78 research outputs found
Effect of Bout Length on Gait Measures in People with and without Parkinsonâs Disease during Daily Life
Although the use of wearable technology to characterize gait disorders in daily life is increasing, there is no consensus on which specific gait bout length should be used to characterize gait. Clinical trialists using daily life gait quality as study outcomes need to understand how gait bout length affects the sensitivity and specificity of measures to discriminate pathological gait as well as the reliability of gait measures across gait bout lengths. We investigated whether Parkinsonâs disease (PD) affects how gait characteristics change as bout length changes, and how gait bout length affects the reliability and discriminative ability of gait measures to identify gait impairments in people with PD compared to neurotypical Old Adults (OA). We recruited 29 people with PD and 20 neurotypical OA of similar age for this study. Subjects wore 3 inertial sensors, one on each foot and one over the lumbar spine all day, for 7 days. To investigate which gait bout lengths should be included to extract gait measures, we determined the range of gait bout lengths available across all subjects. To investigate if the effect of bout length on each gait measure is similar or not between subjects with PD and OA, we used a growth curve analysis. For reliability and discriminative ability of each gait measure as a function of gait bout length, we used the intraclass correlation coefficient (ICC) and area under the curve (AUC), respectively. Ninety percent of subjects walked with a bout length of less than 53 strides during the week, and the majority (\u3e50%) of gait bouts consisted of less than 12 strides. Although bout length affected all gait measures, the effects depended on the specific measure and sometimes differed for PD versus OA. Specifically, people with PD did not increase/decrease cadence and swing duration with bout length in the same way as OA. ICC and AUC characteristics tended to be larger for shorter than longer gait bouts. Our findings suggest that PD interferes with the scaling of cadence and swing duration with gait bout length. Whereas control subjects gradually increased cadence and decreased swing duration as bout length increased, participants with PD started with higher than normal cadence and shorter than normal stride duration for the smallest bouts, and cadence and stride duration changed little as bout length increased, so differences between PD and OA disappeared for the longer bout lengths. Gait measures extracted from shorter bouts are more common, more reliable, and more discriminative, suggesting that shorter gait bouts should be used to extract potential digital biomarkers for people with PD
Laboratory versus daily life gait characteristics in patients with multiple sclerosis, Parkinsonâs disease, and matched controls
Background and purpose
Recent findings suggest that a gait assessment at a discrete moment in a clinic or laboratory setting may not reflect functional, everyday mobility. As a step towards better understanding gait during daily life in neurological populations, we compared gait measures that best discriminated people with multiple sclerosis (MS) and people with Parkinsonâs Disease (PD) from their respective, age-matched, healthy control subjects (MS-Ctl, PD-Ctl) in laboratory tests versus a week of daily life monitoring. Methods
We recruited 15 people with MS (age meanâ±âSD: 49â±â10 years), 16 MS-Ctl (45â±â11 years), 16 people with idiopathic PD (71â±â5 years), and 15 PD-Ctl (69â±â7 years). Subjects wore 3 inertial sensors (one each foot and lower back) in the laboratory followed by 7 days during daily life. MannâWhitney U test and area under the curve (AUC) compared differences between PD and PD-Ctl, and between MS and MS-Ctl in the laboratory and in daily life. Results
Participants wore sensors for 60â68 h in daily life. Measures that best discriminated gait characteristics in people with MS and PD from their respective control groups were different between the laboratory gait test and a week of daily life. Specifically, the toe-off angle best discriminated MS versus MS-Ctl in the laboratory (AUC [95% CI]â=â0.80 [0.63â0.96]) whereas gait speed in daily life (AUCâ=â0.84 [0.69â1.00]). In contrast, the lumbar coronal range of motion best discriminated PD versus PD-Ctl in the laboratory (AUCâ=â0.78 [0.59â0.96]) whereas foot-strike angle in daily life (AUCâ=â0.84 [0.70â0.98]). AUCs were larger in daily life compared to the laboratory. Conclusions
Larger AUC for daily life gait measures compared to the laboratory gait measures suggest that daily life monitoring may be more sensitive to impairments from neurological disease, but each neurological disease may require different gait outcome measures
Measuring freezing of gait during daily-life: an open-source, wearable sensors approach
Background
Although a growing number of studies focus on the measurement and detection of freezing of gait (FoG) in laboratory settings, only a few studies have attempted to measure FoG during daily life with body-worn sensors. Here, we presented a novel algorithm to detect FoG in a group of people with Parkinsonâs disease (PD) in the laboratory (Study I) and extended the algorithm in a second cohort of people with PD at home during daily life (Study II). Methods
In Study I, we described of our novel FoG detection algorithm based on five inertial sensors attached to the feet, shins and lumbar region while walking in 40 participants with PD. We compared the performance of the algorithm with two expert clinical raters who scored the number of FoG episodes from video recordings of walking and turning based on duration of the episodes: very short (\u3câ1 s), short (2â5 s), and long (\u3eâ5 s). In Study II, a different cohort of 48 people with PD (with and without FoG) wore 3 wearable sensors on their feet and lumbar region for 7 days. Our primary outcome measures for freezing were the % time spent freezing and its variability. Results
We showed moderate to good agreement in the number of FoG episodes detected in the laboratory (Study I) between clinical raters and the algorithm (if wearable sensors were placed on the feet) for short and long FoG episodes, but not for very short FoG episodes. When extending this methodology to unsupervised home monitoring (Study II), we found that percent time spent freezing and the variability of time spent freezing differentiated between people with and without FoG (pâ\u3câ0.05), and that short FoG episodes account for 69% of the total FoG episodes. Conclusion
Our findings showed that objective measures of freezing in PD using inertial sensors on the feet in the laboratory are matching well with clinical scores. Although results found during daily life are promising, they need to be validated. Objective measures of FoG with wearable technology during community-living would be useful for managing this distressing feature of mobility disability in PD
Recommended from our members
Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice.
Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24-30Â months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age-related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF
Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFÎČ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFÎČ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH
Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study
BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12âgâdl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (â„week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] gâdl-1 for neonates in week 1, 9.6 [7.7 to 10.4] gâdl-1 in week 2 and 8.0 [7.3 to 9.0] gâdl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] mlâkg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] gâdl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348
Die neuronalen Korrelate des Kreativen Schreibens-eine fMRT-Studie
In der vorliegenden Studie nutzten wir die funktionelle Magnetresonanztomographie (fMRT), um verschiedene Teilaspekte des kreativen Schreibprozesses zu untersuchen. 28 Probanden wurden dazu einem Testverfahren unterzogen, das auf einem gĂ€nzlich neuen fMRT-Paradigma basierte. Es beinhaltete die Aufgaben âBrainstormingâ (Ideengeneration hinsichtlich einer individuellen Textfortsetzung eines gegebenen literarischen Textausschnitts) und âKreatives Schreibenâ (tatsĂ€chliches Niederschreiben einer kreativen Fortsetzung des gegebenen Textausschnitts) sowie die Kontrollbedingungen âLesenâ und âAbschreibenâ. Die Erfassung der individuellen verbalen KreativitĂ€t eines jeden Probanden erfolgte zum einen mit Hilfe eines verbalen KreativitĂ€tstests, zum anderen durch eine professionelle Beurteilung aller Texte. Die Aufgabe des âBrainstormingsâ zeigte ein Netzwerk von parieto-fronto-temporalen Gehirnaktivierungen, das kognitive, sprachliche und kreative Prozesse widerspiegelte. Des Weiteren aktivierte die Aufgabe des âBrainstormingsâ visuelle Funktionen sowie das Vorstellungsvermögen und induzierte darĂŒberhinaus bereits die motorische Vorbereitung des Schreibens. Die HirnaktivitĂ€ten wĂ€hrend der Aufgabe des âKreativen Schreibensâ zeigten die motorischen und visuellen Funktionen des handschriftlichen Schreibens ebenso wie kognitive und sprachassoziierte Prozesse. Eine Subtraktionsanalyse zwischen den Aktivierungen des âKreativen Schreibensâ und des (bloĂen) âAbschreibensâ eines Textes stellte die folgenden kognitiv-kreativen Leistungen dar: den Abruf episodischer GedĂ€chtnisinhalte, eine hohe Beteiligung semantischer Integrationsprozesse sowie die Anwendung eines frei-assoziativen und spontanen Denkstils. Diese Prozesse zeigten sich in rechts-hemisphĂ€risch betonten Aktivierungen beider Temporalpole, beider Hippocampusformationen und des bilateralen posterioren cingulĂ€ren Kortex. Eine Korrelationsanalyse zwischen den Ergebnissen der Subtraktionsanalyse âKreatives Schreiben minus Abschreibenâ und den Ergebnissen des verbalen KreativitĂ€tstests stellte Aktivierungen im linken inferioren frontalen Gyrus (Brodmann Areal (BA) 45) und im linken superioren temporalen Gyrus am Ăbergang zum Temporalpol (BA 38) dar. Diese Ergebnisse weisen darauf hin, dass an den untersuchten Schreibprozessen verbal-kreative FĂ€higkeiten wie Wortgewandtheit, semantischer GedĂ€chtnisabruf sowie semantische Integrationsprozesse beteiligt sind.Cerebral activations involved in actual writing of a new story and the associated correlates with creative performance are still unexplored. To investigate the different aspects of the creative writ- ing process, we used functional magnetic resonance imaging while 28 healthy participants performed a new paradigm related to creative writing: ââbrainstormingââ (planning a story) and ââcreative writingââ (writing a new and creative continuation of a given literary text), as well as an additional control paradigm of ââreadingââ and ââcopying.ââ Individual verbal creativity was assessed with a verbal creativ- ity test and creative performance with a qualitative rating of the creative products. ââbrainstormingââ engaged cognitive, linguistic, and creative brain functions mainly represented in a parieto-frontal- temporal network, as well as writing preparation, and visual and imaginative processing. ââcreative writingââ activated motor and visual brain areas for handwriting and additionally, cognitive and linguistic areas. Episodic memory retrieval, free-associative and spontaneous cognition, and semantic integration were observed in a right lateralized activation pattern in bilateral hippocampi, bilateral temporal poles (BA 38), and bilateral posterior cingulate cortex in a ââcreative writingââ minus ââcopy- ingââ comparison. A correlation analysis of ââcreative writingââ minus ââcopyingââ with the creativity index revealed activation in the left inferior frontal gyrus (BA 45) and the left temporal pole (BA 38). Thus, verbal creativity during ââcreative writingââ is associated with verbal and semantic memory as well as semantic integration
Improved nTMS- and DTI-derived CST tractography through anatomical ROI seeding on anterior pontine level compared to internal capsule
Imaging of the course of the corticospinal tract (CST) by diffusion tensor imaging (DTI) is useful for function-preserving tumour surgery. The integration of functional localizer data into tracking algorithms offers to establish a direct structureâfunction relationship in DTI data. However, alterations of MRI signals in and adjacent to brain tumours often lead to spurious tracking results. We here compared the impact of subcortical seed regions placed at different positions and the influences of the somatotopic location of the cortical seed and clinical co-factors on fibre tracking plausibility in brain tumour patients.The CST of 32 patients with intracranial tumours was investigated by means of deterministic DTI and neuronavigated transcranial magnetic stimulation (nTMS). The cortical seeds were defined by the nTMS hot spots of the primary motor area (M1) of the hand, the foot and the tongue representation. The CST originating from the contralesional M1 hand area was mapped as intra-individual reference. As subcortical region of interests (ROI), we used the posterior limb of the internal capsule (PLIC) and/or the anterior inferior pontine region (aiP). The plausibility of the fibre trajectories was assessed by a-priori defined anatomical criteria. The following potential co-factors were analysed: Karnofsky Performance Scale (KPS), resting motor threshold (RMT), T1-CE tumour volume, T2 oedema volume, presence of oedema within the PLIC, the fractional anisotropy threshold (FAT) to elicit a minimum amount of fibres and the minimal fibre length.The results showed a higher proportion of plausible fibre tracts for the aiP-ROI compared to the PLIC-ROI. Low FAT values and the presence of peritumoural oedema within the PLIC led to less plausible fibre tracking results. Most plausible results were obtained when the FAT ranged above a cut-off of 0.105. In addition, there was a strong effect of somatotopic location of the seed ROI; best plausibility was obtained for the contralateral hand CST (100%), followed by the ipsilesional hand CST (>95%), the ipsilesional foot (>85%) and tongue (>75%) CST. In summary, we found that the aiP-ROI yielded better tracking results compared to the IC-ROI when using deterministic CST tractography in brain tumour patients, especially when the M1 hand area was tracked. In case of FAT values lower than 0.10, the result of the respective CST tractography should be interpreted with caution with respect to spurious tracking results. Moreover, the presence of oedema within the internal capsule should be considered a negative predictor for plausible CST tracking
Is trained communication about desire to die harmful for patients receiving palliative care? A cohort study
Background: Palliative patients frequently express a desire to die. Health professionals report uncertainty regarding potential risks of addressing it. Aim: We aim to evaluate effects of desire to die-conversations on palliative patients. Design: Within a prospective mixed-methods cohort study, we trained health professionals in dealing with desire to die. Afterwards, they held conversations about it with patients. Effects on depressiveness, hopelessness, wish to hasten death, death anxiety, patient-health professional-relationship, and will to live were evaluated at baseline (t0), 1 (t1), and 6 weeks afterwards (t2). Results were analyzed descriptively. Setting/participants: From April 2018 to March 2020, 43 health professionals asked 173 patients from all stationary and ambulatory palliative care settings (within 80 km radius) for participation. Complete assessments were obtained from n = 85 (t0), n = 64 (t1), and n = 46 (t2). Results: At t1, patients scored significantly lower on depressiveness (med = 8, M = 8.1, SD = 5.4) than at t0 (med = 9.5, M = 10.5, SD = 5.8) with Z = -3.220, p = 0.001 and Cohen's d = 0.42. This was due to medium-severely depressed patients: At t1, their depressiveness scores decreased significantly (med = 9, M = 9.8; SD = 5.1) compared to t0 (med = 14, M = 15.2; SD = 3.9) with Z = -3.730, p <= 0.000 and Cohen's d = 1.2, but others' did not. All other outcomes showed positive descriptive trends. Conclusions: Desire to die-conversations through trained health professionals do not harm palliative patients. Results cautiously suggest temporary improvement
- âŠ