for patients with GBM is extremely poor. Often, complete removal of the tumor is impossible and it often recurs. Therefore, in addition to standard regimens, modern methods such as modulated electrohyperthermia, monoclonal antibodies and individualised multimodal immunotherapy (IMI) based on vaccines and oncolytic viruses are also used in the treatment of GBM. Radioiodine therapy (RIT) also holds out hope for an effective treatment of this extremely aggressive brain tumor. The expression of the sodium iodide symporter (NIS) gene has been proven to have a positive effect on the treatment of selected cancers. Research confirm the presence of expression of this gene in GBM cells, although only in animal studies. Is it possible and therapeutically effective to treat GBM with RIT without the use of an exogenous NIS gene? The safety of therapy is relevant, as the only more serious adverse effect may be hypothyroidism. The use of RIT requires further clinical studies in patients. Perhaps it is worth revolutionizing GBM therapy to give sufferers a "new life".

PMID:37756465 | DOI:10.36740/Merkur202304119

Perspect Biol Med. 2023;66(2):327-343. doi: 10.1353/pbm.2023.0018.

ABSTRACT

In 2022, John Abramson published Sickening: How Big Pharma Broke American Healthcare and How We Can Repair It. The book illustrates how large pharmaceutical companies have become misinformation machines that have corrupted peer-reviewed journals, systematic review authors, and guideline committees. Industry influence includes selective reporting of clinical trial results and selection of control groups likely to enhance benefits and disguise side effects. Other documented forms of influence include clear conflicts of interest for members of guideline committees and even direct intimidation. The book concludes with a series of implementable reforms, such as ensuring the accuracy and completeness of evidence, developing an independent National Health Board, designing clinical research to optimize health outcomes, requiring the posting of research data so that independent scholars can replicate analyses, and ensuring the accuracy of direct consumer advertising. Abramson's book is a must read for students of medicine, public health, and public policy.

PMID:37755720 | DOI:10.1353/pbm.2023.0018

Eur J Hosp Pharm. 2023 Sep 27:ejhpharm-2023-003908. doi: 10.1136/ejhpharm-2023-003908. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the impact of the presence of a pharmacist on medication usage in long-term care facilities.

METHODS: The study followed a retrospective cohort design, with a sample of patients aged ≥65 years admitted to three long-term care facilities over 30 months. Data on age, gender, type of stay, the presence or absence of a pharmacist and pharmacotherapeutic profile at admission and discharge were obtained for study patients. Variations in the number of medicines, anticholinergic burden and potentially inappropriate medications at admission and discharge were assessed as outcome variables. Anticholinergic burden and potentially inappropriate medications were assessed using the Anticholinergic Cognitive Burden scale and the EU(7)-PIM List, respectively. One-sample t-tests were used to compare the mean values of the outcome variables. A four-way ANOVA was used to test the association between background and outcome variables. Partial eta squared (η2) was used to measure the effect size.

RESULTS: A total of 1366 patients were studied. All outcome variables showed a statistically significant increase at discharge compared with admission. The presence of a pharmacist was statistically significant in improving the number of medicines (p<0.001) and the anticholinergic burden score (p<0.001), while no statistically significant value was reached on potentially inappropriate medications (p=0.642). Small effect size values were obtained for the impact of the pharmacist on the number of medicines and anticholinergic burden scores (η2=0.021 and η2=0.011, respectively).

CONCLUSION: These findings suggest that the presence of a long-term care pharmacist can positively impact the use of medication associated with poor health outcomes. An integrated interprofessional approach is needed to address potentially inappropriate medications, anticholinergic burden and polypharmacy in long-term care settings, particularly at the time of discharge.

PMID:37758319 | DOI:10.1136/ejhpharm-2023-003908

Drug Ther Bull. 2023 Oct;61(10):149-150. doi: 10.1136/dtb.2023.000046.

ABSTRACT

Commentary on: Kaundal R, Bhatia P, Jain A, et al. Randomized controlled trial of twice-daily versus alternate-day oral iron therapy in the treatment of iron-deficiency anemia. Ann Hematol. 2020;99:57-63. Series Editor: Dr Teck Khong, DTB Associate Editor, Clinical Pharmacology, St George's, University of London, UK.

PMID:37758277 | DOI:10.1136/dtb.2023.000046

Clin Transplant. 2023 Sep 27:e15144. doi: 10.1111/ctr.15144. Online ahead of print.

ABSTRACT

INTRODUCTION: Cardiovascular and renal complications define the outcomes of diabetic kidney transplant recipients (KTRs). The new diabetes medications have changed the management of diabetes. However, transplant physicians are still reluctant to use sodium-glucose cotransporter 2 inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA) post kidney transplantation due to fear of drug related complications and lack of established guidelines.

PATIENTS AND METHODS: We collected 1-year follow-up data from records of 98 diabetic KTRs on SGLT2I, 41 on GLP- 1RA and 70 on standard-of-care medicines. Patients were more than 3 months post-transplant with a minimum estimated glomerular filtration rate (eGFR) of 25 ml/min/1.73 m2 . Demographic data were similar except for a slightly lower HbA1c in the control group and higher albuminuria in SGLT2i group.

RESULTS: HbA1c dropped significantly by .4% in both SGLT2i and GLP-1RA compared to .05% in the control group. A significant decrease in BMI by .32 in SGLT2i and .34 in GLP-1RA was observed compared to an increase by .015 in control group. A tendency for better eGFR in study groups was observed but was non-significant except for the SGLT2i group with an eGFR above 90 (p = .0135). The usual dip in eGFR was observed in the SGLT2i group at 1-3 months. Albuminuria was significantly reduced in both study groups. Adverse events were minimal with comparable safety in all groups.

CONCLUSION: The use of SGLT2i and GLP-1RA appears to be effective and safe in diabetic KTRs with good outcomes. Randomized control trials are required to confirm these findings and establish guidelines.

PMID:37755118 | DOI:10.1111/ctr.15144