What should patients do if they miss a dose? A systematic review of patient information leaflets and summaries of product characteristics

PurposeMedicines regulatory authorities advise that patient information leaflets (PILs) should provide specific advice on what actions to take if one or more doses are missed. We aimed to assess the content in this regard, of PILs and Summaries of Product Characteristics (SmPCs) of prescription only medicines (POMs) marketed in the UK.MethodsPILs and SmPCs were accessed via the electronic Medicines Compendium. The following terms were used in the advanced search facility: miss(ed), omit(ted), adhere(d), delay(ed), forgot, forget, lapse. Identified documents were screened for instructions on missed doses which were categorised according to level of specificity, and cross-referenced to the National Patient Safety Agency (NPSA) grading of risk of harm from omitted and delayed medicines. Any supporting clinical or pharmacological evidence was identified from SmPCs.ResultsTwo thousand two hundred eighty-four documents were identified from 7248 PILs and SmPCs relating to 1501 POMs. Seven hundred eighty-three (52%) POMs had SmPCs or PILs with no instructions on missed doses; 487 POMs (32%) included non-specific advice (e.g. "take as soon as possible"); 138 (9%) provided specific instructions; and 93 (6%) referred patients to seek medical advice. SmPCs for only 13/138 (9%) of those which included specific instructions provided any supporting clinical or pharmacological evidence. Instructions were absent for several medicines where the NPSA assessed that dose omissions may result in significant risk of harm.ConclusionsAdvice on missed doses is generally inadequate. Pharmaceutical companies and regulatory authorities should produce clear and concise instructions on what patients should do if they miss doses, with supporting evidence where necessary

The Possible Roles of CD73 and Adenosine in the Osteoimmunological Bone Resorption of Periradicular Periodontitis

Introduction: Periradicular periodontitis is an inflammatory disease caused by perpetual microbial infection in the root canal system which, if left untreated, results in the destruction of tooth supporting tissues. Tenacious infection of virulent bacteria can lead to continuous activation of host immune response which results in excess production of proinflammatory mediators, including the bone resorption factor RANKL. To date, attempts to minimize the destruction of tooth supporting tissues have included laser therapy and phototherapy, but these approaches have been confined to treating and monitoring the exogenous etiology, i.e., bacterial infection. Therefore, to improve the diagnosis and treatment of periradicular periodontitis, new technologies are needed to control host cell biological responses and evaluate the level of inflammation in the root canal system and periradicular area. Objectives: Intracellular generated adenosine triphosphate (ATP) and its metabolite, adenosine (ADO), act as major energy currencies in the cell system. Only recently has it been reported that extracellular ATP (eATP) released from activated neutrophils elicits proinflammatory responses, while ADO, which is generated via enzymatic conversion of ATP by cell surface-expressed ecto-5′-nucleotidase (CD73) and Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39), functions as anti-inflammatory mediator. Accordingly, this study investigated the effects of CD73 and ADO on osteoimmunological bone resorption in periradicular periodontitis. Methods: The possible anti-bone loss role of ADO was examined in vitro by reacting RANKL-stimulated RAW264.7 osteoclast precursors with ADO receptor agonist 5′-(N-Ethylcarboxamido) adenosine (NECA). More specifically, the effects of NECA on RANKL-induced osteoclastogenesis were evaluated by monitoring TRAP+ multinucleated cell number and pit formation. Since activated T cells are the major cellular source of RANKL in periradicular periodontitis, the effects of NECA on proliferation and sRANKL production by TCR/CD28-stimulated T cells were examined in vitro. The therapeutic efficacy of NECA on the pathogenic bone loss induced in periradicular periodontitis was evaluated in a pulp exposure-induced periradicular periodontitis model using C57BL/6 wild-type (WT) mice. On the other hand, the impact of ADO loss-of-function was compared between CD73-/-Foxp3-GFP+/+ mice and WT mice, both with experimentally induced periradicular lesion. Periradicular tissues were isolated from sacrificed mice, and the mRNAs of inflammation-associated and bone remodeling-related genes, amount of ATP and size of periradicular lesions were monitored up to 3 weeks using qPCR and µCT. Expressions of CD73 and other proteins in the periradicular tissues were examined by immunohistochemistry and immunofluorescence staining. Results: As determined from the in vitro experiments, NECA significantly suppressed not only RANKL-mediated osteoclastogenesis from RAW264.7 cells (P<0.05), but also significantly downregulated proliferation and RANKL production from TCR/CD28-activated T cells (P<0.05), suggesting that the elicited signal could downregulate RANKL-induced osteoclastogenesis. As determined from the in vivo experiments, the amount of ATP and expression of CD73 mRNA were significantly increased in the mouse periradicular lesion in a time-dependent manner. NECA-treated wild-type (WT) mice demonstrated significantly elevated mRNAs for CD39, CD73, alkaline phosphatase, and RUNX2, while showing decreased expressions of RANKL and IL1-β mRNAs, accompanied by diminished size of periradicular lesion, compared to nondrug-treated control WT mice experimentally induced with periradicular lesion. Finally, the amount of ATP and mRNAs for RANKL, IL1-β, IL-6, and TNF-α, as well as the size of periradicular lesion, were significantly larger (P<0.05) in CD73-/-Foxp3-GFP+/+ compared to control WT-mice. Conclusion: By its catalytic action to convert ATP to ADO, increased CD73, by its catalytic action to convert ATP to ADO, in the periradicular lesion may play a role in downregulating inflammatory bone loss, suggesting the CD73/ADO axis as a novel therapeutic target for periradicular periodontitis, leading to the development of a therapeutic regime which, beyond controlling bacterial infection, can control host cell biological responses and, hence, the level of inflammation in the affected root apex

Coherent Laser Induced Synthesis of Rare Earth Doped Nanocrystallites of 50PbO-25Bi2_2O3_3-20Ga2_2O3_3-5BaO

A principal possibility of formation the nanostructures on the surfaces of 50PbO-25Bi$_2$O$_3$-20Ga$_2$O$_3$-5BaO (doped by Eu3+, Er3+, Dy3+) is demonstrated by using multi-coherent beams. As a sources of the photoinducing coherent light we have used nanosecond Nd:YAG and Er:Yb lasers generating at 1064 nm and 1540 nm, respectively. The morphology of the photoinduced surfaces is sensitive to the type of rare earth ions. The thickness of the layer was about 20-30 nm. Possible mechanisms are explained by coherent photoinduction of the valence electrons

A cross-sectional assessment of health-related quality of life among healthcare providers in Alkharj, Saudi Arabia

Purpose: To determine the current level of health-related quality of life (HRQoL), and evaluate factors influencing it among health-care providers (HCPs) in Alkharj, Saudi Arabia.Methods: A prospective cross-sectional study was conducted among HCPs in Alkharj, Saudi Arabia, using the standardized research tool, BREF-WHOQOL. A self-administered questionnaire was distributed in hospitals, in the medical colleges of Prince Sattam Bin Abdulaziz University, andcommunity pharmacies in Alkharj, Saudi Arabia. Descriptive, comparative, and inferential statistics were performed using SPSS.Results: A total of 289 HCPs agreed to participate in the study, 52 % of whom were female. Most participants were married (69 %), and most had fewer than 10 years of experience (58 %). Statistically significant differences in marital status, education level, income, and year of practice were found that correlated with HCPs’ HRQoL (p ≤ 0.05). Overall, respondents reported an above-average score for all survey items.Conclusion: The results indicate that HCPs see their general quality of life as good - a particularly important consideration in view of the demanding nature of their job. This study will help the concerned authorities to exactly know the current level of HRQoL among HCPs in Alkharj, Saudi Arabia, as well as help in designing better healthcare policies in Saudi Arabia. Keywords: Healthcare providers (HCP), Health-related quality of life (HRQoL), Healthcare policies, Occupational stres

Understanding Patients' Preferences towards the Treatments for Colorectal Cancer

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Assessing adherence to inhaled corticosteroids among adults with asthma in kuwait using the medication adherence report scale for asthma

Purpose: Inhaled corticosteroids (ICS) are the mainstay maintenance therapy for asthma management. Non-adherence to ICS, which can lead to exacerbations and poor asthma control, is commonly reported among adult patients with asthma. The level of adherence to ICS among adult patients with asthma in Kuwait has not been previously published. The aim of this study was to assess adherence to ICS among adults with asthma in Kuwait. Patients and Methods: A cross-sectional study was conducted among adult patients with asthma using ICS therapy at ambulatory asthma clinics in Kuwait. Adherence to ICS was assessed using the Medication Adherence Report Scale for Asthma (MARS-A). Descriptive and logistic regression analyses were conducted using SPSS version 23. Results: One hundred and forty-nine patients with a mean age of 41.42 (12.75) years participated in the study. The majority of the participants (82.6%) reported low adherence to ICS. Approximately, three-quarters of the participants reported that they used ICS either when needed or when they felt breathless. Furthermore, about half of them admitted that they tried to avoid using ICS (46.3%), or forgot to take ICS (51%), or only used ICS before performing an exercise that made them breathless (54%). In the multivariate logistic regres-sion analysis, independent predictors (age, education, and smoking status) were not found to significantly influence the overall adherence to ICS therapy. Conclusion: Adherence to ICS among adult patients with asthma was found to be low in ambulatory care settings in Kuwait. Future studies should aim to determine the barriers to ICS adherence among patients with asthma, with a focus on developing effective intervention strategies. 2020 Albassam et al.Scopu

Barriers and facilitators for oral health screening among tobacco users: a mixed-methods study

Abstract Objectives Tobacco consumption adversely affects general and oral health and is considered one of the significant public health burdens globally. The present study aims to assess the barriers and facilitators for attending oral and dental health screening among tobacco users who seek cessation advice. Methodology The present mixed-methods study used group concept mapping (GCM) to identify the facilitators/barriers to attending oral health screening among young adults attending face-to-face and virtual Tobacco Cessation Clinic at King Saud University (Riyadh, Saudi Arabia) between September 2022 and April 2023. Study investigators included healthcare social workers, dental interns, and oral and maxillofacial medicinists. Information about demographics, general health, oral/dental health and tobacco use were collected using self-completed questionnaires. The barriers and facilitators were assessed following GCM by brainstorming, sorting, rating, and interpretation activities. Descriptive, multidimensional scaling and hierarchical cluster analysis were used to describe the study participants and produce concept maps of the generated statements. Results The study included 148 participants who generated 67 statements summarised into 28 statements as facilitators or barriers. Based on a 5-point importance scale, the participants indicated the importance of facilitators under health-related cluster [e.g. when I feel pain] as the highest, followed by personal [e.g. to maintain my mouth hygiene], social [e.g. the quality of treatment] and financial clusters [e.g. the reasonable cost]. Concerning barriers, financial factors [e.g. high cost] acted as the highest-rated barrier, followed by personal [e.g. lack of dental appointments] and health-related [e.g. worry that dental problems will worsen]. The social factors were the least considerable barrier [e.g. lack of time]. Clustering these facilitators/barriers on the concept map indicated their conceptual similarity by an average stress value of 0.23. Conclusion Pain was the most important facilitator to attending oral health screening by young adults seeking tobacco cessation advice. Notable barriers included the high cost of dental treatment and the lack of scheduled appointments. Thus, oral health care providers need to consider scheduling periodic and timely dental check-ups to prevent and reduce the burden of tobacco-associated and pain-causing oral diseases

Knowledge, perceptions and confidence of physicians and pharmacists towards pharmacogenetics practice in Kuwait.

BACKGROUND:Pharmacogenetics practice has been successfully implemented in many developed countries to enhance personalized medicine and improve clinical and economic outcomes. An understanding of healthcare providers' knowledge, perceptions, confidence towards pharmacogenetics, and their active enrollment with pharmacogenetic testing is essential for test acceptance and utilization. This study was designed to assess physicians' and pharmacists' knowledge, perceptions, and confidence towards pharmacogenetics, determine the preferred learning format for their future education in pharmacogenetics, and identify the barriers to its application in their practice settings. METHODS:A cross-sectional survey was conducted using a pretested self-administered questionnaire on a sample of 629 randomly selected physicians and pharmacists. Descriptive and comparative analyses were used in data analysis. RESULTS:The response rate was 98.1%. Less than one-tenth of respondents were exposed to pharmacogenetics education or training (8.9%), applied pharmacogenetics testing in their practice (9.4%), or provided patient counselling on the results of the pharmacogenetic testing (9.1%), and over 90% of them were physicians. The overall respondents' mean (SD) total knowledge score percentage was low [45.0% (24)] and there was no significant difference between the physicians and pharmacists scores (p>0.05). Only 16.0% of participants indicated that they felt confident in applying pharmacogenetics in their practice settings. Despite these low levels of knowledge and self-confidence, 70.2% of participants expressed overall positive perceptions towards pharmacogenetics and its clinical implications. These positive overall perceptions were found to be significantly more common among pharmacists compared to physicians (p<0.05). The top two perceived barriers facing the implementation of pharmacogenetics in Kuwait were lack of education or training and clinical guidelines. CONCLUSIONS:These findings highlight important concerns and will aid in the assessment of current pharmacogenetics practice. Also, they will provide further insight in designing future targeted multifaceted interventions to promote the adoption and utilization of pharmacogenetics testing in Kuwait

Awareness, perception, and barriers of healthcare providers toward the revised consensus guideline for therapeutic monitoring of vancomycin

Background: A revised consensus guideline published in 2020 recommended transitioning vancomycin monitoring to the area under the concentration–time curve over 24 h to minimum inhibitory concentration (AUC24/MIC). The decision to transition to AUC24/MIC monitoring or to continue trough-based monitoring is made at the institutional level and is influenced by several factors, including healthcare providers and system-related factors. Changing current practices is expected to be difficult, and it is important to understand healthcare providers’ perceptions and potential barriers before the transition. This study assessed the awareness and perception of physicians and pharmacists toward the revised guideline and identified barriers to their implementation in Kuwait. Methods: A cross-sectional survey that employed a self-administered questionnaire was used. A random sample of physicians (n = 390), clinical microbiologists (n = 37), and clinical pharmacists (n = 48) across six Kuwaiti public hospitals were surveyed. Descriptive and comparative statistical analyses were performed. Factors associated with awareness and perceptions among the participants were identified. Results: The response rate was 85.3% (n = 431). Participants had a high (median = 75%) awareness score for the updated vancomycin guideline, as well as a positive perception (median = 5). The main factor identified to affect the awareness and perception of participants following the group analysis was the years of experience. The main barriers identified were a lack of training to perform vancomycin AUC24 calculations, a lack of accurate documentation sample time, and a long turnaround time for serum levels, which might hinder the implementation of the updated guideline. Conclusion: Physicians, clinical microbiologists, and pharmacists working in Kuwait public hospitals were aware of the 2020 vancomycin monitoring guidelines with positive perceptions. Participants agreed on the several barriers to transitioning to the AUC24/MIC approach, which should be considered by stakeholders before implementation

Inhibition of cytochrome P450 enzymes by thymoquinone in human liver microsomes

The aim of the present study was to investigate the potential effect of thymoquinone (TQ) on the metabolic activity of four major drug metabolizing enzymes in human liver microsomes, namely cytochrome P450 (CYP) 1A2, CYP2C9, CYP2D6 and CYP3A4. The inhibition of CYP enzymatic activities by TQ was evaluated by incubating typical substrates (phenacetin for CYP1A2, tolbutamide for CYP2C9, dextromethorphan for CYP2D6, and testosterone for CYP3A4) with human liver microsomes and NADPH in the absence or presence of TQ (1, 10 and 100 µM). The respective metabolite of the substrate that was formed was measured by HPLC. Results of the presented study presented that the metabolic activities of all the investigated CYP enzymes, viz. CYP1A2, CYP2C9, CYP2D6 and CYP3A4, were inhibited by TQ. At 1 µM TQ, CYP2C9 enzyme activity was maximally inhibited by 46.35%, followed by CYP2D6 (20.26%) > CYP1A2 (13.52%) > CYP3A4 (12.82%). However, at 10 µM TQ, CYP2C9 enzyme activity was maximally inhibited by 69.69%, followed by CYP3A4 (23.59%) > CYP1A2 (23.51%) > CYP2D6 (11.42%). At 100 µM TQ, CYP1A2 enzyme activity was maximally inhibited by 81.92%, followed by CYP3A4 (79.24%) > CYP2C9 (69.22%) > CYP2D6 (28.18%). The IC50 (mean ± SE) values for CYP1A2, CYP2C9, CYP2D6 and CYP3A4 inhibition were 26.5 ± 2.9 µM, 0.5 ± 0.4 µM, >500 µM and 25.2 ± 3.1 µM, respectively. These findings suggest that there is a high probability of drug interactions resulting from the co-administration of TQ or herbs containing TQ with drugs that are metabolized by the CYP enzymes, particularly CYP2C9. Keywords: Thymoquinone, Cytochrome P450, Metabolism, Human liver microsome