Introduction:
Medicine shortages result in great risk for the continuity of patient care especially for antimicrobial treatment, potentially enhancing resistance rates and having a higher economic ...impact. This study aims to identify, describe, assess, and assign risk priority levels to potential failures following substitution of antimicrobial treatment due to shortages among European hospitals. Furthermore, the study investigated the impact of corrective actions on risk reduction so as to provide guidance and improve future patient care.
Methods:
Health-care failure mode and effect analysis (HFMEA) was applied to hospitals in Austria (H-AT), Belgium (H-BE), Croatia (H-CR), Greece (H-GR), Spain (H-SP), and Serbia (H-SR). Multidisciplinary teams identified processes, failure modes, causes, and corrective actions related to antibiotic substitution following medicine shortages. Characteristics of study hospitals as well as severity, probability, and hazard scores (HSs) of failure modes/causes were analyzed using Microsoft Office Excel 2010 and IBM SPSS Statistics® via descriptive and inferential statistics.
Results:
Through HFMEA, 74 failure modes were identified, with 53 of these scoring 8 or above on the basis of assigned severity and probability for a failure. Severity of failure modes differed before and after corrective actions in H-CR, H-GR, and H-SR (
p
< 0.005). Their probability differed in all study hospitals (
p
< 0.005) when compared before and after corrective actions aimed to be implemented. The highest number of failure-mode causes was detected in H-CR (46) and the lowest in H-SP (16). Corrective actions can address failure modes and lower HSs; therein, all teams proposed the following: structuring communication among stakeholders, introducing electronic prescribing, strengthening pharmacists' involvement, and increasing effectiveness of the ward stock assessment. These proposed actions led to HS reductions up to 83%.
Conclusion:
There is a lack of structure in addressing risks associated with antibiotic substitution following shortages. Furthermore, lack of communication, data scarcity on availability of antibiotics, non-supportive information technology (IT) systems, and lack of internal substitution protocols hinder quick assessment of alternatives addressing patient needs. Nevertheless, the study shows that health-care professionals manage to secure optimal antimicrobial treatment for patients using available IT and human resources.
R
=
Indomethacin or naproxen residue; Q
=
CH
2, CHOH or (CH
2)
2; X
=
H or COOC
2H
5.
We have designed and synthesized a series of novel molecules having a residue of a classical NSAID and an ...antioxidant moiety, both attached through amide bonds to a known nootropic structure, an
l-proline,
trans-4-hydroxy-
l-proline or
dl-pipecolinic acid residue. The compounds were found to retain anti-inflammatory and antioxidant activities, to acquire hypocholesterolemic action, and to possess a greatly reduced gastrointestinal toxicity. The novel molecules could find useful applications, among others, in slowing the progression or delaying the onset of neurodegenerative diseases.
Nivolumab is an FDA-approved immune checkpoint inhibitor (ICI) for patients with advanced, pre-treated non-small cell lung cancer (NSCLC). However, treatment profiles and patient outcomes often ...differ in routine clinical practice while the financial impact of approved therapies is largely unknown. In this study, we investigated the efficacy, tolerability, and economic impact of nivolumab in real-world settings (RWS) in Greece.
Patients diagnosed with advanced pre-treated NSCLC, receiving nivolumab were recruited from October 2015 until November 2019 across 18 different clinical centers in Greece. Endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Cost analysis was conducted using a third-party public-payer perspective (National Organization for Healthcare Services Provision; EOPYY).
A total of 346 patients, median age 66.5 years, were included. With 43.4 months median follow-up, median PFS was 7.8 months and median OS 15.8 months. The 1-year OS rate was 56.5%, 2-year OS 38.8%, and 3-year OS 27.3%. The ORR was 29.5% and DCR 58.7%, with a median response duration of 26.8 months. Patients with objective response were more likely to experience long-term survival (HR=0.14, p<0.001). Only 8.4% of patients experienced grade 3-4 adverse events. The presence of immune-related adverse events was associated with improved OS (HR=0.77, p=0.043). Nivolumab-associated economic burden accounted for €2,214.10 per cycle for each patient, mainly attributed to drug-acquisition costs.
This is the first report of real-world efficacy, safety, and economic burden of nivolumab in pre-treated patients with NSCLC in Greece. Indirectly compared to clinical trials, nivolumab was associated with improved efficacy in RWS, further supporting its use in clinical practice and providing insights on clinical prognosticators. The main cost component affecting the nivolumab economic burden was drug-acquisition costs, while toxicity-associated cost was negligible.
Rifapentine, a synthetic derivate of rifampicin which was developed in 1965, has interesting pharmacological properties, including a long terminal half-life (13 h, compared to 2-3 h for rifampicin) ...and promising bactericidal activity against Mycobacterium tuberculosis. Despite being approved in 1998 by the US Food and Drug Administration (FDA) for the treatment of pulmonary tuberculosis, its global use has been limited by unavailability. In the past decade, new evidence has emerged to define rifapentine as a key component for treatment of active disease and latent infection with M. tuberculosis (LTBI).
A series of new compounds that contain lipoic acid and trolox connected through spacers were synthesized and examined for their antioxidant activity and their protective effects against reperfusion ...arrhythmias in isolated heart preparations. All compounds tested are strong inhibitors of lipid peroxidation in rat liver microsomal membranes induced by ferrous ions and ascorbate. N-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N ‘-(1,2-dithiolane-3-pentanoyl)-1,2-phenylenediamine (13) exhibits anti-lipid peroxidation activity at the nanomolar range. N-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carbonyl)-N‘-(1,2-dithiolane-3-pentanoyl)ethylenediamine (10) and 13 totally suppressed reperfusion arrhythmias.
Reactive oxygen species and free radical reactions are related to several pathologic conditions including inflammation and gastric ulceration. The latter is the major undesired side-effect of almost ...all NSAIDs. Since this effect of NSAIDs is greatly influenced not only by the type of cyclooxygenase which is inhibited but also by the acidic nature of the molecule, we considered it interesting to modify their structure in such a way that it would lead to an antioxidant, neutral molecule or a molecule with greatly reduced acidic character. Thus, we synthesized amide derivatives of four well-known NSAIDs, i.e. diclofenac acid, tolfenamic acid, ibuprofen and indomethacin, with cysteamine, a well-known antioxidant. The synthesized derivatives, with demonstrated good anti-inflammatory and antioxidant activities, showed very significant reduction of ulcerogenicity in the investigation of gastrointestinal (GI) toxicity. As indices of ulcerogenic toxicity in rats, we used the mortality (%), the incidence of GI ulcers (%), body weight reduction (g/100 g BW) and the incidence of melena. All amide derivatives of the NSAIDs with cysteamine were almost non-toxic in the GI tract, under our experimental conditions, in contrast to their parent NSAIDs. These results are attributed to the acquired antioxidant activity as well as to the reduction of acidic character compared with the parent compounds. Therefore, it can be concluded that the combination of these two properties, anti-inflammatory and antioxidant activity, with a simultaneous drastic reduction of acidic character, may lead to the development of novel, useful anti-inflammatory and cytoprotective pharmacomolecules, with potentially important therapeutic applications.
Stress is implicated in the pathogenesis of numerous disorders such as cardiovascular diseases or neurodegeneration. The extensive overlap between diseases attributed to stress and oxidative damage ...is indicative of their potential relationship. We hereby study the influence of α‐tocopherol (α‐toc) on the development of stress biomarkers (morphological and biochemical), on specific biomarkers of radical insult (lipid peroxidation, oxidized proteins, or glutathione content in brain and liver), as well as on drug metabolism. In our experimental protocol two groups of female rats are exposed to stress conditions, i.e. cold plus starvation. Before stress and during its application one group is treated with α‐toc for 20 d (0.42 mmol/kg per os, once daily). Our results indicate that oxidative damage accompanies the development of stress, while treatment with α‐toc completely prevents stress‐induced radical attack and reduces stress indices like plasma corticosterone, uropepsinogen, and morphological changes. It is found that stress increases the drug metabolic potential of the liver (total P450, CYP2E1, or CYP3A1 activity). Administration of α‐toc, in combination with stress, further increases erythro mycin N‐demethylation (CYP3A1) compared to stress control, while 4‐nitrophenol hydroxylation (CYP2E1) is not affected significantly.
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