Pharmacogenomic testing is a method to prevent adverse drug reactions. Pharmacogenomics could be relevant to optimize statin treatment, by identifying patients at high risk for adverse drug... Show morePharmacogenomic testing is a method to prevent adverse drug reactions. Pharmacogenomics could be relevant to optimize statin treatment, by identifying patients at high risk for adverse drug reactions. We aim to investigate the clinical validity and utility of pre-emptive pharmacogenomics screening in primary care, with SLCO1B1 c.521T>C as a risk factor for statin-induced adverse drug reactions. The focus was on changes in therapy as a proxy for adverse drug reactions observed in statin-users in a population-based Dutch cohort. In total, 1136 statin users were retrospectively genotyped for the SLCO1B1 c.521T>C polymorphism (rs4149056) and information on their statin dispensing was evaluated as cross-sectional research. Approximately half of the included participants discontinued or switched their statin treatment within three years. In our analyses, we could not confirm an association between the SLCO1B1 c.521T>C genotype and any change in statin therapy or arriving at a stable dose sooner in primary care. To be able to evaluate the predictive values of SLCO1B1 c.521T>C genotype on adverse drug reactions from statins, prospective data collection of actual adverse drug reactions and reasons to change statin treatment should be facilitated. Show less
Naruse, M.; Murakami, M.; Katabami, T.; Kocjan, T.; Parasiliti-Caprino, M.; Quinkler, M.; ... ; Suzuki, T. 2023
Objective: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain... Show moreObjective: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. Design: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. Results: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. Conclusions: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA. Show less
Verwaaijen, E.J.; Torre, P. van der; Vormoor, J.; Pieters, R.; Fiocco, M.; Hartman, A.; Heuvel-eibrink, M.M. van den 2023
Simple Summary Children treated for hemato-oncological diseases are at risk of muscle deterioration, such as loss of muscle mass and muscle weakness, with consequent impaired physical functioning.... Show moreSimple Summary Children treated for hemato-oncological diseases are at risk of muscle deterioration, such as loss of muscle mass and muscle weakness, with consequent impaired physical functioning. An easy screening tool will facilitate the early identification of children at risk and will support clinical decision making. We investigated the accuracy of an easy screening tool: the pediatric SARC-F (PED-SARC-F), for identifying functional sarcopenia in pediatric hemato-oncology patients. Functional sarcopenia indicates low muscle strength combined with low physical performance. We showed that the PED-SARC-F has a 90% accuracy in identifying pediatric hemato-oncology patients with functional sarcopenia. A PED-SARC-F cut-off point of >= 5 had the highest specificity (91%) and limits unnecessary assessments in patients who are not at risk of sarcopenia. This tool can be used to identify children that need a physiotherapy assessment and further interventions to prevent physical deterioration during and shortly after treatment for a hemato-oncology disease. Sarcopenia in pediatric hemato-oncology patients is undesirable because of the consequences it may have for treatment continuation and outcome, physical abilities and participation in daily life. An easy-to-use screening tool for sarcopenia will facilitate the identification of children at risk who need interventions to prevent serious physical deterioration. In the elderly, the use of the SARC-F score as a case-finding tool for sarcopenia is recommended. The aim of this cross-sectional study was to investigate the accuracy of the pediatric SARC-F (PED-SARC-F) for identifying sarcopenia in pediatric hemato-oncology patients, including the determination of a cut-off point for clinical use. Patients 3-20 years of age, under active treatment or within 12 months after treatment cessation were eligible. Patients had a physiotherapy assessment including a PED-SARC-F (0-10) and measurements of muscle strength (handheld dynamometry), physical performance (various tests) and/or muscle mass (bio-impedance analysis), as part of the standard of care. Spearman's correlation coefficient (r(s)) between the PED-SARC-F and physiotherapy outcomes were calculated. Structural sarcopenia was defined as low appendicular skeletal muscle mass (ASMM) in combination with low muscle strength and/or low physical performance. Functional sarcopenia indicated low muscle strength combined with low physical performance. Multiple logistic regression models were estimated to study the associations between the PED-SARC-F and structural/functional sarcopenia. To evaluate which cut-off point provides the most accurate classification, the area under the receiver operating characteristic curve (AUCs), sensitivity and specificity per point were calculated. In total, 215 assessments were included, 62% were performed in boys and the median age was 12.9 years (interquartile range: 8.5-15.8). The PED-SARC-F scores correlated moderately with the measurements of muscle strength (r(s) = -0.37 to -0.47, p < 0.001) and physical performance (r(s) = -0.45 to -0.66, p < 0.001), and weakly with ASMM (r(s) = -0.27, p < 0.001). The PED-SARC-F had an AUC of 0.90 (95% confidence interval (CI) = 0.84-0.95) for functional sarcopenia and 0.79 (95% CI = 0.68-0.90) for structural sarcopenia. A cut-off point of >= 5 had the highest specificity of 96% and a sensitivity of 74%.In conclusion, we adapted the SARC-F to a pediatric version, confirmed its excellent diagnostic accuracy for identifying functional sarcopenia and defined a clinically useful cut-off point in pediatric hemato-oncology patients. Show less
Wiese, M.; Schuren, F.H.J.; Smits, W.K.; Kuijper, E.J.; Ouwens, A.; Heerikhuisen, M.; ... ; Vossen, J.M.B.M. van der 2022
BackgroundClostridioides difficile is a Gram-positive anaerobic bacterium that can produce the toxins TcdA and/or TcdB and is considered an opportunistic pathogen. C. difficile is mainly... Show moreBackgroundClostridioides difficile is a Gram-positive anaerobic bacterium that can produce the toxins TcdA and/or TcdB and is considered an opportunistic pathogen. C. difficile is mainly transmitted as endospores, which germinate to produce the pathogenic vegetative cells under suitable conditions in the gut. To efficiently screen novel therapeutic- interventions against the proliferation of C. difficile within a complex microbial community, platforms are needed that facilitate parallel experimentation. In order to allow for screening of novel interventions a medium-to-high throughput in vitro system is desirable. To this end, we have developed the 96-well CDi-screen platform that employs an adapted simulated ileal effluent medium (CDi-SIEM) and allows for culturing of pathogenic C. difficile. MethodsC. difficile strain ATCC 43599 was inoculated in the form of vegetative cells and spores into the CDi-screen in the presence and absence of a cultured fecal microbiota and incubated for 48h. To demonstrate its utility, we investigated the effect of the human milk oligosaccharide 2'-Fucosyllactose (2'-FL) at 4 and 8 mg/mL on C. difficile outgrowth and toxin production in the CDi-screen. The test conditions were sampled after 24 and 48 hours. C. difficile -specific primers were used to monitor C. difficile growth via qPCR and barcoded 16S rRNA gene amplicon sequencing facilitated the in-depth analysis of gut microbial community dynamics. ResultsC. difficile ATCC 43599 proliferated in CDi-SIEM, both when inoculated as spores and as vegetative cells. The strain reached cell numbers expressed as C. difficile genome equivalents of up to 10 (8) cells per mL after 24h of incubation. 2'-FL significantly inhibited the outgrowth of the ATTC 43599 strain within a complex human gut microbial community in the CDi-screen. In addition, a dose-dependent modulation of the gut microbial community composition by 2'-FL supplementation was detected, with a significant increase in the relative abundance of the genus Blautia in the presence of 2'-FL. ConclusionThe CDi-screen is suitable for studying C. difficile proliferation in a complex gut ecosystem and for screening for anti-pathogenic interventions that target C. difficile directly and/or indirectly through interactions with the gut microbiota. Different doses of compounds such as in this study the dose of the human milk oligosaccharide 2'-FL can be screened for efficacy in the inhibition of C. difficile proliferation. Show less
Dysphagia care and management may differ between countries and healthcare settings. This study aims to describe the management and care of dysphagia in rehabilitation centres and health houses... Show moreDysphagia care and management may differ between countries and healthcare settings. This study aims to describe the management and care of dysphagia in rehabilitation centres and health houses across Norway. Two national surveys were developed targeting either managers or healthcare professionals. Both surveys focused on staff and client populations; screening and assessment of dysphagia; dysphagia management and interventions; staff training and education; and self-perceived quality of dysphagia care. A total of 71 managers and clinicians from 45 out of 68 identified rehabilitation centres and health houses in Norway completed the surveys. The resulting overall response rate was 72.1%. Significant differences in dysphagia care and management were identified between rehabilitation services across Norway. Rehabilitation centres and health houses often had neither a speech therapist among their staff nor had access to external healthcare professionals. Screening was most frequently performed using non-standardised water swallows and only limited data were available on non-instrumental assessments. None of the respondents reported having access to instrumental assessments. Dysphagia interventions mainly consisted of compensatory strategies, including bolus modification, with very infrequent use of rehabilitative interventions, such as swallow manoeuvres. Although almost half of all respondents perceived the overall quality of care for clients with eating and swallowing problems as good, lack of awareness of dysphagia and its symptoms, consequences and options for treatment may have influenced quality ratings. There is a need to raise awareness of dysphagia and provide training opportunities for healthcare professionals in both screening and assessment, and dysphagia care and management. Show less
Subclinical hypothyroidism (SCHT) is defined as a consistently elevated thyroid stimulating hormone (TSH) with a free T4 (fT4) within the reference range. This diagnosis may lead to additional... Show moreSubclinical hypothyroidism (SCHT) is defined as a consistently elevated thyroid stimulating hormone (TSH) with a free T4 (fT4) within the reference range. This diagnosis may lead to additional monitoring, levothyroxine therapy and increased patient concerns, despite lack of evidence of treatment benefit in older adults. In order to avoid this diagnosis, we evaluated the efficiency of fT4-based screening for thyroid dysfunction, in older adults in primary care and compared it with TSH-based screening. Individuals aged >65years in primary care were selected for this retrospective study when both TSH and fT4 were individually requested irrespective of the TSH value. Exclusion criteria were C-reactive protein > 10 mg/l or a history of thyroid hormone monitoring in the previous year. Screening based on fT4 instead of TSH decreased reflex testing from 23.8% to 11.2%. The positive predictive value (PPV) for clinical hypothyroidism increased from 17.3% to 52.2%. The negative predictive value was 96.1% with TSH-based screening versus 97.8% with fT4-based screening. Elevation of the TSH cutoff value from 4.2 to 6.5 mU/l resulted in a reflex test percentage of 12.5% and a PPV of 31.0%. Our results suggest that screening for thyroid dysfunction in older individuals in primary care can be improved by screening based on fT4 instead of TSH or by adjusting the TSH cutoff value. Adjustment of the screening strategy may be of interest to health policy makers because of potential cost reduction. From a patient perspective, medical concerns and unnecessary biochemical follow-up might be reduced by circumventing the diagnosis SCHT. Show less
Trzcionkowska, K.; Schalij-Delfos, N.E.; Akker-van Marle, E.M.E. van den 2022
Purpose: Evaluate possibilities to reduce the number of infants screened for retinopathy of prematurity (ROP) and investigate costs and number of infants detected of current and alternative... Show morePurpose: Evaluate possibilities to reduce the number of infants screened for retinopathy of prematurity (ROP) and investigate costs and number of infants detected of current and alternative screening strategies in the Netherlands. Methods: Prospective population-based study including clinical data from all infants born in 2017 and referred for ROP screening (NEDROP-2 study). Cost and effects of screening strategies were evaluated that differed on the criteria gestational age (GA), birth weight (BW) and presence of one or more specific risk factor(s) (RF): mechanical ventilation, sepsis, necrotizing enterocolitis, postnatal corticoids and/or hypotension treated with inotropic agents. RF obtained from the Dutch perinatal registry (Perined). Results: Of the possible efficient strategies, the annual costs varied from euro137 966 (inclusion of BW < 700, 63 infants eligible for screening, detection of 17/39 treated ROP) to euro492 689 (GA < 30 weeks and BW < 1250 grams, together with infants with GA 30-32 and BW 1250-1500 grams with presence of one more RF, 744 infants eligible for screening, all treated infants detected). Total annual costs of the current Dutch guideline that detects all infants that need treatment for ROP amount to euro552 143). Conclusion: The current Dutch ROP guideline can be improved by implementing new screening inclusion criteria. The most effective strategy detecting all severe and treated infants, reduces the number of screened infants by 24% compared to the current guideline and the overall annual costs by euro59454. Show less
Organ transplantation is performed worldwide, but policies regarding donor imaging are not uniform. An overview of the policies in different regions is missing. This study aims to investigate the... Show moreOrgan transplantation is performed worldwide, but policies regarding donor imaging are not uniform. An overview of the policies in different regions is missing. This study aims to investigate the various protocols worldwide on imaging in deceased organ donation. An online survey was created to determine the current policies. Competent authorities were approached to fill out the survey based on their current protocols. In total 32 of the 48 countries approached filled out the questionnaire (response rate 67%). In 16% of the countries no abdominal imaging is required prior to procurement. In 50%, abdominal ultrasound (US) is performed to screen the abdomen and in 19% an enhanced abdominal Computed Tomography (CT). In 15% of the countries both an unenhanced abdominal CT scan and abdominal US are performed. In 38% of the countries a chest radiographic (CXR) is performed to screen the thorax, in 28% only a chest CT, and in 34% both are performed. Policies regarding radiologic screening in deceased organ donors show a great variation between different countries. Consensus on which imaging method should be applied is missing. A uniform approach will contribute to quality and safety, justifying (inter)national exchange of organs. Show less
Meester, R.G.S.; Schootbrugge-vandermeer, H.J. van de; Breekveldt, E.C.H.; Jonge, L. de; Toes-Zoutendijk, E.; Kooyker, A.; ... ; Dutch colorectal canc screening working group 2022
Objectives: To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC).... Show moreObjectives: To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC). Design: Prognostic model. Setting: Dutch biennial FIT-based screening programme during 2014-2018. Participants: 265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 mu g Hb/g faeces) in rounds 1 and 2. Interventions: Colonoscopy follow-up in participants with a positive FIT (F-Hb >= 47 mu g Hb/g faeces). Main outcomes: We evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5-1.0), the degree of risk stratification and C-statistics in external validation. Results: Among study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept -0.008 to -0.099; slope 0.982-0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91). Conclusion: Participants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information. Show less
Slootweg, Y.M.; Zwiers, C.; Koelewijn, J.M.; Schoot, E. van der; Oepkes, D.; Kamp, I.L. van; Haas, M. de 2022
Objective To evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The... Show moreObjective To evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The second objective was assessment of the current prevalence of RhD immunisations. Design Prospective cohort study. Setting The Netherlands. Population Two-year nationwide cohort of alloimmunised RhD-negative women. Methods RhD-negative women in their first RhD immunised pregnancy were included for risk factor analysis. We compared risk factors for RhD immunisation, occurring either in the previous non-immunised pregnancy or in the index pregnancy, with national population data derived from the Dutch perinatal registration (Perined). Results In the 2-year cohort, data from 193 women were eligible for analysis. Significant risk factors in women previously experiencing a pregnancy of an RhD-positive child (n = 113) were: caesarean section (CS) (OR 1.7, 95% CI 1.1-2.6), perinatal death (OR 3.5, 95% CI 1.1-10.9), gestational age >42 weeks (OR 6.1, 95% CI 2.2-16.6), postnatal bleeding (>1000 ml) (OR 2.0, 95% CI 1.1-3.6), manual removal of the placenta (MRP) (OR 4.3, 95% CI 2.0-9.3); these factors often occurred in combination. The miscarriage rate was significantly higher than in the Dutch population (35% versus 12.-5%, P < 0.001). Conclusion Complicated deliveries, including cases of major bleeding and surgical interventions (CS, MRP), must be recognised as a risk factor, requiring estimation of fetomaternal haemorrhage volume and adjustment of RhIg dosing. The higher miscarriage rate suggests that existing RhIg protocols need adjustment or better compliance. Show less
Heart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target... Show moreHeart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target for reducing incident HF in DM. Left ventricular (LV) dysfunction secondary to DM is heterogeneous, with phenotypes including predominantly systolic, predominantly diastolic, and mixed dysfunction. Indeed, the pathogenesis of HF in this setting is heterogeneous. Effective management of this problem will require detailed phenotyping of the contributions of fibrosis, microcirculatory disturbance, abnormal metabolism, and sympathetic innervation, among other mechanisms. For this reason, an imaging strategy for the detection of HF risk needs to not only detect subclinical LV dysfunction (LVD) but also characterize its pathogenesis. At present, it is possible to identify individuals with DM at increased risk HF, and there is evidence that cardioprotection may be of benefit. However, there is insufficient justification for HF screening, because we need stronger evidence of the links between the detection of LVD, treatment, and improved outcome. This review discusses the options for screening for LVD, the potential means of identifying the underlying mechanisms, and the pathways to treatment. Show less
Optimizing emergency care for the aging population is an important future challenge, as the proportion of older patients at the emergency department (ED) rapidly increases. Older patients,... Show moreOptimizing emergency care for the aging population is an important future challenge, as the proportion of older patients at the emergency department (ED) rapidly increases. Older patients, particularly those who are frail, have a high risk of adverse outcomes after an ED visit, such as functional decline, institutionalization, and death. The ED can have a key position in identifying frail older patients who benefit most from comprehensive geriatric care [including delirium preventive measures, early evaluation of after-discharge care, and a comprehensive geriatric assessment (CGA)]. However, performing extensive frailty assessment is not suitable at the ED. Therefore, quick and easy-to-use instruments are needed to identify older patients at risk for adverse outcomes. This narrative review outlines the importance and complexity of frailty assessment at the ED. It aligns the available screening instruments, including clinical judgment as frailty assessment, and summarizes arguments for and against frailty assessment at the ED. Show less
Background Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based... Show moreBackground Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based contrast agent, screening with DCE-MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast-enhanced alternative to DCE is desirable.Purpose To investigate whether velocity selective arterial spin labeling (VS-ASL) can be used to identify increased perfusion and vascularity within breast lesions compared to surrounding tissue.Study Type Prospective.Population Eight breast cancer patients.Field Strength/Sequence A 3 T; VS-ASL with multislice single-shot gradient-echo echo-planar-imaging readout.Assessment VS-ASL scans were independently assessed by three radiologists, with 3-25 years of experience in breast radiology. Scans were scored on lesion visibility and artifacts, based on a 3-point Likert scale. A score of 1 corresponded to "lesions being distinguishable from background" (lesion visibility), and "no or few artifacts visible, artifacts can be distinguished from blood signal" (artifact score). A distinction was made between mass and nonmass lesions (based on BI-RADS lexicon), as assessed in the standard clinical exam.Statistical Tests Intra-class correlation coefficient (ICC) for interobserver agreement.Results The ICC was 0.77 for lesion visibility and 0.84 for the artifact score. Overall, mass lesions had a mean score of 1.27 on lesion visibility and 1.53 on the artifact score. Nonmass lesions had a mean score of 2.11 on lesion visibility and 2.11 on the artifact score.Data Conclusion We have demonstrated the technical feasibility of bilateral whole-breast perfusion imaging using VS-ASL in breast cancer patients.Evidence Level 1Technical Efficacy Stage 1 Show less
Early detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives,... Show moreEarly detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives, overdiagnosis). Furthermore, while breast cancer risk is highly variable within the population, most screening programs use age to determine eligibility. A risk-based approach is expected to improve the benefit-harm ratio of breast cancer screening programs. The PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project seeks to improve personalized risk assessment to allow for a cost-effective, population-based approach to risk-based screening and determine best practices for implementation in Canada. This commentary describes the four inter-related activities that comprise the PERSPECTIVE I&I project. 1: Identification and validation of novel moderate to high-risk susceptibility genes. 2: Improvement, validation, and adaptation of a risk prediction web-tool for the Canadian context. 3: Development and piloting of a socio-ethical framework to support implementation of risk-based breast cancer screening. 4: Economic analysis to optimize the implementation of risk-based screening. Risk-based screening and prevention is expected to benefit all women, empowering them to work with their healthcare provider to make informed decisions about screening and prevention. Show less
To improve early detection of autism spectrum disorder in preventive care, a Dutch guideline was developed 5 years ago. The guideline provides preventive care physicians at well-baby clinics action... Show moreTo improve early detection of autism spectrum disorder in preventive care, a Dutch guideline was developed 5 years ago. The guideline provides preventive care physicians at well-baby clinics action-oriented advice and describes a step-by-step approach for children identified at an increased risk for autism spectrum disorder during general healthcare surveillance. This qualitative study evaluated the guideline adherence and studied barriers regarding early detection of autism spectrum disorder at well-baby clinics. Semi-structured interviews were undertaken with 12 preventive care physicians (one representative per province). Interviews were analyzed using grounded theory. It was found that the vast majority of participants did not follow-up general surveillance with an autism spectrum disorder-specific screener as prescribed by the guideline. Six barriers, to be divided in personal, guideline-related and external factors, were found regarding early detection of autism spectrum disorder and adherence to the guideline. The results of this study highlight the importance of an integrative approach, raising awareness of the benefits regarding early detection of autism spectrum disorder in preventive care, the need of continuous investment in easy and accessible training and active screening, and a closer collaboration between preventive care organizations and autism spectrum disorder experts.Lay AbstractTo improve early detection of autism spectrum disorder in preventive care, a Dutch guideline was developed 5 years ago. The guideline provides preventive care physicians at well-baby clinics action-oriented advice and describes a step-by-step approach for children identified at an increased risk for autism spectrum disorder during general healthcare surveillance. The present qualitative study evaluated adherence to the guideline and studied barriers regarding early detection of autism spectrum disorder at well-baby clinics. Interviews were undertaken with 12 preventive care physicians (one representative per province). It was found that the vast majority of participants did not follow-up general surveillance with an autism spectrum disorder -specific screener as prescribed by the guideline. Six barriers (limited knowledge about autism spectrum disorder symptoms in infant and toddlerhood, professional attitude toward early detection, problems in discussing initial worries with parents, limited use of screening instruments, perceptions toward cultural and language differences and constraints regarding availability of healthcare services) were found. The results of this study highlight the importance of an integrative approach, raising awareness of the benefits regarding early detection of autism spectrum disorder in preventive care, the need of continuous investment in easy and accessible training and active screening, and a closer collaboration between preventive care organizations and autism spectrum disorder experts. Show less
Jong, M. de; Peters, S.A.E.; Ritter, R. de; Kallen, C.J.H. van der; Sep, S.J.S.; Woodward, M.; ... ; Vos, R.C. 2021
Background Insight in sex disparities in the detection of cardiovascular risk factors and diabetes-related complications may improve diabetes care. The aim of this systematic review is to study... Show moreBackground Insight in sex disparities in the detection of cardiovascular risk factors and diabetes-related complications may improve diabetes care. The aim of this systematic review is to study whether sex disparities exist in the assessment of cardiovascular risk factors and screening for diabetes-related complications.MethodsPubMed was systematically searched up to April 2020, followed by manual reference screening and citations checks (snowballing) using Google Scholar. Observational studies were included if they reported on the assessment of cardiovascular risk factors (HbA1c, lipids, blood pressure, smoking status, or BMI) and/or screening for nephropathy, retinopathy, or performance of feet examinations, in men and women with diabetes separately. Studies adjusting their analyses for at least age, or when age was considered as a covariable but left out from the final analyses for various reasons (i.e. backward selection), were included for qualitative analyses. No meta-analyses were planned because substantial heterogeneity between studies was expected. A modified Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to assess risk of bias.ResultsOverall, 81 studies were included. The majority of the included studies were from Europe or North America (84%).The number of individuals per study ranged from 200 to 3,135,019 and data were extracted from various data sources in a variety of settings. Screening rates varied considerably across studies. For example, screening rates for retinopathy ranged from 13% to 90%, with half the studies reporting screening rates less than 50%. Mixed findings were found regarding the presence, magnitude, and direction of sex disparities with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, with some evidence suggesting that women, compared with men, may be more likely to receive retinopathy screening and less likely to receive foot exams.ConclusionOverall, no consistent pattern favoring men or women was found with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, and screening rates can be improved for both sexes. Show less
Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable... Show morePancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: -57% for "Progressive-only" vs -41% for "Indolent Included"). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals. Show less
Grootveld, R. van; Paassen, J. van; Boer, M.G.J. de; Claas, E.C.J.; Kuijper, E.J.; Beek, M.T. van der; LUMC-COVID-19 Research Grp 2021
Background A high prevalence of COVID-19 associated pulmonary aspergillosis (CAPA) has been reported, though histopathological evidence is frequently lacking. To assess the clinical significance of... Show moreBackground A high prevalence of COVID-19 associated pulmonary aspergillosis (CAPA) has been reported, though histopathological evidence is frequently lacking. To assess the clinical significance of Aspergillus species in respiratory samples of mechanically ventilated COVID-19 patients, we implemented routine screening for Aspergillus in tracheal aspirate (TA).Patients/methods From all adult COVID-19 patients admitted to the intensive care unit (ICU), TA samples were collected twice a week for Aspergillus screening by PCR and or culture. Bronchoalveolar lavage (BAL) sampling was performed in patients with a positive screening result if possible. Clinical information was obtained from the electronic patient record and patients were categorised according to the recently published consensus case definition for CAPA.Results Our study population consisted of 63 predominantly (73%) male patients, with a median age of 62 years and total median ICU stay of 18 days. Aspergillus species were present in TA screening samples from 15 patients (24%), and probable CAPA was diagnosed in 11 (17%) patients. Triazole resistance was detected in one patient (14%). Concordance between TA and BAL was 86%, and all TA culture positives were confirmed in BAL. We were able to withhold treatment in three of fifteen patients with positive screening (20%) but negative BAL results.Conclusions Positive culture, molecular detection and or antigen detection of Aspergillus species do not equal infection. Until we understand the clinical relevance of Aspergillus species detected in respiratory samples of COVID-19 patients, minimal-invasive screening by TA is a feasible method to monitor patients. Positive screening results should be an indication to perform a BAL to rule out upper airway colonisation. Show less
Cardol, C.K.; Tommel, J.; Middendorp, H. van; Ciere, Y.; Sont, J.K.; Evers, A.W.M.; Dijk, S. van 2021
Many patients with lifestyle-related chronic diseases find it difficult to adhere to a healthy and active lifestyle, often due to psychosocial difficulties. The aim of the current study was to... Show moreMany patients with lifestyle-related chronic diseases find it difficult to adhere to a healthy and active lifestyle, often due to psychosocial difficulties. The aim of the current study was to develop an eHealth care pathway aimed at detecting and treating psychosocial and lifestyle-related difficulties that fits the needs and preferences of individual patients across various lifestyle-related chronic diseases. Each intervention component was developed by (1) developing initial versions based on scientific evidence and/or the Behavior Change Wheel; (2) co-creation: acquiring feedback from patients and health professionals; and (3) refining to address users' needs. In the final eHealth care pathway, patients complete brief online screening questionnaires to detect psychosocial and lifestyle-related difficulties, i.e., increased-risk profiles. Scores are visualized in personal profile charts. Patients with increased-risk profiles receive complementary questionnaires to tailor a 3-month guided web-based cognitive behavioral therapy intervention to their priorities and goals. Progress is assessed with the screening tool. This systematic development process with a theory-based framework and co-creation methods resulted in a personalized eHealth care pathway that aids patients to overcome psychosocial barriers and adopt a healthy lifestyle. Prior to implementation in healthcare, randomized controlled trials will be conducted to evaluate its cost-effectiveness and effectiveness on psychosocial, lifestyle, and health-related outcomes. Show less
