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  • 1
    In: European Child & Adolescent Psychiatry, Springer Science and Business Media LLC, Vol. 31, No. 8 ( 2022-08), p. 1-12
    Abstract: This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD ( n  = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period ( n  = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment ( n  = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p   〈  0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36–0.84, p  = 0.01) and was inversely associated with ADHD symptom severity ( β  = − 2.52, 95% CI − 4.16–0.88, p   〈  0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD.
    Type of Medium: Online Resource
    ISSN: 1018-8827 , 1435-165X
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1463026-6
    SSG: 5,2
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  • 2
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-02-23)
    Abstract: Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD] , and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2609311-X
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  • 3
    In: Critical Care, Springer Science and Business Media LLC, Vol. 26, No. 1 ( 2022-12)
    Abstract: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. Methods Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. Results Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60–63] years vs 64 [62–66] years, p   〈  0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6–9.0] vs 5.8 [5.3–6.4] , p   〈  0.001) and increased, while more female patients (26 [23–29]% vs 41 [35–48] %, p   〈  0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2–7.2| days vs 9.7 [8.9–10.5] days, p   〈  0.001). The PaO 2 /FiO 2 at admission was lower (132 [123–141] mmHg vs 101 [91–113] mmHg, p   〈  0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20–48] mmHg vs 70 [41–100] mmHg, p  = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4–7]% vs 20 [14–29] , p   〈  0.001) and non-invasive mechanical ventilation (14 [11–18]% vs 24 [17–33] %, p   〈  0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76–86]% vs 74 [64–82] %, p   〈  0.001). The ICU mortality (23 [19–26]% vs 17 [12–25] %, p   〈  0.001) and length of stay (14 [13–16] days vs 11 [10–13] days, p   〈  0.001) decreased over 19 months of the pandemic. Conclusion Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.
    Type of Medium: Online Resource
    ISSN: 1364-8535
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2051256-9
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  • 4
    In: BMC Neurology, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2008-12)
    Type of Medium: Online Resource
    ISSN: 1471-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 2041347-6
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  • 5
    Online Resource
    Online Resource
    American Psychiatric Association Publishing ; 2005
    In:  American Journal of Psychiatry Vol. 162, No. 5 ( 2005-05), p. 899-905
    In: American Journal of Psychiatry, American Psychiatric Association Publishing, Vol. 162, No. 5 ( 2005-05), p. 899-905
    Type of Medium: Online Resource
    ISSN: 0002-953X , 1535-7228
    RVK:
    Language: English
    Publisher: American Psychiatric Association Publishing
    Publication Date: 2005
    detail.hit.zdb_id: 1500554-9
    SSG: 5,2
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  • 6
    Online Resource
    Online Resource
    BMJ ; 2022
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 93, No. 6 ( 2022-06), p. A110.2-A110
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 93, No. 6 ( 2022-06), p. A110.2-A110
    Abstract: The PREDICT-PD study is a web-based study which aims to identify individuals aged 60–80 at risk of future Parkinson’s disease (PD) from the UK general population. Soon after enrolment, representative groups of individuals that were classified as higher risk (HR) or lower risk (LR) (highest and lowest 15% of risks scores) were reviewed ‘in person’ with HR group being more likely to show subtle motor impairment compared with the LR group. Methods Individuals were examined using the motor part of Unified PD Rating Scale (MDS-UPDRS-III) after a minimum of 5-year follow-up. Findings We reviewed 132 participants (HR:33, LR:99). HR subjects were predominantly male (74.2%) and older (77.2yo vs 73.6yo, p 〈 0.001). At 5-year follow-up a bigger change in MDS-UPDRS-III was seen amongst HR individuals compared to LR group (36% vs 13% increasing 〉 5 points in the motor scale). In contrast to the baseline analysis, where there were no significant differences on a keyboard tapping test (BRAIN test), HR participants performed worse than LR participants (43.7key/sec vs 53.9key/sec, p 〈 0.001) after 5 years. Two participants received a PD diagnosis during follow-up with respective motor signs demonstrated 2 and 5 years before fulfilling clinical diagnosis criteria. Conclusions This study identifies early motor features and their evolution during PD pre-diagnostic phase. Remotely administered tools may be capable of detecting subtle motor dysfunction at early stages of PD. c.simonet@qmul.ac.uk|NIHR Bursary 40
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1480429-3
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  • 7
    Online Resource
    Online Resource
    BMJ ; 2019
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 90, No. 12 ( 2019-12), p. e39.2-e39
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 90, No. 12 ( 2019-12), p. e39.2-e39
    Abstract: Smell loss (anosmia) is a common finding in people with PD, although it is also quite common in older age (Ross 2008). Population studies assessing the prodromal phase of PD have therefore included individuals with smell loss. However, the differential diagnosis of anosmia is broad, and it is likely that only a subset are linked to neurodegeneration. Some evidence suggests that people with the anosmic prodrome have a different phenotype to other forms of prodromal PD (Rees 2019). Methods We assessed neurologically healthy patients aged 60–80y from two specialist ENT clinics (James Paget Hospital, Norfolk; RNTNE, London). All participants had a diagnosis of idiopathic anosmia after comprehensive investigation. Participants completed online PREDICT-PD testing (www.predictpd.com) followed by an in-person assessment with standardised physical, cognitive and autonomic tests. Results We recruited 28 participants (17 women) mean age 69.9y (SD 4.9y). Participants had a mean of 14.4 years of education (SD 3.1). Adjusted MoCA scores had a mean of 25.9/30 (SD 2.6). There was a range of subtle motor impairment, median MDS-UPDRS III 4.5 (IQR 1.0- 8.0, max 20) and median 3m up- & -go time 8.5s (IQR 7.8–9.6). Those with the highest risk had higher tremor scores in the MDS-UPDRS Conclusions There is a correlation between risk of PD and cognition. There is no significant gross motor or autonomic dysfunction in these patients, but the highest risk participants had higher tremor subscores. Further recruitment will allow clear delineation of the anosmic prodrome of PD.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 1480429-3
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  • 8
    Online Resource
    Online Resource
    BMJ ; 2020
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 91, No. 4 ( 2020-04), p. 418-425
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 91, No. 4 ( 2020-04), p. 418-425
    Abstract: Dementia is common in Parkinson’s disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD. Methods We assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content. Results We found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p 〈 0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p 〈 0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures. Conclusions Brain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1480429-3
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  • 9
    Online Resource
    Online Resource
    BMJ ; 2022
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 93, No. 6 ( 2022-06), p. A94.3-A95
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 93, No. 6 ( 2022-06), p. A94.3-A95
    Abstract: Patients with established Parkinson’s disease (PD) display differences in blood biomarkers of immune function, including leukocyte differentials, compared to controls. These may be useful biomarkers to predict PD and inform pathogenesis. We sought to identify whether peripheral immune dysregulation was associated with risk of subsequent PD. Methods We examined the relationship between incident PD and baseline leukocyte differential count in UK Biobank, a longitudinal cohort with 〉 500,000 participants. We used a range of sensitivity analyses and Mendelian randomization (MR) to further explore the nature of associations. Results After excluding individuals with comorbidities which could influence inflammation biomarkers, 465 incident PD cases and 312,125 controls remained. Lower lymphocyte count was associated with increased risk of PD diagnosis (per 1-SD decrease in count OR 1.18, 95% CI 1.07–1.32, padjusted=0.01). The association between lower lymphocyte count and increased PD risk remained robust to sensitivity analyses. MR suggested that the effect of lower lymphocyte count on PD risk may be causal (per 1-SD decrease in lymphocyte count; ORMR 1.09, 95% CI 1.01–1.18, p=0.02). Conclusions We provide converging evidence from observational analyses in UKB and MR that lower lymphocyte count is associated with an increased risk of subsequent PD. m.jensen@cantab.net
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1480429-3
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  • 10
    Online Resource
    Online Resource
    BMJ ; 2020
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 91, No. 6 ( 2020-06), p. 563-565
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 91, No. 6 ( 2020-06), p. 563-565
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1480429-3
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