Construct and concurrent validity of a patient-reported adverse drug event questionnaire:a cross-sectional study

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 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 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

Potential Overtreatment and Undertreatment of Diabetes in Different Patient Age Groups in Primary Care After the Introduction of Performance Measures

OBJECTIVETo assess whether after the introduction of diabetes performance measures decreases in undertreatment correspond with increases in overtreatment for blood pressure (BP) and glycemic control in different patient age groups.RESEARCH DESIGN AND METHODSWe conducted a cohort study using data from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database. General practices were included when data were available from 1 year before to at least 1 year after the introduction of diabetes performance measures. Included patients had a confirmed diagnosis of type 2 diabetes. Potential overtreatment was defined as prescribing maximum treatment or a treatment intensification to patients with a sustained low-risk factor level. Potential undertreatment was defined as a lack of treatment intensification in patients with a sustained high-risk factor level. Percentages of over- and undertreated patients at baseline were compared with those in subsequent years, and stratified analyses were performed for different patient age groups.RESULTSFor BP, undertreatment significantly decreased from 61 to 57% in the first year after the introduction of performance measures. In patients >75 years of age, undertreatment decreased from 65 to approximate to 61%. Overtreatment was relatively stable (approximate to 16%). For glycemic control, undertreatment significantly increased from 49 to 53%, and overtreatment remained relatively stable (approximate to 7%).CONCLUSIONSThe improvement of BP undertreatment after introduction of the performance measures did not correspond with an increase in overtreatment. The performance measures appeared to have little impact on improving glucose-regulating treatment. The trends did not differ among patient age groups

Sex disparities in treatment patterns after metformin initiation among patients with type 2 diabetes mellitus

PURPOSE: To assess sex differences in treatment patterns after metformin initiation among type 2 diabetes mellitus (T2D) patients.METHODS: A cohort study was conducted using the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) primary care database. Patients aged ≥18 years initiating metformin were followed 2-5 years. Markov modeling was conducted to estimate treatment transition rates and calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI) comparing men with women adjusted for age, HbA1c level at initiation, and cardiovascular disease history. Kaplan-Meier analyses and Cox proportional-hazards models were used to determine the time to and likelihood of getting treatment intensification. HbA1c levels at initiation and intensification were compared using Mann-Whitney U tests.RESULTS: In total, 11 508 metformin initiators were included (50.1% women). The most common transition after initiation was a dose increase (probability women 0.52, men 0.59, no significant difference). Women were more likely than men to switch to any other non-insulin hypoglycemic agent after initiation (aHR 1.66; 95% CI 1.31-2.12), after dose increase (aHR 1.48; 95% CI 1.10-1.98) and after dose decrease (aHR 2.64; 95% CI 1.28-5.46). Time to intensification was longer, time to switching was shorter, and HbA1c levels at initiation and intensification were lower for women than men.CONCLUSIONS: Sex disparities were observed in treatment transitions after metformin initiation. Women more often switched treatment than men, which suggest that prescribers acknowledge more tolerance or other problems for metformin in women. Men intensified treatment earlier and at higher HbA1c levels, indicative of a higher need for treatment intensification.</p

Prediction of the Effects of Empagliflozin on Cardiovascular and Kidney Outcomes Based on Short-Term Changes in Multiple Risk Markers

Aims: The EMPA-REG OUTCOME trial demonstrated that the sodium-glucose cotransporter-2 inhibitor (SGLT2) empagliflozin reduces the risk of cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes. We previously developed the parameter response efficacy (PRE) score, which translates drug effects on multiple short-term risk markers into a predicted long-term treatment effect on clinical outcomes. The main objective of this study was to assess the accuracy of the PRE score in predicting the efficacy of empagliflozin in reducing the risk of CV and kidney outcomes. Methods: Short-term (baseline to 6-months) changes in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), urinary-albumin-creatinine-ratio (UACR), hemoglobin, body weight, high-density-lipoprotein (HDL) cholesterol, low-density-lipoprotein (LDL) cholesterol, uric acid, and potassium were determined among 7020 patients with type 2 diabetes and established CV disease in the EMPA-REG OUTCOME trial. The beta-coefficients, derived from a Cox proportional hazards model in a pooled database consisting of 6355 patients with type 2 diabetes, were applied to the short-term risk markers in the EMPA-REG OUTCOME trial to predict the empagliflozin-induced impact on CV (defined as a composite of non-fatal myocardial infarction, non-fatal stroke, or CV death) and kidney (defined as a composite of doubling of serum creatinine or end-stage kidney disease) outcomes. Results: Empagliflozin compared to placebo reduced HbA1c (0.6%), SBP (4.2 mmHg), UACR (13.0%), body weight (2.1 kg), uric acid (20.4 μmol/L), and increased hemoglobin (6.6 g/L), LDL-cholesterol (0.1 mmol/L) and HDL-cholesterol (0.04 mmol/L) (all p<0.01). Integrating these effects in the PRE score resulted in a predicted relative risk reduction (RRR) for the CV outcome of 6.4% (95% CI 1.4–11.7), which was less than the observed 14.7% (95% CI 1.3–26.4%) RRR. For the kidney outcome, the PRE score predicted a RRR of 33.4% (95% CI 26.2–39.8); the observed RRR was 46.9% (95% CI 26.8–61.5). In a subgroup of 2,811 patients with UACR ≥30 mg/g at baseline, the PRE score predicted RRR was 40.8% (95% CI 31.2–49.1) vs. the observed RRR of 40.8% (95% CI 12.4–60.0) for the kidney outcome. Conclusions: Integrating multiple short-term risk marker changes in the PRE score underestimated the effect of empagliflozin on CV and kidney outcomes, suggesting that the currently used risk markers do not fully capture the effect of empagliflozin. In patients with increased albuminuria, the PRE score adequately predicted the effect of empagliflozin on kidney outcomes

Self-Reported Effectiveness and Safety of Trokie (R) Lozenges:A Standardized Formulation for the Buccal Delivery of Cannabis Extracts

Therapeutic use of cannabinoids, the main active ingredients of Cannabis sativa L., is often hindered by their limited bioavailability and undesirable psychoactivity. We conducted an observational study in December 2016 and another one in February 2018 to investigate respectively: (i) the effectiveness of Trokie (R) lozenges, a standardized formulation containing cannabis extracts, to deliver cannabinoids via buccal absorption and (ii) its long-term safety. Participants were members of the Palliative Care Corporation health clinic, registered California cannabis patients, and had a diagnosis of chronic non-cancer pain. For the effectiveness study, 49 participants were asked to self-report pain perception before and after 1-12 weeks of taking Trokie (R) lozenges, using an 11-point pain intensity numeric rating scale (PI-NRS). A mean reduction in PI-NRS score of 4.9 +/- 2.0 points was observed. Onset of analgesia typically varied between 5 and 40 min, which seems consistent with, at least partial, buccal absorption. In the safety study, 35 participants were asked to complete a questionnaire about adverse events (AEs) associated with Trokie (R) lozenges. AEs were reported by 16 subjects (46%), the most common being dizziness/unsteadiness (N = 7), bad taste (N = 5), and throat irritation/dry mouth (N = 4). None of the self-reported AEs resulted in a serious medical situation and most of them had limited impact on daily functions. Despite the AEs, 90% of participants reported being "satisfied" or "very satisfied" with the product. These observations suggest that buccal administration of standardized extracts via Trokie (R) lozenges may represent an efficacious and safe approach to cannabis administration

The Role of Patients' Age on Their Preferences for Choosing Additional Blood Pressure-Lowering Drugs:A Discrete Choice Experiment in Patients with Diabetes

ObjectivesTo 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 MethodsPatients 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 (aged) using Pearson chi(2)-tests. Multinomial logit models were used to assess and compare the importance attached to the characteristics.ResultsOf 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).ConclusionsAged 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.</p

Drug Safety Issues Covered by Lay Media:A Cohort Study of Direct Healthcare Provider Communications Sent between 2001 and 2015 in The Netherlands

Background: Some drug safety issues communicated through direct healthcare professional communications (DHPCs) receive substantial media coverage, while others do not. Objectives: The objective of this study was to assess the extent of coverage of drug safety issues that have been communicated through DHPCs in newspapers and social media. A secondary aim was to explore which determinants may be associated with media coverage. Methods: Newspaper articles covering drug safety issues communicated through 387 DHPCs published between 2001 and 2015 were retrieved from LexisNexis Academic™. Social media postings were retrieved from Coosto™ for drugs included in 220 DHPCs published between 2010 and 2015. Coverage of DHPCs by newspapers and social media was assessed during the 2-month and 14-day time periods following issuance of the DHPC, respectively. Multivariate logistic regression was used to assess potential DHPC- and drug-related determinants of media coverage. Results: 41 (10.6%) DHPC safety issues were covered in newspaper articles. Newspaper coverage was associated with drugs without a specialist indication [adjusted odds ratio 5.32; 95% confidence interval (2.64–10.73)]. Negative associations were seen for time since market approval [3–5 years 0.30; (0.11–0.82), 6–11 years 0.18; (0.06–0.58)] and year of the DHPC [0.88; (0.81–0.96)]. In the social media, 180 (81.8%) drugs mentioned in 220 DHPCs were covered. Social media coverage was associated with drugs without a specialist indication [6.92; (1.56–30.64)], and for DHPCs communicating clinical safety issues [5.46; (2.03–14.66)]. Conclusions: Newspapers covered a small proportion of DHPC safety issues only. Most drugs mentioned in DHPCs were covered in social media. Coverage in both media were higher for drugs without a specialist indication

Sex Differences in Adverse Drug Reactions of Metformin:A Longitudinal Survey Study

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 &#x003C; 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 &#x003C; 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 &#x003C; 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

Medication beliefs, treatment complexity, and non-adherence to different drug classes in patients with type 2 diabetes

AbstractObjectiveTo assess the relationship of patients' medication beliefs and treatment complexity with unintentional and intentional non-adherence for three therapeutic groups commonly used by patients with type 2 diabetes.MethodsSurvey data about adherence (Medication Adherence Report Scale) and beliefs about medicines (Beliefs about Medicines Questionnaire) were combined with prescription data from the Groningen Initiative to ANalyse Type 2 diabetes Treatment (GIANTT) database. Patients were classified as being adherent, mainly unintentional non-adherent, or partly intentional non-adherent per therapeutic group (glucose-, blood pressure-, and lipid-lowering drugs). Treatment complexity was measured using the Medication Regimen Complexity Index, which includes the dosage form, dosing frequency and additional directions of taking the drug. Analyses were performed using Kruskal–Wallis and Mann–Whitney U-tests.ResultsOf 257 contacted patients, 133 (52%) returned the questionnaire. The patients had a mean age of 66years and 50% were females. Necessity beliefs were not significantly different between the adherers, mainly unintentional non-adherers, and partly intentional non-adherers (differences smaller than 5 points on a scale from 5 to 25). For blood pressure-lowering drugs, patients reporting intentional non-adherence had higher concern beliefs than adherers (8 point difference, P=0.01). Treatment complexity scores were lower for adherers but similar for mainly unintentional and partly intentional non-adherers to glucose- and blood pressure-lowering drugs.ConclusionTreatment complexity was related to non-adherence in general. Beliefs about necessity were not strongly associated with non-adherence, while patients' concern beliefs may be associated with intentional non-adherence. However, the role of these determinants differs per therapeutic group

Patient-Reported Adverse Events of Radiopharmaceuticals:Development and Validation of a Questionnaire

Introduction Radiopharmaceuticals may cause adverse events. Knowledge about adverse events from a patient's perspective could help healthcare professionals to detect, understand, and manage adverse events more efficiently when using radiopharmaceuticals. Researchers need a validated questionnaire that can be used in patients to assess adverse events with radiopharmaceuticals. Objective The aim of this study was to develop, validate the content of, and perform initial testing of a questionnaire assessing patient-reported adverse events of radiopharmaceuticals. Methods Based on existing literature, six professionals drafted and evaluated a first version of the questionnaire. Further content validation was performed using cognitive interviews with six patients undergoing a nuclear medicine examination. After adaptations, the questionnaire was developed into a web-based questionnaire. One hundred patients undergoing nuclear examination tested this version, and the results were used to assess its acceptability and evaluate reported adverse events. Results Questions and answer options were revised in the initial questionnaire to improve clarity. In addition, some questions were removed. The final version consisted of 18 questions. In the test phase, the acceptability of the questionnaire was demonstrated (e.g. 79% of the patients who received the questionnaire completed it, and the median time to complete the questionnaire was 12 min for patients who reported an adverse event). Of the 100 patients (53% men, median age 64 years), 12 reported a total of 22 adverse events. One of these adverse events had a high causal association. Conclusion After validation and testing, the developed questionnaire to study patient-reported adverse events of radiopharmaceuticals is a suitable and valid instrument which can be used in future research