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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: In primary care, identifying patients with type 2 diabetes (T2D) who are at increased risk of hypoglycaemia is important for the prevention of hypoglycaemic events. We aimed to develop a screening tool based on machine learning to identify such patients using routinely available demographic and medication data. Methods: We used a cohort study design and the Groningen Initiative to ANalyse Type 2 diabetes Treatment (GIANTT) medical record database to develop models for hypoglycaemia risk. The first hypoglycaemic event in the observation period (2007–2013) was the outcome. Demographic and medication data were used as predictor variables to train machine learning models. The performance of the models was compared with a model using additional clinical data using fivefold cross validation with the area under the receiver operator characteristic curve (AUC) as a metric. Results: We included 13,876 T2D patients. The best performing model including only demographic and medication data was logistic regression with least absolute shrinkage and selection operator, with an AUC of 0.71. Ten variables were included (odds ratio): male gender (0.997), age (0.990), total drug count (1.012), glucose‐lowering drug count (1.039), sulfonylurea use (1.62), insulin use (1.769), pre‐mixed insulin use (1.109), insulin count (1.827), insulin duration (1.193), and antidepressant use (1.05). The proposed model obtained a similar performance to the model using additional clinical data. Conclusion: Using demographic and medication data, a model for identifying patients at increased risk of hypoglycaemia was developed using machine learning. This model can be used as a tool in primary care to screen for patients with T2D who may need additional attention to prevent or reduce hypoglycaemic events. [ABSTRACT FROM AUTHOR]

Aims: Polypharmacy is common in people with diabetes and is associated with the use of potentially inappropriate medication (PIM). This study aimed to assess trends in the prevalence of polypharmacy and PIM in older and middle‐aged people with diabetes. Methods: A repeated cross‐sectional study using the University Groningen IADB.nl prescription database was conducted. All people aged 45 years and over who were treated for diabetes registered in the period 2012–2016 were included. Polypharmacy was assessed for three age groups. PIMs were assessed using Beers criteria for people ≥65 years old, and PRescribing Optimally in Middle‐aged People's Treatments (PROMPT) criteria for 45–64 years old. Chi‐square tests and regression analysis were applied. Results: The prevalence of polypharmacy increased significantly in all age groups in the study period. In 2016, the prevalence of polypharmacy was 36.9% in patients aged 45–54 years, 50.3% in those aged 55–64 years, and 66.2% in those aged ≥65 years. The prevalence of older people with at least one PIM decreased by 3.1%, while in the middle‐aged group this prevalence increased by 0.9% from 2012 to 2016. The most common PIMs in both age groups were the use of long‐term high‐dose proton pump inhibitors, benzodiazepines and strong opioids without laxatives. Of those, only benzodiazepines showed a decreasing trend. Conclusions: Polypharmacy increased in older and middle‐aged people with diabetes. While the prevalence of PIM decreased over time in older age, this trend was not observed in middle‐aged people with diabetes. Efforts are needed to decrease the use of PIMs in populations already burdened with many drugs, notably at middle age. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of a targeted and tailored pharmacist‐led intervention among patients with type 2 diabetes (T2DM) who are nonadherent to antihypertensive drugs. Methods: A cluster‐randomised controlled trial was conducted in 10 community health centres (CHCs) in Indonesia among T2DM patients aged ≥18 years who reported nonadherence to antihypertensive drugs according to the Medication Adherence Report Scale (MARS‐5). Patients in CHCs randomised to the intervention group received a tailored intervention based on their adherence barriers (eg, forgetfulness, lack of knowledge, lack of motivation and/or other drug‐related problems) using a simple question‐based flowchart at baseline and 1‐month follow‐up. Patients in control CHCs received usual care. Primary outcome was the between‐group difference in change in MARS‐5 score from baseline to 3‐month follow‐up. Secondary outcomes included changes in patients' blood pressure and their medication beliefs. Differences in difference in primary and secondary outcomes between groups were assessed using general linear models. Results: In total, 201 patients were screened for eligibility, 113 met the inclusion criteria and participated, and 89 (79%) patients had complete follow‐up. Forgetfulness (42%) and lack of knowledge (18%) were the most common adherence barriers identified at baseline. The intervention improved medication adherence by 4.62 points on the MARS‐5 scale (95% CI 0.93 to 8.34, P value = 0.008). There were no significant changes in blood pressure levels and beliefs about antihypertensive drugs. Conclusion: A tailored low‐cost pharmacist‐led intervention aimed at nonadherent T2DM patients resulted in an improvement in medication adherence to antihypertensive drugs. There were no significant changes in secondary outcomes. [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]

Aims: Less strict glycated hemoglobin (HbA1c) thresholds have been recommended in older and/or frail type 2 diabetes (T2D) patients than in younger and less frail patients for initiating hypoglycemic agents since 2011. We aimed to assess trends in HbA1c thresholds at initiation of a first hypoglycemic agent(s) in T2D patients and the influence of age and frailty on these trends. Materials and methods: The groningen initiative to analyze type 2 diabetes treatment (GIANTT) database was used, which includes primary care T2D patients from the north of the Netherlands. Patients initiating a first non‐insulin hypoglycemic agent(s) between 2008 and 2014 with an HbA1c measurement within 120 days before initiation were included. The influence of calendar year, age, or frailty and the interaction between calendar year and age or frailty were assessed using multilevel regression analyses adjusted for confounders. Results: We included 4588 patients. The mean HbA1c threshold at treatment initiation was 7.4% up to 2010, decreasing to 7.1% in 2011 and increasing to 7.4% in 2014. This quadratic change over the years was significant (P < 0.001). Patients aged 60 to 79 initiated treatments at lower HbA1c and patients of different frailty at similar HbA1c levels. The interaction between year and age or frailty was not significant (P > 0.05). Conclusions: HbA1c thresholds at initiation of a first hypoglycemic agent(s) changed significantly over time, showing a decrease after 2010 and an increase after 2012. The HbA1c threshold at initiation was not influenced by age or frailty, which is in contrast with recommendations for more personalized treatment. [ABSTRACT FROM AUTHOR]

Aim: To assess the potential of supervised machine‐learning techniques to identify clinical variables for predicting short‐term and long‐term glycated haemoglobin (HbA1c) response after insulin treatment initiation in patients with type 2 diabetes mellitus (T2DM). Materials and methods: We included patients with T2DM from the Groningen Initiative to Analyse Type 2 diabetes Treatment (GIANTT) database who started insulin treatment between 2007 and 2013 and had a minimum follow‐up of 2 years. Short‐ and long‐term responses at 6 (±2) and 24 (±2) months after insulin initiation, respectively, were assessed. Patients were defined as good responders if they had a decrease in HbA1c ≥ 5 mmol/mol or reached the recommended level of HbA1c ≤ 53 mmol/mol. Twenty‐four baseline clinical variables were used for the analysis and an elastic net regularization technique was used for variable selection. The performance of three traditional machine‐learning algorithms was compared for the prediction of short‐ and long‐term responses and the area under the receiver‐operating characteristic curve (AUC) was used to assess the performance of the prediction models. Results: The elastic net regularization‐based generalized linear model, which included baseline HbA1c and estimated glomerular filtration rate, correctly classified short‐ and long‐term HbA1c response after treatment initiation, with AUCs of 0.80 (95% CI 0.78–0.83) and 0.81 (95% CI 0.79–0.84), respectively, and outperformed the other machine‐learning algorithms. Using baseline HbA1c alone, an AUC = 0.71 (95% CI 0.65–0.73) and 0.72 (95% CI 0.66–0.75) was obtained for predicting short‐term and long‐term response, respectively. Conclusions: Machine‐learning algorithm performed well in the prediction of an individual's short‐term and long‐term HbA1c response using baseline clinical variables. [ABSTRACT FROM AUTHOR]

Aim: To explore the added value of diabetes‐related genetic risk scores (GRSs) to readily available clinical variables in the prediction of glycated haemoglobin (HbA1c) levels after initiation of glucose‐regulating drugs. Materials and methods: We conducted a cohort study in people with type 2 diabetes (T2DM) from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database who initiated metformin (MET) or sulphonylurea derivatives (SUs) and for whom blood samples were genotyped. The primary outcome was HbA1c level at 6 months, adjusted for baseline HbA1c. GRSs were based on single nucleotide polymorphisms linked to insulin sensitivity, β‐cell activity, and T2DM risk in general. Associations were analysed using multiple linear regression to assess whether adding the GRSs increased the explained variance in a prediction model that included age, gender, diabetes duration and cardio‐metabolic biomarkers. Results: We included 282 patients initiating MET and 89 patients initiating SUs. In the MET prediction model, diabetes duration of >3 months when starting MET was associated with 2.7‐mmol/mol higher HbA1c level. For SUs, no significant clinical predictors were identified. Addition of the GRS linked to insulin sensitivity (for MET), β‐cell activity (for SUs) and T2DM risk (for both) to the models did not improve the explained variance significantly (22% without vs. 22% with GRS) for the MET and (14% without vs. 14% with GRS) for the SUs model, respectively. Conclusion: This study did not indicate a significant effect of GRS related to T2DM in general or to the drugs' mechanism of action for prediction of inter‐individual HbA1c variability in the short term after initiation of MET or SU therapy. [ABSTRACT FROM AUTHOR]

Purpose Little is known about adverse drug events (ADEs) experienced over time during chronic drug use. The purpose of this study was to assess ADE patterns experienced by patients with diabetes. Methods: Patients who received an oral glucose‐lowering drug completed a daily diary for 13 weeks. The diary asked for experienced symptoms and whether patients related these symptoms to any drug they used. Summaries of Product Characteristics were used to check whether the ADEs were known adverse drug reactions (ADRs) of the drugs used. Patterns of weekly occurring ADEs were assessed with descriptive statistics. Results: We included 78 patients. Almost half of them reported at least one ADE (N = 36; 46%). In total, 80 ADEs were reported. Of these ADEs, 71 (90%) were known ADRs. ADEs lasted less than 1 week in 27 cases (34%) and between 2 and 12 weeks in 15 cases (19%). The remaining ADEs fluctuated (16 cases; 20%) or persisted (22 cases; 28%) during the entire study period. Conclusions: ADEs experienced by patients with diabetes can fluctuate or persist over long periods of drug use. [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]

Aims: To identify subgroups of patients with type 2 diabetes mellitus (T2DM) following distinct trajectories of HbA1c after insulin initiation and explore underlying differences in clinical characteristics. Materials and methods: A cohort study was conducted in patients with T2DM initiating insulin in 2007–2013 with a follow‐up of 2 to 4 years. Data were collected from the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was subgroups with different trajectories of HbA1c patterns after insulin initiation, as identified by latent class growth modeling. Differences between subgroups were tested using one‐way ANOVA, Kruskal‐Wallis or chi‐square tests, where appropriate. Results: From 1459 patients, three subgroups with distinct HbA1c patterns were identified. Group 1 (8%) initially showed a moderate decrease followed by an increase in HbA1c 2 years later, despite receiving more comedication. Group 2 (84%) showed a stable decrease. Group 3 (8%) had a high initial level of HbA1c and a rapid decline within the first year, followed by a slow increase thereafter. Group 1 patients were on average 6–7 years younger than patients in groups 2 and 3 and were more likely to receive sulfonylureas than Group 3 patients. Group 3 patients had a shorter diabetes duration and were less well‐controlled for HbA1c, systolic blood pressure and LDL‐cholesterol at insulin initiation. Conclusions: Most patients showed a stable HbA1c response, but one out of six patients showed either a poor response, or a rapid initial response only after insulin initiation. Response patterns were associated with age, diabetes duration and risk‐factor controls at the time of insulin initiation. [ABSTRACT FROM AUTHOR]

Aims: To assess variability in systolic blood pressure (SBP) and albuminuria (urinary albumin creatinine ratio [UACR]) responses in patients with type 2 diabetes mellitus initiating renin angiotensin aldosterone system (RAAS) inhibition, and to assess the association of response variability with cardiovascular outcomes. Material and Methods: We performed an observational cohort study in patients with type 2 diabetes who started RAAS inhibition between 2007 and 2013 (n = 1600). Patients were identified from general practices in the Netherlands. Individual response in SBP and UACR was assessed during 15 months’ follow‐up. Patients were categorized as: good responders (∆SBP <0 mm Hg and ∆UACR <0%); intermediate responders (∆SBP <0 mm Hg and ∆UACR >0% or ∆SBP >0 mm Hg and ∆UACR <0%); or poor responders (∆SBP >0 mm Hg and ∆UACR >0%). Multivariable Cox regression was performed to test the association between initial RAAS inhibition response and subsequent cardiovascular outcomes. Results: After starting RAAS inhibition, the mean SBP change was −13.2 mm Hg and the median UACR was −36.6%, with large between‐individual variability, both in SBP [5th to 95th percentile: 48.5‐20] and UACR [5th to 95th percentile: −87.6 to 171.4]. In all, 812 patients (51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268 (17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor responders. Good responders had a lower risk of cardiovascular events than poor responders (hazard ratio 0.51, 95% confidence interval 0.30‐0.86; P = .012). Conclusions: SBP and UACR response after RAAS inhibition initiation varied between and within individual patients with type 2 diabetes treated in primary care. Poor responders had the highest risk of cardiovascular events, therefore, more efforts are needed to develop personalized treatment plans for these patients. [ABSTRACT FROM AUTHOR]

Background Decision aids can be used to support shared decision making ( SDM). A patient-oriented treatment decision aid ( DA) was developed for type 2 diabetes but its use by general practice staff appeared to be limited. Objectives To explore views of practice staff towards SDM and the DA. Design A mixed-methods study within the Dutch PORTDA-diab trial. Setting and participants Included were 17 practices with staff members who were responsible for routine diabetes care and had worked with the DA, and 209 of their patients. Methods Interviews were conducted focusing on applicability, usefulness and feasibility of the DA. Interviews were tape-recorded, transcribed verbatim and subjected to content analysis for identifying and classifying views. Patient-reported data about the use of the DA were collected. Associations between specific views and use of the DA were tested using Pearson point-biserial correlation. Results The majority of practice staff expressed positive views towards SDM, which was associated with making more use of the DA. Most of the staff expressed that the DA stimulated a two-way conversation. By using the DA, several became aware of their paternalistic approach. Some staff experienced a conflict with the content of the DA, which was associated with making less use of the DA. Conclusions The DA was considered useful by practice staff to support SDM. A positive view towards SDM was a facilitator, whereas experiencing a conflict with the content of the DA was a barrier for making use of the DA. [ABSTRACT FROM AUTHOR]

The McIntosh Archive consists of hand-drawn solar Carrington maps created by Patrick McIntosh from 1964 to 2009, using Hα, He 10830 Å, and photospheric magnetic measurements to trace polarity inversion lines, filaments, sunspots, and plage and coronal holes, yielding a unique 45 year record of the evolution of the solar magnetic field. We discuss our efforts to preserve and digitize this archive. [ABSTRACT FROM AUTHOR]

Purpose The STOPP/START criteria are increasingly used to assess prescribing quality in elderly patients at practice level. Our aim was to test computerized algorithms for applying these criteria to a medical record database. Methods STOPP/START criteria-based computerized algorithms were defined using Anatomical-Therapeutic-Chemical (ATC) codes for medication and International Classification of Primary Care (ICPC) codes for diagnoses. The algorithms were applied to a Dutch primary care database, including patients aged ≥65 years using ≥5 chronic drugs. We tested for associations with patient characteristics that have previously shown a relationship with the original STOPP/START criteria, using multivariate logistic regression models. Results Included were 1187 patients with a median age of 75 years. In total, 39 of the 62 STOPP and 18 of the 26 START criteria could be converted to a computerized algorithm. The main reasons for inapplicability were lack of information on the severity of a condition and insufficient covering of ICPC-codes. We confirmed a positive association between the occurrence of both the STOPP and the START criteria and the number of chronic drugs (adjusted OR ranging from 1.37, 95% CI 1.04-1.82 to 3.19, 95% CI 2.33-4.36) as well as the patient's age (adjusted OR for STOPP 1.30, 95% CI 1.01-1.67; for START 1.73, 95% CI 1.35-2.21), and also between female gender and the occurrence of STOPP criteria (adjusted OR 1.41, 95% CI 1.09-1.82). Conclusion Sixty-five percent of the STOPP/START criteria could be applied with computerized algorithms to a medical record database with ATC-coded medication and ICPC-coded diagnoses. [ABSTRACT FROM AUTHOR]

Since the mid-1970s, the Defense Meteorological Satellite Program (DMSP) spacecraft have operated instruments for monitoring the space environment from low Earth orbit. As the program evolved, so have the measurement capabilities such that modern DMSP spacecraft include a comprehensive suite of instruments providing estimates of precipitating electron and ion fluxes, cold/bulk plasma composition and moments, the geomagnetic field, and optical emissions in the far and extreme ultraviolet. We describe the creation of a new public database of precipitating electrons and ions from the Special Sensor J (SSJ) instrument, complete with original counts, calibrated differential fluxes adjusted for penetrating radiation, estimates of the total kinetic energy flux and characteristic energy, uncertainty estimates, and accurate ephemerides. These are provided in a common and self-describing format that covers 30+ years of DMSP spacecraft from F06 (launched in 1982) to F18 (launched in 2009). This new database is accessible at the National Centers for Environmental Information and the Coordinated Data Analysis Web. We describe how the new database is being applied to high-latitude studies of the colocation of kinetic and electromagnetic energy inputs, ionospheric conductivity variability, field-aligned currents, and auroral boundary identification. We anticipate that this new database will support a broad range of space science endeavors from single observatory studies to coordinated system science investigations. [ABSTRACT FROM AUTHOR]

Aim To provide an overview of factors predicting metformin and sulphonylurea treatment response. Background A large variability between individuals in treatment response to metformin and sulphonylurea derivatives exists. Understanding which factors determine response to these drugs may pave the way for more individualized therapy. Methods We conducted a systematic search in the MEDLINE, Cochrane and EMBASE databases, between 2003 and 2012 for articles assessing demographic and clinical prediction factors of treatment response in initial users of metformin or sulphonylurea. A literature search of articles referenced within the studies identified was also performed. Treatment response was defined as change in HbA1c level, reaching target HbA1c levels or time to treatment change. Studies were assessed on quality, sample size and type of analysis. Results were summarized by tabulating positive, null and negative associations observed for included predictors. Results A total of 10 articles (six trial reports and four cohort studies) were obtained, including three of sufficient quality. For metformin, baseline HbA1c, older age, lower BMI and shorter disease duration were found to be predictors of better treatment response in at least three studies of sufficient quality. For sulphonylurea derivatives, baseline HbA1c and shorter duration were identified as predictors of better treatment response in at least two studies of sufficient quality. Race, smoking status, lipid levels, blood pressure, kidney function and comorbidities were not significantly associated with treatment response. Conclusions Several demographic and clinical factors were identified as possible predictors of response to metformin and sulphonylurea, but the number of studies with sufficient quality was small. Generally, early treatment seems important for achieving better glycaemic outcomes. [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]

ABSTRACT Purpose Lareb Intensive Monitoring, LIM, is a non-interventional observational cohort method which follows first-time users of certain drugs during a certain period of time and collects information about adverse drug reactions, ADRs. In order for LIM to be a useful pharmacovigilance tool, it is important to know whether the LIM population is comparable to the whole population using the drug. The aim of this study is to compare the LIM diabetes population with an external diabetes reference population on characteristics that may influence the patient's susceptibility for ADRs. Methods In this study, a LIM diabetes population was compared to a reference diabetes population derived from The Groningen Initiative to ANalyse Type 2 diabetes Treatment project. Comparisons were made regarding age, gender, body mass index and polypharmacy, as well as diabetes medication used and disease/treatment duration. Results LIM patients were more often men (58.5% vs 50.8%) and in general younger (59.1 vs 64.7 years) and healthier, by that meaning they had a higher percentage of de novo treated patients (55.5% vs 53.2%), a shorter diabetes treatment duration (3.7 vs 5.5 years) and used less co-medication than patients in the reference population. Conclusions This study shows that diabetes patients participating in a web-based intensive monitoring system differ from a reference population. The observed differences might lead to an underestimation of ADRs, but it is not clear whether this would also influence the type or time-course of the reported ADRs. When interpreting results from LIM studies, one should take these differences into account. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To identify the relevant prescribing quality domains of type 2 diabetes mellitus care as a basis for the selection of a minimal set of prescribing quality indicators from a set of previously validated indicators. Methods We used the principal factor analysis to identify the underlying dimensions or domains of prescribing quality for 76 general practitioners participating to the Groningen Initiative to Analyse Type 2 Diabetes Treatment project in the Netherlands. From a set of 10 prescribing quality indicators covering various aspects of cardiovascular and metabolic management, we selected a subset of indicators with the highest loading within each identified domain. Next, we evaluated the effect of using this subset on the quintile ranking of practices on their prescribing quality scores. Results We identified five prescribing quality domains in our data set: two assessing initiation of pharmacotherapy for different risk factors in diabetic patients, two on stepwise intensification of treatment, and one on treatment of patients with cardiovascular disease. A composite score comprising the indicators selected from each of the domains showed good agreement with the composite score comprising all indicators with 82% of general practitioners either not changing their position or shifting their ranking by only one quintile. Conclusions We showed that a minimal set of prescribing quality indicators for type 2 diabetes mellitus care should not just focus on the management of different clinical risk factors but also reflect different steps of treatment intensification. The results of our study are relevant for stakeholders when selecting quality indicators to assess the quality of prescribing in diabetic patients. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose Assessment of quality of cardiometabolic risk management in diabetes in primary care. Methods In a descriptive cohort study including 95 Dutch general practices, we assessed medication treatment in relation to the level of control for HbA1c, systolic blood pressure (SBP) and LDL-cholesterol (LDL-c) in 2007. We also applied a prospective measure of treatment quality by assessing treatment modifications in not well-controlled patients. In a subpopulation of 23 practices, we studied trends in these quality indicators from 2004 (2059 patients) to 2007 (2929 patients). Results In 2007, averages for HbA1c, SBP and LDL-c were 6.9%, 142 mmHg and 2.3 mmol/l, respectively. Of the patients with an HbA1c > 8.5%, 16% were treated with one oral drug class and 50% used insulin. In 27% of these patients, therapy modification occurred subsequently. During the 4-year period, a slight decrease in average HbA1c was observed, but no changes in treatment level. In 2007, 56% of the patients had an SBP ≥140 mmHg, 19% of whom were not using antihypertensives. In the 13% with an SBP >160 mmHg, 23% received a therapy modification. During the 4-year period, the average SBP decreased with 6 mmHg but the treatment level showed no substantial increase. In 2007, 39% had an LDL-c level ≥2.5 mmol/l, 49% of whom were not using statins. Of the patients with an LDL-c >3.5 mmol/l, only 9% received a therapy modification. Conclusions The decreasing population averages of HbA1c, SBP and LDL-c values suggest improvement in quality of care. However, the relatively few therapy modifications observed in insufficiently controlled patients show room for improvement. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose Valid prescribing indicators (PI) are needed for reliable assessment of prescribing quality. The purpose of this study is to describe the validity of existing PI for type 2 diabetes mellitus and cardiovascular risk management. Methods We conducted a systematic literature search for studies describing the development and assessment of relevant PIs between January 1990 and January 2009. We grouped identified PI as drug- or disease-oriented, and according to the aspects of prescribing addressed and the additional clinical information included. We reviewed the clinimetric characteristics of the different types of PI. Results We identified 59 documents describing the clinimetrics of 16 types of PI covering relevant prescribing aspects, including first-choice treatment, safety issues, dosing, costs, sufficient and timely treatment. We identified three types of drug-oriented, and five types of disease-oriented PI with proven face and content validity as well as operational feasibility in different settings. PI focusing on treatment modifications were the only indicators that showed concurrent validity. Several solutions were proposed for dealing with case-mix and sample size problems, but their actual effect on PI scores was insufficiently assessed. Predictive validity of individual PI is not yet known. Conclusion We identified a range of existing PI that are valid for internal quality assessment as they are evidence-based, accepted by professionals, and reliable. For external use, problems of patient case-mix and sample size per PI should be better addressed. Further research is needed for selecting indicators that predict clinical outcomes. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Several measures using prescription data have been developed for estimating medication refill adherence. Few studies have made direct comparisons, and little is known about the accuracy of these measures in patients on a multiple-drug regimen. Purpose To compare different calculation methods using prescription data for assessing refill adherence. Method An observational cohort study among type 2 diabetes patients was conducted. Adherence to oral glucose-lowering, antihypertensive and lipid-lowering medication was assessed for 2004. We calculated medication possession ratios in a flexible period (MPRF), per calendar year (MPRY) and gaps between refills (GAP) at drug class and therapeutic level. Individual review of drug prescription profiles was conducted to validate identified cases of suboptimal refill adherence. Differences in Area Under the Curve (AUC) of ROC-curves were calculated to compare the methods. Results Of the 3877 patients, 2969 (77%) patients received oral glucose-lowering medication, 2715 (70%) antihypertensives and 1797 (46%) lipid-lowering medication. Using cutoffs for MPR < 80% and GAP > 30 days, overall rates of suboptimal adherence for these drug classes were 32, 35 and 23% respectively. AUC for measures calculated at drug class level (range 0.85-0.90) were significantly larger than those calculated at therapeutic level (0.72-0.90). For oral glucose-regulating medication and antihypertensives, AUCs were largest for the MPRY and GAP measures (0.87-0.88). For lipid-lowering medication, the AUC was largest for the GAP measure (0.90). Conclusions Differences between adherence measures were small and favoured calculation on drug class level. For multiple drug use, both MPRY and GAP were good measures for identifying suboptimal refill adherence. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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]

Rationale, aims and objectives Peer review groups are considered helpful for quality improvement in primary care. An interactive educational programme for small peer groups was developed, focusing on the implementation of newly developed treatment guidelines. The aim is to evaluate the effect of the programme on adherence to treatment guidelines in general practice. Methods A cluster randomized trial using a balanced incomplete block design was used; one arm received a programme on treatment of chronic heart failure (CHF), the other on hypertension treatment in diabetes mellitus type 2 (T2DM). A random sample of 10 CHF and 10 T2DM patients per GP was drawn, for whom data were extracted from electronic patient records 1 years before and 6 months after the intervention. The outcomes were prescribing of ACE inhibitors, and antihypertensive treatment in T2DM. The effect was analysed separately for both programmes using multilevel regression models. Results All 27 peer review groups in one region in the Netherlands were randomized, of which 16 participated. No significant effects were observed in the CHF group or in the T2DM group. The opportunity for change was limited, as only 53% of the CHF patients and 60% of the T2DM patients had a contact with their GP between the intervention and follow-up measurement. Conclusion The peer review programme was not successful for changing the treatment of chronic patients, although the programme focused on dealing with barriers perceived by the participants. Not all problems perceived can be solved in a peer group discussion. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore trends in primary care prescribing for chronic heart failure (CHF) over a 5-year period (1996–2000). This study consisted of repeated cross-sectional surveys in a dynamic cohort from the Integrated Primary Care Information (IPCI) primary care database. The cohort comprised all patients aged ≥55 years with a CHF diagnosis and prescribed a cardiovascular medication during the study period. The point prevalence per calendar year was determined for each of the main drug groups used to treat CHF. The study population consisted of 3121 CHF patients. Small increases were seen in the percentage of CHF patients prescribed spironolactone (4.6%, 95% CI: 2.3–6.9%), β-blockers (6.1%, 95% CI: 2.6–9.5%) and angiotensin II antagonists (6.8%, 95% CI: 5.1–8.6%) during the study period, while the prescribing of digoxin decreased (-4.4%, 95% CI: -8.2 to -0.7). Prescribing of diuretics (difference: -0.7% 95% CI: -2.7–4.2) and ACE inhibitors (difference: 4.0% 95% CI: -0.1–8.2%) remained unchanged. Prescription of some drug groups for CHF increased. However, given the new scientific evidence that has emerged in past 15 years regarding CHF pharmacotherapy, the changes observed were less than expected. Copyright © 2003 John Wiley & Sons, Ltd. [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]