Understanding the association between sleep, shift work and COVID-19 vaccine immune response efficacy: protocol of the S-CORE study

This protocol describes an innovative study to investigate the relationship between sleep, shift work and the immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) vaccination. As the COVID-19 pandemic is a global crisis with devastating health, social and economic impacts, there is a pressing need for effective vaccination programmes. Previous influenza and hepatitis vaccination studies suggest that lack of sleep can negatively alter immune responsiveness, while circadian misalignment most likely may also play an important role in the immune response to vaccination. Our present study will be the first to address this question in actual shift workers and in relation to COVID-19 vaccination. We hypothesise that the occurrence of recent night shifts and diminished sleep will negatively alter the immune response to vaccination in shift workers compared to dayworkers. We aim to recruit 50 shift workers and 50 dayworkers. Participants will receive an mRNA-based vaccination, through the Dutch vaccination programme. To assess immune responsiveness, blood will be drawn at baseline (before first vaccination), 10 days after first vaccination, the day prior to the second vaccination; and 28 days, 6 and 12 months after the second vaccination. Actigraphy and daily sleep e-diaries will be implemented for 7 days around each vaccination to assess sleep. The Pittsburgh Sleep Quality Index will be used to monitor sleep in the long term. Optimising the efficacy of the COVID-19 vaccines is of outmost importance and results of this study could provide insights to develop sleep and circadian-based interventions to enhance vaccination immunity, and thereby improve global health.Paroxysmal Cerebral Disorder

COvid MEdicaTion (COMET) study: protocol for a cohort study

Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARSCoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19

Medication-related hospital admissions and readmissions in older patients: an overview of literature

Background The number of medication related hospital admissions and readmissions are increasing over the years due to the ageing population. Medication related hospital admissions and readmissions lead to decreased quality of life and high healthcare costs. Aim of the review To assess what is currently known about medication related hospital admissions, medication related hospital readmissions, their risk factors, and possible interventions which reduce medication related hospital readmissions. Method We searched PubMed for articles about the topic medication related hospital admissions and readmissions. Overall 54 studies were selected for the overview of literature. Results Between the different selected studies there was much heterogeneity in definitions for medication related admission and readmissions, in study population and the way studies were performed. Multiple risk factors are found in the studies for example: polypharmacy, comorbidities, therapy non adherence, cognitive impairment, depending living situation, high risk medications and higher age. Different interventions are studied to reduce the number of medication related readmission, some of these interventions may reduce the readmissions like the participation of a pharmacist, education programmes and transition-of-care interventions and the use of digital assistance in the form of Clinical Decision Support Systems. However the methods and the results of these interventions show heterogeneity in the different researches. Conclusion There is much heterogeneity in incidence and definitions for both medication related hospital admissions and readmissions. Some risk factors are known for medication related admissions and readmissions such as polypharmacy, older age and additional diseases. Known interventions that could possibly lead to a decrease in medication related hospital readmissions are spare being the involvement of a pharmacist, education programs and transition-care interventions the most mentioned ones although controversial results have been reported. More research is needed to gather more information on this topic

Medication in older patients reviewed multiple ways (MORE) study

Background Polypharmacy in older patients can lead to potentially inappropriate prescribing. The risk of the latter calls for effective medication review to ensure proper medication usage and safety. Objective Provide insight on the similarities and differences of medication review done in multiple ways that may lead to future possibilities to optimize medication review. Setting This study was conducted in Zuyderland Medical Centre, the second largest teaching hospital in the Netherlands. Method This descriptive study compares the quantity and content of remarks identified by medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System. The content of remarks is categorized in seven categories of possible pharmacotherapeutic problems: ‘indication without medication’, ‘medication without indication’, ‘contra-indication/interaction/side-effect’, ‘dosage problem’, ‘double medication’, ‘incorrect medication’ and ‘therapeutic drug monitoring’. Main outcome measure Number and content of remarks on medication review. Results The Clinical Decision Support System (1.8 ± 0.8 vs. 0.9 ± 0.9, p < 0.001) and outpatient pharmacist (1.8 ± 0.8 vs. 0.9 ± 0.9, p = 0.045) both noted remarks in significantly more categories than the geriatricians. The Clinical Decision Support System provided more remarks on ‘double medication’, ‘dosage problem’ and ‘contraindication/interaction/side effects’ than the geriatrician (p < 0.050), while the geriatrician did on ‘medication without indication’ (p < 0.001). The Clinical Decision Support System noted significantly more remarks on ‘contraindication/interaction/side effects’ and ‘therapeutic drug monitoring’ than the outpatient pharmacist, whereas the outpatient pharmacist reported more on ‘indication without medication’ and ‘medication without indication’ than the Clinical Decision Support System (p ≤ 0.007). Conclusion Medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System provides different insights and should be combined to create a more comprehensive report on medication profiles

Pharmacokinetics, analgesic effect, and tolerability of a single preprocedural dose of intranasal fentanyl in patients undergoing drain removal after breast reduction or augmentation surgery: A prospective, randomized, double-blind, placebo-controlled study

Background: Although acetaminophen is used to reduce pain after breast reduction or augmentation surgery, pain during the removal of the surgical drains is typically not specifically treated. Intranasally administered fentanyl may be suitable for pain control during removal of drains. The reported therapeutic window of fentanyl is between 0.2 and 1.2 ng/mL. Objective: The aim of this study was to evaluate the analgesic effect, tolerability, and pharmacokinetics of a single preprocedural dose of intranasal fentanyl administered before removal of surgical drains in patients who had undergone breast reduction or augmentation surgery. Methods: This was a randomized, double-blind, prospective study in healthy women (American Society of Anesthesiologists physical status I or II) between the ages of 18 and 65 years who were scheduled to undergo removal of surgical drains 1 to 4 days after breast reduction or augmentation surgery. A single dose of fentanyl nasal spray 0.05 mg/0.1 mL or placebo (preserved normal saline) 0.1 mL was administered 10 minutes before removal of drains. Because drain removal is generally carried out without specific analgesia, no rescue medication was provided. Pain intensity was measured on a visual analog scale (VAS) from 0 = no pain at all to 100 = worst pain possible. Pain intensity was evaluated immediately before administration of study medication (t = 0), at the time of drain removal (t = 10), and at 15, 20, 25, 40, and 70 minutes after administration of study medication. Safety measures included oxygen saturation, respiratory rate, heart rate, and blood pressure. Local and systemic adverse events were elicited by direct questioning throughout the study. Blood samples for pharmacokinetic analysis were collected at baseline and at 5, 10, 15, 30, 60, and 120 minutes after administration of study medication. The population pharmacokinetic parameters of fentanyl were calculated according to a 1-compartment open model with an iterative 2-stage Bayesian fitting procedure. Results: Thirty-six women were randomized to treatment, and 33 completed the study. Their mean (SD) age was 39.2 (13.0) years, and their mean weight was 68.9 (10.7) kg. Mean VAS scores at baseline were 14.8 (17.8) for the fentanyl group and 6.0 (9.7) for the placebo group (P = NS); at the time of drain removal, the corresponding VAS scores were 31.0 (20.6) and 33.8 (25.7) (P = NS). Analysis of a random-effects model with mean VAS scores as a function of time as the dependent variable indicated a significant difference in mean VAS scores between the fentanyl and placebo groups (P = 0.006). The overall incidence of adverse events was 39.4% (13/33). Among the 17 patients in the fentanyl group, 8 reported >/=1 adverse event; among the 16 patients in the placebo group, 9 reported >/=1 adverse event. A mean estimated C(max) of 0.184 (0.069) ng/mL was reached at 13.76 (3.56) minutes after administration of intranasal fentanyl. The mean measured C(max) was 0.22 (0.088) ng/mL. Conclusions: In these women who had undergone breast reduction or augmentation surgery, a single preprocedural dose of intranasal fentanyl was significantly more effective than placebo in reducing pain intensity over the hour after removal of surgical drains. However, there was no significant difference in pain intensity between fentanyl at the time of drain removal and placebo. Intranasal fentanyl was generally well tolerated. At the dose used (0.05 mg), plasma fentanyl concentrations were below the reported therapeutic window

Clinical decision support system supported interventions in hospitalized older patients:a matter of natural course and adequate timing

Background: Drug-related problems (DRPs) and potentially inappropriate prescribing (PIP) are associated with adverse patient and health care outcomes. In the setting of hospitalized older patients, Clinical Decision Support Systems (CDSSs) could reduce PIP and therefore improve clinical outcomes. However, prior research showed a low proportion of adherence to CDSS recommendations by clinicians with possible explanatory factors such as little clinical relevance and alert fatigue. Objective:To investigate the use of a CDSS in a real-life setting of hospitalized older patients. We aim to (I) report the natural course and interventions based on the top 20 rule alerts (the 20 most frequently generated alerts per clinical rule) of generated red CDSS alerts (those requiring action) over time from day 1 to 7 of hospitalization; and (II) to explore whether an optimal timing can be defined (in terms of day per rule). Methods: All hospitalized patients aged ≥ 60 years, admitted to Zuyderland Medical Centre (the Netherlands) were included. The evaluation of the CDSS was investigated using a database used for standard care. Our CDSS was run daily and was evaluated on day 1 to 7 of hospitalization. We collected demographic and clinical data, and moreover the total number of CDSS alerts; the total number of top 20 rule alerts; those that resulted in an action by the pharmacist and the course of outcome of the alerts on days 1 to 7 of hospitalization.Results: In total 3574 unique hospitalized patients, mean age 76.7 (SD 8.3) years and 53% female, were included. From these patients, in total 8073 alerts were generated; with the top 20 of rule alerts we covered roughly 90% of the total. For most rules in the top 20 the highest percentage of resolved alerts lies somewhere between day 4 and 5 of hospitalization, after which there is equalization or a decrease. Although for some rules, there is a gradual increase in resolved alerts until day 7. The level of resolved rule alerts varied between the different clinical rules; varying from &gt; 50–70% (potassium levels, anticoagulation, renal function) to less than 25%. Conclusion: This study reports the course of the 20 most frequently generated alerts of a CDSS in a setting of hospitalized older patients. We have shown that for most rules, irrespective of an intervention by the pharmacist, the highest percentage of resolved rules is between day 4 and 5 of hospitalization. The difference in level of resolved alerts between the different rules, could point to more or less clinical relevance and advocates further research to explore ways of optimizing CDSSs by adjustment in timing and number of alerts to prevent alert fatigue.</p

Introduction to the Pharmacoeconomics of Herbal Medicines

This article explores the need to perform pharmacoeconomic evaluations of herbal medicines and assesses the extent to which this approach has been applied so far to these products. There seems to be no compelling need for pharmacoeconomic analyses of herbal over-the-counter medicines, but such analyses are certainly warranted for herbal prescription medicines that have a high level of reimbursement. Such preparations are used in Germany, in particular, where physicians prescribed ginkgo, hawthorn, St John's wort, horse-chestnut and saw palmetto to a value of more than DM50 million each in 1996. In our survey, only a single pharmacoeconomic study, of uncertain quality, was found on these 5 herbs, whereas several pharmacoeconomic reports on synthetic competitors were retrieved. The time has come to submit highly reimbursed herbal prescription medicines to the same rigorous pharmacoeconomic evaluations as their synthetic competitors. At present, such studies are particularly important for Germany, but in the future they may also become relevant for other countries, inside as well as outside Europe.Cost analysis, Herbal medicine, Pharmacoeconomics