| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 3. |
- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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| 4. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 5. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 6. |
- Prins, J. T. H., et al.
(författare)
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Surgical stabilization versus nonoperative treatment for flail and non-flail rib fracture patterns in patients with traumatic brain injury
- 2022
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1863-9941. ; 48:4, s. 3327-3338
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Literature on outcomes after SSRF, stratified for rib fracture pattern is scarce in patients with moderate to severe traumatic brain injury (TBI; Glasgow Coma Scale <= 12). We hypothesized that SSRF is associated with improved outcomes as compared to nonoperative management without hampering neurological recovery in these patients. Methods A post hoc subgroup analysis of the multicenter, retrospective CWIS-TBI study was performed in patients with TBI and stratified by having sustained a non-flail fracture pattern or flail chest between January 1, 2012 and July 31, 2019. The primary outcome was mechanical ventilation-free days and secondary outcomes were in-hospital outcomes. In multivariable analysis, outcomes were assessed, stratified for rib fracture pattern. Results In total, 449 patients were analyzed. In patients with a non-flail fracture pattern, 25 of 228 (11.0%) underwent SSRF and in patients with a flail chest, 86 of 221 (38.9%). In multivariable analysis, ventilator-free days were similar in both treatment groups. For patients with a non-flail fracture pattern, the odds of pneumonia were significantly lower after SSRF (odds ratio 0.29; 95% CI 0.11-0.77; p = 0.013). In patients with a flail chest, the ICU LOS was significantly shorter in the SSRF group (beta, - 2.96 days; 95% CI - 5.70 to - 0.23; p = 0.034). Conclusion In patients with TBI and a non-flail fracture pattern, SSRF was associated with a reduced pneumonia risk. In patients with TBI and a flail chest, a shorter ICU LOS was observed in the SSRF group. In both groups, SSRF was safe and did not hamper neurological recovery.
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| 7. |
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| 8. |
- Buffart, L. M., et al.
(författare)
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Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer : Aggregate data and individual patient data meta-analyses
- 2020
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Ingår i: Clinical Psychology Review. - : Elsevier BV. - 0272-7358 .- 1873-7811. ; 80
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects.METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs.RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (β = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (β = -0.16,95%CI = -0.25;-0.07) and anxiety (β = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05).CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.
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| 9. |
- Prins, H. A. B., et al.
(författare)
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Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naive individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA)
- 2023
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier. - 0924-8579 .- 1872-7913. ; 61:1
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Tidskriftsartikel (refereegranskat)abstract
- To the authors' knowledge, there is currently no literature or guidance recommendation regard-ing whether the dose of dolutegravir (DTG) should be increased when co-administered with darunavir/ritonavir (DRV/r) in patients with acute human immunodeficiency virus infection (AHI). This study assessed the pharmacokinetics (PK) of twice-daily (BID) DTG and once-daily (QD) DRV/r, and com-pared this with DTG QD without DRV/r in patients with AHI. Forty-six participants initiated antiretro-viral therapy within < 24 h of enrolment: DTG 50 mg BID, DRV/r 80 0/10 0 mg QD, and two nucleoside reverse transcriptase inhibitors (NRTIs) for 4 weeks (Phase I); and DTG 50 mg QD with two NRTIs there-after (Phase II: reference). Total DTG trough concentration (Ctrough) and area under the concentration-time profile of 0-24 h (AUC0-24h) were predicted using a population PK model. DTG glucuronidation metabolic ratio (MR) and DTG free fraction were determined and compared per treatment phase using geometric mean ratio (GMR) and 90% confidence interval (CI). Participants had a predicted geometric mean steady-state DTG Ctrough of 2.83 [coefficient of variation (CV%) 30.3%] mg/L (Phase I) and 1.28 (CV% 52.4%) mg/L (Phase II), with GMR of 2.20 (90% CI 1.90-2.55). Total exposure during DTG BID increased but did not double [AUC0-24h GMR 1.65 (90% CI 1.50-1.81) h.mg/L]. DTG glucuronidation MR increased by approxi-mately 29% during Phase I. DTG Ctrough was above in-vivo EC90 (0.32 mg/L) during both phases, except in one participant during Phase I. At Week 8, 84% of participants had viral loads <= 40 copies/mL. The drug-drug interaction between DTG (BID) and DRV/r (QD) was due to induced glucuronidation, and is not clinically relevant in patients with AHI.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
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| 10. |
- Dekker, Joost, et al.
(författare)
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Definition and Characteristics of Behavioral Medicine, and Main Tasks and Goals of the International Society of Behavioral Medicine : an International Delphi Study
- 2021
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Ingår i: International Journal of Behavioral Medicine. - New York : Springer. - 1070-5503 .- 1532-7558. ; 28:3, s. 268-276
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the past decades, behavioral medicine has attained global recognition. Due to its global reach, a critical need has emerged to consider whether the original definition of behavioral medicine is still valid, comprehensive, and inclusive, and to reconsider the main tasks and goals of the International Society of Behavioral Medicine (ISBM), as the umbrella organization in the field. The purpose of the present study was to (i) update the definition and scope of behavioral medicine and its defining characteristics; and (ii) develop a proposal on ISBM's main tasks and goals.Method: Our study used the Delphi method. A core group prepared a discussion paper. An international Delphi panel rated questions and provided comments. The panel intended to reach an a priori defined level of consensus (i.e., 70%).Results: The international panel reached consensus on an updated definition and scope of behavioral medicine as a field of research and practice that builds on collaboration among multiple disciplines. These disciplines are concerned with development and application of behavioral and biomedical evidence across the disease continuum in clinical and public health domains. Consensus was reached on a proposal for ISBM's main tasks and goals focused on supporting communication and collaboration across disciplines and participating organizations; stimulating research, education, and practice; and supporting individuals and organizations in the field.Conclusion: The consensus on definition and scope of behavioral medicine and ISBM's tasks and goals provides a foundational step toward achieving these goals.
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| 11. |
- Prins, Jonne T H, et al.
(författare)
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Outcome after surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures and moderate to severe traumatic brain injury (CWIS-TBI).
- 2021
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Ingår i: The journal of trauma and acute care surgery. - 2163-0763. ; 90:3, s. 492-500
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Tidskriftsartikel (refereegranskat)abstract
- Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared to nonoperative management, is associated with favorable outcomes in patients with TBI.A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were Intensive Care Unit (ICU-LOS) and hospital length of stay (HLOS), tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS 9-12) and severe (GCS ≤8) TBI.The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. SSRF was performed at a median of 3 days and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (OR 0.59 (95% CI 0.38-0.98), p=0.043) and 30-day mortality (OR 0.32 (95% CI 0.11-0.91), p=0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (0.19 (95% CI 0.04-0.88), p=0.034).In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI.Therapeutic, level IV.
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| 12. |
- Prins, Jonne T H, et al.
(författare)
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Surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures following cardiopulmonary resuscitation: An international, retrospective matched case-control study.
- 2022
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Ingår i: The journal of trauma and acute care surgery. - 2163-0763. ; 93:6, s. 727-735
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Tidskriftsartikel (refereegranskat)abstract
- The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay (LOS). Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR.An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012, and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU LOS.Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28 [72%] vs. n = 31 [47%]; p = 0.015) and a higher median number of displaced ribs (2 [P 25 -P 75 , 0-3] vs. 0 [P 25 -P 75 , 0-3]; p = 0.014). Surgical stabilization of rib fractures was performed at a median of 5 days (P 25 -P 75 , 3-8 days) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days [P 25 -P 75 , 9-23 days] vs. 9 days [P 25 -P 75 , 5-15 days]; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar.Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated. A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other nonradiographic or injury-related variables.Therapeutic/Care Management; Level III.
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| 13. |
- Vermunt, L., et al.
(författare)
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Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean +/- SD age = 64 +/- 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95-0.99]), high education (OR = 1.64 [1.23-2.17]), male sex (OR = 1.56 [1.19-2.04]), and positive family history of dementia (OR = 1.66 [1.19-2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02-1.10]) and APOE e4 allele carriership (OR = 2.99 [1.81-4.94]). These results were similar across prescreen settings. Conclusions Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.
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| 14. |
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| 15. |
- Kullberg, R. F. J., et al.
(författare)
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Gut microbiota of adults with asthma is broadly similar to non-asthmatics in a large population with varied ethnic origins
- 2021
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Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0976 .- 1949-0984. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial gut communities might predispose children to develop asthma. Yet, little is known about the role of these micro-organisms in adult asthmatics. We aimed to profile the relationship between fecal microbiota and asthma in a large-scale, ethnically diverse, observational cohort of adults. Fecal microbiota composition of 1632 adults (172 asthmatics and 1460 non-asthmatics) was analyzed using 16S ribosomal RNA gene sequencing. Using extremely randomized trees machine learning models, we assessed the discriminatory ability of gut bacterial features to identify asthmatics from non-asthmatics. Asthma contributed 0.019% to interindividual dissimilarities in intestinal microbiota composition, which was not significant (P = .97). Asthmatics could not be distinguished from non-asthmatics based on individual microbiota composition by an extremely randomized trees classifier model (area under the receiver operating characteristic curve = 0.54). In conclusion, there were no prominent differences in fecal microbiota composition in adult asthmatics when compared to non-asthmatics in an urban, large-sized and ethnically diverse cohort.
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| 16. |
- McMichael, C. N. H., et al.
(författare)
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30,000 years of landscape and vegetation dynamics in a mid-elevation Andean valley
- 2021
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Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 258
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Tidskriftsartikel (refereegranskat)abstract
- The mid-elevation settings of the Andes are important biodiversity hotspots, yet little is known of their long-term ecology or environmental change. Here, we assess 30,000 years of landscape and vegetation dynamics on an alluvial terrace located in a mid-elevation valley of the Ecuadorian Andes (Campo Libre). We used loss-on-ignition and particle size analysis to reconstruct past river dynamics, charcoal analysis to reconstruct past fire regimes, and phytolith analysis to reconstruct vegetation change through time. Our results show that Campo Libre was a part of the active floodplain system of the Quijos River until 18,000 cal yr BP. The biggest vegetation change in vegetation at Campo Libre occurred ca. 13,000 cal yr BP, when the site warmed and dried, transforming the swampy alluvial terrace into a palm forest. As Ho-locene precipitation increased, the site transformed back into a swamp around 7500 cal yr BP, and it remained that way until maize agriculture began around 4600 cal yr BP. Local and regional fires were absent from the system until regional fires were detected ca. 3300 cal yr BP. By ca. 2700 cal yr BP, maize cultivation became frequent and regular. Climate, tectonic activity, and the human history have shaped the modern vegetation around Campo Libre, although during different periods of the Holocene. Our results demonstrate the ability of phytoliths to reconstruct vegetation change through time, and show that the mid-elevation Andean valley systems were highly dynamic over the last 30,000 years.
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| 17. |
- Xu, Yu, et al.
(författare)
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An atlas of genetic scores to predict multi-omic traits
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 616:7955, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.
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| 18. |
- Ulugut, Hulya, et al.
(författare)
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The natural history of primary progressive aphasia : beyond aphasia
- 2022
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 269:3, s. 1375-1385
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Primary progressive aphasia (PPA) is divided into three prototypical subtypes that are all characterized by their single core symptom of aphasia. Although later in their course, other cognitive, behavioral, and motor domains may become involved, little is known about the progression profile of each subtype relative to the other subtypes. Methods: In this longitudinal retrospective cohort study, based on the recent biomarker-supported diagnostic criteria, 24 subjects diagnosed with semantic variant (svPPA), 22 with non-fluent variant (nfvPPA), and 18 with logopenic variant (lvPPA) were collected and followed up for 1–6 years. Symptom distribution, cognitive test and neuropsychiatric inventory scores, and progression into another syndrome were assessed. Results: Over time, lvPPA progressed with broader language problems (PPA-extended) and nfvPPA progressed to mutism, whereas semantic impairment remained the major problem in svPPA. Apart from linguistic problems, svPPA developed pronounced behavioral disturbances, whereas lvPPA exhibited a greater cognitive decline. By contrast, in nfvPPA motor deficits were more common. Furthermore, within 5 years (IQR = 2.5) after clinical onset, 65.6% of the patients additionally fulfilled the clinical criteria for another neurodegenerative syndrome (PPA-plus). Fourteen out of 24 (58%) svPPA patients additionally met the diagnostic criteria of behavioral variant frontotemporal dementia (5.1 years, IQR = 1.1), whereas the clinical features of 15/18 (83%) lvPPA patients were consistent with Alzheimer disease dementia (4.5 years IQR = 3.4). Furthermore, 12/22 (54%) of the subjects with the nfvPPA progressed to meet the diagnostic criteria of corticobasal syndrome, progressive supranuclear palsy, or motor neuron disease (5.1 years IQR = 3.4). Discussion: Despite aphasia being the initial and unique hallmark of the syndrome, our longitudinal results showed that PPA is not a language limited disorder and progression differs widely for each subtype, both with respect to the nature of symptoms and disease duration.
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| 19. |
- Waeijen-Smit, Kiki, et al.
(författare)
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Global mortality and readmission rates following COPD exacerbation-related hospitalisation : a meta-analysis of 65 945 individual patients
- 2024
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods A systematic review was performed identifying studies that reported in-hospital mortality, postdischarge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations < 12 months prior to the index event. Conclusions This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.
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