Search Results (14)

Pharmacogenomics (PGx) has emerged as a powerful tool to personalize drug selection and dosing based on a patient’s genetic profile. However, there are a range of challenges that impede uptake in current clinical practice. For example, clinicians often express frustration with commercially available PGx panel tests, which fail to consistently include all key actionable PGx genes (according to the Clinical Pharmacogenetics Implementation Consortium (CPIC), Food and Drug Administration (FDA) PGx guidelines, or The Dutch Pharmacogenetics Working Group (DPWG) guidelines) and instead are too long with clinically unimportant information (unvalidated genotypes). Additionally, the lack of EMR integration, clinician education and awareness of the benefits of PGx impedes uptake. This paper examines key challenges identified in clinical practice and proposes future directions, focusing on limiting PGx reports to essential data, providing point-of-prescription alerts, and establishing reimbursement pathways that encourage adoption. Future directions include leveraging large language models, integrating point-of-prescription alerts and phenoconversion calculators into the electronic medical record, increasing the genomic diversity of PGx study populations, and streamlining coverage by payers. Full article

Deidentifying sensitive information in electronic health records (EHRs) is increasingly important as legal obligations to data privacy evolve along with the need to protect patient and institutional confidentiality. This study aims to comparatively evaluate the performance of two state-of-the-art deidentification systems, Deduce and Deidentify, on both real-world and synthetic Dutch medical texts, thereby providing insights into their relative strengths and limitations in preserving privacy while maintaining data utility. We employ a replication-extension research design, utilizing two distinct datasets: (1) the Annotation-Based Dataset from the Utrecht University Medical Center (UMC Utrecht), comprising manually annotated patient records spanning 1987 to 2021, and (2) the Synthetic Dataset, generated using a two-step process involving OpenAI’s GPT-4 model. Utilizing precision, recall, and $F_1$ scores as evaluation metrics, we uncover the relative strengths and limitations of the two methods. Our findings indicate that both techniques show variable performance across different entities of deidentifying text information. Deduce outperforms Deidentify in overall accuracy by a margin of 0.42 on the synthetic datasets. On the real-world annotation-based dataset, the generalization ability of Deidentify is lower than Deduce by 0.2. However, the performance of both techniques is affected by the limitations of the dataset. In conclusion, this study provides valuable insights into the comparative performance of Deduce and Deidentify for deidentifying Dutch EHRs, contributing to the development of more effective privacy preservation techniques in the healthcare domain. Full article

Background and Objectives: Observational studies with data from real-world clinical practice with patients with difficult-to-treat depression (DTD) are rare. This study aims to collect observational data from the real-world clinical practice of a Portuguese community mental health team (CMHT) on the prevalence of DTD and to explore differences between DTD and non-DTD groups. Materials and Methods: We conducted a retrospective chart review study using data from Electronic Health Records (EHRs) of adult patients with psychiatric disorders followed by a CMHT from the Department of Psychiatry of the Coimbra Local Health Unit (between 1 December 2020–31 December 2022). The Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD) was used to assess the degree of treatment resistance and the Charlson Comorbidity Index (CCI) to measure medical comorbidity. Results: A quantity of 473 patients were referred to Cantanhede CMHT for a first assessment. Of these, 219 patients met the criteria for a primary diagnosis of any depressive disorder. Assistant psychiatrists identified 57 patients with DTD during follow-up (approximately 26%). The DTD group had higher rates of depressive episodes, greater depression severity, increased service use, higher DM-TRD scores, and a higher prevalence of comorbid anxiety symptoms, personality disorders, and severe medical comorbidities. The DTD group also had a higher prescription rate of antidepressants. Differences were observed in the use of antidepressant augmentation strategies and in the prescription of anticoagulant/antiplatelet drugs and analgesics, with higher prescription rates in the DTD group. We found correlations between DM-TRD and CCI scores, and between DM-TRD scores and all service use variables. Conclusions: Our results are consistent with a similar study in the United Kingdom, highlighting the need for a different approach to the management of DTD patients, who continue to live with a significant burden despite usual pharmacological and non-pharmacological treatments. Full article

The COVID-19 pandemic has had a significant impact on healthcare systems worldwide, including the postponing or canceling of appointments and procedures for type 2 diabetes (T2D) care by general practitioners (GPs) in the Netherlands. The aim of this study was to investigate the impact of the COVID-19 pandemic on primary healthcare use and clinical measurements for people with T2D. Additionally, we aimed to determine if changes were observed among specific risk groups: (1) persons 70 years or older, or below 70 years, (2) patients who were meeting their HbA1c targets and those who were not, and (3) patients with high-risk and non-high-risk T2D. This retrospective cohort study among persons with T2D was conducted using data from the DIAbetes MANagement and Treatment (DIAMANT) data infrastructure, deriving data from electronic medical records of Dutch GPs. The study assessed GP visit counts, and counts and values of clinical measurements, including hemoglobin A1c (HbA1c), body mass index (BMI), low-density lipoprotein (LDL) cholesterol, and systolic blood pressure (SBP). Adjusted negative binomial (NB) regression and generalized estimating equations (GEE) models were used to estimate GP visit counts and population averages of clinical measurements, respectively, comparing 2019 (pre-pandemic) with 2020 (during the pandemic). Changes in specific groups were examined by stratifying outcomes for the aforementioned subgroups. The cohort consisted of 182,048 patients with T2D (47% female, mean age 69 ± 13 years) on 1 March 2019, of which 168,097 persons (92%) still contributed follow-up data in 2020. We observed an increase in total GP visits in 2020, with an adjusted rate ratio (RR) of 1.09 (95% CI 1.08–1.09). The frequency increased for office visits (RR 1.06; 1.06–1.07) and phone calls (RR 1.33; 1.31–1.35) but remained stable for home visits (RR 1.02; 0.99–1.04). On both population and individual levels, HbA1c values increased in 2020 by 1.65 (1.59–1.70) mmol/mol compared to 2019. Observed changes in 2020 for BMI, LDL, and SBP values were also statistically significant but small. Subgroup stratifications showed higher scores of all clinical measurements in younger persons (<70 years), those who met their HbA1c target, and non-high-risk T2D patients than their respective high-risk subgroups. During the first year of the COVID-19 pandemic in the Netherlands, changes in primary healthcare use were observed among persons with T2D, with an increase in GP office visits and phone calls and a decreased number of clinical measurements and GP home visits. HbA1c levels increased among patients with T2D in 2020. Further research is necessary to determine the impact of the COVID-19 pandemic on long-term clinical outcomes and (long-term) T2D complications. Full article

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classification only partially takes into account extraskeletal manifestations and the high genetic variability. Little is known about the relation between genetic variants and phenotype as of yet. The aim of the study was to create a clinically relevant genetic stratification of a cohort of 675 Dutch OI patients based on their pathogenic variant types and to provide an overview of their respective medical care demands. The clinical records of 675 OI patients were extracted from the Amsterdam UMC Genome Database and matched with the records from Statistics Netherlands (CBS). The patients were categorized based on their harbored pathogenic variant. The information on hospital admissions, outpatient clinic visits, medication, and diagnosis-treatment combinations (DTCs) was compared between the variant groups. OI patients in the Netherlands appear to have a higher number of DTCs, outpatient clinic visits, and hospital admissions when compared to the general Dutch population. Furthermore, medication usage seems higher in the OI cohort in comparison to the general population. The patients with a COL1A1 or COL1A2 dominant negative missense non-glycine substitution appear to have a lower health care need compared to the other groups, and even lower than patients with COL1A1 or COL1A2 haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient’s phenotype. Full article

In this study, the association of pretreatment physical and geriatric parameters with treatment tolerance and survival in elderly patients with stage I–II NSCLC was evaluated. Retrospective data for patients aged ≥70 years, diagnosed between 2016 and 2020 with stage I–II NSCLC, and who underwent surgery or stereotactic ablative radiotherapy (SABR) in a large Dutch teaching hospital were retrieved from medical records. Associations of pretreatment physical and geriatric parameters with treatment tolerance and survival were analyzed. Of 160 patients, 49 of 104 (47%) patients who underwent surgery and 21 of 56 (38%) patients who received SABR did not tolerate treatment. In univariable analysis, World Health Organization (WHO) performance status ≥ 2, short nutritional assessment questionnaire score > 1, short physical performance battery score ≤ 9, and geriatric-8 score ≤ 14 were significantly associated with postoperative complications. Forced expiratory volume of one second < 80% of predicted was significantly associated with intolerance of SABR. In multivariable analysis, WHO performance status ≥ 2 and diffusing capacity for carbon monoxide < 80% were significantly associated with decreased overall survival. This is the first study that investigated the association between pretreatment physical and geriatric parameters and treatment outcomes in patients with stage I–II NSCLC. Evaluation of physical and geriatric parameters before treatment initiation seems highly recommended to select patients who might benefit from preventive interventions before and/or during treatment. Full article

Background: How molecular profiles are associated with tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC) is incompletely understood. Therefore, we analyzed the TME and molecular profiles of HGSOC and assessed their associations with overall survival (OS). Methods: Patients with advanced-stage HGSOC treated in three Dutch hospitals between 2008–2015 were included. Patient data were collected from medical records. BRCA1/2 mutation, BRCA1 promotor methylation analyses, and copy number variations were used to define molecular profiles. Immune cells were assessed with immunohistochemical staining. Results: 348 patients were categorized as BRCA mutation (BRCAm) (BRCAm or promotor methylation) (30%), non-BRCA mutated HRD (19%), Cyclin E1 (CCNE1)-amplification (13%), non-BRCAmut HRD and CCNE1-amplification (double classifier) (20%), and no specific molecular profile (NSMP) (18%). BRCAm showed highest immune cell densities and CCNE1-amplification lowest. BRCAm showed the most favorable OS (52.5 months), compared to non-BRCAmut HRD (41.0 months), CCNE1-amplification (28.0 months), double classifier (27.8 months), and NSMP (35.4 months). Higher immune cell densities showed a favorable OS compared to lower, also within the profiles. CD8+, CD20+, and CD103+ cells remained associated with OS in multivariable analysis. Conclusions: Molecular profiles and TME are associated with OS. TME differs per profile, with higher immune cell densities showing a favorable OS, even within the profiles. HGSOC does not reflect one entity but comprises different entities based on molecular profiles and TME. Full article

Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care. Full article

Bloodstream infections (BSIs), especially those caused by Gram-negative rods (GNR) and viridans group streptococci (VGS), are common and potentially life-threatening complications of pediatric acute myeloid leukemia (AML) treatment. Limited literature is available on prophylactic regimens. We retrospectively evaluated the effect of different antibacterial prophylaxis regimens on the incidence of febrile neutropenic (FN) episodes and bacterial BSIs. Medical records of children (0–18 years) diagnosed with de novo AML and treated at two Dutch centers from May 1998 to March 2021 were studied. Data were analyzed per chemotherapy course and consecutive neutropenic period. A total of 82 patients had 316 evaluable courses: 92 were given with single-agent ciprofloxacin, 138 with penicillin plus ciprofloxacin, and 51 with teicoplanin plus ciprofloxacin. The remaining 35 courses with various other prophylaxis regimens were not statistically compared. During courses with teicoplanin plus ciprofloxacin, significantly fewer FN episodes (43 vs. 90% and 75%; p < 0.0001) and bacterial BSIs (4 vs. 63% and 33%; p < 0.0001) occurred than with single-agent ciprofloxacin and penicillin plus ciprofloxacin, respectively. GNR and VGS BSIs did not occur with teicoplanin plus ciprofloxacin and no bacterial BSI-related pediatric intensive care unit (PICU) admissions were required, whereas, with single-agent ciprofloxacin and penicillin plus ciprofloxacin, GNR BSIs occurred in 8 and 1% (p = 0.004), VGS BSIs in 24 and 14% (p = 0.0005), and BSI-related PICU admissions were required in 8 and 2% of the courses (p = 0.029), respectively. Teicoplanin plus ciprofloxacin as antibacterial prophylaxis is associated with a lower incidence of FN episodes and bacterial BSIs. This may be a good prophylactic regimen for pediatric AML patients during treatment. Full article

Sexually transmitted infections are one of the important risk factors for preterm delivery, which is among the important contributors to perinatal morbidity and mortality. The aim of this study was to assess the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in women with imminent preterm delivery in Curaçao, an island of the Dutch Caribbean. All women from Curaçao with either preterm premature rupture of the membranes or preterm labor, common indications of imminent preterm delivery, and presenting at the Curaçao Medical Center between 15 November 2019 and 31 December 2020, were included in this single cohort study. Data were retrospectively collected from medical records. The presence of Chlamydia trachomatis and Neisseria gonorrhoeae was assessed by Cepheid GeneXpert ^® (Xpert) CT/NG assay (Sunnyvale, CA, USA). In the included cohort, the prevalence of Chlamydia trachomatis infection was 15.5% and of Neisseria gonorrhoeae infection was 2.1%. All patients infected with Neisseria gonorrhoeae were co-infected with Chlamydia trachomatis. The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients with imminent preterm delivery in Curaçao is high. It is recommended to test all patients with imminent preterm delivery for these sexually transmitted infections and possibly consider testing all women in early pregnancy on the island. Full article

Huntington’s Disease (HD) is a rare, neurodegenerative disorder characterized by chorea, cognitive decline, and behavioral changes. Despite wide clinical use since the mid-1980s, tiapride was recently withdrawn from the Dutch market without rationale. Although alternatives are available, many patients experienced dysregulation after this unwanted change. We provide insight into the impact of sudden tiapride withdrawal by reviewing medical records of HD patients who were using tiapride at the time of withdrawal. In addition, we performed a systematic search in five databases on tiapride efficacy and its safety profile in HD. Original research and expert opinions were included. In our patient group on tiapride, 50% required tiapride import from abroad. Regarding the review, 12 articles on original datasets and three expert opinions were included. The majority of studies showed an improvement in chorea while patients were on tiapride. Due to limited sample sizes, not all studies performed statistical tests on their results. Fifty percent of clinical experts prefer tiapride as initial chorea monotherapy, especially when comorbid behavioral symptoms are present. Side effects are often rare and mild. No safety concerns were reported. In conclusion, tiapride is almost irreplaceable for some patients and is an effective and safe chorea treatment in HD. Full article

Almost all European citizens rank patient safety as very or fairly important in their country. However, few patient safety initiatives have been undertaken or implemented in Poland. The aim was to identify patient safety strategies perceived as important in Poland and compare them with those identified in an earlier Dutch study. A web-based survey was conducted among primary healthcare providers in Poland. The findings were compared with those obtained from eight other countries. The strategies regarded as most important in Poland included the use of integrated medical records for communication with specialists and others, patient-held medical records, acceptable workload in general practice, and availability of information technology. However, despite being seen as important, these strategies have not been widely implemented in Poland. This is the first study to identify strategies considered by primary care physicians in Poland to be important for improving patient safety. These strategies differed significantly from those indicated in other countries. Full article

Urinary tract infections in the elderly are common. Treatment with nitrofurantoin in men may not be sufficient if concomitant tissue involvement is present, resulting in treatment failure. The aim of this study is to determine the prevalence of nitrofurantoin failure in the elderly, and to assess the effect of gender and age. A retrospective observational study was conducted using a Dutch general practice medical record database of 21,789 men and 26,622 women aged 65 years or older in 2015. First, nitrofurantoin prescriptions in 2015 were analyzed. Nitrofurantoin failure (subsequent prescription of antibiotic within 30 days) for men, women, and different age categories were compared. The effect of age and gender was assessed using multivariate logistic regression. A total of 3537 patients had a first nitrofurantoin prescription in 2015; 506 men and 3031 women. Overall, 584 patients (17%) experienced nitrofurantoin failure; 135 (27%) men and 449 (15%) women. Male gender (odds ratio (OR) = 2.09, 95% confidence interval (CI) 1.68–2.61) and age (OR = 1.02, 95% CI 1.01–1.03) was associated with higher treatment failure. Our findings indicate that in a substantial number of elderly men, nitrofurantoin might not be the appropriate treatment. Nitrofurantoin, as a first choice in elderly men with urinary tract infections, should be reconsidered. Full article

Bariatric surgery is currently the most durable weight loss solution for patients with morbid obesity. The extent of weight loss achieved, however, is subject to variation due to various factors, including patients’ behaviour. In this study, we aimed to identify pre- and post-surgical predictors of weight loss following bariatric surgery. This prospective study included 57 participants who went through bariatric surgery (laparoscopic Roux-en-Y gastric bypass: n = 30; laparoscopic sleeve gastrectomy: n = 23; one anastomosis gastric bypass-mini gastric bypass: n = 4) in two tertiary referral hospitals. Consenting participants were assessed prior to surgery (T₀), and three months (T₁) and six months (T₂) after surgery. The assessment included interview and anthropometric measurements. The interview was done with the aid of instruments, including the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression screening and the Dutch Eating Behaviour Questionnaire (DEBQ) for eating behaviour assessment. Baseline comorbidity status was obtained from medical records. A Generalised Estimating Equation (GEE) was developed to determine predictors of weight loss. Participants in the study were mostly women (n = 37, 65%) with a mean age of 39.4 (SD = 10.01) years. The mean excess BMI loss (EBMIL) and total weight loss (TWL) at the sixth month was 63.31% and 23.83%, respectively. Anxiety, depression, and external eating scores reduced over time. Advancing age, high BMI, and higher scores for emotional and external eating emerged as significant negative predictors for TWL%. It can be concluded that the patients experienced substantial weight loss after surgery. Continuous monitoring of psychological well-being and eating behaviour are essential for optimal weight loss. Full article