Therapeutic Advances in Drug Safety最新文献

Background: Inpatient Self-administration of Medication (SAM) increases patient involvement in medication management and may increase medication safety. Its implementation is impeded. Successful and sustainable implementation of SAM strongly depends on patients' willingness to participate. This study aimed to identify and quantify patients' views on SAM, related (dis)advantages and prerequisites, patient's willingness to engage in SAM schemes, and their preferences in medication management during hospitalisation.

Methods: A mixed-methods study was conducted among hospitalised adult patients in four Dutch hospitals during December 2018 and March 2019. Semi-structured one-to-one interviews were performed to identify patients' views on SAM. Interview transcripts were subjected to thematic-content analysis. These outcomes were used to construct a questionnaire about patient's willingness to engage in SAM schemes, their preferences for inpatient medication management and level of agreement with statements about SAM's (dis)advantages and prerequisites of SAM. Data were descriptively analysed.

Results: Nineteen hospitalised patients [mean (standard deviation; SD) age 61.0 (13.4) years old; 52.6% male] were interviewed. Most patients had a positive view on SAM, but some doubted the necessity to change standard care. Also, patients expressed concerns about medication safety. Prerequisites for SAM implementation were identified. These covered four main themes: information provision, accessible and safe storage, assurance of safety, and clear responsibilities. A total of 234 patients [mean (SD), age 65.3 (13.5) years; 54.7% male] participated in the questionnaire. Although 50.0% of the patients were willing to self-administer medication, patients were ambivalent as only 36.5% preferred SAM over nurse-led administration.

Conclusion: The majority of patients were positive about SAM. Although half of the patients were willing to perform SAM, most patients did not prefer SAM over standard care. This ambivalent attitude may be overcome when the stated prerequisites are met and patients experience SAM in clinical practice. Based on patients' views, it can be concluded that implementation of SAM seems possible.

Plain language summary: Research to identify patients' views on Self-administration of Medication during hospitalisation Background: Patient involvement is desired by patients. Nevertheless, currently healthcare providers take over patient's medication management when hospitalised. Capable patients administering their own medication during hospitalisation, known as 'Self-administration of Medication' (SAM) is one possible way to increase patient involvement in hospital care and to improve medication safety. Understanding patients' views on SAM, before its actual practice, could help to successfully implement it. In this research, we

Could natural plant pigment (chlorophyll) derivatives (chlorophyllins) improve the safety of the antiviral Molnupiravir, used to treat COVID-19 disease? Molnupiravir, a specific SARS-CoV-2 antiviral, may cause adverse genetic changes and thereby create potential host cell damage (through genotoxicity and DNA stressors). In our opinion, this side effect of treatment could be reduced if the antiviral was taken as a combined therapy with chlorophyllins. Specifically, we hypothesise that chlorophyllins might improve the overall effectiveness of molnupiravir, typically used to treat patients suffering from COVID-19. Chlorophyllins, antioxidants derived from natural plant chlorophyll, are safe, effective and non-toxic antioxidants that could combat possible genotoxic flow-on effects of molnupiravir. In addition, as they possess antiviral properties, treatment with chlorophyllins may enhance the overall antiviral effect via a mechanism different to molnupiravir.

In the context of an ageing population, the burden of disease and medicine use is also expected to increase. As such, medicine safety and preventing avoidable medicine-related harm are major public health concerns, requiring further research. Potentially suboptimal medicine regimens is an umbrella term that captures a range of indicators that may increase the risk of medicine-related harm, including polypharmacy, underprescribing and high-risk prescribing, such as prescribing potentially inappropriate medicines. This narrative review aims to provide a background and broad overview of the patterns and implications of potentially suboptimal medicine regimens among older adults. Original research published between 1990 and 2021 was searched for in MEDLINE, using key search terms including polypharmacy, inappropriate prescribing, potentially inappropriate medication lists, medication errors, drug interactions and drug prescriptions, along with manual checking of reference lists. The review summarizes the prevalence, risk factors and clinical outcomes of polypharmacy, underprescribing and potentially inappropriate medicines. A synthesis of the evidence regarding the longitudinal patterns of polypharmacy is also provided. With an overview of the existing literature, we highlight a number of key gaps in the literature. Directions for future research may include a longitudinal investigation into the risk factors and outcomes of extended polypharmacy, research focusing on the patterns and implications of underprescribing and studies that evaluate the applicability of tools measuring potentially inappropriate medicines to study settings.

Plain language summary: A review on potentially inappropriate medicine regimens Medicine use in older age is common. Older adults with more than one chronic condition are likely to use multiple medicines to manage their health. However, there are times when taking multiple medicines may be unsafe and the number of medicines, or the combination of medicines used, may increase the risk of poor health outcomes. The term medicine regimens is used to describe all the medicines an individual takes. There are several ways to measure when a medicine regimen may be inappropriate and, therefore, potentially harmful. Much research has been published looking into potentially inappropriate medicine regimens. To bring together the current research, this review provides a background on the different measures of potentially inappropriate medicine regimens. It also summarizes how many people may experience potentially inappropriate medicine regimens, the impact it is having on their health and who may be at greater risk. In doing so, we found a number of gaps in the existing evidence, indicating that our understanding of potentially inappropriate medicine regimens is incomplete. This review highlights gaps in knowledge that can be addressed by future research. With an improved understanding of potentiall

Background: As lifetime expectancy in Greenland is steadily increasing, so is the proportion of elderly Greenlanders. Old age is associated with polypharmacy, and in this study, we aim to describe the prevalence and characteristics of polypharmacy among the care home residents in Greenland.

Methods: Eight care homes in Greenland were visited between 2010 and 2016. Questionnaires including information on prescribed medication and comorbidities were collected and analyzed. Drugs were categorized according to Anatomical Therapeutic Chemical (ATC) category, and potential drug-drug interactions (pDDIs) were assessed using the Danish Interaction Database. Polypharmacy was defined as five or more prescribed drugs.

Results: All 244 eligible residents were included in the study. The median number of prescribed drugs per resident was six, and women were prescribed more drugs than men (median six versus five). More than 60% of all residents fulfilled the criteria for polypharmacy. The residents in the polypharmacy group had a higher body mass index (26.9 versus 24.3) and more chronic diseases (median two versus one), and more often pulmonary (14% versus 1%) or endocrine disease (22% versus 2%) than in the non-polypharmacy group. The most prescribed drugs belonged to ATC category N (nervous system, 78% of the residents). Finally, pDDIs were found among 61% of the residents and were more common in the capital (77%), which also had the highest proportion of residents with polypharmacy (77%).

Conclusion: This is the first study to describe the patterns of polypharmacy and pDDIs among the elderly in care homes in Greenland. Our findings indicate that polypharmacy is as common in Greenland as elsewhere in the Western world, but there are local differences in the prevalence.

Plain language summary: Polypharmacy among the elderly in care homes in Greenland The lifetime expectancy of the Greenlandic population is increasing, and so is the number of elderly Greenlanders. Previous studies have shown that the elderly have a higher risk of being treated with five drugs or more which is called polypharmacy. Polypharmacy can cause unwanted interactions and side effects. In this study, we examine the characteristics of the residents in Greenlandic care homes belonging to this group.Using questionnaires, we gathered information from 244 residents from care homes in eight different towns and settlements in Greenland. Data included types of medication prescribed to the resident, age, gender, cause of stay, and medical history, which allowed us to compare the results between genders and towns.We found that among 244 residents, more than half of all residents were prescribed five or more different drugs, and women were generally prescribed more drugs than men. Those prescribed five or more drugs had a higher body mass i

[This corrects the article DOI: 10.1177/20420986211052344.].

Introduction: Alkalising agents have the potential to enhance the efficacy of many antimicrobial agents used in the treatment of Urinary Tract Infections; they also have the potential to cause significant patient harm if used incorrectly. This work seeks to illustrate and quantify these risks and synergies by modelling drug solubility and supersaturation against pharmacokinetic data for commonly used antibiotic agents.

Methods: Solubility-pH relationships are employed to quantify the crystalluria risk for compounds which may be reasonably expected to be co-prescribed-or co-administered-with urinary alkalisers (amoxicillin, nitrofurantoin, trimethoprim, sulfamethoxazole and ciprofloxacin). These results are correlated against reports of crystalluria in the literature and in the EU Adverse Drug Reaction database.

Results and discussion: We find a correlation between the maximum theoretical supersaturation attainable and crystalluria reports for sulfamethoxazole, amoxicillin and ciprofloxacin. Shifts in urine pH which can be induced by alkalising agents may produce supersaturated states (and thus induce crystalluria) and may also affect antimicrobial efficacy. The importance of employing biorelevant media to improve predictive capacity of this analysis is also discussed.

Conclusion: Despite their widespread use, alkalising agents have significant effects on the pharmacokinetics of the most common drugs used to treat UTIs. With self-care set to increase, all OTC products should be critically re-evaluated to ensure patient safety, particularly within contexts where healthcare professionals are not involved in treatment selection. This analysis suggests a need for consistency across patient and healthcare professional documents to improve clarity. Plain Language Summary OTC Alkalising agents need additional warning information Alkalising agents (e.g., sodium and potassium citrate) can be purchased in many locations without the supervision of a healthcare professional.Although they are thought as innocuous agents, alkalisers can greatly influence the way some antibiotics behave in the body and this can potentially cause patient harm.This work illustrates these risks and synergies by modelling drug solubility and supersaturation against pharmacokinetic data for commonly used antibiotic agents.Manufacturers and patients should be aware that the use of alkalising agents with these drugs (and potentially many others) may cause unintended consequences.

Aim: Quarantine due to the COVID-19 pandemic altered the supply and demand of health services. This, together with the 'infodemic' and generalized panic, could alter the patterns of self-medication in the population. The objective was to characterize the patterns of self-medication in four cities of Colombia during mandatory preventive isolation in 2020.

Methods: This was a cross-sectional study done in four Colombian cities during mandatory national preventive isolation between June and September 2020. A sample of 397 adults who responded to an online survey, based on the Instrument for Systematic Data Collection for Self-medication (Instrumento de Recolección Sistemática de Datos para la Automedicación-IRIS-AM), was obtained. The use of social networks (including WhatsApp) as the source of information about medications was explored.

Results: The 397 people surveyed had a median age of 31.0 years, and 58.2% were women. The prevalence of self-medication during lockdown was 34.3% (n = 136). Medications targeting the nervous system (n = 117; 86.0% of those participants with self-medication) and the musculoskeletal system (n = 68; 50.0%) were the most commonly used. Ten (7.4%) of the self-medicated patients reported doing so to prevent COVID-19, and 15 (11.0%) named social networks as the source of information.

Conclusion: More than one-third of the participants reported self-medication during COVID-19 lockdown, mainly with analgesic-type nervous system medications. People who reported self-medication to prevent COVID-19 often got their information from social networks, the Internet, and WhatsApp.

Plain language summary: Self-medication during mandatory COVID-19 isolation: Introduction: Self-medication refers to the use of medications to treat self-diagnosed disorders or symptoms, and it can lead to health problems. This habit is widely practiced by the people, especially in low- and middle-income countries. The objective was to characterize the patterns of self-medication in four cities of Colombia during mandatory preventive isolation in 2020 due the quarantine by COVID-19 explored pandemic. Methods: We made a cross-sectional study between June and September 2020, and a sample of 397 adults who responded to an online survey. The use of social networks (including WhatsApp) as the source of information about medications was explored. Results: The prevalence of self-medication during lockdown was 34.3% (n = 136). Medications targeting the nervous system (n = 117; 86.0% of those participants with self-medication) and the musculoskeletal system (strategies n = 68; 50.0%) were the most commonly used. Conclusion: People who reported self-medication to prevent COVID-19 often got their information from social networks, the Internet, and WhatsApp. These findings ra

Background: Interventional studies on polypharmacy often fail to significantly improve patient-relevant outcomes, or confine themselves to measuring surrogate parameters. Interventions and settings are complex, with many factors affecting results. The AdAM study's aim is to reduce hospitalization and death by requiring general practitioners (GPs) to use a computerized decision-support system (CDSS). The study will undergo a process evaluation to identify factors for successful implementation and to assess whether the intervention was implemented as intended.

Objective: To evaluate our complex intervention, based on the Medical Research Council's guideline dimensions.

Research questions: We will assess implementation (reach, fidelity, dose, tailoring) by asking: (1) Who took part in the intervention (proportion of GPs using the CDSS, proportion of patients enrolled in them)? Information on GPs' and patients' characteristics will also be collected. (2) How many and which medication alerts were dealt with? (3) Was the intervention implemented as intended? (4) On what days did GPs use the intervention tool?

Methods: The process evaluation is part of a stepped-wedge cluster-randomized controlled trial. Characteristics of practices, GPs and patients using the CDSS will be compared with the non-participating population. CDSS log data will be analyzed to evaluate how the number of medication alerts changed between baseline and 2 months later, and to identify the kind of alerts that were dealt with. Comparison of enrolled patients on weekdays versus weekends will shed light on GPs' use of the CDSS in the absence or presence of patients. Outcomes will be presented using descriptive statistics, and significance tests will be used to identify associations between them. We will conduct subgroup analyses, including time effects to account for software improvements.

Discussion: This study protocol is the basis for conducting analyses of the quantitative process evaluation. By providing insight into how GPs conduct medication reviews, the evaluation will provide context to the trial results and support their interpretation. The evaluation relies on the proper documentation by GPs, potentially limiting its explanatory power.

Registration: PROSPERO: CRD42020210645.

Introduction: We aimed to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older patients with type 2 diabetes with inadequate glycaemic control.

Methods: We included randomized controlled trials (RCTs) in older (⩾65 years) patients with type 2 diabetes. The intervention group was randomized to treatment with any DPP-4 inhibitors. A systematic search in MEDLINE and Embase was performed in December 2020. For assessing the risk of bias, RoB 2 tool was applied. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We pooled outcomes using random effects meta-analyses.

Results: We identified 16 RCTs that included 19,317 patients with a mean age of greater than 70 years. The mean HbA1c level ranged between 7.1 and 10.0 g/dl. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly [risk ratio (RR) 1.04; 95% confidence interval (CI) 0.89-1.21]. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia (RR 1.08; 95% CI 1.01-1.16), but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas (RR 0.88; 95% CI 0.75-1.04). DPP-4 inhibitors probably reduce the risk for hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis.

Conclusion: There is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case second-line treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas.

Plain language summary: Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: Introduction:: We performed the review to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older type 2 diabetes patients with blood sugar outside the normal level.Methods:: To answer the question, we searched various electronic databases. We included studies in older (⩾65 years) patients with type 2 diabetes that assessed the safety of DPP-4 inhibitors. The data from the different studies were quantitatively summarized using statistical methods. We assessed the quality of the data to judge the certainty of the findings.Results:: We identified 16 studies that included 19,317 patients with a mean age greater than 70 years. The average blood sugar level of patients in the included studies was slightly or moderat

Purpose: Weekly gemcitabine + paclitaxel (wGT) administration is widely applied in real-world clinical practice. The 28-day and 21-day regimens of wGT are the most widely accepted regimens. We evaluated the efficacy and safety of wGT administration in patients with metastatic breast cancer (MBC) and compared the two regimens.

Methods: Patients with human epidermal growth factor receptor 2 (HER-2)-negative MBC who received wGT between October 2013 and October 2016 were identified using an electronic database. The outcome variables included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profile. Propensity score matching was performed to minimize potential confounders.

Results: A total of 140 patients were included. The median PFS and OS was 7.8 [95% confidence interval (CI) = 7.0-8.7] months and 22.5 (95% CI = 18.8-26.1) months, respectively. The toxicity of wGT was manageable. Among the patients, 90 (64.3%) received the 21-day regimen and 50 (35.7%) received the 28-day regimen. A higher number of younger patients and patients receiving later-line therapy received the 28-day regimen. There was no significant difference between the two groups in PFS after propensity score matching, though subgroup analysis showed that patients with early relapse benefited more from the 28-day regimen. The ORR was numerically higher in 28-day regimen (37.8% versus 28.0%, p = 0.310). However, the 21-day regimen was better tolerated than the 28-day regimen.

Conclusion: wGT administration showed efficacy and safety in patients with MBC. The efficacy was comparable between the two regimens after adjustment for confounding factors while the 21-day regimen was better tolerated.

Plain language summary: 21-day regimen of wGT was well tolerated in patients with metastatic breast cancer Weekly gemcitabine + paclitaxel (wGT) administration is widely applied in real-world clinical practice. The 28-day and 21-day regimens of wGT are the most widely accepted regimens. We evaluated the efficacy and safety of wGT administration in patients with metastatic breast cancer (MBC) and compared the two regimens. Patients with human epidermal growth factor receptor 2 (HER-2)-negative MBC who received wGT between October 2013 and October 2016 were identified using an electronic database. The outcome variables included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profile. Propensity score matching was performed to minimize potential confounders. We found that the efficacy was comparable between the two regimens after adjustment for confounding factors while the 21-day regimen was better tolerated.