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- Panneman, Daan M., et al.
(författare)
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Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- 2023
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media SA. - 2296-634X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
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| 2. |
- Wyns, A., et al.
(författare)
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The Biology of Stress Intolerance in Patients with Chronic Pain-State of the Art and Future Directions
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Stress has been consistently linked to negative impacts on physical and mental health. More specifically, patients with chronic pain experience stress intolerance, which is an exacerbation or occurrence of symptoms in response to any type of stress. The pathophysiological mechanisms underlying this phenomenon remain unsolved. In this state-of-the-art paper, we summarised the role of the autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis, the two major stress response systems in stress intolerance. We provided insights into such mechanisms based on evidence from clinical studies in both patients with chronic pain, showing dysregulated stress systems, and healthy controls supported by preclinical studies, highlighting the link between these systems and symptoms of stress intolerance. Furthermore, we explored the possible regulating role for (epi)genetic mechanisms influencing the ANS and HPA axis. The link between stress and chronic pain has become an important area of research as it has the potential to inform the development of interventions to improve the quality of life for individuals living with chronic pain. As stress has become a prevalent concern in modern society, understanding the connection between stress, HPA axis, ANS, and chronic health conditions such as chronic pain is crucial to improve public health and well-being.
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| 3. |
- Douglas, Pamela S, et al.
(författare)
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Comparison of an Initial Risk-Based Testing Strategy vs Usual Testing in Stable Symptomatic Patients With Suspected Coronary Artery Disease: The PRECISE Randomized Clinical Trial.
- 2023
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Ingår i: JAMA cardiology. - 2380-6591.
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Tidskriftsartikel (refereegranskat)abstract
- Trials showing equivalent or better outcomes with initial evaluation using coronary computed tomography angiography (cCTA) compared with stress testing in patients with stable chest pain have informed guidelines but raise questions about overtesting and excess catheterization.To test a modified initial cCTA strategy designed to improve clinical efficiency vs usual testing (UT).This was a pragmatic randomized clinical trial enrolling participants from December 3, 2018, to May 18, 2021, with a median of 11.8 months of follow-up. Patients from 65 North American and European sites with stable symptoms of suspected coronary artery disease (CAD) and no prior testing were randomly assigned 1:1 to precision strategy (PS) or UT.PS incorporated the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) minimal risk score to quantitatively select minimal-risk participants for deferred testing, assigning all others to cCTA with selective CT-derived fractional flow reserve (FFR-CT). UT included site-selected stress testing or catheterization. Site clinicians determined subsequent care.Outcomes were clinical efficiency (invasive catheterization without obstructive CAD) and safety (death or nonfatal myocardial infarction [MI]) combined into a composite primary end point. Secondary end points included safety components of the primary outcome and medication use.A total of 2103 participants (mean [SD] age, 58.4 [11.5] years; 1056 male [50.2%]) were included in the study, and 422 [20.1%] were classified as minimal risk. The primary end point occurred in 44 of 1057 participants (4.2%) in the PS group and in 118 of 1046 participants (11.3%) in the UT group (hazard ratio [HR], 0.35; 95% CI, 0.25-0.50). Clinical efficiency was higher with PS, with lower rates of catheterization without obstructive disease (27 [2.6%]) vs UT participants (107 [10.2%]; HR, 0.24; 95% CI, 0.16-0.36). The safety composite of death/MI was similar (HR, 1.52; 95% CI, 0.73-3.15). Death occurred in 5 individuals (0.5%) in the PS group vs 7 (0.7%) in the UT group (HR, 0.71; 95% CI, 0.23-2.23), and nonfatal MI occurred in 13 individuals (1.2%) in the PS group vs 5 (0.5%) in the UT group (HR, 2.65; 95% CI, 0.96-7.36). Use of lipid-lowering (450 of 900 [50.0%] vs 365 of 873 [41.8%]) and antiplatelet (321 of 900 [35.7%] vs 237 of 873 [27.1%]) medications at 1 year was higher in the PS group compared with the UT group (both P < .001).An initial diagnostic approach to stable chest pain starting with quantitative risk stratification and deferred testing for minimal-risk patients and cCTA with selective FFR-CT in all others increased clinical efficiency relative to UT at 1 year. Additional randomized clinical trials are needed to verify these findings, including safety.ClinicalTrials.gov Identifier: NCT03702244.
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| 4. |
- Udelson, James E, et al.
(författare)
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Deferred Testing in Stable Outpatients With Suspected Coronary Artery Disease: A Prespecified Secondary Analysis of the PRECISE Randomized Clinical Trial.
- 2023
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Ingår i: JAMA cardiology. - 2380-6591.
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines recommend deferral of testing for symptomatic people with suspected coronary artery disease (CAD) and low pretest probability. To our knowledge, no randomized trial has prospectively evaluated such a strategy.To assess process of care and health outcomes in people identified as minimal risk for CAD when testing is deferred.This randomized, pragmatic effectiveness trial included prespecified subgroup analysis of the PRECISE trial at 65 North American and European sites. Participants identified as minimal risk by the validated PROMISE minimal risk score (PMRS) were included.Randomization to a precision strategy using the PMRS to assign those with minimal risk to deferred testing and others to coronary computed tomography angiography with selective computed tomography-derived fractional flow reserve, or to usual testing (stress testing or catheterization with PMRS masked). Randomization was stratified by PMRS risk.Composite of all-cause death, nonfatal myocardial infarction (MI), or catheterization without obstructive CAD through 12 months.Among 2103 participants, 422 were identified as minimal risk (20%) and randomized to deferred testing (n = 214) or usual testing (n = 208). Mean age (SD) was 46 (8.6) years; 304 were women (72%). During follow-up, 138 of those randomized to deferred testing never had testing (64%), whereas 76 had a downstream test (36%) (at median [IQR] 48 [15-78] days) for worsening (30%), uncontrolled (10%), or new symptoms (6%), or changing clinician preference (19%) or participant preference (10%). Results were normal for 96% of these tests. The primary end point occurred in 2 deferred testing (0.9%) and 13 usual testing participants (6.3%) (hazard ratio, 0.15; 95% CI, 0.03-0.66; P = .01). No death or MI was observed in the deferred testing participants, while 1 noncardiovascular death and 1 MI occurred in the usual testing group. Two participants (0.9%) had catheterizations without obstructive CAD in the deferred testing group and 12 (5.8%) with usual testing (P = .02). At baseline, 70% of participants had frequent angina and there was similar reduction of frequent angina to less than 20% at 12 months in both groups.In symptomatic participants with suspected CAD, identification of minimal risk by the PMRS guided a strategy of initially deferred testing. The strategy was safe with no observed adverse outcome events, fewer catheterizations without obstructive CAD, and similar symptom relief compared with usual testing.ClinicalTrials.gov Identifier: NCT03702244.
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