Prescribing patterns, adherence and LDL-cholesterol response of type 2 diabetes patients initiating statin on low-dose versus standard-dose treatment:a descriptive study

AimsThe aim of this study was to describe and compare treatment modifications and discontinuation, adherence levels and response to treatment in patients with type 2 diabetes initiating on low-dose vs. standard-dose statin treatment.MethodsA 2-year follow-up cohort study was performed using data from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database in patients with type 2 diabetes initiating statin treatment between January 2007 and December 2012. First, we determined whether there were differences in treatment modifications and discontinuation after statin initiation between patients starting on a low-dose vs. standard-dose. Second, we looked at differences in adherence and LDL-cholesterol response after 2 years follow-up between these groups.ResultsAround 22% of patients initiated statin treatment on a dose lower than recommended. More than half of them remained on a low dose during a 2-year follow-up period, whereas less than 15% received a dose increase. Of the patients initiating on standard-dose, also more than half remained on the same treatment during this period, whereas 8% received a dose decrease without subsequent increase. Over 25% of patients starting on low-dose or standard-dose treatment discontinued treatment, often within the first 180 days after initiation or after a first treatment change. Patients on low-dose treatment had lower adherence levels and were less likely to have adequate LDL-cholesterol response compared with patients on standard-dose after 2 years follow-up.ConclusionsCurrent patterns of statin treatment in patients with type 2 diabetes are suboptimal, with discontinuation, inadequate adherence levels and lack of treatment intensification seen in those who had inadequate LDL-cholesterol response after 2 years of follow-up. Patients starting on low-dose had more treatment modifications, discontinuation and adherence problems as compared with those starting on standard-dose treatment, which calls for a closer look at the rationale of starting patients on low-dose statin treatment.</p

Differential Effects of Comorbidity on Antihypertensive and Glucose-Regulating Treatment in Diabetes Mellitus – A Cohort Study

BACKGROUND: Comorbidity is often mentioned as interfering with "optimal" treatment decisions in diabetes care. It is suggested that diabetes- related comorbidity will increase adequate treatment, whereas diabetes- unrelated comorbidity may decrease this process of care. We hypothesized that these effects differ according to expected priority of the conditions. METHODS: We evaluated the relationship between comorbidity and treatment intensification in a study of 11,248 type 2 diabetes patients using the GIANTT (Groningen Initiative to Analyse type 2 diabetes Treatment) database. We formed a cohort of patients with a systolic blood pressure >/= 140 mmHg (6,820 hypertensive diabetics), and a cohort of patients with an HbA1c >/= 7% (3,589 hyperglycemic diabetics) in 2007. We differentiated comorbidity by diabetes-related or unrelated conditions and by priority. High priority conditions include conditions that are life- interfering, incident or requiring new medication treatment. We performed Cox regression analyses to assess association with treatment intensification, defined as dose increase, start, or addition of drugs. RESULTS: In both the hypertensive and hyperglycemic cohort, only patients with incident diabetes-related comorbidity had a higher chance of treatment intensification (HR 4.48, 2.33-8.62 (p<0.001) for hypertensives; HR 2.37, 1.09-5.17 (p = 0.030) for hyperglycemics). Intensification of hypertension treatment was less likely when a new glucose-regulating drug was prescribed (HR 0.24, 0.06-0.97 (p = 0.046)). None of the prevalent or unrelated comorbidity was significantly associated with treatment intensification. CONCLUSIONS: Diabetes-related comorbidity induced better risk factor treatment only for incident cases, implying that appropriate care is provided more often when complications occur. Diabetes- unrelated comorbidity did not affect hypertension or hyperglycemia management, even when it was incident or life-interfering. Thus, the observed "undertreatment" in diabetes care cannot be explained by constraints caused by such comorbidity

Nationwide evaluation of mutation-tailored treatment of gastrointestinal stromal tumors in daily clinical practice

Background Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international guidelines. We performed a nationwide study into the application of predictive mutation testing in GIST patients and its impact on targeted treatment decisions in clinical practice. Methods Real-world clinical and pathology information was obtained from GIST patients with initial diagnosis in 2017-2018 through database linkage between the Netherlands Cancer Registry and the nationwide Dutch Pathology Registry. Results Predictive mutation analysis was performed in 89% of the patients with high risk or metastatic disease. Molecular testing rates were higher for patients treated in expertise centers (96%) compared to non-expertise centers (75%, P < 0.01). Imatinib therapy was applied in 81% of the patients with high risk or metastatic disease without patient's refusal or adverse characteristics, e.g., comorbidities or resistance mutations. Mutation analysis that was performed in 97% of these imatinib-treated cases, did not guarantee mutation-tailored treatment: 2% of these patients had the PDGFRA p.D842V resistance mutation and 7% initiated imatinib therapy at the normal instead of high dose despite of having a KIT exon 9 mutation. Conclusion In conclusion, nationwide real-world data show that over 81% of the eligible high risk or metastatic disease patients receive targeted therapy, which was tailored to the mutation status as recommended in guidelines in 88% of cases. Therefore, still 27% of these GIST patients misses out on mutation-tailored treatment. The reasons for suboptimal uptake of testing and treatment require further study

Mutation-tailored treatment selection in non-small cell lung cancer patients in daily clinical practice

Objectives: The number of targeted drugs in non-small cell lung cancer (NSCLC) is ever-expanding and requires testing of an increasing number of predictive biomarkers. We present a comprehensive real-world evaluation of molecular testing and treatment selection in stage IV NSCLC patients in the Netherlands from 2017 to 2019. Materials and methods: Molecular pathology reports of NSCLC patients were collected from the Dutch Pathology Registry in time intervals between Oct-2017 and April-2019 (N = 5,038 patients) to study diagnostic yield. Linkage between the Dutch Pathology Registry and the Netherlands Cancer Registry enabled studying molecular testing rates for stage IV NSCLC initially diagnosed in 2017-Q4 (N = 1,193) and application of targeted therapy in stage IV NSCLC patients with potentially druggable alterations reported between Oct-2017 and June-2018 (N = 401). Results: Predictive molecular testing was performed in 85.0% of adenocarcinomas, 60.4% of NSCLC-not otherwise specified (NOS) and 17.4% of squamous cell carcinomas. Testing rates were highest for EGFR and ALK (adenocarcinoma: 82.7% and 80.7%, respectively). Incidence of molecular driver alterations (i.e. EGFR, KRAS, ALK, ROS1, BRAF, MET, ERBB2, FGFR1) was 61.1% for adenocarcinomas, 42.3% for NSCLC-NOS, and 24.7% for squamous cell carcinomas. Therapeutically relevant alterations were detected at a higher frequency by NGS- versus non-NGS-approaches (adenocarcinoma: 62.4% versus 56.5%, respectively (P = 0.004)) due to a lower failure rate, more comprehensive testing and higher sensitivity. Uptake of treatment with a registered targeted therapy in eligible patients varied per actionable target, i.e. EGFR: 85.8%, ALK: 74.7%, ROS1: 33.7%, BRAF: 51.5%. Treatment with agents in clinical studies/compassionate use was lower, i.e. MET: 22.8%, HER2: 18.9%, RET: 6.7%. Conclusion: Real-world data show NGS-based approaches to be superior to non-NGS. Uptake of molecular testing and the corresponding targeted treatments was less than expected based on guidelines and even more so for trials, off-label use and compassionate use, indicating less than optimal access to rational treatment options

Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients

Objectives: Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. Materials and Methods: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. Results: 6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%-71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%-40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%-73.4%) and 29.2% (14.7%-43.9%) using the 1% and 50% cutoffs, respectively. Conclusion: Considerable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data

Epilepsy, psychiatry and learning difficulty

Objectives: To compare economic outcomes between patients with asthma or chronic obstructive pulmonary disease (COPD) receiving continuous maintenance inhaled corticosteroid/long-acting beta agonist (ICS/LABA) treatment with Symbicort and those switching from Symbicort to DuoResp. Methods: This was a historical cohort study using anonymised data from two UK primary care databases, the Optimum Patient Care Research Database and the Clinical Practice Research Datalink. Included patients had ≥ 2 years of continuous data (1-year baseline pre- and 1-year outcome post-index date). Patients switching to DuoResp were matched (1:3) with those continuing on Symbicort. Mean asthma/ COPD-related healthcare costs (medication, primary care and hospital visits) were calculated in 2014 £ and compared between groups, adjusting for confounders. Risk domain control of disease (RDC), a composite measure defining absence of exacerbations, adjusted for rhinitis, was used to assess disease control. Costeffectiveness was assessed based on total treatment costs and the absolute proportion of patients achieving RDC. Results: Patients who switched to DuoResp had lower baseline respiratory-related costs than the Symbicort group when ICS costs were included (p= 0.036). In the outcome year, switching to DuoResp was associated with significantly lower mean costs per patient in total respiratory medication (-£80; p<0.001), primary care consultations (-£13; p<0.001) and total respiratory-related costs including ICS (-£92; p<0.001). The adjusted proportion of patients achieving RDC was 58% for DuoResp versus 54% for Symbicort. Adjusted mean cost was £492 (95% CI: £461, £523) for DuoResp users and £597 (£575, £620) for Symbicort users, for a difference of -£105 (-£132, -£78) after adjusting for all baseline costs. Bootstrap sensitivity analysis found DuoResp to be less costly and more effective than Symbicort with 93.7% consistency. Conclusions: Compared with patients with asthma or COPD continuing Symbicort treatment, those switching to DuoResp demonstrated a favourable cost-effectiveness ratio in the UK primary care setting

Longitudinal Systemic Corticosteroid Utilisation for Asthma and Other Diseases in the United Kingdom from 1990 to 2018 : A Population-based Cohort Analysis

Funding: This work was supported by AstraZeneca.Peer reviewedPostprin

Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization

Funding This work was supported by a grant from the European Union, MSCA joint doctoral project MoGlyNet [675527].Peer reviewedPublisher PD