Effects of a multicomponent communication training to involve older people in decisions to DEPRESCRIBE cardiometabolic medication in primary care (CO-DEPRESCRIBE): protocol for a cluster randomized controlled trial with embedded process and economic evaluation.

BACKGROUND: Deprescribing of medication for cardiovascular risk factors and diabetes has been incorporated in clinical guidelines but proves to be difficult to implement in primary care. Training of healthcare providers is needed to enhance deprescribing in eligible patients. This study will examine the effects of a blended training program aimed at initiating and conducting constructive deprescribing consultations with patients. METHODS: A cluster-randomized trial will be conducted in which local pharmacy-general practice teams in the Netherlands will be randomized to conducting clinical medication reviews with patients as usual (control) or after receiving the CO-DEPRESCRIBE training program (intervention). People of 75 years and older using specific cardiometabolic medication (diabetes drugs, antihypertensives, statins) and eligible for a medication review will be included. The CO-DEPRESCRIBE intervention is based on previous work and applies models for patient-centered communication and shared decision making. It consists of 5 training modules with supportive tools. The primary outcome is the percentage of patients with at least 1 cardiometabolic medication deintensified. Secondary outcomes include patient involvement in decision making, healthcare provider communication skills, health/medication-related outcomes, attitudes towards deprescribing, medication regimen complexity and health-related quality of life. Additional safety and cost parameters will be collected. It is estimated that 167 patients per study arm are needed in the final intention-to-treat analysis using a mixed effects model. Taking loss to follow-up into account, 40 teams are asked to recruit 10 patients each. A baseline and 6-months follow-up assessment, a process evaluation, and a cost-effectiveness analysis will be conducted. DISCUSSION: The hypothesis is that the training program will lead to more proactive and patient-centered deprescribing of cardiometabolic medication. By a comprehensive evaluation, an increase in knowledge needed for sustainable implementation of deprescribing in primary care is expected. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (identifier: NCT05507177).

Willingness of people with type 2 diabetes to engage in healthy eating, physical activity and medication taking.

AIM: To assess the willingness of people with type 2 diabetes (T2D) to engage in healthy eating, physical activity and medication taking, and explore associated patient factors. METHODS: Online survey among recently diagnosed T2D patients recruited in the Netherlands and the United Kingdom (UK). Patient factors included general factors and behaviour-specific beliefs. Logistic regression analyses and explorative comparisons were conducted. RESULTS: Overall, 48% of 67 patients were willing to engage in all three management options, whereas 6% were not willing to follow any of them. 73% were willing to manage T2D with healthy eating, 73% with physical activity, and 72% with medication. Country of recruitment was significantly associated with willingness for healthy eating, with higher willingness among Dutch participants. Beliefs surrounding capability, opportunity, and motivation were significantly associated with willingness to engage in physical activity and medication taking. Many beliefs were similar regardless of willingness but those willing to engage in physical activity perceived less barriers and those willing to take medication had more positive and less negative outcome beliefs than those not willing. CONCLUSIONS: Willingness to engage in all management options was limited among recently diagnosed patients, and partly associated with behaviour-specific patient beliefs.

Prescription Sequence Symmetry Analysis (PSSA) to assess prescribing cascades: a step-by-step guide.

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.

Tailoring Type II Diabetes Treatment: Investigating the Effect of 5-HTT Polymorphisms on HbA1c Levels after Metformin Initiation.

Aims: To investigate the effect of serotonin transporter (5-HTT) polymorphisms on change in HbA1c levels six months after metformin initiation in type 2 diabetes patients. Materials and Methods: Participants of PROVALID (PROspective cohort study in patients with type 2 diabetes mellitus for VALidation of biomarkers) within the GIANTT (Groningen Initiative to ANalyse Type 2 Diabetes Treatment) cohort who initiated metformin were genotyped for combined 5-HTTLPR/rs25531 (L∗L∗, L∗S∗, and S∗S∗) and 5-HTT VNTR (STin 2.12, 12/-, and 10/-) polymorphisms, respectively. Multiple linear regression was applied to determine the change in HbA1c level from baseline date to six months across 5-HTTLPR/VNTR genotype groups, adjusted for baseline HbA1c, age, gender, triglyceride level, low-density lipoprotein level, and serum creatinine. Results: 157 participants were included, of which 56.2% were male. The average age was 59.3 ± 9.23 years, and the mean baseline HbA1c was 7.49% ± 1.21%. 5-HTTLPR was characterized in 46 patients as L∗L∗, 70 patients as L∗S∗, and 41 patients as S∗S∗ genotypes. No significant association was found between 5-HTTLPR and 5-HTT VNTR genotypes and change in HbA1c after adjustments. Conclusions: 5-HTT polymorphisms did not affect HbA1c levels six months after the start of metformin. Further long-term studies in large samples would be relevant to determine which polymorphisms can explain the variation in response to metformin treatment.

Process evaluation of a pharmacist-led intervention aimed at deprescribing and appropriate use of cardiometabolic medication among adult people with type 2 diabetes.

BACKGROUND: A quasi-experimental study investigated a pharmacist-led intervention aimed at deprescribing and medication management among adult patients with type 2 diabetes at risk of hypoglycaemia. OBJECTIVE: This study aimed to evaluate the process of implementing the intervention consisting of a tailored clinical medication review (CMR) supported by a training and a toolbox. METHODS: Mixed-methods study based on the Grant framework, including the domains "recruitment," "delivery of intervention" and "response" of pharmacists and patients. Data collected were administrative logs, semi-structured observations of patient consultations (n = 8), interviews with pharmacists (n = 16) and patient-reported experience measure (PREM) questionnaires (n = 66). RESULTS: Tailored CMRs were conducted largely as intended for 90 patients from 14 pharmacies. Although patient selection based on a medication-derived hypoglycaemia risk score was considered useful, pharmacists experienced barriers to proposing deprescribing in patients with recent medication changes, without current hypoglycaemic events, or treated by medical specialists. The training and toolbox were evaluated positively by the pharmacists. Overall, patients were satisfied with the CMR. CONCLUSION: Pharmacists and patients valued the CMR focusing on deprescribing and medication management. To optimize implementation and effectiveness of the intervention, improvements can be made to the patient selection, pharmacist training and the collaboration between healthcare professionals.

Prescribing Cascades with Recommendations to Prevent or Reverse Them: A Systematic Review.

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.

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.

Community pharmacist-led interventions for patients with type 2 diabetes in low-income and middle-income countries: A scoping review.

BACKGROUND: Studies assessing community pharmacist-led interventions conducted in high-income countries indicate that community pharmacists are successful in taking opportunities to support diabetes management. It is not yet clear as to what extent this is also true for low-income and middle-income countries. OBJECTIVES: To provide an overview of the types of interventions performed by community pharmacists and available evidence about their effects on patients with type 2 diabetes mellitus in low-income and middle-income countries. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for (non) randomized controlled, before-and-after, and interrupted time series design studies. There was no restriction on publication language. Interventions to be included had to be delivered by community pharmacists in a primary care or community setting. Study quality was assessed using the National Institute of Health tools, with results analyzed qualitatively, and the review itself was conducted in accordance with guidelines for scoping reviews. RESULTS: Twenty-eight studies were included, representing 4,434 patients (mean age from 47.4 to 59.5 years, 55.4% female) from community pharmacies (16 studies), primary care centers (8 studies) or community setting (4 studies). Four studies were single-component and the remaining represented multi-component interventions. Face-to-face counseling of patients was the most common intervention, often combined with the provision of printed materials, remote consultations, or conducting medication reviews. Generally, studies showed improved outcomes in the intervention group, including clinical, patient-reported and medication safety outcomes. In most studies, at least one domain was judged to be of poor quality, with heterogeneity among studies. CONCLUSIONS: Community pharmacist-led interventions on type 2 diabetes mellitus patients showed various positive effects but the quality of the evidence was poor. Face-to-face counseling of varying intensity, often combined with other strategies and representing a multi-component intervention, was the most common type. Although these findings support the expansion of the community pharmacist's role in diabetes care in low-income and middle-income countries, better quality studies are needed to evaluate the impact of specific interventions.

Pharmacist-led intervention aimed at deprescribing and appropriate use of cardiometabolic medication among people with type 2 diabetes.

BACKGROUND: Potential overtreatment with cardiometabolic medication (i.e., glucose lowering medication, antihypertensives and statins) has been observed in 10-40% of older people with type 2 diabetes (T2D). OBJECTIVE: The potential effects of a pharmacist-led clinical medication review targeted at T2D patients who were at high risk of hypoglycaemia will be investigated. METHODS: A quasi-experimental study was conducted in 14 Dutch community pharmacies. Patients with a high risk of hypoglycaemia were identified using a previously developed algorithm. Pharmacists confirmed eligibility and selected patients for the intervention. Remaining eligible patients were included as controls receiving usual care. The primary outcome was the proportion of intervention patients for whom an action on deprescribing or appropriate use of cardiometabolic medication was implemented. After three months, changes in cardiometabolic medication were compared between the intervention and control group using a Fischer exact test. RESULTS: In total 90 intervention patients and 107 control patients were included. Intervention patients had an average age of 70, used on average 10 medications, five of which were cardiometabolic medication. For half of the intervention patients an action on deprescribing cardiometabolic medication was implemented (n = 25) and/or an advice about appropriate use of cardiometabolic medication was given (n = 22). In 48% of intervention patients at least one cardiometabolic medication (e.g. insulin, sulfonylurea, diuretic, beta-blocker, statin) was either stopped or reduced in dose compared to 31% of control patients (p = 0.018). CONCLUSIONS: A pharmacist-led tailored clinical medication review has the potential to increase deprescribing and improve appropriate use of cardiometabolic medication in half of T2D patients at high risk of hypoglycaemia.

Attitudes towards deprescribing and patient-related factors associated with willingness to stop medication among older patients with type 2 diabetes (T2D) in Indonesia: a cross-sectional survey study.

BACKGROUND: Deprescribing of preventive medication is recommended in older patients with polypharmacy, including people with type 2 diabetes (T2D). It seems that many patients in low-middle-income countries are not willing to have their medicines deprescribed. This study aims to assess attitudes of Indonesian patients with T2D towards deprescribing in general and regarding specific cardiometabolic medicines, and factors influencing their willingness to stop medicines. METHODS: Primary care patients with T2D of ≥60 years in Indonesia completed the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Attitudes in general and for cardiometabolic medicines were reported descriptively. Proportions of patients willing to stop one or more medicines when recommended by different healthcare professionals were compared with Chi-square test. Multiple regression analysis was used to analyse the influence between patient-related factors and the willingness to stop medicines. RESULTS: The survey was completed by 196 participants (median age 69 years, 73% female). The percentages willing to stop medicines were 69, 67, and 41%, when the general practitioner (GP), the specialist, or the pharmacist initiates the process (p-value < 0.001). Higher perceived burden of medicines (p-value = 0.03) and less concerns about stopping (p-value < 0.001) were associated with a higher willingness to stop medicines if proposed by the GP. Patients using multiple glucose-regulating medicines were less willing to stop (p-value = 0.02). Using complementary or alternative medicines was not associated with the willingness to stop. If proposed by their pharmacist, patients without substantial education were more willing to stop than educated patients. CONCLUSIONS: Only two-thirds of older people with T2D in Indonesia were willing to stop one or more of their medicines if the GP or specialist recommended this, and even less when the pharmacist proposed this. Attention should be given to concerns about stopping specific medicines, especially among patients using multiple glucose-lowering medicines, who may be more eligible but were less willing to accept deprescribing.

Role of Serum Lipids, Blood Glucose and Blood Pressure in Breast Cancer Risk for Women with Type 2 Diabetes Mellitus.

Purpose: Women with type 2 diabetes mellitus (T2DM) have an increased risk of breast cancer. We aimed to determine the contribution of lipids, glucose and blood pressure to this risk based on the multifactorial nature of T2DM. Patients and Methods: This population-based cohort study used data from a Dutch database (the Groningen Initiative to Analyse Type 2 Diabetes Treatment) for the period 2004-2013. The cohort included women diagnosed with T2DM, aged 30-80 years, with no history of breast cancer and with follow-up data for at least 1 year. We used Cox proportional hazards models to estimate the associations of exposures with breast cancer occurrence, reporting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Exposures of interest included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glycated hemoglobin A (HbA1c) and systolic blood pressure (SBP). Results: During a median of 4.45 years' follow-up, 183 of 10,183 included women received a breast cancer diagnosis. We observed U-shaped associations with breast cancer incidence for total cholesterol and HDL-C at baseline. Compared with moderate elevations, women had significantly higher breast cancer risks associated with high total cholesterol (aHR, 95% CI: 1.72, 1.15-2.55) and HDL-C (aHR, 95% CI: 1.74, 1.18-2.58) levels, while low total cholesterol (aHR, 95% CI: 1.43, 0.94-2.19) and HDL-C (aHR, 95% CI: 1.44, 0.95-2.17) levels produced marginal effects without significance. Women with high LDL-C levels more often received a breast cancer diagnosis than those with medium levels (aHR, 95% CI: 1.56, 1.03-2.35). Conclusion: This real-world dataset highlights the importance of balancing lipid profiles, particularly total cholesterol and HDL-C. Dysregulation of the lipid profile, not the glucose or blood pressure profiles, may increase the risk of breast cancer in women with T2DM.

Sex disparities in medication prescribing amongst patients with type 2 diabetes mellitus managed in primary care.

BACKGROUND: Sex differences in clinical outcomes have been observed for patients with type 2 diabetes mellitus (T2DM). These could be related to sex disparities in treatment. OBJECTIVES: To determine whether there are sex disparities in medication prescribing amongst patients with T2DM. METHODS: A cohort study was conducted using the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) database, which includes data from primary care patients with T2DM from the north of the Netherlands. Data on demographics, physical examinations, laboratory measurements and prescribing were extracted. A set of validated prescribing quality indicators assessing the prevalence, start, intensification and safety of glucose-, lipid-, blood pressure- and albuminuria-lowering medication was applied for the calendar year 2019. Univariate logistic regression analyses were conducted. RESULTS: We included 10,456 patients (47% females). Females were less often treated with metformin (81.7% vs. 86.5%; OR 0.70, 95% CI 0.61-0.80), and were less often prescribed a renin-angiotensin-aldosterone inhibitor (RAAS-i) when treated with multiple blood pressure-lowering medicines (81.9% vs. 89.3%; OR 0.55, 95% CI 0.46-0.64) or when having albuminuria (74.7% vs. 82.1%; OR 0.64, 95% CI 0.49-0.85) than males. Statin treatment was less frequently started (19.7% vs. 24.7%; OR 0.75, 95% CI 0.58-0.96) and prescribed (58.7% vs. 63.9%; OR 0.80, 95% CI 0.73-0.89) in females. There were no differences in starting and intensifying glucose-, blood pressure- and albuminuria-lowering medication. CONCLUSIONS: Sex disparities in medication prescribing amongst T2DM patients were seen, including less starting with statins and potential undertreatment with RAAS-i in females. Such disparities may partly explain higher excess risks for cardiovascular and renal complications associated with diabetes observed in females.

Factors Influencing Preferences and Responses Towards Drug Safety Communications: A Conjoint Experiment Among Hospital-Based Healthcare Professionals in the Netherlands.

INTRODUCTION: Healthcare professionals (HCPs) are informed about new drug safety issues through Direct Healthcare Professional Communications (DHPCs). The influence of DHPC content on the impact of the communication is unclear. OBJECTIVES: The aim of this study was to assess the effect of content elements 'frequency of the safety issue', 'seriousness of the safety issue', 'need to take action', 'life span of drug involved' and 'type of evidence supporting the safety issue' on hospital-based HCPs' preferences and responses towards DHPCs. METHODS: A survey study including a conjoint experiment was performed among hospital-based HCPs in the Netherlands. Hypothetical DHPCs varying on the five content elements were constructed. Each respondent received eight out of 16 hypothetical DHPCs and was asked about (1) importance to be informed (fixed-point scale), (2) preferred communication timing (multiple options) and (3) their stated actions (multiple options). Associations were tested using generalized linear mixed models. RESULTS: In total, 178 HCPs participated. DHPCs concerning more frequent or serious safety issues, or requiring action, were associated with a higher perceived importance to be informed and a preference for immediate communication. Periodic communication was preferred for DPHCs concerning less frequent or serious safety issues. The most commonly stated action was to discuss the DHPC with colleagues. Monitoring was common when this was recommended. High frequency and seriousness were associated with more prescribing-related actions. CONCLUSION: Frequency and seriousness of the safety issue and the recommended action are likely to influence the impact of DHPCs. The timing of communication could be tailored depending on the content, where less urgent safety issues might be communicated periodically.

Less Timely Initiation of Glucose-Lowering Medication Among Younger and Male Patients With Diabetes and Similar Initiation of Blood Pressure-Lowering Medication Across Age and Sex: Trends Between 2015 and 2020.

Aims: We aimed to assess trends in glycosylated hemoglobin A1c (HbA1c) and systolic blood pressure (SBP) thresholds at initiation of glucose- and blood pressure-lowering medication among patients with type 2 diabetes and assess the influence of age and sex on these trends. Materials and Methods: We used the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) primary care database. Patients initiating a first non-insulin glucose-lowering or any blood pressure-lowering medication between 2015 and 2020 with an HbA1c or SBP measurement in the 120 days before initiation were included. We used multilevel regression analyses adjusted for potential confounders to assess the influence of calendar year, age or sex, and the interaction between calendar year and age or sex on trends in HbA1c and SBP thresholds at initiation of medication. Results: We included 2,671 and 2,128 patients in the analyses of HbA1c and SBP thresholds, respectively. The overall mean HbA1c threshold at initiation of glucose-lowering medication significantly increased from 7.4% in 2015 to 8.0% in 2020 (p < 0.001), and particularly in the younger age groups. Compared to patients ≥80 years, patients aged 60-69 years initiated medication at lower levels mainly in the early years. Patients <60 years and between 70-79 years initiated medication at similar levels as patients ≥80 years. Females initiated medication at lower levels than males throughout the study period (p < 0.001). The mean SBP threshold at initiation of blood pressure-lowering medication varied from 145 to 149 mmHg without a clear trend (p = 0.676). There were no differences in SBP thresholds between patients of different ages or sex. Conclusion: The rising trend in the HbA1c threshold for initiating glucose-lowering medication in the lower age groups was unexpected and requires further investigation. Males appear to receive less timely initiation of glucose-lowering medication than females. The lack of higher thresholds for the oldest age group or lower thresholds for the youngest age group in recent years is not in line with the age-related recommendations for personalized diabetes care and calls for health systems interventions.

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

Aims: The LEADER trial demonstrated that the glucagon-like peptide-1 receptor agonist (GLP1-RA) liraglutide reduces kidney and cardiovascular (CV) risk in patients with type 2 diabetes. We previously developed a Parameter Response Efficacy (PRE) score that translates multiple short-term risk marker changes, from baseline to first available follow-up measurement, into a predicted long-term drug effect on clinical outcomes. The objective of this study was to assess the accuracy of the PRE score in predicting the efficacy of liraglutide in reducing the risk of kidney and CV outcomes. Methods: Short-term changes in glycated hemoglobin (HbA1c), systolic blood pressure (BP), urinary-albumin-creatinine-ratio (UACR), hemoglobin, body weight, high-density-lipoprotein (HDL) cholesterol, low-density-lipoprotein (LDL) cholesterol, and potassium were monitored in the LEADER trial. Associations between risk markers and kidney or CV outcomes were established using a multivariable Cox proportional hazards model in a separate pooled database of 6,355 patients with type 2 diabetes. The regression coefficients were then applied to the short-term risk markers in the LEADER trial to predict the effects of liraglutide on kidney (defined as a composite of doubling of serum creatinine or end-stage kidney disease) and CV (defined as a composite of non-fatal myocardial infarction, non-fatal stroke, and CV death) outcomes. Results: Liraglutide compared to placebo reduced HbA1c (1.4%), systolic BP (3.0 mmHg), UACR (13.2%), body weight (2.3 kg), hemoglobin (2.6 g/L), and increased HDL-cholesterol (0.01 mmol/L) (all p-values <0.01). Integrating multiple risk marker changes in the PRE score resulted in a predicted relative risk reduction (RRR) of 16.2% (95% CI 13.7-18.6) on kidney outcomes which was close to the observed RRR of 15.5% (95% CI -9.0-34.6). For the CV outcome, the PRE score predicted a 7.6% (95% CI 6.8-8.3) RRR, which was less than the observed 13.2% (95% CI 3.2-22.2) RRR. Conclusion: Integrating multiple short-term risk markers using the PRE score adequately predicted the effect of liraglutide on the composite kidney outcome. However, the PRE score underestimated the effect of liraglutide for the composite CV outcome, suggesting that the risk markers included in the PRE score do not fully capture the CV benefit of liraglutide.

Handling of New Drug Safety Information in the Dutch Hospital Setting: A Mixed Methods Approach.

INTRODUCTION: The implementation of new drug safety information and Direct Healthcare Professional Communications (DHPCs) in hospitals is important for patient safety. OBJECTIVES: The aim of this study was to gain insight into which procedures and practices are in place to handle new drug safety information and particularly DHPCs in the Dutch hospital setting. METHODS: We first conducted focus groups including medical specialists and hospital pharmacists, focusing on handling of drug safety information at the individual and organisational level. A survey was then developed and distributed among hospital pharmacists in all Dutch hospitals to quantify the existence of specific procedures and committees to handle drug safety information and DHPCs. RESULTS: Eleven specialists and 14 pharmacists from six hospitals participated in focus groups. Drug safety information was usually considered before drugs were included in formularies or treatment protocols. Furthermore, drug safety information was consulted in response to patients experiencing adverse events. DHPCs were mostly dealt with by individual professionals. DHPCs could lead to actions but this was very uncommon. Completed surveys were received from 40 (53%) of the hospitals. In 32 (80%), the hospital pharmacy had procedures to deal with new drug safety information, whereas in 11 (28%) a hospital-wide procedure was in place. Drug safety was considered in committees concerning drug formulary decisions (69%) and antibiotic policies (63%). DHPCs were assessed by a hospital pharmacist in 50% of the hospitals. CONCLUSIONS: Drug safety information was used for evaluation of new treatments and in response to adverse events. Assessment of whether a DHPC requires action was primarily an individual task.

Differences in Older Patients' Attitudes Toward Deprescribing at Contextual and Individual Level.

BACKGROUND: Deprescribing requires patients' involvement and taking patients' attitudes toward deprescribing into account. To understand the observed variation in these attitudes, the influence of contextual-level factors, such as country or healthcare setting, should be taken into account. METHODS: We conducted a systematic review of studies using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire among older adults. We searched articles in Medline and Embase up to 30 June 2021. PRISMA guideline was used for the search process and reporting. We summarized the outcomes from the rPATD and compared attitudes at study population level between high or low-middle-income countries, global regions, and healthcare settings using ANOVA testing. Correlations of the rPATD outcomes with the mean age of the study populations were tested. Associations with the rPATD outcomes at individual patient level extracted from the included studies were summarized. RESULTS: Sixteen articles were included. Percentages of patients willing to stop medication were significantly lower in low-middle-income countries (<70% in Nepal and Malaysia) compared to high-income countries (>85% in USA, Australia, European countries). No significant differences were observed when results were compared by global region or by healthcare setting but a high willingness (>95%) was seen in the two studies conducted in an inpatient population. A higher mean age at study level was associated with a higher willingness to stop medication. At individual level, associations between patient characteristics, including demographics and education, and attitudes toward deprescribing showed inconsistent results. CONCLUSION: Findings about attitudes toward deprescribing are influenced by contextual factors. Future research should pay more attention to the influence of the healthcare system and setting as well as the culture on patients' attitudes.

Barriers and Enablers of Healthcare Providers to Deprescribe Cardiometabolic Medication in Older Patients: A Focus Group Study.

INTRODUCTION: Benefits and risks of preventive medication change over time for ageing patients and deprescribing of medication may be needed. Deprescribing of cardiovascular and antidiabetic drugs can be challenging and is not widely implemented in daily practice. OBJECTIVE: The aim of this study was to identify barriers and enablers of deprescribing cardiometabolic medication as seen by healthcare providers (HCPs) of different disciplines, and to explore their views on their specific roles in the process of deprescribing. METHODS: Three focus groups with five general practitioners, eight pharmacists, three nurse practitioners, two geriatricians, and two elder care physicians were conducted in three cities in The Netherlands. Interviews were recorded and transcribed verbatim. Directed content analysis was performed on the basis of the Theoretical Domains Framework. Two researchers independently coded the data. RESULTS: Most HCPs agreed that deprescribing of cardiometabolic medication is relevant but that barriers include lack of evidence and expertise, negative beliefs and fears, poor communication and collaboration between HCPs, and lack of resources. Having a guideline was considered an enabler for the process of deprescribing of cardiometabolic medication. Some HCPs feared the consequences of discontinuing cardiovascular or antidiabetic medication, while others were not motivated to deprescribe when the patients experienced no problems with their medication. HCPs of all disciplines stated that adequate patient communication and involving the patients and relatives in the decision making enables deprescribing. Barriers to deprescribing included the use of medication initiated by specialists, the poor exchange of information, and the amount of time it takes to deprescribe cardiometabolic medication. The HCPs were uncertain about each other's roles and responsibilities. A multidisciplinary approach including the pharmacist and nurse practitioner was seen as the best way to support the process of deprescribing and address barriers related to resources. CONCLUSION: HCPs recognized the importance of deprescribing cardiometabolic medication as a medical decision that can only be made in close cooperation with the patient. To successfully accomplish the process of deprescribing they strongly recommended a multidisciplinary approach.