Mining treatment patterns of glucose-lowering medications for type 2 diabetes in the Netherlands

Rationale and objectives Different classes of glucose-lowering medications are used for patients with type 2 diabetes mellitus (T2DM) management. It is unclear how often these medications are prescribed in clinical practice. In this study, we aimed to describe treatment patterns of glucose-lowering medications in patients with T2DM in the Netherlands. Methods We studied a cohort of 73 819 patients with T2DM, aged ≥45 years with a first prescription for oral glucose-lowering medication between 2011 and 2017. We used the NControl database with dispensing data from 800 pharmacies in the Netherlands. Prevalence of each glucose-lowering medication class during 6 years after the index date was calculated. Using SQL Server, we identified stepwise patterns of medication prescription in this population. Findings During the study period, prevalence of biguanides (BIGU) decreased from 95.6% to 80.8% and use of sulfonylureas (SU) increased from 27.3% to 42.3%. 55.2% of all patient

Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort: The ABIDE project

Introduction The objective of this study was to assess the usefulness of the appropriate use criteria (AUC) for amyloid imaging in an unselected cohort. Methods We calculated sensitivity and specificity of appropriate use (increased confidence and management change), as defined by Amyloid Imaging Taskforce in the AUC, and other clinical utility outcomes. Furthermore, we compared differences in post–positron emission tomography diagnosis and management change between “AUC-consistent” and “AUC-inconsistent” patients. Results Almost half (250/507) of patients were AUC-consistent. In both AUC-consistent and AUC-inconsistent patients, post–positron emission tomography diagnosis (28%–21%) and management (32%–17%) change was substantial. The Amyloid Imaging Taskforce's definition of appropriate use occurred in 55/507 (13%) patients, detected by the AUC with a sensitivity of 93%, and a specificity of 56%. Diagnostic changes occurred independently of AUC status (sensitivity: 57%, specificity: 53%). Discussion The current AUC are not sufficiently able to discriminate between patients who will benefit from amyloid positron emission tomography and those who will not

Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design.

INTRODUCTION: The Alzheimer's biomarkers in daily practice (ABIDE) project is designed to translate knowledge on diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI). METHODS: ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods. RESULTS: Based on retrospective data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient-clinician conversations. DISCUSSION: Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their results

Noacs replace VKA as preferred oral anticoagulant among new patients

Background: In 2012, around 400,000 patients in the Netherlands were treated with vitamin K antagonists (VKA) for thromboembolic diseases. Since 2011, non-VKA oral anticoagulants (NOACs) have been available. NOACs do not require frequent INR monitoring and cause less bleeding, which benefits patients, but also imposes a risk of reduced therapy adherence. Objectives: The objective of this study is to describe uptake of and patient compliance with NOACs in The Netherlands between July 2011 and October 2016. Methods: We analysed prescription data for 247.927 NOAC and/or VKA patients across 560 pharmacies. All patients who received at least one prescription of either VKA or NOACs between 1 July 2011 and 30 September 2016 were included in the study. Our database contained (not exhaustive) the following information about the prescriptions: dispensed medication and quantity, dispensing date, prescribed dosage and prescriber type, patient age and gender. We used these data to describe patient profiles, uptake of NOACs among new naïve patients and switch of patients between VKA and NOACs. We developed an algorithm to classify patients as new naïve starters, switcher or repeat patients. We calculated therapy compliance as the percentage of days covered (PDC). To obtain reliable results, in our PDC calculations we included only patients with a time period of at least 12 months between their first and last prescription. Results: During the studied period the share of NOACs in oral anticoagulants has grown to 57% of prescriptions to new patients. More than 70% of new NOAC users were new naïve patients and around 26% switched from VKA. The overall share of NOACs among starters is largest in the group of patients of 50-80 years. Calculated percentages of days covered (PDC) for NOAC patients show that 87% of all users were compliant. Conclusions: NOACs have overtaken VKA as the major treatment prescribed to patients starting on oral anticoagulants, and the number of starters on VKA is at present decreasing. We expect that almost all oral anticoagulants prescribed to new patients will be NOACs. NOAC users are in general compliant with therapy. This may provide additional confidence to physicians in prescribing NOACs instead of VKAs

Risk communication in a patient decision aid for radiotherapy in breast cancer:How to deal with uncertainty?

Background and aim: Patient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy. Methods: Firstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise. Results: Consensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible sideeffects were explained using verbal labels. Conclusions: We developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801)

A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome

BACKGROUND. Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve synergistic effects. METHODS. This 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab. RESULTS. Overall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20+ B cells and a greater and more sustained depletion of peripheral CD19+ B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren's syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo. CONCLUSION. The safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes

A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome

BACKGROUND: Primary Sjögren’s syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20(+) B cells. Combined, these 2 mechanisms may achieve synergistic effects. METHODS: This 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab. RESULTS: Overall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20(+) B cells and a greater and more sustained depletion of peripheral CD19(+) B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren’s syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo. CONCLUSION: The safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02631538. FUNDING: Funding was provided by GSK

Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study

Background Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models—a demographics model, a hippocampal volume model, and a CSF biomarkers model—by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework. Findings We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59–0·65), validated hippocampal volume model (0·67, 0·62–0·72), and updated CSF biomarkers model (0·72, 0·68–0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71–0·76). Interpretation We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour