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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]

Background: Individualizing goals for people with type 2 diabetes may result in deintensification of medication, but a comprehensive picture of deprescribing practices is lacking. Aims: To conduct a scoping review in order to assess the rates, determinants and success of implementing deprescribing of glucose‐, blood pressure‐ or lipid‐lowering medications in people with diabetes. Methods: A systematic search on MEDLINE and Embase between January 2007 and January 2019 was carried out for deprescribing studies among people with diabetes. Outcomes were rates of deprescribing related to participant characteristics, the determinants and success of deprescribing, and its implementation. Critical appraisal was conducted using predefined tools. Results: Fourteen studies were included; eight reported on rates, nine on determinants and six on success and implementation. Bias was high for studies on success of deprescribing. Deprescribing rates ranged from 14% to 27% in older people with low HbA1c levels, and from 16% to 19% in older people with low systolic blood pressure. Rates were not much affected by age, gender, frailty or life expectancy. Rates were higher when a reminder system was used to identify people with hypoglycaemia, which led to less overtreatment and fewer hypoglycaemic events. Most healthcare professionals accepted the concept of deprescribing but differed on when to conduct it. Deprescribing glucose‐lowering medications could be successfully conducted in 62% to 75% of participants with small rises in HbA1c. Conclusions: Deprescribing of glucose‐lowering medications seems feasible and acceptable, but was not widely implemented in the covered period. Support systems may enhance deprescribing. More studies on deprescribing blood pressure‐ and lipid‐lowering medications in people with diabetes are needed. [ABSTRACT FROM AUTHOR]

Background: Increasingly, genetic analyses are conducted using information from subjects with established disease, who often receive concomitant treatment. We determined when treatment may bias genetic associations with a quantitative trait. Methods: Graph theory and simulated data were used to explore the impact of drug prescriptions on (longitudinal) genetic effect estimates. Analytic derivations of longitudinal genetic effects are presented, accounting for the following scenarios: 1) treatment allocated independently of a genetic variant, 2) treatment that mediates the genetic effect, 3) treatment that modifies the genetic effect. We additionally evaluate treatment modelling strategies on bias, the root mean squared error (RMSE), coverage, and rejection rate. Results: We show that in the absence of treatment by gene effect modification or mediation, genetic effect estimates will be unbiased. In simulated data we found that conditional models accounting for treatment, confounding, and effect modification were generally unbiased with appropriate levels of confidence interval coverage. Ignoring the longitudinal nature of treatment prescription, however (e.g. because of incomplete records in longitudinal data), biased these conditional models to a similar degree (or worse) as simply ignoring treatment. Conclusion: The mere presence of (drug) treatment affecting a GWAS phenotype is insufficient to bias genetic associations with quantitative traits. While treatment may bias associations through effect modification and mediation, this might not occur frequently enough to warrant general concern at the presence of treated subjects in GWAS. Should treatment by gene effect modification or mediation be present however, current GWAS approaches attempting to adjust for treatment insufficiently account for the multivariable and longitudinal nature of treatment trajectories and hence genetic estimates may still be biased. [ABSTRACT FROM AUTHOR]

Background. Quality assessment is a key element for improving the quality of care. Currently, a comprehensive indicator set for measuring the quality of medication treatment in patients with chronic kidney disease (CKD) is lacking. Our aim was to develop and validate a set of prescribing quality indicators (PQIs) for CKD care, and to test the feasibility of applying this set in practice. Methods. Potential indicators were based on clinical practice guidelines and evaluated using the RAND/UCLA Appropriateness Method. This is a structured process in which an expert panel assesses the validity of the indicators. Feasibility was tested in a Dutch primary care database including >4500 diabetes patients with CKD. Results. An initial list of 22 PQIs was assessed by 12 experts. After changing 10 PQIs, adding 2 and rejecting 8, a final list of 16 indicators was accepted by the expert panel as valid. These PQIs focused on the treatment of hypertension, albuminuria, mineral and bone disorder, statin prescribing and possible unsafe medication. The indicators were successfully applied to measure treatment quality in the primary care database, but for some indicators the number of eligible patients was too small for reliable calculation. Results showed that there was room for improvement in the treatment quality of this population. Conclusions. We developed a set of 16 PQIs for measuring the quality of treatment in CKD patients, which had sufficient content and face validity as well as operational feasibility. These PQIs can be used to point out priority areas for improvement. [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]

Prescribing quality assessment is increasingly used in improvement programs and pay-for-performance policies. Within the area of diabetes many quality indicators have been developed. Some measure prescribing on a general level, e.g. calculating percentages of patients prescribed any statins. Others are very specific, e.g. percentages of patients with an elevated LDL-cholesterol in whom lipid-lowering treatment is started unless contraindicated or return to control within 3 months. Although the latter seems more precise, we question how far one should go in developing such indicators. Using the example of diabetes treatment, we highlight the need, opportunities, and feasibility of assessing prescribing quality in the context of individualised treatment. We conclude that it is not realistic to develop indicators that take all possible aspects of therapy non-respons, intolerance and patient preferences into account. We do recommend further development of indicators that better address subpopulations in need of adjusted treatment, such as elderly or patients with comorbidity. [ABSTRACT FROM AUTHOR]

Abstract: Results of studies conducted 10–20 years ago show the prominence of commercial information sources in the adoption process of new drugs. Over the past decade, there has been a growing emphasis on practicing evidence-based medicine in drug prescribing. This raises the question whether professional information sources currently counterbalance the influence of commercial information sources in the adoption process. The aim of this study was to identify determinants influencing the adoption of a new drug class, the angiotensin II receptor blockers (ARBs), by general practitioners (GPs) in The Netherlands. A retrospective study was conducted to assess prevalent ARB prescribing for hypertensive patients using the Integrated Primary Care Information (IPCI) database. We conducted a survey among all GPs who participated in the IPCI project in 2003 to assess their exposure to commercial and professional information sources, perceived benefits and risks of ARBs, perceived influences of the professional network, and general characteristics. Multilevel logistic regression was applied to identify determinants of ARB adoption while adjusting for patient characteristics. Data were obtained from 70 GPs and 9470 treated hypertensive patients. A total of 1093 patients received ARBs (12%). GPs who reported frequent use of commercial information sources were more likely to prescribe ARBs routinely in preference to other antihypertensives, whereas GPs who used a prescribing decision support system and those who were involved in pharmacotherapy education were less likely to prescribe ARBs. Other factors that were associated with higher levels of ARB adoption included a more positive perception of ARBs regarding their effectiveness in lowering blood pressure, and working in single-handed practices or in rural areas. Aside from determinants related to the patient population, adoption of a new drug class among Dutch GPs is still determined more by their reliance on promotional information than by their use of professional information sources. [Copyright &y& Elsevier]

Aims The aim of this study was to investigate the impact of new insights and revised guidelines on initial and follow-up treatment with antihyperglycaemic drugs over the period 1998–2003. Methods The InterAction Database (IADB), which contains pharmacy dispensing data from 53 community pharmacies in the Northern and Eastern part of the Netherlands, was used in this study. Prevalence and incidence rates of oral antihyperglycaemic drug use were calculated for each year. Follow-up treatment was compared for two cohorts of initial users of oral antihyperglycaemic drugs, starting treatment either 1 year before or 1 year after guideline revision. Results The prevalence and incidence rate of oral antihyperglycaemic drug use increased over the study period from 1.8% to 2.4% ( P < 0.001) and 0.3% to 0.4% ( P = 0.04). The proportion of metformin as initial treatment increased rapidly in the observation period from 14% to 50% ( P < 0.001). Initial users of metformin in 2000 received additional treatment with a sulphonylurea in the follow-up period less often compared with those who started metformin in 1998 (46% vs. 60%, P < 0.004). In contrast, initial users of sulphonylurea in 2000 received additional treatment with metformin more often compared with those who started a sulphonylurea in 1998 (42% vs. 36%, P < 0.008). The new drugs, thiazolidinediones and meglitinides, were seldom used as initial treatment Conclusions New insights and the revision of the practice guideline were followed by a significant increase in both initial and follow-up treatment with metformin among patients with Type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to determine to what extent barriers perceived by general practitioners (GPs) for prescribing angiotensin-converting enzyme inhibitors (ACE-I) in chronic heart failure (CHF) patients are related to underuse and underdosing of these drugs in actual practice. Methods: Barriers were assessed with a semi-structured questionnaire. Prescribing data were extracted from GPs' computerised medical records for a random sample of their CHF patients. Relations between barriers and prescribing behaviour were assessed by means of Spearman rank correlation and multivariate regression modelling. Results: GPs prescribed ACE-I to 45% of their patients and had previously initiated such treatment in an additional 3.5%, in an average standardised dose of 13.5 mg. They perceived a median of four barriers in prescribing ACE-I or optimising ACE-I dose. Many GPs found it difficult to change treatment initiated by a cardiologist. Furthermore, initiating ACE-I in patients already using a diuretic or stable on their current medication was perceived as barrier. Titrating the ACE-I dose was seen as difficult by more than half of the GPs. No significant relationships could be found between the barriers perceived and actual ACE-I prescribing. Regarding ACE-I dosing, the few GPs who did not agree that the ACE-I should be as high as possible prescribed higher ACE-I doses. Conclusion: Variation between GPs in prescribing ACE-I for CHF cannot be explained by differences in the barriers they perceive. Tailor-made interventions targeting only those doctors that perceive a specific barrier will therefore not be an efficient approach to improve quality of care. [ABSTRACT FROM AUTHOR]

Background Many initiatives are taken to improve prescribing decisions. Educational strategies for doctors have been effective in at least 50% of cases. Some reflection on one's own performance seems to be a common feature of the most effective strategies. So far, such reflections have mainly focused on the observed outcomes of the doctors' decisions, i.e. on what doctors do in practice. Studies in other fields have shown that another form of feedback based on the analysis of judgements may be useful as well. Objectives The objectives of the study were to discuss the principles underlying clinical judgement analysis, give examples of its use in the medical context, and discuss its potential for improving prescribing decisions. Results Clinical judgement analysis can look behind the outcome of a decision to the underlying decision process. Carefully constructed or selected case material is required for this analysis. Combining feedback on outcomes with feedback based on clinical judgement analysis offers doctors insight both in what they do, and why or when they do it. It may reveal determinants of decision making which are not available through unaided introspection. Interventions using this combination of feedback for improving doctors' prescribing behaviour have been (partly) successful in 4 cases and unsuccessful in one case. Conclusions Clinical judgement analysis gives doctors a structured reflection on the decision-making policy, and can help them to improve their future decisions. It may be especially useful for groups of doctors who try to work towards a consensus policy. The approach is not very helpful when simple decision rules are appropriate. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the use of prescribing quality indicators (PQI) in patients with type 2 diabetes based on the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The variables used in the PQI include prescribing of glucose-lowering drugs, statins, antihypertensives and renin-angiotensin-aldosterone system (RAAS) blockers. Other factors considered are low-density lipoprotein (LDL) cholesterol, systolic blood pressure (SBP) and blood glucose.