Search

Background: Chronic obstructive pulmonary disease (COPD) patients often have poor health literacy, leading to non-adherence to treatment and poor inhalation technique. Technological solutions can help manage COPD, but adherence tends to be low due to various factors., Objectives and Methods: We conducted a qualitative study to determine the needs of COPD patients and healthcare practitioners (HCPs) towards a mobile application and a web platform. We also aimed to identify potential barriers or facilitators to the use of such digital tools and their potential impact, and to assess the current state of collaboration between healthcare practitioners., Results: Our study found that COPD patients face difficulties in managing the disease and treatments, lack information and need easier contact with caregivers. Patients' needs include access to reliable information about COPD, its medical treatments and smoking cessation, help in maintaining good physical condition through adapted exercises, incentives and reminders, and crisis management protocols or a logbook. As patient needs can differ, it would be ideal if the mobile application could be customized. HCPs cite patient adherence, correct intake of the treatment, communication and lack of patient motivation as challenges. In particular, they would like to have access to information on patient follow-up and logbooks, as well as scientific documentation. They believe that interprofessional collaboration is essential for good patient care. However, lack of time is a major hurdle in optimizing this collaboration., Conclusion: Our study showed that most patients and HCPs view a technological platform positively to support the care of COPD patients and promote interprofessional collaboration., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Recognition of the mRNA 5' end is a critical step needed for translation initiation. This step is performed by the cap binding protein eIF4E, which joins the larger eIF4G subunit to form the eIF4F complex. Trypanosomatids have a minimum of five different eIF4F-like complexes formed through specific but not well-defined interactions between four different eIF4E and five eIF4G homologues. The EIF4E6/EIF4G5 complex has been linked with the stage-specific translation of mRNAs encoding the major Trypanosoma brucei virulence factors. Here, to better define the molecular basis for the TbEIF4E6/TbEIF4G5 interaction, we describe the identification of the peptide interacting with TbEIF4E6 in the region comprising residues 79-166 of TbEIF4G5. The TbEIF4E6-TbEIF4G5_79-116 complex reconstituted with recombinant proteins is highly stable even in the absence of cap-4. The crystal structure of the complex was subsequently solved, revealing extensive interacting surfaces. Comparative analyses highlight the conservation of the overall structural arrangement of different eIF4E/eIF4G complexes. However, highly different interacting surfaces are formed with distinct binding contacts occurring both in the canonical and noncanonical elements within eIF4G and the respective eIF4E counterpart. These specific pairs of complementary interacting surfaces are likely responsible for the selective association needed for the formation of distinct eIF4F complexes in trypanosomatids., (© 2024. The Author(s).)

Background: Natural health products (NHPs), including vitamins, minerals, and herbal supplements, are the most common complementary and alternative medicine (CAM) among cancer patients. Our survey determined the attitudes and behaviors of cancer patients toward natural complementary therapies that should be considered to implement an integrative approach in the future., Methods: Our survey was conducted in four hospitals in Belgium. Questionnaires were posted online from October 2020 to October 2021 for cancer patients. Descriptive statistics were used to analyze the data. A [Formula: see text] test was applied to study the type of NHP consumed according to diagnosis time. Fischer's exact test compared patients who had changed their consumption since diagnosis and those who had not., Results: Out of 349 questionnaires collected, only 59 met all inclusion criteria. 83.1 % of the patients agreed that conventional medicine (CM) could benefit from complementary therapies, but they did not estimate (72.3 % of the patients) that those latter are more effective than conventional medicine. More than half of the patients used five or more NHPs. The most frequent NHPs consumed daily were vitamins (64.4 %), followed by other products (i.e., probiotics, gemmotherapy, birch sap and omega 3/6) (42.4 %) and herbs (40.7 %). Almost all patients started taking NHPs before their cancer diagnosis, but 72.7 % have changed their consumption significantly (p = 0.009) since their diagnosis. Boosting the immune system (79.7 %) and limiting conventional treatment side effects (76.9 %) were the most common reasons for NHPs' use. 74.4 % of the patients did not take complementary therapies to delay or avoid conventional treatment., Conclusions: The combination and high diversity of NHPs consumption highlight the importance of educating patients and healthcare providers (HCPs) about the risk of drug interactions associated with these natural products. Most cancer patients are more interested in using this non-mainstream medicine to complement their conventional treatment than as an alternative. Knowing the patients' reasons and understanding patients' attitudes toward NHPs will be essential for HCPs to address NHPs' use., (© 2023. The Author(s).)

Asthma and chronic obstructive pulmonary disease (COPD) are major chronic conditions. It is possible to limit their impact by controlling symptoms, which limits exacerbations and worsening of the disease, by choosing the appropriate treatment and ensuring that the patient adheres to it. The main purpose of this study was to assess medication adherence and persistence with inhaled medications for chronic treatment of asthma and COPD, as well as to evaluate the factors influencing this adherence. Medication adherence was measured from January 2013 to December 2016 using continuous multiple-interval measures of medication availability (CMA). Persistence was evaluated by treatment episodes (TE). We analyzed the influence of different factors on CMA such as sex, age, type of device, and the realization of the "new medicines service" (NMS), introduced in Belgium in October 2013 to support patients in adhering to their treatment. We also analyzed the consumption of these inhaled medications within the Belgian population and compared them with the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations. Medication adherence varied greatly between the different pharmacological classes: inhaled corticosteroids (ICS) alone or in combination with long-acting beta agonists (LABA) had the lowest medication adherence and persistence, while adherence was highest for the long-acting muscarinic antagonists (LAMA) and LABA/LAMA associations. The NMS seemed to have a positive impact on medication adherence, although few patients completed the two guidance interviews offered by the service. In addition, only a minority of the targeted patients took advantage of this new service.

Objective: To develop and validate a standardized Best Possible Medication History (BPMH) form that could be used by clinical pharmacists., Methods: The draft version was presented to a focus group and was adapted following their comments. A three-rounds e-Delphi method was used to validate content, usability and face validity of the BPMH form. We supplemented the quantitative analysis with a qualitative analysis of comments for each Delphi round., Results: The draft BPMH form contained 23 items grouped into eight tabs. Refinement of these tabs and items by the focus group resulted in 7 tabs and 21 items, which were included in the Delphi survey. The consensus was obtained for all tabs within the second round (p=0.072). Consensus was reached on 76% (16/21) of items in the third round. 20 items were included following the qualitative analysis of the experts' comments in the third round., Conclusions: The findings of this study provide data on the content of the BPMH form. This form can be used to help clinical pharmacists to collect a complete and accurate medication list on admission. It could have an impact on inpatient safety and improve inpatient management. Studies with an international e-Delphi should be conducted for wider use., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Nicotinamide adenine dinucleotide kinases (NAD kinases) are essential and ubiquitous enzymes involved in the production of NADP(H) which is an essential cofactor in many metabolic pathways. Targeting NAD kinase (NADK), a rate limiting enzyme of NADP biosynthesis pathway, represents a new promising approach to treat bacterial infections. Previously, we have produced the first NADK inhibitor active against staphylococcal infection. From this linear di-adenosine derivative, namely NKI1, we designed macrocyclic analogues. Here, we describe the synthesis and evaluation of an original series of cyclic diadenosine derivatives as NADK inhibitors of two pathogenic bacteria, Listeria monocytogenes and Staphylococcus aureus. The nature and length of the link between the two adenosine units were examined leading to sub-micromolar inhibitors of NADK1 from L. monocytogenes, including its most potent in vitro inhibitor reported so far (with a 300-fold improvement compared to NKI1)., 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 © 2022 Elsevier Masson SAS. All rights reserved.)

Multidrug resistance is a major public health problem that requires the urgent development of new antibiotics and therefore the identification of novel bacterial targets. The activity of nicotinamide adenine dinucleotide kinase, NADK, is essential in all bacteria tested so far, including many human pathogens that display antibiotic resistance leading to the failure of current treatments. Inhibiting NADK is therefore a promising and innovative antibacterial strategy since there is currently no drug on the market targeting this enzyme. Through a fragment-based drug design approach, we have recently developed a NAD + -competitive inhibitor of NADKs, which displayed in vivo activity against Staphylococcus aureus. Here, we show that this compound, a di-adenosine derivative, is inactive against the NADK enzyme from the Gram-negative bacteria Pseudomonas aeruginosa (PaNADK). This lack of activity can be explained by the crystal structure of PaNADK, which was determined in complex with NADP + in this study. Structural analysis led us to design and synthesize a benzamide adenine dinucleoside analogue, active against PaNADK. This novel compound efficiently inhibited PaNADK enzymatic activity in vitro with a K i of 4.6 μm. Moreover, this compound reduced P. aeruginosa infection in vivo in a zebrafish model., (© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John's wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care., (© 2022. The Author(s).)

The co-administration of a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), has been shown to be beneficial in the management of non-communicable chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). The resulting relaxation of the airways can be synergistically enhanced, reducing symptoms and optimizing lung function. This provides an insight into more effective treatments. In this study, the LABAs formoterol fumarate dihydrate (FOR) and indacaterol maleate (IND) were each associated with tiotropium bromide monohydrate (TIO) to assess their synergistic potential. This was done using an appropriate ex vivo model of isolated perfused guinea pig tracheal rings, and pharmacological models of drug interaction. Among the dose ratios studied for both types of combination, a higher synergistic potential was highlighted for FOR/TIO 2:1 ( w/w ). This was done through three steps by using multiple additions of drugs to the organ baths based on a non-constant dose ratio and then on a constant dose ratio, and by a single addition to the organ baths of specific amounts of drugs. In this way, the synergistic improvement of the relaxant effect on the airways was confirmed, providing a basis for improving therapeutic approaches in asthma and COPD. The synergy found at this dose ratio should now be confirmed on a preclinical model of asthma and COPD by assessing lung function.

(1) Asthma is one of the most common chronic diseases in the world among children. The main purpose of this study was to analyze the consumption of asthma medications in order to investigate asthma in children (2-18 years) and the association with health care consumption; (2) a retrospective study using anonymized administrative data for 2013-2018 from the third largest Belgian health insurer was conducted; (3) in 2018, 12.9% of children received at least one asthma medication and 4.4% received at least two packages with a minimum of 30 days between purchases. Preschool children (2-6 years) were three times more likely to take asthma medication than older children (7-18 years). ICS, in combination or not with LABA, were the most dispensed drugs among children. Children with asthma medications were almost twice as likely to receive antibiotics, more likely to end up in the emergency room, and twice as likely to be hospitalized; (4) most children took ICS, according to the GINA guidelines. High rates of nebulization in young children were observed, despite the recommendation to use an inhaler with a spacing chamber as much as possible. Finally, children who took asthma medications were more likely to end up in the ER or be hospitalized.