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Prescribing cascades occur when patients are prescribed medication to treat the adverse drug reaction of previously prescribed medication. Prescription sequence symmetry analysis (PSSA) can be used to assess the association between two medications in prescription or dispensing databases and thus the potential occurrence of prescribing cascades. In this article, a step-by-step guide is presented for conducting PSSA to assess prescribing cascades. We describe considerations for medication data collection and setting time periods for relevant parameters, including washout window, exposure window, continued exposure interval and blackout period. With two examples, we illustrate the impact of changes in these parameters on the strengths of associations observed. Given the impact seen, we recommend that researchers clearly specify and explain all considerations regarding medication included and time windows set when studying prescribing cascades with PSSA, and conduct subgroup and sensitivity analyses. [ABSTRACT FROM AUTHOR]

Background: To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent. Objective: This systematic review aims to provide an overview of prescribing cascades, including dose-dependency information and recommendations that healthcare providers can use to prevent or reverse them. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Relevant literature was identified through searches in OVID MEDLINE, OVID Embase, OVID CINAHL, and Cochrane. Additionally, Web of Science and Scopus were consulted to analyze reference lists and citations. Publications in English were included if they analyzed the occurrence of prescribing cascades. Prescribing cascades were included if at least one study demonstrated a significant association and were excluded when the adverse drug reaction could not be confirmed in the Summary of Product Characteristics. Two reviewers independently extracted and grouped similar prescribing cascades. Descriptive summaries were provided regarding dose-dependency analyses and recommendations to prevent or reverse these prescribing cascades. Results: A total of 95 publications were included, resulting in 115 prescribing cascades with confirmed adverse drug reactions for which at least one significant association was found. For 52 of these prescribing cascades, information regarding dose dependency or recommendations to prevent or reverse prescribing cascades was found. Dose dependency was analyzed and confirmed for 12 prescribing cascades. For example, antipsychotics that may cause extrapyramidal syndrome followed by anti-parkinson drugs. Recommendations focused on dosage lowering, discontinuing medication, and medication switching. Explicit recommendations regarding alternative options were given for three prescribing cascades. One example was switching to ondansetron or granisetron when extrapyramidal syndrome is experienced using metoclopramide. Conclusions: In total, 115 prescribing cascades were identified and an overview of 52 of them was generated for which recommendations to prevent or reverse them were provided. Nonetheless, information regarding alternative options for managing prescribing cascades was scarce. [ABSTRACT FROM AUTHOR]

Introduction: Healthcare professionals (HCPs) and patients have various motives to report adverse drug reactions (ADRs) to their national agency. These motives may differ between countries.Objective: The aim of this study was to assess to what extent motives of HCPs and patients to report ADRs differ between countries.Methods: HCPs and patients from Croatia (HR), The Netherlands (NL), and the UK were asked to complete a web-based survey containing questions regarding demographics and ADR reporting. HCPs and patients could select all motives for reporting that applied to them, with a total of 23 and 24 motives, respectively. Descriptive statistics are presented and Chi-square tests were used to test for differences across the countries, with effect sizes calculated using Cramer's V.Results: In total, 296 HCPs and 423 patients were included (60% and 32% from Croatia, 19% and 44% from NL, and 21% and 24% from the UK, respectively). For most of the motives to report or not to report an ADR, there were no differences between countries. Most HCPs from all countries would be motivated to report an ADR if there was a strong suspicion of causality (89%), if it concerned a severe/serious ADR (86%), and if it concerned an ADR for a new, recently marketed drug (77%). Most patients from all countries agreed that they would report an ADR if it concerned a severe ADR (96%), if the ADR influenced their daily activities (91%), and if they were worried about their own situation (90%). Differences across the countries (p < 0.05 and V ≥ 0.21) were observed for three and four of the HCP and patient motives, respectively. For HCPs, these differences were seen in motives related to legal obligation (65% HR, 24% NL, 38% UK), black triangle medicines (27% HR, 4% NL, 77% UK), and the reporting of well-known ADRs (53% HR, 85% NL, 69% UK). For patients, these differences were seen in motives related to a linkage between the ADR report and the medical notes (59% HR, 60% NL, 30% UK), complexity and time taken to report (25% HR, 13% NL, 40% UK), medicines purchased on the internet (59% HR, 39% NL, 65% UK), and the reporting of embarrassing ADRs (32% HR, 11% NL, 35% UK).Conclusions: HCPs' and patients' motives to report or not to report ADRs to the national agency were mostly similar across the three countries. Such motives can be used in general strategies to promote and increase ADR reporting. The observed differences provide guidance to further fine-tune ADR reporting at a national level. [ABSTRACT FROM AUTHOR]

Introduction: In general, women more often experience metformin-associated adverse drug reactions (ADRs) than men.Objectives: We aimed to assess whether sex differences in reported ADRs for metformin are observed at different times after initiation, and to explore their concurrence with sex differences in the dose of metformin over time. This may guide future studies in assessing the involved mechanisms of sex differences in metformin-associated ADRs and may guide sex-specific management of ADRs in clinical practice.Methods: This study has a longitudinal design using data about patients initiating metformin collected by the Dutch National Pharmacovigilance Center Lareb through their Intensive Monitoring program. Patients were asked to complete a web-based questionnaire six times after initiation (i.e., at 2 weeks, 6 weeks and at 3, 6, 9, and 12 months). The outcome variables were the proportion of patients reporting any ADR (primary) and the dose of metformin (secondary). Sex differences in the proportions of ADRs and in the dose were tested at each assessment using Pearson Chi-Squared tests and Wilcoxon rank-sum tests, respectively. Using Bonferroni adjustment for multiple testing, a p value < 0.01 was considered statistically significant.Results: The number of included patients was 1712 (40.9% women). Women reported an ADR more often than men, which was statistically significant at the assessment at 2 weeks (34% vs 25%, p < 0.001), and 6 weeks (37% vs 28%, p = 0.001) after initiation. In general, women were reported to be prescribed a lower dose than men, which became statistically significant at the 9-month assessment (p < 0.01).Conclusions: Sex differences in reported ADRs were seen in the first weeks after metformin initiation, whereas statistically significant differences in self-reported prescribed dosing were observed after several months. Patients, in particular women, might benefit from being prescribed lower metformin doses at treatment initiation. [ABSTRACT FROM AUTHOR]

Aims: We aimed to assess and characterize sex differences in adverse drug reactions (ADRs) reported to the national pharmacovigilance centre in the Netherlands while considering differences in drug use. Methods: ADRs spontaneously reported by healthcare professionals and patients to the Netherlands pharmacovigilance centre Lareb were used. Drug–ADR combinations reported at least 10 times between 2003–2016 for drugs used by ≥10,000 persons in that period were included. Data about the number of drug users was obtained from the National Health Care Institute. Sex‐specific ADRs, like gynaecological problems, were excluded. Sex differences in specific drug–ADR combinations were tested using bivariate logistic regression analyses in which the number of drug users per sex was taken into account. Results: In total, 2483 drug–ADR combinations were analysed. Possibly relevant sex differences were shown in 363 combinations (15%). Most of these drug–ADR combinations were reported more often for women (322 combinations). Drugs with the highest number of ADRs that were more often reported for women included thyroid hormones (32 combinations) and antidepressants (16 combinations for the centrally acting sympathomimetics; 14 combinations for other antidepressants). Some ADRs were predominantly reported for women across a range of drugs such as headache and dizziness whereas other ADRs such as tendon ruptures and aggression were reported more often for men. Conclusions: Identified sex differences in reported ADRs often referred to women. These differences may have various causes, including pharmacological and behavioural causes, which need to be further assessed. The results may ultimately lead to sex‐specific prescribing or monitoring recommendations. [ABSTRACT FROM AUTHOR]

Introduction: Previously, an app has been developed for healthcare professionals (HCPs) and patients to report adverse drug reactions (ADRs) to national medicines agencies and to receive drug safety information.Objective: This study aimed to assess (1) European HCPs' and patients' interest in an app for this two-way risk communication; (2) their preferences and perceptions towards specific app characteristics; and (3) which HCPs and patients are particularly interested in the app. In addition, these aspects were studied specifically for the countries where such an app was already available, i.e. Croatia, The Netherlands, and The UK.Methods: European HCPs and patients were asked to complete a web-based survey developed in the context of the Web-Recognizing Adverse Drug Reactions (Web-RADR) project. Data on app interest and preferences and perceptions towards app characteristics were analysed descriptively. Logistic regression analyses were conducted to assess the association of HCP characteristics and patient characteristics on the level of interest in the app (i.e. very interested vs. not/somewhat interested).Results: In total, 399 HCPs and 656 patients completed the survey. About half of the patients (48%; ranging from 38% from The Netherlands to 54% from The UK), and 61% of the HCPs (ranging from 42% from The Netherlands to 54% from The UK) were very interested in the app. A faster means of reporting ADRs and easier access to the reporting form were the main perceived benefits. HCPs and patients who already use a health app were particularly interested in the app (HCPs: odds ratio [OR] 3.52; 95% confidence interval [CI] 1.96-6.30, patients: OR 1.64; 95% CI 1.19-2.27).Conclusions: An app is positively perceived by HCPs and patients for reporting ADRs quickly and for receiving drug safety information from national medicines agencies. In particular, HCPs and patients who already use other health apps were interested in the app. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether patients’ willingness to add a blood pressure-lowering drug and the importance they attach to specific treatment characteristics differ among age groups in patients with type 2 diabetes. Materials and Methods: Patients being prescribed at least an oral glucose-lowering and a blood pressure-lowering drug completed a questionnaire including a discrete choice experiment. This experiment contained choice sets with hypothetical blood pressure-lowering drugs and a no additional drug alternative, which differed in their characteristics (i.e. effects and intake moments). Differences in willingness to add a drug were compared between patients <75 years (non-aged) and ≥75 years (aged) using Pearson χ2-tests. Multinomial logit models were used to assess and compare the importance attached to the characteristics. Results: Of the 161 patients who completed the questionnaire, 151 (72%) could be included in the analyses (mean age 68 years; 42% female). Aged patients were less willing to add a drug than non-aged patients (67% versus 84% respectively; P = 0.017). In both age groups, the effect on blood pressure was most important for choosing a drug, followed by the risk of adverse drug events and the risk of death. The effect on limitations due to stroke was only significant in the non-aged group. The effect on blood pressure was slightly more important in the non-aged than the aged group (P = 0.043). Conclusions: Aged patients appear less willing to add a preventive drug than non-aged patients. The importance attached to various treatment characteristics does not seem to differ much among age groups. [ABSTRACT FROM AUTHOR]

Aims To compare the values regulators attach to different drug effects of oral antidiabetic drugs with those of doctors and patients. Methods We administered a 'discrete choice' survey to regulators, doctors and patients with type 2 diabetes in The Netherlands. Eighteen choice sets comparing two hypothetical oral antidiabetic drugs were constructed with varying drug effects on glycated haemoglobin, cardiovascular risk, bodyweight, duration of gastrointestinal complaints, frequency of hypoglycaemia and risk of bladder cancer. Responders were asked each time which drug they preferred. Results Fifty-two regulators, 175 doctors and 226 patients returned the survey. Multinomial conditional logit analyses showed that cardiovascular risk reduction was valued by regulators positively (odds ratio 1.98, 95% confidence interval 1.11-3.53), whereas drug choices were negatively affected by persistent gastrointestinal problems (odds ratio 0.24, 95% confidence interval 0.14-0.41) and cardiovascular risk increase (odds ratio 0.49, 95% confidence interval 0.27-0.87). Doctors and patients valued these effects in a similar manner to regulators. The values that doctors attached to large changes in glycated haemoglobin and that both doctors and patients attached to hypoglycaemia and weight gain also reached statistical significance. No group's drug choice was affected by a small absolute change in risk of bladder cancer when presented in the context of other drug effects. When comparing the groups, the value attached by regulators to less frequent hypoglycaemic episodes was significantly smaller than by patients ( P = 0.044). Conclusions Regulators may value major benefits and risks of drugs for an individual diabetes patient mostly in the same way as doctors and patients, but differences may exist regarding the value of minor or short-term drug effects. [ABSTRACT FROM AUTHOR]

Background Direct patient-reported information about adverse drug events (ADEs) is important since it adds to healthcare professional-reported information about the safety of drugs. Previously, we developed an instrument to assess patient-reported ADEs in research settings. The aim of this study is to assess the construct and concurrent validity of the questionnaire. Methods Patients on at least an oral glucose-lowering drug completed the ADE questionnaire, the World Health Organization Quality of Life-BREF, and the Treatment Satisfaction Questionnaire for Medication (TSQM). The ADE questionnaire assesses ADEs for any drug that the patient uses. Construct validity was assessed by testing whether patients reporting an ADE had a lower general quality of life and physical health than those not reporting an ADE, using Mann-Whitney U-tests and t-tests (significance level <0.05). For concurrent validity, we tested whether ADEs that patients associate with particular drugs in the ADE questionnaire are documented in the Summary of Product Characteristics (SPC) of those drugs, and whether patients who report an ADE with the use of metformin on the TSQM, mention metformin as a drug associated with an ADE on the ADE questionnaire. Agreement of 70% with the SPC was considered satisfactory. Sensitivity and positive predictive value (PPV) were calculated for the comparison with the TSQM, where 70% was used as the cutoff level for sufficient concurrent validity. Results We included 135 patients (mean age 64 years, 35% women). Patients who reported an ADE (N = 37) had a lower general quality of life and physical health than those not reporting an ADE (P < 0.05). For 78 of the 146 reported ADEs (53%), patients mentioned at least 1 particular drug associated with the ADE. After clustering related ADEs, this resulted in 56 patient-reported ADE-drug associations. Of these, 41 (73%) were in agreement with information in the SPC. Finally, the questionnaire had a sensitivity of 38% and PPV of 79% for assessing ADEs associated with metformin. Conclusions The construct validity of the patient-reported ADE questionnaire was sufficient for reporting any versus no ADE, but the concurrent validity was only partly demonstrated. Therefore, the questionnaire needs to be adapted before it can be used. [ABSTRACT FROM AUTHOR]

Background: Direct patient reporting of adverse drug events (ADEs) is relevant for the evaluation of drug safety. To collect such data in clinical trials and postmarketing studies, a valid questionnaire is needed that can measure all possible ADEs experienced by patients.Objective: Our aim was to develop and test a generic questionnaire to identify ADEs and quantify their nature and causality as reported by patients.Methods: We created a draft list of common ADEs in lay-terms, which were classified in body categories and mapped to the Medical Dictionary for Regulatory Activities (MedDRA(®)) terminology. Questions about the nature and causality were derived from existing questionnaires and causality scales. Content validity was tested through cognitive debriefing, revising the questionnaire in an iterative process. Feasibility and reliability were assessed using a Web-based version of the questionnaire. Patients received the questionnaire twice. Feasibility was assessed by the reported time needed for completion and ease of use. Reliability was calculated using Cohen's kappa and proportion of positive agreement (PPA) on: (1) any ADE at patient level; (2) similar ADEs at MedDRA(®) System Organ Class level; and (3) the same ADE at ADE-specific level.Results: In the development phase, 28 patients with type 2 diabetes or asthma/chronic obstructive pulmonary disease (COPD) participated. Questions and answer options were rephrased, layout was improved, and changes were made in the classification of ADEs. The final questionnaire consisted of 252 ADEs organized in 16 body categories, and included 14 questions per reported ADE. A total of 135 patients using a median of five different drugs completed the Web-based questionnaire twice. The median completion time was 15 min for patients not reporting any ADE, and 30 min for patients reporting at least one ADE. Three quarters of the patients found the questionnaire easy to use. Test-retest reliability was acceptable at patient level (κ = 0.50, PPA 0.64) and at MedDRA(®) System Organ Class level (κ = 0.52, PPA 0.54), but was low at ADE-specific level (κ = 0.38, PPA 0.38).Conclusion: We developed a generic patient-reported ADE questionnaire and confirmed its content validity. The questionnaire was feasible and reliable for reporting any ADE and similar ADEs at MedDRA(®) System Organ Class level. Additional work is, however, needed to reliably quantify specific ADEs reported by patients. [ABSTRACT FROM AUTHOR]

This study describes coping strategies that patients with heart failure (HF) use to manage adverse drug events (ADEs). The included coping strategies were social support seeking, information seeking, non-adherence and taking alleviating medication. The role of beliefs about medication and ADE perceptions in explaining these coping strategies was assessed using the Self-Regulation Model. We performed a cross-sectional study including 250 HF patients who experienced an ADE. Patients completed validated questionnaires assessing their coping strategies, ADE perceptions and medication beliefs. Social support (60%) and information seeking (32%) were the most commonly used strategies to cope with ADEs. Non-adherence was reported by 7% of the patients. Multivariate linear regression analysis showed that demographics, clinical factors and medication beliefs explained only a small amount of the variance in coping strategies, whereas ADE perceptions explained a substantial amount of variance. Path analysis showed that patients’ perceptions about the timeline, consequences and controllability of ADEs by the health care provider were directly related to their coping behaviour. The effect of patients’ medication beliefs on their coping strategies was consistent with mediation through their ADE perceptions. Our results support the value of the Self-Regulation Model in understanding patients’ coping behaviour with regard to ADEs. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Identifying patients with heart failure (HF) who are at risk of experiencing symptomatic adverse drug events (ADEs) is important for improving patient care and quality of life. Several demographic and clinical variables have been identified as potential risk factors for ADEs but limited knowledge is available on the impact of HF patients’ beliefs and perceptions on their experience of ADEs. Objective: The purpose of the study was to identify the relationship between HF patients’ illness perception and medication beliefs and self-reported ADEs. Design: A cross-sectional survey was performed between November 2008 and March 2009. Settings: One university medical centre, two regional hospitals and 20 general practitioners in the Netherlands participated in the study. Participants: 495 patients with HF were included. Methods: Patients completed the validated Revised Illness Perception Questionnaire (IPQ-R) and the Beliefs about Medication Questionnaire (BMQ) which collected data on their illness perception and medication beliefs. In addition, data on ADEs as experienced in the previous four weeks were collected through an open-ended question and a symptom checklist. Multivariate logistic regression was performed to identify factors associated with these ADEs. Results: In total, 332 (67%) patients had experienced ADEs in the previous four weeks, of whom 28% reported dry mouth, 27% dizziness and 19% itchiness as the most prevalent. In the adjusted multivariate analysis, disease-related symptoms (illness identity) (OR for 1–5 symptoms 3.57; 95% CI 2.22–5.75, OR for >5 symptoms 7.37; 95% CI 3.44–15.8), and general beliefs about medication overuse (OR 1.07; 95% CI 1.01–1.13) were independently associated with experiencing ADEs, whereas none of the demographic or clinical factors were significant. Conclusions: HF patients who perceive a high number of disease symptoms and have negative medication beliefs are at higher risk of experiencing self-reported ADEs. We suggest that future studies and interventions to improve ADE management should focus on negative medication beliefs and assisting patients in differentiating disease symptoms from ADEs. [Copyright &y& Elsevier]