Impact of implementing Dutch versus European guideline risk factor targets in older patients with ischaemic heart disease.

BACKGROUND: In patients with ischaemic heart disease (IHD) aged > 70 years, Dutch and European guidelines recommend different treatment targets: low-density lipoprotein cholesterol (LDL-c) < 2.6 versus < 1.4 mmol/l and systolic blood pressure (SBP) < 140 versus < 130 mm Hg, respectively. How this impacts cardiovascular event-free life expectancy has not been investigated. The study objective was to compare estimated lifelong treatment benefits of implementing Dutch and European LDL­c and SBP targets. METHODS: Data from patients aged 71-80 years hospitalised for IHD in 2017-2019 were extracted from the PHARMO Database Network, which links primary and secondary healthcare settings, with follow-up until 31 December 2020. Potential benefit according to treatment strategy (in gain in event-free years) was estimated using the SMART-REACH model. RESULTS: Of the 3003 eligible patients, 1186 (39%) had missing LDL­c and/or SBP measurements. Of the 1817 included patients (36% women, median age at event: 74 years (interquartile range (IQR): 72-77), 84% achieved the Dutch targets for both LDL­c and SBP; for European targets, this was 23% and 61%, respectively. If Dutch targets were met for LDL­c and SBP (n = 1281), the additional effect of reaching European targets was a median gain of 0.6 event-free life years (IQR: 0.3-1.0). The greatest effect could be reached in patients not reaching Dutch targets (n = 501), with a median gain of 0.6 (IQR: 0.2-1.2) and 1.7 (IQR: 1.2-2.5) event-free years with Dutch versus European targets. CONCLUSION: In patients aged > 70 years with IHD, implementation of European targets resulted in a greater gain of event-free years compared with Dutch targets, especially in patients with poorer risk factor control. The considerable number of patients with missing risk factor documentation suggested additional opportunities for risk reduction.

Prevalence of chronic kidney disease in the Netherlands and its cardiovascular and renal complications.

BACKGROUND: Knowledge on prevalence, comorbidities and consequences of chronic kidney disease (CKD) is mandatory to estimate the potential of cardiovascular risk management on a population level. We studied the prevalence of CKD with or without type 2 diabetes mellitus (T2D) and/or heart failure and its cardiorenal complications in The Netherlands. METHODS: A descriptive cross-sectional and longitudinal cohort study was performed, using data from the Dutch PHARMO Data Network. Prevalence of CKD at a single time point was determined by a recorded diagnosis or by ≥ 2 estimated glomerular filtration rate (eGFR) measurements and urine albumin/creatinine ratio (UACR) that define CKD. A representative group of adults with CKD was included in a longitudinal analysis to study cardiorenal complications. Those were followed until first complication, end of study or death, whichever occurred first. RESULTS: The prevalence of CKD was 8.9% in a representative population of 2,187,962 adult Dutch individuals. The average age of persons with CKD was 72 years, 57% were female, 19.9% had T2D, 7.7% heart failure, and 3.0% both T2D and heart failure. In the longitudinal analysis, cerebrovascular events (11/1,000 person-years), hospitalizations for heart failure (10/1,000 person-years), myocardial infarction (5.5/1,000 person-years), and hospitalization for CKD (6.2/1,000 person-years) were the most common first cardiorenal complications. People with CKD with T2D and/or heart failure generally had higher rates of cardiovascular or renal complications or mortality than people with CKD without these comorbidities. CONCLUSION: The prevalence of CKD in The Netherlands is 8.9%. People with T2D or heart failure, or both, in addition to CKD, had numerically higher mortality and cardiorenal complication rates than people without these comorbidities. Optimizing up-to-date cardiovascular risk management in these high-risk individuals may provide health benefits.

Infliximab use in the Netherlands: Uptake and characteristics of originator and biosimilars over time.

AIMS: The objective of this retrospective cohort study was to provide an overview of the utilization of originator and biosimilar infliximab in the Netherlands. METHODS: All infliximab dispensings were selected from the PHARMO In-patient Pharmacy Database from 2002-2018. Descriptive analyses were performed in order to characterise initiators and to describe switching patterns over time. RESULTS: Overall, 3840 patients with 61 274 infliximab dispensings were identified. 2496 patients initiated an originator infliximab and 777 patients initiated a biosimilar infliximab. Overall, 57% of the patients was female and mean age was 43.2 years. Both originators and biosimilars were mostly prescribed by gastroenterologists, followed by internists and rheumatologists. After market authorisation of the first biosimilar, the proportion of new patients initiating the biosimilar increased from 39% in 2015 to 91% in 2018. Out of 704 patients eligible for switching 34% switched. Among switchers, the proportion of females was 60% and mean age at index was 45.1 years. Among nonswitchers, 55% were female and mean age was 39.8 years. The median time to switch was 1.7 years and switchers were most frequently initiated on infliximab by a rheumatologist (42%), while nonswitchers were most frequently initiated by a gastroenterologist (42%). CONCLUSION: The results of this large population-based cohort show an increase in biosimilar initiation in daily clinical practice. The number of switchers remains relatively low as nonmedical switch is not encouraged in the Netherlands.

Impact of EU regulatory label changes for diclofenac in people with cardiovascular disease in four countries: Interrupted time series regression analysis.

OBJECTIVE: Due to cardiovascular safety concerns, the European Medicines Agency (EMA) recommended new contraindications and changes to product information for diclofenac across Europe in 2013. This study aims to measure their impact among targeted populations. METHOD: Quarterly interrupted time series regression (ITS) analyses of diclofenac initiation among cohorts with contraindications (congestive cardiac failure [CHF], ischaemic heart disease [IHD], peripheral arterial disease [PAD], cerebrovascular disease [CVD]) and cautions (hypertension, hyperlipidaemia, diabetes) from Denmark, the Netherlands, England and Scotland. RESULTS: The regulatory action was associated with significant immediate absolute reductions in diclofenac initiation in all countries for IHD (Denmark -0.08%, 95%CI -0.13, -0.03; England -0.09%, 95%CI -0.13 to -0.06%; the Netherlands -1.84%, 95%CI -2.51 to -1.17%; Scotland -0.34%, 95%CI -0.38 to -0.30%), PAD and hyperlipidaemia, the Netherlands, England and Scotland for hypertension and diabetes, and England and Scotland for CHF and CVD. Post-intervention there was a significant negative trend in diclofenac initiation in the Netherlands for IHD (-0.12%, 95%CI -0.19 to -0.04), PAD (-0.13%, 95%CI -0.22 to -0.05), hypertension, hyperlipidaemia and diabetes, and in Scotland for CHF (-0.01%, 95%CI -0.02 to -0.007%), IHD (-0.017, 95%CI -0.02, -0.01%), PAD and hypertension. In England, diclofenac initiation rates fell less steeply. In Denmark changes were more strongly associated with the earlier EMA 2012 regulatory action. CONCLUSION: Although significant reductions in diclofenac initiation occurred, patients with contraindications continued to be prescribed diclofenac, the extent of which varied by country and target condition. Understanding reasons for such variation may help to guide the design or dissemination of future safety warnings.

Impact of EMA regulatory label changes on hydroxyzine initiation, discontinuation and switching to other medicines in Denmark, Scotland, England and the Netherlands: An interrupted time series regression analysis.

BACKGROUND: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. METHOD: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. RESULTS: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (-12.05, 95%CI -18.47 to -5.63) and Scotland (-19.01, 95%CI -26.99 to -11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (-1.72, 95%CI -2.69 to -0.75) and Scotland (-2.38, 95%CI -3.32 to -1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. CONCLUSION: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants.

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands.

PURPOSE: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. METHODS: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. RESULTS: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be a more limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (-0.42%, 95% CI, -0.66% to -0.18%), England (-0.09%, 95% CI, -0.11% to -0.08%), and Scotland (-0.67%, 95% CI, -0.79% to -0.55%); and falling trends in diclofenac initiation in the Netherlands (-0.03%, 95% CI, -0.06% to -0.01% per quarter) and Scotland (-0.04%, 95% CI, -0.05% to -0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. CONCLUSIONS: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching.

Sex- and site-specific differences in colorectal cancer risk among people with type 2 diabetes.

PURPOSE: The prevalence of colorectal cancer is higher among patients with type 2 diabetes mellitus (T2D) than among patients without diabetes. Furthermore, men are at higher risk for developing colorectal cancer than women in the general population and also subsite-specific risks differ per sex. The aim was to evaluate the impact of T2D on these associations. METHODS: A population-based matched cohort study was performed using data from the PHARMO Database Network. Patients with T2D were selected and matched (1:4) to diabetes free controls. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CRC and its subsites. HRs were determined per sex and adjusted for age and socioeconomic status. The ratio of distal versus proximal colon cancer was calculated for people with T2D and controls per sex and stratified by age. RESULTS: Over 55,000 people with T2D were matched to > 215,000 diabetes free controls. Men and women with T2D were 1.3 times more likely to develop colorectal cancer compared to controls. Men with T2D were at higher risk to develop distal colon cancer (hazard ratio (95% confidence interval), 1.42 (1.08-1.88)), and women with T2D were at higher risk for developing proximal colon cancer (hazard ratio (95% confidence interval), 1.58 (1.13-2.19)). For rectal cancer, no statistically significant risk was observed for both men and women. CONCLUSIONS: Sex-specific screening strategies and prevention protocols should be considered for people with T2D. More tailored screening strategies may optimize the effectiveness of colorectal cancer screening in terms of reducing incidence and mortality.

Risk of dipeptidyl peptidase-4 (DPP-4) inhibitors on site-specific cancer: A systematic review and meta-analysis.

The long-term impact of dipeptidyl peptidase-4 (DPP-4) inhibition is unknown, and there are concerns about the influence of DPP-4 inhibition on carcinogenesis of the pancreas and thyroid. As DPP-4 is a rather unselective enzyme present in many tissues, we focused on all specific cancer types. PubMed and EMBASE were searched between January 2005 and April 2017 to identify studies comparing DPP-4 inhibitors with either placebo or active drugs on cancer risk. Studies were included if they reported on at least one specific cancer outcome and had a follow-up of at least 1 year after start of drug use. Methodological quality of the studies was assessed by the Cochrane Collaboration's tool and the Newcastle-Ottawa Scale. Twenty-five studies met the inclusion criteria (12 randomized controlled trials and 13 observational studies). Sample sizes of the DPP-4 inhibitor groups ranged from 29 to 8212 patients for randomized controlled trials and from 2422 to 71 137 patients for observational studies. Mean age ranged from 51 to 76 years, and mean follow-up was 1.5 years. None of the pooled (sensitivity) analyses, except the observational studies studying breast cancer (hazard ratio [95% CI]: 0.76 [0.60-0.96]), showed evidence for an association between DPP-4 inhibitors and site-specific cancer. Also for pancreatic and thyroid cancer, no statistically significant risk was found. Based on the current literature, it is not possible to conclude whether DPP-4 inhibitors were associated with an increased risk of site-specific cancer. Future studies should address the methodological limitations and follow patients for a longer period to determine the long-term cancer risk of DPP-4 inhibitors.

Clinical effectiveness of liraglutide vs basal insulin in a real-world setting: Evidence of improved glycaemic and weight control in obese people with type 2 diabetes.

AIMS: To compare real-world antidiabetic treatment outcomes over 12 months in obese people with type 2 diabetes mellitus (T2DM) who previously received oral antidiabetic therapy and then initiated a first injectable therapy with liraglutide or basal insulin. PATIENTS AND METHODS: This was a retrospective, propensity score-matched, longitudinal cohort study using real-world data (January 2010 to December 2015) from the Dutch PHARMO Database Network. Adult obese (body mass index [BMI] ≥35 kg/m2 ) patients with T2DM with ≥2 dispensing dates for liraglutide or basal insulin supported oral therapy (BOT) were selected. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline during 12 months of follow-up. The secondary endpoints were the changes in weight, BMI and cardiovascular risk factors from baseline. Clinical data were analysed using descriptive statistics and compared using mixed models for repeated measures. RESULTS: Obese patients with T2DM (N = 1157) in each treatment group were matched (liraglutide cohort, n = 544; BOT cohort, n = 613). From 3 months onwards, glycaemic control improved in both cohorts but improved significantly more with liraglutide than with BOT (12 months: -12.2 mmol/mol vs -8.8 mmol/mol; P = .0053). In addition, weight and BMI were significantly lower for treatments with liraglutide vs BOT (12 months: -6.0 kg vs -1.6 kg and - 2.1 kg/m2 vs -0.5 kg/m2 , respectively; P < .0001 for both). No significant differences were seen in changes in cardiovascular risk factors. CONCLUSIONS: The results of this real-world study in matched obese patients with T2DM showed that liraglutide was more effective than BOT for HbA1c control and weight/BMI reductions. Patients were more likely to maintain glycaemic control over time after initiating liraglutide than after initiating BOT.

No Evidence for an Association Between Renal Function and Serious Bleeding Events in Patients Treated With Coumarins: A Population-Based Study.

BACKGROUND: Although anticoagulation therapy is closely monitored in the Netherlands, coumarin-induced serious bleeding events are still observed. Current literature suggests that renal impairment may contribute to this. OBJECTIVE: To explore the association between renal function and bleeding events during coumarin treatment. METHODS: A nested case-control study was conducted using data from the PHARMO Database Network. Patients hospitalized for a bleeding event during coumarin treatment were selected as cases and matched on sex, birth year, and geographic region to up to 2 controls using coumarins without hospitalization for bleeding. All values of estimated glomerular filtration rates (eGFRs) were selected in the year before index date (case hospitalization date) and compared between cases and controls using logistic regression analyses. RESULTS: In total, 2224 cases were matched to 4398 controls (61% male; mean ± SD age 75 ± 11 and 78 ± 11 years among cases and controls, respectively). Availability of eGFR values was higher among cases compared with controls (mean ± SD eGFR values 4.5 ± 7.1 vs 3.2 ± 5.5), reflected in the significantly shorter time since last eGFR value (at index date, mean ± SD = 2.7 ± 3.0 vs 3.8 ± 3.1 months; odds ratio [OR] = 0.91, 95%CI = 0.89-0.92). No statistically significant difference was found for the mean eGFR value in the year before index date (mean ± SD 65.7 ± 22.8 vs 64.6 ± 20.9 mL/min/1.73 m2; OR per 10 units [95%CI] = 0.99 [0.96-1.02]). CONCLUSIONS: No association between renal function and serious bleeding events during coumarin treatment was observed.

Brand and generic use of inhalation medication and frequency of switching in children and adults: A population-based cohort study.

BACKGROUND: The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. AIM: To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. METHODS: From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). RESULTS: The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). CONCLUSION: Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted.

Post authorization safety study comparing quetiapine to risperidone and olanzapine.

OBJECTIVES: To compare rates of specific adverse outcomes between patients starting quetiapine, olanzapine, or risperidone use in the Netherlands. METHODS: Observational study using the PHARMO Database Network, including patients starting quetiapine (4658), olanzapine (5856), or risperidone (7229) in 2000-2009, comparing rates of all-cause mortality, failed suicide attempts, extrapyrimidal symptoms (EPS), diabetes mellitus (DM), hypothyroidism, and acute myocardial infarction (AMI). KEY FINDINGS: Median follow-up until discontinuation/end of follow-up was 0.6 years. Prescribed doses were generally lower than the approved defined daily doses, especially for quetiapine. Quetiapine was significantly associated with lower EPS rates (HR 0.18; 95% CI 0.13-0.24), but higher failed suicide attempt rates (HR 2.07; 95% CI 1.35-3.16) compared to risperidone. Quetiapine was significantly associated with lower EPS rates (HR 0.59; 95% CI 0.42-0.84) and DM rates (HR 0.66; 95% CI 0.44-0.97) compared to olanzapine. Rates for all-cause mortality, hypothyroidism, and stroke were similar between groups. AMI events were too infrequent to draw conclusions. CONCLUSIONS: Quetiapine was associated with lower EPS, but higher failed suicide attempt rates compared to risperidone. Quetiapine was associated with lower EPS and DM rates compared to olanzapine. The results should be interpreted with caution because of possible channelling and residual confounding. Copyright © 2016 John Wiley & Sons, Ltd.

Effectiveness of initiating extrafine-particle versus fine-particle inhaled corticosteroids as asthma therapy in the Netherlands.

BACKGROUND: Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a real-life population initiating ICS therapy in the Netherlands. METHODS: Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 - 60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, ≥2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine-particle ICS (fluticasone propionate or non-extrafine-particle-BDP). Patients were matched (1:1) on relevant demographic and clinical characteristics over 1-year baseline. Primary outcomes were severe exacerbation rates, risk domain asthma control and overall asthma control during the year following first ICS prescription. Secondary outcomes, treatment stability and being prescribed higher versus lower category of short-acting ß2 agonists (SABA) dose, were compared over a 1-year outcome period using conditional logistic regression models. RESULTS: Following matching, 1399 patients were selected in each treatment cohort (median age: 43 years; males: 34 %). Median (interquartile range) initial ICS doses (fluticasone-equivalents in µg) were 160 (160 - 320) for extrafine-particle versus 500 (250 - 500) for fine-particle ICS (p < 0.001). Following adjustment for residual confounders, matched patients prescribed extrafine-particle ICS had significantly lower rates of exacerbations (adjusted rate ratio [95 % CI], 0.59 [0.47-0.73]), and significantly higher odds of achieving asthma control and treatment stability in the year following initiation than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. Patients prescribed extrafine-particle ICS had lower odds of being prescribed higher doses of SABA (0.50 [0.44-0.57]). CONCLUSION: In this historical, matched study, extrafine-particle ICS was associated with better odds of asthma control than fine-particle ICS in patients prescribed their first ICS therapy in the Netherlands. Of importance, this was reached at significantly lower prescribed dose.

Burden of Exacerbations in Patients with Moderate to Very Severe COPD in the Netherlands: A Real-life Study.

OBJECTIVE: The objective of this study was to compare rates of different types of acute exacerbations of COPD (AECOPDs) and healthcare utilization among patients with different severities of COPD. METHODS: Data for this study was obtained from the PHARMO Database Network, which includes drug dispensing records from pharmacies, hospitalization records and information from general practitioners. Patients with moderate to very severe COPD (GOLD II-III-IV) and a moderate or severe AECOPD between 2000 and 2010 were included in the study. Moderate and severe AECOPDs were defined by drug use and hospitalizations respectively. Study patients were followed from the first AECOPD to end of registration in PHARMO, death or end of study period, whichever occurred first. During follow-up, all recurrent AECOPDs were characterized and healthcare utilization was assessed. RESULTS: Of 886 patients in the study, 52% had GOLD-II, 34% GOLD-III and 14% had GOLD-IV. The overall AECOPD recurrence rate per person year (PY) increased from 0.63 for patients with GOLD-II to 1.09 for patients with GOLD-III and 1.33 for patients with GOLD-IV. The rate of severe AECOPD was 0.06, 0.14 and 0.17 per PY, respectively. CONCLUSION: AECOPD recurrence rates and healthcare utilization are significantly higher among patients with more severe COPD.

Type 2 Diabetes, the Epidemic: Trends in Prevalence and Incidence, 2004-2020.

Aims/Hypothesis: Only a few studies reported the incidence of type 2 diabetes (T2D). Understanding recent trends in diabetes is vital for planning future diabetes care. This study updated national trends in the prevalence and incidence of type 2 diabetes (T2D) in the Netherlands from 2004-2020. Methods: The DIAbetes, MANagement and Treatment (DIAMANT) cohort was used. A cross-sectional design with yearly measurements for the study period was used. The prevalence was calculated by dividing the total number of people with T2D by the total number of all residents. The incidence was calculated by dividing new cases of T2D by the resident population at risk during the calendar year of interest. Results: Among men, the prevalence of T2D in the Netherlands increased from 2.3% in 2004 to 6.3% in 2020. Women's prevalence increased from 2.3% in 2004 to 5.3% in 2020. During 2005-2009, the incidence rate for both men and women was relatively stable Between 2010 and 2020, the incidence rate fell about 1.5 per 1000 in both men and women. Conclusion: From 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.

Research in context What is already known about this subject? Many studies have reported the increasing prevalence of type 2 diabetes (T2D). However, only a few studies reported the incidence.In a recent systematic review of all these studies, the incidence fell in over a third of the most high-income populations and increased in a minority of populations. Data from the Netherlands were included, but they date back to 1996.Understanding recent trends in diabetes, the prevalence and incidence are vital for planning future diabetes care.What is the key question? To update national trends in the prevalence and incidence of T2D in the Netherlands for 2004-2020.What are the new findings? During 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.How might this impact on clinical practice in the foreseeable future? It demonstrates the effectiveness of preventive strategies, public health education and awareness campaigns contributing to this trend.

Improving Diagnosis and Care for Patients With Sarcoma: Do Real-World General Practitioners Data and Prospective Data Collections Have a Place Next to Clinical Trials?

There has been growing interest in the use of real-world data (RWD) to address clinically and policy-relevant (research) questions that cannot be answered with data from randomized controlled trials (RCTs) alone. This is, for example, the case in rare malignancies such as sarcomas as limited patient numbers pose challenges in conducting RCTs within feasible timeliness, a manageable number of collaborators, and statistical power. This narrative review explores the potential of RWD to generate real-world evidence (RWE) in sarcoma research, elucidating its application across different phases of the patient journey, from prediagnosis to the follow-up/survivorship phase. For instance, examining electronic health records (EHRs) from general practitioners (GPs) enables the exploration of consultation frequency and presenting symptoms in primary care before a sarcoma diagnosis. In addition, alternative study designs that integrate RWD with well-designed observational RCTs may offer relevant information on the effectiveness of clinical treatments. As, especially in cases of ultrarare sarcomas, it can be an extreme challenge to perform well-powered randomized prospective studies. Therefore, it is crucial to support the adaptation of novel study designs. Regarding the follow-up/survivorship phase, examining EHR from primary and secondary care can provide valuable insights into identifying the short- and long-term effects of treatment over an extended follow-up period. The utilization of RWD also comes with several challenges, including issues related to data quality and privacy, as described in this study. Notwithstanding these challenges, this study underscores the potential of RWD to bridge, at least partially, gaps between evidence and practice and holds promise in contributing to the improvement of sarcoma care.

Completeness and Representativeness of the PHARMO General Practitioner (GP) Data: A Comparison with National Statistics.

Purpose: When using incomplete or non-representative real-world data (RWD), bias is more likely to occur. The aim of the current study was to assess the completeness and representativeness of the PHARMO GP data for the Dutch population. Patients and Methods: A cross-sectional study was performed. The PHARMO GP data comprise data from electronic health records registered by GPs. Data on the Dutch population were obtained from Statistics Netherlands (CBS), which offers publicly available data on several themes. The standardized difference (std.diff) was used to compare proportions between the PHARMO GP population and the Dutch population. An absolute std.diff >0.2 was considered a difference. Results: On January 1st, 2018, 3,466,321 persons were included in the PHARMO GP data (mean age: 41.6 years, 49.7% males). The sex and age distribution was similar to the Dutch population. The PHARMO GP data captured less not urbanized areas compared to the Dutch population (not urbanized areas: 9.4% vs 17.1% [std.diff: -0.23]). Regarding medication use, only the pharmacological subgroups "viral vaccines" and "hormonal contraceptives for systemic use" differed (std.diff >0.2); use in the GP data was more complete than in the Statistics Netherlands (CBS) data. No differences were observed regarding diagnoses. Conclusion: The PHARMO GP data are representative of the Dutch population with regard to the demographic characteristics and diagnoses in primary care. Medication data in the PHARMO GP data are more complete than national statistics, and differences are related to reimbursement. Use of the data and interpretation of results based on these sources should be done with experts on the data sources, the Dutch healthcare system and (pharmaco)epidemiology.

[Prevalence and drug treatment of people with type 2 diabetes mellitus and a very high risk of cardiovascular disease]. / Diabetes type 2 én een hoog risico op hart- en vaatziekten.

OBJECTIVE: Dutch diabetes guidelines have been updated to incorporate specific therapies with cardiovascular and kidney outcomes benefit in type 2 diabetes patients (T2D) at very high risk for cardiorenal complications. This is part of a comprehensive approach to reduce the risk of diabetes-related complications, including management of glycemia, blood pressure, and lipids. The current study examines the prevalence of T2D at very high cardiorenal risk and the deployment of evidence-based approaches to lower this risk. DESIGN: Cross-sectional, observational study. METHOD: A representative population) with T2D in primary care (N= 64,224) was selected from the PHARMO Data Network. A very high risk of CVD was defined as: 1) established CVD, 2) CKD with (very) high cardiovascular risk and 3) heart failure. Drug treatment was determined according to prescriptions in 2019. RESULTS: 25,901 subjects with T2D had a very high risk of CVD (mean age 73.3 years; 42% female). Established CVD, CKD with (very) high cardiovascular risk, and heart failure were observed in 82%, 26% and 22% of patients, respectively. Low-dose salicylates, lipid-lowering and blood pressure-lowering medication were used by 39%, 70% and 69%, respectively. Glucose-lowering medication use included metformin (53%), sulfonylurea-derivatives (24%), and insulin (19%). 2% of the population used a SGLT2 inhibitor or GLP1-receptor agonist. CONCLUSION: 40% of people with DM2 have a very high risk of CVD. Although our findings reflect the recommendations of the previous treatment guideline for DM2, they also show that the new guideline has significant implications for the treatment of a large proportion of people with DM2.

Identification of frailty in primary care: accuracy of electronically derived measures.

BACKGROUND: Routinely collected clinical data based on electronic medical records could be used to define frailty. AIM: To estimate the ability of four potential frailty measures that use electronic medical record data to identify older patients who were frail according to their GP. DESIGN AND SETTING: This retrospective cohort study used data from 36 GP practices in the Dutch PHARMO Data Network. METHOD: The measures were the Dutch Polypharmacy Index, Charlson Comorbidity Index (CCI), Chronic Disease Score (CDS), and Frailty Index. GPs' clinical judgement of patients' frailty status was considered the reference standard. Performance of the measures was assessed with the area under the receiver operating characteristic curve (AUC). Analyses were done in the total population and stratified by age and sex. RESULTS: Of 31 511 patients aged ≥65 years, 3735 (11.9%) patients were classified as frail by their GP. The CCI showed the highest AUC (0.79, 95% confidence interval [CI] = 0.78 to 0.80), followed by the CDS (0.69, 95% CI = 0.68 to 0.70). Overall, the measures showed poorer performance in males and females aged ≥85 years than younger age groups (AUC 0.55-0.58 in females and 0.57-0.60 in males). CONCLUSION: This study showed that of four frailty measures based on electronic medical records in primary care only the CCI had an acceptable performance to assess frailty compared with frailty assessments done by professionals. In the youngest age groups diagnostic performance was acceptable for all measures. However, performance declined with older age and was least accurate in the oldest age group, thereby limiting the use in patients of most interest.

Incidence of malignancies in patients with multiple sclerosis versus a healthy matched cohort: A population-based cohort study in the Netherlands using the PHARMO Database Network.

This study estimated the incidence of malignancy in patients with multiple sclerosis (MS) versus a matched general population cohort in the Netherlands. Adults with a diagnosis of MS between 2006 and 2014 in the General Practitioner (GP) Database of the PHARMO Database Network with ≥ 1 year of patient history were matched to four non-MS individuals based on year of birth, sex, and GP practice. Patients were followed-up until the earliest malignancy diagnosis, death, or end of data collection. Age-adjusted incidence rates (IR) were measured overall and by cancer type. Standardized incidence ratios (SIR) were calculated as the ratio of stratification-specific IRs in the MS and non-MS cohorts. A total of 1,692 MS patients were matched to 6,768 non-MS patients. Age-adjusted IR of any malignancy, excluding non-melanoma skin cancer (n = 27), in the MS cohort was 48.3 (95%CI:30.1-66.5) per 10,000 PY. An increased incidence of any malignancy was observed in the MS cohort versus the non-MS cohort (SIR 1.8 [95%CI:1.1-2.5]). The most commonly observed malignancies in the MS cohort were breast cancer (n = 8; IR 20.4 [95%CI:6.3-34.5] per 10,000 PY) and melanoma (n = 6; IR 14.8 [95%CI:3.0-26.7] per 10,000 PY). The corresponding SIR observed between cohorts was 1.4 (95%CI:0.4-2.4) and 3.4 (95%CI:0.7-6.2), respectively. While the small increased incidence of malignancy in the MS cohort could be an artefact created by a different distribution of risk factors, an increased incidence of malignancy in MS patients in the Netherlands cannot be excluded.