search
Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
18 Research products, page 1 of 2

  • Canada
  • Publications
  • Research data
  • Other research products
  • Restricted
  • Canadian Institutes of Health Research
  • Aurora Universities Network

10
arrow_drop_down
Relevance
arrow_drop_down
  • Restricted English
    Authors: 
    Sara García-Viñuales; Rashik Ahmed; Michele Sciacca; Valeria Lanza; Maria Laura Giuffrida; Stefania Zimbone; Valeria Romanucci; Armando Zarrelli; Corrado Bongiorno; Natalia Spinella; +4 more
    Publisher: American Chemical Society, Washington, D.C. , Stati Uniti d'America
    Country: Italy
    Project: EC | INCIPIT (665403), CIHR , NSERC

    Alzheimer's disease (AD) is linked to the abnormal accumulation of amyloid ? peptide (A?) aggregates in the brain. Silybin B, a natural compound extracted from milk thistle (Silybum marianum), has been shown to significantly inhibit A? aggregation in vitro and to exert neuroprotective properties in vivo. However, further explorations of silybin B's clinical potential are currently limited by three main factors: (a) poor solubility, (b) instability in blood serum, and (c) only partial knowledge of silybin's mechanism of action. Here, we address these three limitations. We demonstrate that conjugation of a trehalose moiety to silybin significantly increases both water solubility and stability in blood serum without significantly compromising its antiaggregation properties. Furthermore, using a combination of biophysical techniques with different spatial resolution, that is, TEM, ThT fluorescence, CD, and NMR spectroscopy, we profile the interactions of the trehalose conjugate with both A? monomers and oligomers and evidence that silybin may shield the "toxic" surfaces formed by the N-terminal and central hydrophobic regions of A?. Finally, comparative analysis with silybin A, a less active diastereoisomer of silybin B, revealed how even subtle differences in chemical structure may entail different effects on amyloid inhibition. The resulting insight on the mechanism of action of silybins as aggregation inhibitors is anticipated to facilitate the future investigation of silybin's therapeutic potential.

  • Restricted English
    Authors: 
    Marc A. Rodger; Jean-Christophe Gris; Johanna I.P. de Vries; Ida Martinelli; Évelyne Rey; Ekkehard Schleussner; Saskia Middeldorp; Risto Kaaja; Nicole Langlois; Tim Ramsay; +9 more
    Countries: France, Netherlands
    Project: CIHR

    International audience; BACKGROUND:Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and birth of a small-for-gestational-age (SGA) neonate. These complications are leading causes of maternal, fetal, and neonatal morbidity and mortality in high-income countries. Affected women are at high risk of recurrence in subsequent pregnancies; however, effective strategies to prevent recurrence are absent. Findings from our previous study-level meta-analysis suggested that low-molecular-weight heparin reduced the risk of recurrent placenta-mediated pregnancy complications. However, we identified significant heterogeneity in the results, possibly due to trial design or inclusion criteria. To identify which patients benefit from, and which outcomes are prevented by, low-molecular-weight heparin, we did an individual patient data meta-analysis.METHODS:We did a systematic review in May, 2013, which identified eight eligible randomised trials done between 2000 and 2013 of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. We excluded studies on the basis of the wrong population, the study being ongoing, inability to confirm eligibility of participants, intervention stopped too early, and no response from the principal investigator. We requested individual patient data from the study authors for eligible women (women pregnant at the time of the study with a history of previous pregnancy that had been complicated by one or more of the following: pre-eclampsia, placental abruption, birth of an SGA neonate [<10th percentile], pregnancy loss after 16 weeks' gestation, or two losses after 12 weeks' gestation) and recoded, combined, and analysed the data for our meta-analysis. The primary outcome was a composite of early-onset (<34 weeks) or severe pre-eclampsia, birth of an SGA neonate (<5th percentile), late pregnancy loss (≥20 weeks' gestation), or placental abruption leading to delivery, assessed on an intention-to-treat basis. We assessed risk of bias with the Cochrane Risk of Bias tool. This study is registered with PROSPERO, number CRD42013006249.FINDINGS:We analysed data from 963 eligible women in eight trials: 480 randomly assigned to low-molecular-weight heparin and 483 randomly assigned to no low-molecular-weight heparin. Overall, the risk of bias was not substantial enough to affect decisions regarding trial inclusion. Participants were mostly white (795/905; 88%) with a mean age of 30·9 years (SD 5·0) and 403/963 (42%) had thrombophilia. In the primary analysis, low-molecular-weight heparin did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (low-molecular-weight heparin 62/444 [14%] versus no low-molecular-weight heparin 95/443 (22%) absolute difference -8%, 95% CI -17·3 to 1·4, p=0·09; relative risk 0·64, 95% CI 0·36-1·11, p=0·11). We noted significant heterogeneity between single-centre and multicentre trials. In subgroup analyses, low-molecular-weight heparin in multicentre trials reduced the primary outcome in women with previous abruption (p=0·006) but not in any of the other subgroups of previous complications.INTERPRETATION:Low-molecular-weight heparin does not seem to reduce the risk of recurrent placenta-mediated pregnancy complications in at-risk women. However, some decreases in event rates might have been too small for the power of our study to explore.FUNDING:Canadian Institutes of Health Research.

  • Restricted English
    Authors: 
    Danielle M. Backes; Claire Bosire; Michael G. Hudgens; Ali Fokar; Kawango Agot; Felix Opiyo; Stephen Moses; Chris J.L.M. Meijer; Robert C. Bailey; Peter J.F. Snijders; +1 more
    Country: Netherlands
    Project: CIHR

    Prospective data are limited on human papillomavirus (HPV) acquisition and clearance among circumcised men from resource-limited geographical regions, particularly Africa. The goal of this study was to estimate incidence and clearance of type-specific genital HPV infection in men. Penile exfoliated cell specimens were collected from the glans/coronal sulcus and shaft of 1,037 circumcised Kenyan men at baseline and 6-, 12- and 18-month follow-up visits between 2003–2007. Specimens were tested with GP5+/6+ PCR to detect 44 HPV types. The median age of participants at baseline was 21 years (range 18–28). The 12- and 18-month incidence rates (IRs) for any HPV were 34.9/100 person-years (95% confidence interval [CI]: 31.2–39.0) and 36.4/100 person-years (95% CI: 32.9–40.2), respectively. The 18-month cumulative risk for high-risk HPV was 30% compared to 16% for low-risk HPV. Cumulative risk was not associated with age or anatomical site. The estimated probability of any HPV infection clearing by 12 months was 0.92. Time until HPV clearance was not associated with age, anatomical site, or whether HPV infection type was high-risk or low-risk. HPV IRs among circumcised men in this study were comparable to other circumcised populations.

  • Publication . Other literature type . Article . 2019
    Restricted English
    Authors: 
    Derrick Y. Tam; Faisal G. Bakaeen; Dmitriy N. Feldman; Philippe Kolh; Gaetano Antonio Lanza; Marc Ruel; Raffaele Piccolo; Stephen E. Fremes; Mario Gaudino;
    Country: Belgium
    Project: CIHR

    The management of severe left main (LM) disease remains controversial and continues to evolve as new evidence emerges. Patient selection for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) relies on both predicting mortality with CABG from clinical characteristics using the Society of Thoracic Surgeons (STS) risk score and anatomical complexity, using the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score. LM stenting techniques continue to evolve; for bifurcation lesions, the use of the double-kiss crush technique may reduce the incidence of late target vessel revascularization. In patients with acute coronary syndrome (ACS) complicated by cardiogenic shock, PCI is likely the first-line option in those with anatomically amenable disease, whereas all other stable non-ST-elevated ACS should be treated similar to stable ischemic heart disease. Outcomes comparing CABG and PCI have been recently examined in 2 large randomized clinical trials. In general, early outcomes of periprocedural myocardial infarction and stroke favoured PCI or were not different from outcomes with CABG. However, the conclusions of both trials are at present discordant with respect to late major adverse cardiac and cerebral events; additional follow-up of the trial patients is important for informed patient decision making. The appropriate mode of revascularization should be selected according to patient clinical characteristics and the complexity of the coronary lesions according to European and American guidelines. In those with low or intermediate SYNTAX scores, particularly with high surgical risk, PCI may be preferred to CABG in most other scenarios. A multidisciplinary heart team is recommended to help individualize revascularization decisions.

  • Restricted
    Authors: 
    Magri, Stefania; Daniela, Di Bella; Taroni, Franco;
    Publisher: Zenodo
    Project: CIHR

    Next Generation Sequencing data of leukodystrophy gene panel analysis and segregation study data Sudy supported by Italian Ministry of Health. Grant Numbers: GR2016_02363337, RF2016_02361285

  • Restricted English
    Authors: 
    Erin M Macri; James J Young; Lina Holm Ingelsrud; Karim M Khan; Berend Terluin; Carsten Bogh Juhl; Jackie L Whittaker; Adam G Culvenor; Kay M Crossley; Ewa M Roos;
    Country: Netherlands
    Project: CIHR

    ObjectiveWe synthesised and assessed credibility (ie, trustworthiness) of thresholds that define meaningful scores for patient-reported outcome measures (PROMs) following interventions for anterior cruciate ligament (ACL) tear or traumatic meniscus injury.DesignSystematic review, narrative synthesis.Data sourcesWe searched five databases, handsearched references of included studies and tracked citations.EligibilityIncluded studies investigated: individuals with ACL tear or meniscus injury; mean age <35 years; and PROM thresholds calculated using any method to define a minimal important change (MIC) or a meaningful post-treatment score (Patient Acceptable Symptom State (PASS) or Treatment Failure).ResultsWe included 18 studies (15 ACL, 3 meniscus). Three different methods were used to calculate anchor-based MICs across 9 PROMs, PASS thresholds across 4 PROMs and treatment failure for 1 PROM. Credibility was rated ‘high’ for only one study—an MIC of 18 for the Knee injury and Osteoarthritis Outcome Score Quality-of-life (KOOS-QOL) subscale (using the MID Credibility Assessment Tool). Where multiple thresholds were calculated among ‘low’ credibility thresholds in ACL studies, MICs converged to within a 10-point range for KOOS-Symptoms (−1.2 to 5.4) and function in daily living (activities of daily living, ADL 0.5–8.1) subscales, and the International Knee Documentation Committee Subjective Knee Form (7.1–16.2). Other PROM thresholds differed up to 30 points. PASS thresholds converged to within a 10-point range in KOOS-ADL for ACL tears (92.3–100), and KOOS-Symptoms (73-78) and KOOS-QOL (53-57) in meniscus injuries.ConclusionMeaningful PROM thresholds were highly susceptible to study heterogeneity. While PROM thresholds can aid interpretability in research and clinical practice, they should be cautiously interpreted.

  • Restricted
    Authors: 
    Eva Louwersheimer; Alfredo Ramirez; Carlos Cruchaga; Tim Becker; Johannes Kornhuber; Oliver Peters; Stefanie Heilmann; Jens Wiltfang; Frank Jessen; Pieter Jelle Visser; +7 more
    Country: Netherlands
    Project: CIHR

    We studied the association of SORL1 single-nucleotide polymorphisms genotypes with measures of pathology in patients with probable Alzheimer's disease (AD) using an endophenotype approach. We included (1) 133 patients from the German Dementia Competence Network (71 +/- 8 years; 50% females; Mini Mental State Examination [MMSE], 24 +/- 3); (2) 83 patients from the Alzheimer's Disease Neuroimaging Initiative (75 +/- 8 years; 45% females; MMSE, 24 +/- 2); and (3) 452 patients from the Amsterdam Dementia Cohort 66 +/- 8 years; 47% females; MMSE, 20 +/- 5). As endophenotype markers we used cognitive tests, cerebrospinal fluid (CSF) biomarkers amyloid-beta, total tau (tau), tau phosphorylated at threonine 181, and hippocampal atrophy. We measured 19 SORL1 SNP alleles. Genotype-endophenotype associations were determined by linear regression analyses. There was an association between rs2070045-G allele and increased CSF-tau and more hippocampal atrophy. Additionally, haplotype-based analyses revealed an association between haplotype rs11218340-A/rs3824966-G/rs3824968-A and higher CSF-tau and CSF-tau phosphorylated at threonine 181. In conclusion, we found that SORL1 SNP rs2070045-G allele was related to CSF-tau and hippocampal atrophy, 2 endophenotype markers of AD, suggesting that SORL1 may be implicated in the downstream pathology in AD.

  • Restricted English
    Authors: 
    Almar A L Kok; Mai Stafford; Theodore D. Cosco; Martijn Huisman; Dorly J. H. Deeg; Diana Kuh; Rachel Cooper;
    Country: Netherlands
    Project: CIHR

    BackgroundThere are substantial socioeconomic inequalities in functional limitations in old age. Resilience may offer new insights into these inequalities by identifying constellations of factors that protect some individuals from developing functional limitations despite socioeconomic adversity.MethodsData from 1973 participants in the Medical Research Council National Survey of Health and Development (Great Britain), followed from birth until age 60–64, were used. Functional limitations were defined as reporting difficulty with at least 1 of 16 activities at age 60–64. Lifetime socioeconomic adversity was based on socioeconomic trajectories, categorised into three adversity levels. Analysis of covariance and regression models were used to compare psychosocial factors and health-related behaviours between a ‘Resilient’ group (high adversity but no functional limitations) and five groups with other combinations of adversity and limitations.ResultsPrevalence of functional limitations in high, intermediate and low adversity groups was 44%, 30% and 23% in men, and 61%, 55% and 49% in women, respectively. Compared with the other high adversity group, the resilient group had a lower prevalence of childhood illness (12% vs 19%) and obesity throughout ages 43–64 (70% vs 55%). Partially adjusted models also showed higher adolescent self-management, lower neuroticism, higher prevalence of volunteer work and physical activity (age 60–64) and lower prevalence of smoking (age 43) in the resilient. Marital status and contact frequency were not associated with resilience.ConclusionResults suggest protection against childhood illness, health-behavioural factors and self-regulation as targets for interventions across life that may particularly benefit those with long-term exposure to socioeconomic adversity.

  • Restricted English
    Authors: 
    Faysal Benali; Manon Kappelhof; Johanna Ospel; Aravind Ganesh; Rosalie V McDonough; Alida A Postma; Robert-Jan Berend Goldhoorn; Charles B L M Majoie; Ido van den Wijngaard; Hester F Lingsma; +4 more
    Country: Netherlands
    Project: CIHR

    BackgroundPre-stroke dependent patients (modified Rankin Scale score (mRS) ≥3) were excluded from most trials on endovascular treatment (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Therefore, little evidence exists for EVT in those patients. We aimed to investigate the safety and benefit of EVT in pre-stroke patients with mRS score 3.MethodsWe used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in the Netherlands (MR CLEAN) Registry. All patients treated with EVT for anterior circulation AIS with pre-stroke mRS 3 were included. We assessed causes for dependence and compared patients with successful reperfusion (defined as expanded Thrombolysis in Cerebral Ischemia scale (eTICI) 2b–3) to patients without successful reperfusion. We used regression analyses with pre-specified adjustments. Our primary outcome was 90-day mRS 0–3 (functional improvement or return to baseline).ResultsA total of 192 patients were included, of whom 82 (43%) had eTICI <2b and 108 (56%) eTICI ≥2b. The median age was 80 years (IQR 73–87). Fifty-one of the 192 patients (27%) suffered from previous stroke and 36/192 (19%) had cardiopulmonary disease. Patients with eTICI ≥2b more often returned to their baseline functional state or improved (n=26 (26%) vs n=15 (19%); adjusted odds ratio (aOR) 2.91 (95% CI 1.08 to 7.82)) and had lower mortality rates (n=49 (49%) vs n=50 (64%); aOR 0.42 (95% CI 0.19 to 0.93)) compared with patients with eTICI <2b.ConclusionsAlthough patients with AIS with pre-stroke mRS 3 comprise a heterogenous group of disability causes, we observed improved outcomes when patients achieved successful reperfusion after EVT.

  • Restricted English
    Authors: 
    Maurice Pasternak; Zahra Shirzadi; Henk J. M. M. Mutsaerts; Erik Boot; Nancy J. Butcher; Bradley J. MacIntosh; Tracy Heung; Anne S. Bassett; Mario Masellis;
    Country: Netherlands
    Project: CIHR

    Objectives: Recurrent chromosome 22q11.2 deletions cause 22q11 deletion syndrome (22q11DS), a multisystem disorder associated with high rates of schizophrenia. Neuroanatomical changes on brain MRI have been reported in relation to 22q11DS. However, to date no 22q11DS neuroimaging studies have examined cerebral blood flow (CBF). This exploratory case-control study seeks to identify differences in regional cerebral blood flow between 22q11DS subjects and controls, and their association with psychotic symptoms. Methods: This study of 23 adults used arterial spin labelling MRI to investigate voxel-wise CBF in 22q11DS individuals compared with age- and sex-matched healthy controls. Results: Four significant clusters, involving the right and left putamen, right fusiform gyrus and left middle temporal gyrus, delineated significantly elevated CBF in individuals with 22q11DS compared to controls. Post-hoc analysis determined that this elevation in CBF trended with psychotic symptom diagnosis within the 22q11DS group. Conclusions: These findings suggest possible relevance to schizophrenia risk and support further functional neuroimaging studies of 22q11DS with larger sample sizes to improve our understanding of the underlying pathophysiology.

search
Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
18 Research products, page 1 of 2
  • Restricted English
    Authors: 
    Sara García-Viñuales; Rashik Ahmed; Michele Sciacca; Valeria Lanza; Maria Laura Giuffrida; Stefania Zimbone; Valeria Romanucci; Armando Zarrelli; Corrado Bongiorno; Natalia Spinella; +4 more
    Publisher: American Chemical Society, Washington, D.C. , Stati Uniti d'America
    Country: Italy
    Project: EC | INCIPIT (665403), CIHR , NSERC

    Alzheimer's disease (AD) is linked to the abnormal accumulation of amyloid ? peptide (A?) aggregates in the brain. Silybin B, a natural compound extracted from milk thistle (Silybum marianum), has been shown to significantly inhibit A? aggregation in vitro and to exert neuroprotective properties in vivo. However, further explorations of silybin B's clinical potential are currently limited by three main factors: (a) poor solubility, (b) instability in blood serum, and (c) only partial knowledge of silybin's mechanism of action. Here, we address these three limitations. We demonstrate that conjugation of a trehalose moiety to silybin significantly increases both water solubility and stability in blood serum without significantly compromising its antiaggregation properties. Furthermore, using a combination of biophysical techniques with different spatial resolution, that is, TEM, ThT fluorescence, CD, and NMR spectroscopy, we profile the interactions of the trehalose conjugate with both A? monomers and oligomers and evidence that silybin may shield the "toxic" surfaces formed by the N-terminal and central hydrophobic regions of A?. Finally, comparative analysis with silybin A, a less active diastereoisomer of silybin B, revealed how even subtle differences in chemical structure may entail different effects on amyloid inhibition. The resulting insight on the mechanism of action of silybins as aggregation inhibitors is anticipated to facilitate the future investigation of silybin's therapeutic potential.

  • Restricted English
    Authors: 
    Marc A. Rodger; Jean-Christophe Gris; Johanna I.P. de Vries; Ida Martinelli; Évelyne Rey; Ekkehard Schleussner; Saskia Middeldorp; Risto Kaaja; Nicole Langlois; Tim Ramsay; +9 more
    Countries: France, Netherlands
    Project: CIHR

    International audience; BACKGROUND:Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and birth of a small-for-gestational-age (SGA) neonate. These complications are leading causes of maternal, fetal, and neonatal morbidity and mortality in high-income countries. Affected women are at high risk of recurrence in subsequent pregnancies; however, effective strategies to prevent recurrence are absent. Findings from our previous study-level meta-analysis suggested that low-molecular-weight heparin reduced the risk of recurrent placenta-mediated pregnancy complications. However, we identified significant heterogeneity in the results, possibly due to trial design or inclusion criteria. To identify which patients benefit from, and which outcomes are prevented by, low-molecular-weight heparin, we did an individual patient data meta-analysis.METHODS:We did a systematic review in May, 2013, which identified eight eligible randomised trials done between 2000 and 2013 of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. We excluded studies on the basis of the wrong population, the study being ongoing, inability to confirm eligibility of participants, intervention stopped too early, and no response from the principal investigator. We requested individual patient data from the study authors for eligible women (women pregnant at the time of the study with a history of previous pregnancy that had been complicated by one or more of the following: pre-eclampsia, placental abruption, birth of an SGA neonate [<10th percentile], pregnancy loss after 16 weeks' gestation, or two losses after 12 weeks' gestation) and recoded, combined, and analysed the data for our meta-analysis. The primary outcome was a composite of early-onset (<34 weeks) or severe pre-eclampsia, birth of an SGA neonate (<5th percentile), late pregnancy loss (≥20 weeks' gestation), or placental abruption leading to delivery, assessed on an intention-to-treat basis. We assessed risk of bias with the Cochrane Risk of Bias tool. This study is registered with PROSPERO, number CRD42013006249.FINDINGS:We analysed data from 963 eligible women in eight trials: 480 randomly assigned to low-molecular-weight heparin and 483 randomly assigned to no low-molecular-weight heparin. Overall, the risk of bias was not substantial enough to affect decisions regarding trial inclusion. Participants were mostly white (795/905; 88%) with a mean age of 30·9 years (SD 5·0) and 403/963 (42%) had thrombophilia. In the primary analysis, low-molecular-weight heparin did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (low-molecular-weight heparin 62/444 [14%] versus no low-molecular-weight heparin 95/443 (22%) absolute difference -8%, 95% CI -17·3 to 1·4, p=0·09; relative risk 0·64, 95% CI 0·36-1·11, p=0·11). We noted significant heterogeneity between single-centre and multicentre trials. In subgroup analyses, low-molecular-weight heparin in multicentre trials reduced the primary outcome in women with previous abruption (p=0·006) but not in any of the other subgroups of previous complications.INTERPRETATION:Low-molecular-weight heparin does not seem to reduce the risk of recurrent placenta-mediated pregnancy complications in at-risk women. However, some decreases in event rates might have been too small for the power of our study to explore.FUNDING:Canadian Institutes of Health Research.

  • Restricted English
    Authors: 
    Danielle M. Backes; Claire Bosire; Michael G. Hudgens; Ali Fokar; Kawango Agot; Felix Opiyo; Stephen Moses; Chris J.L.M. Meijer; Robert C. Bailey; Peter J.F. Snijders; +1 more
    Country: Netherlands
    Project: CIHR

    Prospective data are limited on human papillomavirus (HPV) acquisition and clearance among circumcised men from resource-limited geographical regions, particularly Africa. The goal of this study was to estimate incidence and clearance of type-specific genital HPV infection in men. Penile exfoliated cell specimens were collected from the glans/coronal sulcus and shaft of 1,037 circumcised Kenyan men at baseline and 6-, 12- and 18-month follow-up visits between 2003–2007. Specimens were tested with GP5+/6+ PCR to detect 44 HPV types. The median age of participants at baseline was 21 years (range 18–28). The 12- and 18-month incidence rates (IRs) for any HPV were 34.9/100 person-years (95% confidence interval [CI]: 31.2–39.0) and 36.4/100 person-years (95% CI: 32.9–40.2), respectively. The 18-month cumulative risk for high-risk HPV was 30% compared to 16% for low-risk HPV. Cumulative risk was not associated with age or anatomical site. The estimated probability of any HPV infection clearing by 12 months was 0.92. Time until HPV clearance was not associated with age, anatomical site, or whether HPV infection type was high-risk or low-risk. HPV IRs among circumcised men in this study were comparable to other circumcised populations.

  • Publication . Other literature type . Article . 2019
    Restricted English
    Authors: 
    Derrick Y. Tam; Faisal G. Bakaeen; Dmitriy N. Feldman; Philippe Kolh; Gaetano Antonio Lanza; Marc Ruel; Raffaele Piccolo; Stephen E. Fremes; Mario Gaudino;
    Country: Belgium
    Project: CIHR

    The management of severe left main (LM) disease remains controversial and continues to evolve as new evidence emerges. Patient selection for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) relies on both predicting mortality with CABG from clinical characteristics using the Society of Thoracic Surgeons (STS) risk score and anatomical complexity, using the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score. LM stenting techniques continue to evolve; for bifurcation lesions, the use of the double-kiss crush technique may reduce the incidence of late target vessel revascularization. In patients with acute coronary syndrome (ACS) complicated by cardiogenic shock, PCI is likely the first-line option in those with anatomically amenable disease, whereas all other stable non-ST-elevated ACS should be treated similar to stable ischemic heart disease. Outcomes comparing CABG and PCI have been recently examined in 2 large randomized clinical trials. In general, early outcomes of periprocedural myocardial infarction and stroke favoured PCI or were not different from outcomes with CABG. However, the conclusions of both trials are at present discordant with respect to late major adverse cardiac and cerebral events; additional follow-up of the trial patients is important for informed patient decision making. The appropriate mode of revascularization should be selected according to patient clinical characteristics and the complexity of the coronary lesions according to European and American guidelines. In those with low or intermediate SYNTAX scores, particularly with high surgical risk, PCI may be preferred to CABG in most other scenarios. A multidisciplinary heart team is recommended to help individualize revascularization decisions.

  • Restricted
    Authors: 
    Magri, Stefania; Daniela, Di Bella; Taroni, Franco;
    Publisher: Zenodo
    Project: CIHR

    Next Generation Sequencing data of leukodystrophy gene panel analysis and segregation study data Sudy supported by Italian Ministry of Health. Grant Numbers: GR2016_02363337, RF2016_02361285

  • Restricted English
    Authors: 
    Erin M Macri; James J Young; Lina Holm Ingelsrud; Karim M Khan; Berend Terluin; Carsten Bogh Juhl; Jackie L Whittaker; Adam G Culvenor; Kay M Crossley; Ewa M Roos;
    Country: Netherlands
    Project: CIHR

    ObjectiveWe synthesised and assessed credibility (ie, trustworthiness) of thresholds that define meaningful scores for patient-reported outcome measures (PROMs) following interventions for anterior cruciate ligament (ACL) tear or traumatic meniscus injury.DesignSystematic review, narrative synthesis.Data sourcesWe searched five databases, handsearched references of included studies and tracked citations.EligibilityIncluded studies investigated: individuals with ACL tear or meniscus injury; mean age <35 years; and PROM thresholds calculated using any method to define a minimal important change (MIC) or a meaningful post-treatment score (Patient Acceptable Symptom State (PASS) or Treatment Failure).ResultsWe included 18 studies (15 ACL, 3 meniscus). Three different methods were used to calculate anchor-based MICs across 9 PROMs, PASS thresholds across 4 PROMs and treatment failure for 1 PROM. Credibility was rated ‘high’ for only one study—an MIC of 18 for the Knee injury and Osteoarthritis Outcome Score Quality-of-life (KOOS-QOL) subscale (using the MID Credibility Assessment Tool). Where multiple thresholds were calculated among ‘low’ credibility thresholds in ACL studies, MICs converged to within a 10-point range for KOOS-Symptoms (−1.2 to 5.4) and function in daily living (activities of daily living, ADL 0.5–8.1) subscales, and the International Knee Documentation Committee Subjective Knee Form (7.1–16.2). Other PROM thresholds differed up to 30 points. PASS thresholds converged to within a 10-point range in KOOS-ADL for ACL tears (92.3–100), and KOOS-Symptoms (73-78) and KOOS-QOL (53-57) in meniscus injuries.ConclusionMeaningful PROM thresholds were highly susceptible to study heterogeneity. While PROM thresholds can aid interpretability in research and clinical practice, they should be cautiously interpreted.

  • Restricted
    Authors: 
    Eva Louwersheimer; Alfredo Ramirez; Carlos Cruchaga; Tim Becker; Johannes Kornhuber; Oliver Peters; Stefanie Heilmann; Jens Wiltfang; Frank Jessen; Pieter Jelle Visser; +7 more
    Country: Netherlands
    Project: CIHR

    We studied the association of SORL1 single-nucleotide polymorphisms genotypes with measures of pathology in patients with probable Alzheimer's disease (AD) using an endophenotype approach. We included (1) 133 patients from the German Dementia Competence Network (71 +/- 8 years; 50% females; Mini Mental State Examination [MMSE], 24 +/- 3); (2) 83 patients from the Alzheimer's Disease Neuroimaging Initiative (75 +/- 8 years; 45% females; MMSE, 24 +/- 2); and (3) 452 patients from the Amsterdam Dementia Cohort 66 +/- 8 years; 47% females; MMSE, 20 +/- 5). As endophenotype markers we used cognitive tests, cerebrospinal fluid (CSF) biomarkers amyloid-beta, total tau (tau), tau phosphorylated at threonine 181, and hippocampal atrophy. We measured 19 SORL1 SNP alleles. Genotype-endophenotype associations were determined by linear regression analyses. There was an association between rs2070045-G allele and increased CSF-tau and more hippocampal atrophy. Additionally, haplotype-based analyses revealed an association between haplotype rs11218340-A/rs3824966-G/rs3824968-A and higher CSF-tau and CSF-tau phosphorylated at threonine 181. In conclusion, we found that SORL1 SNP rs2070045-G allele was related to CSF-tau and hippocampal atrophy, 2 endophenotype markers of AD, suggesting that SORL1 may be implicated in the downstream pathology in AD.

  • Restricted English
    Authors: 
    Almar A L Kok; Mai Stafford; Theodore D. Cosco; Martijn Huisman; Dorly J. H. Deeg; Diana Kuh; Rachel Cooper;
    Country: Netherlands
    Project: CIHR

    BackgroundThere are substantial socioeconomic inequalities in functional limitations in old age. Resilience may offer new insights into these inequalities by identifying constellations of factors that protect some individuals from developing functional limitations despite socioeconomic adversity.MethodsData from 1973 participants in the Medical Research Council National Survey of Health and Development (Great Britain), followed from birth until age 60–64, were used. Functional limitations were defined as reporting difficulty with at least 1 of 16 activities at age 60–64. Lifetime socioeconomic adversity was based on socioeconomic trajectories, categorised into three adversity levels. Analysis of covariance and regression models were used to compare psychosocial factors and health-related behaviours between a ‘Resilient’ group (high adversity but no functional limitations) and five groups with other combinations of adversity and limitations.ResultsPrevalence of functional limitations in high, intermediate and low adversity groups was 44%, 30% and 23% in men, and 61%, 55% and 49% in women, respectively. Compared with the other high adversity group, the resilient group had a lower prevalence of childhood illness (12% vs 19%) and obesity throughout ages 43–64 (70% vs 55%). Partially adjusted models also showed higher adolescent self-management, lower neuroticism, higher prevalence of volunteer work and physical activity (age 60–64) and lower prevalence of smoking (age 43) in the resilient. Marital status and contact frequency were not associated with resilience.ConclusionResults suggest protection against childhood illness, health-behavioural factors and self-regulation as targets for interventions across life that may particularly benefit those with long-term exposure to socioeconomic adversity.

  • Restricted English
    Authors: 
    Faysal Benali; Manon Kappelhof; Johanna Ospel; Aravind Ganesh; Rosalie V McDonough; Alida A Postma; Robert-Jan Berend Goldhoorn; Charles B L M Majoie; Ido van den Wijngaard; Hester F Lingsma; +4 more
    Country: Netherlands
    Project: CIHR

    BackgroundPre-stroke dependent patients (modified Rankin Scale score (mRS) ≥3) were excluded from most trials on endovascular treatment (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Therefore, little evidence exists for EVT in those patients. We aimed to investigate the safety and benefit of EVT in pre-stroke patients with mRS score 3.MethodsWe used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in the Netherlands (MR CLEAN) Registry. All patients treated with EVT for anterior circulation AIS with pre-stroke mRS 3 were included. We assessed causes for dependence and compared patients with successful reperfusion (defined as expanded Thrombolysis in Cerebral Ischemia scale (eTICI) 2b–3) to patients without successful reperfusion. We used regression analyses with pre-specified adjustments. Our primary outcome was 90-day mRS 0–3 (functional improvement or return to baseline).ResultsA total of 192 patients were included, of whom 82 (43%) had eTICI <2b and 108 (56%) eTICI ≥2b. The median age was 80 years (IQR 73–87). Fifty-one of the 192 patients (27%) suffered from previous stroke and 36/192 (19%) had cardiopulmonary disease. Patients with eTICI ≥2b more often returned to their baseline functional state or improved (n=26 (26%) vs n=15 (19%); adjusted odds ratio (aOR) 2.91 (95% CI 1.08 to 7.82)) and had lower mortality rates (n=49 (49%) vs n=50 (64%); aOR 0.42 (95% CI 0.19 to 0.93)) compared with patients with eTICI <2b.ConclusionsAlthough patients with AIS with pre-stroke mRS 3 comprise a heterogenous group of disability causes, we observed improved outcomes when patients achieved successful reperfusion after EVT.

  • Restricted English
    Authors: 
    Maurice Pasternak; Zahra Shirzadi; Henk J. M. M. Mutsaerts; Erik Boot; Nancy J. Butcher; Bradley J. MacIntosh; Tracy Heung; Anne S. Bassett; Mario Masellis;
    Country: Netherlands
    Project: CIHR

    Objectives: Recurrent chromosome 22q11.2 deletions cause 22q11 deletion syndrome (22q11DS), a multisystem disorder associated with high rates of schizophrenia. Neuroanatomical changes on brain MRI have been reported in relation to 22q11DS. However, to date no 22q11DS neuroimaging studies have examined cerebral blood flow (CBF). This exploratory case-control study seeks to identify differences in regional cerebral blood flow between 22q11DS subjects and controls, and their association with psychotic symptoms. Methods: This study of 23 adults used arterial spin labelling MRI to investigate voxel-wise CBF in 22q11DS individuals compared with age- and sex-matched healthy controls. Results: Four significant clusters, involving the right and left putamen, right fusiform gyrus and left middle temporal gyrus, delineated significantly elevated CBF in individuals with 22q11DS compared to controls. Post-hoc analysis determined that this elevation in CBF trended with psychotic symptom diagnosis within the 22q11DS group. Conclusions: These findings suggest possible relevance to schizophrenia risk and support further functional neuroimaging studies of 22q11DS with larger sample sizes to improve our understanding of the underlying pathophysiology.