Fitness for purpose of routinely recorded health data to identify patients with complex diseases: The case of Sjögren's syndrome

Background: This study is part of the EU-funded project HarmonicSS, aimed at improving the treatment and diagnosis of primary Sjögren's syndrome (pSS). pSS is an underdiagnosed, long-term autoimmune disease that affects particularly salivary and lachrymal glands. Objectives: We assessed the usability of routinely recorded primary care and hospital claims data for the identification and validation of patients with complex diseases such as pSS. Methods: pSS patients were identified in primary care by translating the formal inclusion and exclusion criteria for pSS into a patient selection algorithm using data from Nivel Primary Care Database (PCD), covering 10% of the Dutch population between 2006 and 2017. As part of a validation exercise, the pSS patients found by the algorithm were compared to Diagnosis Related Groups (DRG) recorded in the national hospital insurance claims database (DIS) between 2013 and 2017. Results: International Classification of Primary Care (ICPC) coded general practitioner (GP) contacts combined with the mention of “Sjögren” in the disease episode titles, were found to best translate the formal classification criteria to a selection algorithm for pSS. A total of 1462 possible pSS patients were identified in primary care (mean prevalence 0.7‰, against 0.61‰ reported globally). The DIS contained 208 545 patients with a Sjögren related DRG or ICD10 code (prevalence 2017: 2.73‰). A total of 2 577 577 patients from Nivel PCD were linked to the DIS database. A total of 716 of the linked pSS patients (55.3%) were confirmed based on the DIS. Conclusion: Our study finds that GP electronic health records (EHRs) lack the granular information needed to apply the formal diagnostic criteria for pSS. The developed algorithm resulted in a patient selection that approximates the expected prevalence and characteristics, although only slightly over half of the patients were confirmed using the DIS. Without more detailed diagnostic information, the fitness for purpose of routine EHR data for patient identification and validation could not be determined

Rapid and Sustained Effect of Dupilumab on Work Productivity in Patients with Difficult-to-treat Atopic Dermatitis:Results from the Dutch BioDay Registry

Dupilumab treatment improves signs, symptoms, and quality of life in patients with moderate-to-severe atopic dermatitis. This study evaluated the impact of dupilumab treatment on absenteeism, presenteeism, and related costs in a large multi-centre cohort of adult patients with difficult-to-treat atopic dermatitis in daily practice. Patients treated with dupilumab participating in the Dutch BioDay Registry reporting employment were included. Absenteeism, presenteeism, and related costs at baseline and during follow-up were calculated using the Work Productivity and Activity Impairment questionnaire. A total of 218 adult patients with moderate-to-severe atopic dermatitis were included. Total work impairment reduced significantly from baseline (35.5%) to week 52 (11.5%), p &lt; 0.001. Median weekly productivity losses reduced significantly from baseline (€379.8 (140.7-780.8)) to week 52 (€0.0 (0.0-211.0), p &lt; 0.001). In this study, dupilumab treatment demonstrated a significant improvement in work productivity and reduction in associated costs in a large cohort of patients with difficult-to-treat atopic dermatitis in daily practice.</p

Prevalence and incidence rate of hospital admissions related to medication between 2008 and 2013 in The Netherlands

PURPOSE: In 2009 a Dutch guideline was published containing recommendations to reduce Hospital Admissions Related to Medications (HARMs). This study aims to examine time-trends of HARMs and their potential preventability between 2008 and 2013 in The Netherlands. METHODS: A retrospective prevalence study was conducted using the Dutch PHARMO Database Network. A semi-automated pre-selection was used to make a crude identification of possible HARMs of which four samples were selected. These were independently assessed with respect to causality and potential preventability by a physician and pharmacist. The results were stratified by age into 18-64 years and 65 years and older. For these groups the net prevalences and incidence rates of HARMs and potentially preventable HARMs were calculated for the years 2008, 2009, 2011 and 2013. RESULTS: Four samples of 467 (2008), 447 (2009), 446 (2011) and 408 (2013) admissions were assessed. The net prevalence of HARMs in the 18-64 years group was approximately four times smaller compared to the older group with a mean prevalence of 2.7% (95% confidence interval [CI]:2.4%-3.0%) and 10.2% (95%CI: 9.7%-10.7%) respectively. The potential preventability was 25.1% (18.4%-31.8%) and 48.3% (95%CI: 44.8%-51.8%), respectively. The prevalence of HARMs in both groups did not change significantly between 2008 and 2013 with 2.4% (95%CI: 1.9%-3.0%) and 10.0% (95%CI: 9.0%-11.0%) in 2008 and 3.1% (2.7%-3.5%) and 10.4% (95%CI: 9.4%-11.4%) in 2013, respectively. CONCLUSION: Despite efforts to reduce HARMs, the prevalence did not decrease over time. Additional measures are therefore necessary, especially in the elderly population

Exercising 'soft closure' on lay health knowledge? Harnessing the declining power of the medical profession to improve online health information

This study aims to address the increasingly complex medical predicament of low quality online health information contributing to lay health knowledge and consequently to clinical outcomes. We situate the predicament within a social change paradigm of individualism, choice, diminishing medical power, and emergence of the legitimacy of lay health knowledge. We contend that the prominence of lay health knowledge has been facilitated by the internet, and is due to a surge in broadcasting of experiential knowledge coupled with increased access to and enactment of medical and non-medically sanctioned online information on health and illness. We draw on and further test the application of social closure theory to help conceive a potential solution to this enduring problem. We conduct a quality assessment of an indicative case study, Apicectomies, and test the application of our notion of soft closure on its findings, resulting in targeted, feasible and potentially beneficial solutions to increasing the medical quality of online health information. We further present the extant application of soft closure by Healthtalkonline.org, which collates a medically reliable set of experiential knowledge on a range of health issues. As such, we propose a constructive re-enactment of the traditional closure of the medical profession on medical knowledge

Effects of structured involvement of the primary care team versus standard care after a cancer diagnosis on patient satisfaction and healthcare use: the GRIP randomised controlled trial

Background: The growing number of cancer survivors and treatment possibilities call for more personalised and integrated cancer care. Primary care seems well positioned to support this. We aimed to assess the effects of structured follow-up of a primary care team after a cancer diagnosis. Methods: We performed a multicentre randomised controlled trial enrolling patients curatively treated for breast, lung, colorectal, gynaecologic cancer or melanoma. In addition to usual cancer care in the control group, patients randomized to intervention were offered a “Time Out consultation” (TOC) with the general practitioner (GP) after diagnosis, and subsequent follow-up during and after treatment by a home care oncology nurse (HON). Primary outcomes were patient satisfaction with care (questionnaire: EORTC-INPATSAT-32) and healthcare utilisation. Intention-to-treat linear mixed regression analyses were used for satisfaction with care and other continuous outcome variables. The difference in healthcare utilisation for categorical data was calculated with a Pearson Chi-Square or a Fisher exact test and count data (none versus any) with a log-binomial regression. Results: We included 154 patients (control n = 77, intervention n = 77) who were mostly female (75%), mainly diagnosed with breast cancer (51%), and had a mean age of 61 (SD ± 11.9) years. 81% of the intervention patients had a TOC and 68% had HON contact. Satisfaction with care was high (8 out of 10) in both study groups. At 3 months after treatment, GP satisfaction was significantly lower in the intervention group on 3 of 6 subscales, i.e., quality (− 14.2 (95%CI -27.0;-1.3)), availability (− 15,9 (− 29.1;-2.6)) and information provision (− 15.2 (− 29.1;-1.4)). Patients in the intervention group visited the GP practice and the emergency department more often ((RR 1.3 (1.0;1.7) and 1.70 (1.0;2.8)), respectively). Conclusions: In conclusion, the GRIP intervention, which was designed to involve the primary care team during and after cancer treatment, increased the number of primary healthcare contacts. However, it did not improve patient satisfaction with care and it increased emergency department visits. As the high uptake of the intervention suggests a need of patients, future research should focus on optimizing the design and implementation of the intervention. Trial registration: GRIP is retrospectively (21/06/2016) registered in the ‘Netherlands Trial Register’ (NTR5909)

Allergenic Lipid Transfer Proteins from Plant-Derived Foods Do Not Immunologically and Clinically Behave Homogeneously: The Kiwifruit LTP as a Model

BACKGROUND: Food allergy is increasingly common worldwide. Tools for allergy diagnosis measuring IgE improved much since allergenic molecules and microarrays started to be used. IgE response toward allergens belonging to the same group of molecules has not been comprehensively explored using such approach yet. OBJECTIVE: Using the model of lipid transfer proteins (LTPs) from plants as allergens, including two new structures, we sought to define how heterogeneous is the behavior of homologous proteins. METHODS: Two new allergenic LTPs, Act d 10 and Act c 10, have been identified in green (Actinidia deliciosa) and gold (Actinidia chinensis) kiwifruit (KF), respectively, using clinically characterized allergic patients, and their biochemical features comparatively evaluated by means of amino acid sequence alignments. Along with other five LTPs from peach, mulberry, hazelnut, peanut, mugwort, KF LTPs, preliminary tested positive for IgE, have been immobilized on a microarray, used for IgE testing 1,003 allergic subjects. Comparative analysis has been carried out. RESULTS: Alignment of Act d 10 primary structure with the other allergenic LTPs shows amino acid identities to be in a narrow range between 40 and 55%, with a number of substitutions making the sequences quite different from each other. Although peach LTP dominates the IgE immune response in terms of prevalence, epitope recognition driven by sequence heterogeneity has been recorded to be distributed in a wide range of behaviors. KF LTPs IgE positive results were obtained in a patient subset IgE positive for the peach LTP. Anyhow, the negative results on homologous molecules allowed us to reintroduce KF in patients' diet. CONCLUSION: The biochemical nature of allergenic molecule belonging to a group of homologous ones should not be taken as proof of immunological recognition as well. The availability of panels of homologous molecules to be tested using microarrays is valuable to address the therapeutic intervention

Ligand binding to an Allergenic Lipid Transfer Protein Enhances Conformational Flexibility resulting in an Increase in Susceptibility to Gastroduodenal Proteolysis

Non-specific lipid transfer proteins (LTPs) are a family of lipid-binding molecules that are widely distributed across flowering plant species, many of which have been identified as allergens. They are highly resistant to simulated gastroduodenal proteolysis, a property that may play a role in determining their allergenicity and it has been suggested that lipid binding may further increase stability to proteolysis. It is demonstrated that LTPs from wheat and peach bind a range of lipids in a variety of conditions, including those found in the gastroduodenal tract. Both LTPs are initially cleaved during gastroduodenal proteolysis at three major sites between residues 39–40, 56–57 and 79–80, with wheat LTP being more resistant to cleavage than its peach ortholog. The susceptibility of wheat LTP to proteolyic cleavage increases significantly upon lipid binding. This enhanced digestibility is likely to be due to the displacement of Tyr79 and surrounding residues from the internal hydrophobic cavity upon ligand binding to the solvent exposed exterior of the LTP, facilitating proteolysis. Such knowledge contributes to our understanding as to how resistance to digestion can be used in allergenicity risk assessment of novel food proteins, including GMOs