Clinical Research Center and

Singapore, Singapore

Clinical Research Center and

Singapore, Singapore
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Brehm Christensen P.,University of Southern Denmark | Ladelund S.,Clinical Research Center and | Lund Laursen A.,Aarhus University Hospital | Moller A.,Kolding Hospital | And 7 more authors.
The Journal of infectious diseases | Year: 2017

Background: Knowledge about mortality rates (MRs) in patients with chronic hepatitis C (CHC) with cirrhosis is limited. This study aimed to estimate all-cause MRs among patients with CHC with or without cirrhosis in Denmark compared with the general population.Methods: Patients registered in the Danish Database for Hepatitis B and C with CHC and a liver fibrosis assessment were eligible for inclusion. Liver fibrosis was assessed by means of liver biopsy, transient elastography, and clinical cirrhosis. Up to 20 sex- and age-matched individuals per patient were identified in the general population. Data were extracted from nationwide registries.Results: A total of 3410 patients with CHC (1014 with cirrhosis), and 67 315 matched individuals were included. Adjusted MR ratios (MRRs) between patients with or without cirrhosis and their comparison cohorts were 5.64 (95% confidence interval [CI], 4.76-6.67) and 1.94 (1.55-2.42), respectively. Cirrhosis among patients was associated with an MRR of 4.03 (95% CI, 3.43-4.72). A cure for CHC was associated with an MRR of 0.64 (95% CI, 0.40-1.01) among cirrhotic patients and 2.33 (1.47-3.67) compared with the general population.Conclusions: MRs were high among patients with CHC with or without cirrhosis compared with the general population. Curing CHC was associated with a reduction in MR among cirrhotic patients, but the MR remained higher than the general population.


PubMed | Center for Basic and Translational Obesity Research, Boston Childrens Hospital, Clinical Research Center and, The Broad Institute of MIT and Harvard and Cambridge Broad Institute
Type: | Journal: The American journal of clinical nutrition | Year: 2017

Clinical nutrition research often lacks robust markers of compliance, complicating the interpretation of clinical trials and observational studies of free-living subjects.We aimed to examine metabolomics profiles in response to 3 diets that differed widely in macronutrient composition during a controlled feeding protocol.Twenty-one adults with a high body mass index (in kg/mOf 333 metabolites, we identified 152 whose concentrations differed for 1 diet compared with the others, including diacylglycerols and triacylglycerols, branched-chain amino acids, and markers reflecting metabolic status. Analysis of groups of related metabolites, with the use of either principal components or pathways, revealed coordinated metabolic changes affected by dietary composition, including pathways related to amino acid metabolism. We constructed a classifier using the metabolites that differed between diets and were able to correctly identify the test diet from metabolite profiles in 60 of 63 cases (>95% accuracy). Analyses also suggest differential effects by diet on numerous cardiometabolic disease risk factors.Metabolomic profiling may be used to assess compliance during clinical nutrition trials and the validity of dietary assessment in observational studies. In addition, this methodology may help elucidate mechanistic pathways linking diet to chronic disease risk. This trial was registered at clinicaltrials.gov as NCT00315354.


Yi T.C.,Monash University | Moochhala S.,Clinical Research Center and | Moochhala S.,DSO National Laboratories
Open Biomarkers Journal | Year: 2013

Salivary biomarkers have been increasingly popular in stress research as saliva is easily produced and collection is non-invasive and not limited by geographical distance or lack of infrastructure. Several salivary biomarkers have been utilized in stress research, for instance, salivary cortisol, salivary amylase and salivary immunoglobulin A. Despite being sensitive to changes in fatigue, they have limitations such as inter-individual variability, and interactions with other constituents that may confound the results. Recently, Hyperion Biotechnology has developed the Fatigue Biomarker Index (FBI), which is a measurement of the changes in concentration of salivary peptides with fatigue. The FBI has been shown to be an accurate and objective biomarker of fatigue, and has huge potential for use in various fields and industries. This article will review some of the previous and current salivary biomarkers of stress, as well as critically appraise the new salivary peptide test in terms of its accuracy, application and access. © Ting Chun Yi.


PubMed | Tokyo Women's Medical University, National Hospital Organization Mito Medical Center, University of Tsukuba, Katsuta Hospital Mito GammaHouse and 3 more.
Type: Journal Article | Journal: Journal of neurosurgery | Year: 2016

OBJECTIVE Stereotactic radiosurgery (SRS) without upfront whole-brain radiotherapy (WBRT) has influenced recent treatment recommendations for brain metastasis patients. However, in brain metastasis patients who undergo SRS alone, new brain metastases inevitably appear with relatively high incidences during post-SRS follow-up. However, little is known about the second SRS results. The treatment results of second SRS were retrospectively reviewed, mainly for newly developed or, uncommonly, for recurrent brain metastases in order to reappraise the efficacy of this treatment strategy with a special focus on the maintenance of neurological status and safety. METHODS This was an institutional review board-approved, retrospective cohort study that used a prospectively accumulated database, including 3102 consecutive patients with brain metastases who underwent SRS between July 1998 and June 2015. Among these 3102 patients, 859 (376 female patients; median age 64 years; range 21-88 years) who underwent a second SRS without WBRT were studied with a focus on overall survival, neurological death, neurological deterioration, local recurrence, salvage SRS, and SRS-induced complications after the second SRS. Before the second SRS, the authors also investigated the clinical factors and radiosurgical parameters likely to influence these clinical outcomes. For the statistical analysis, the standard Kaplan-Meier method was used to determine post-second SRS survival and neurological death. A competing risk analysis was applied to estimate post-second SRS cumulative incidences of local recurrence, neurological deterioration, salvage SRS, and SRS-induced complications. RESULTS The post-second SRS median survival time was 7.4 months (95% CI 7.0-8.2 months). The actuarial survival rates were 58.2% and 34.7% at 6 and 12 months after the second SRS, respectively. Among 789 deceased patients, the causes of death could not be determined in 24 patients, but were confirmed in the remaining 765 patients to be nonbrain diseases in 654 (85.5%) patients and brain diseases in 111 (14.5%) patients. The actuarial neurological death-free survival rates were 94.4% and 86.6% at 6 and 12 months following the second SRS. Multivariable analysis revealed female sex, Karnofsky Performance Scale score of 80% or greater, better modified recursive partitioning analysis class, smaller tumor numbers, and higher peripheral dose to be significant predictive factors for longer survival. The cumulative incidences of local recurrence were 11.2% and 14.9% at 12 and 24 months after the second SRS. The crude incidence of neurological deterioration was 7.1%, and the respective cumulative incidences were 4.5%, 5.8%, 6.7%, 7.2%, and 7.5% at 12, 24, 36, 48, and 60 months after the second SRS. SRS-induced complications occurred in 25 patients (2.9%) after a median post-second SRS period of 16.8 months (range 0.6-95.0 months; interquartile range 5.6-29.3 months). The cumulative incidences of complications were 1.4%, 2.0%, 2.4%, 3.0%, and 3.0% at 12, 24, 36, 48, and 60 months after the second SRS, respectively. CONCLUSIONS Carefully selected patients with recurrent tumors-either new or locally recurrent-are favorable candidates for a second SRS, particularly in terms of neurological status maintenance and the safety of this treatment strategy.


Nair S.,Macquarie University | Nair C.H.,PrIME Biologics | Moochhala S.,Clinical Research Center and
Open Biomarkers Journal | Year: 2015

Major Depressive Disorder (MDD) currently affects people worldwide. Despite its multi-faceted origins and symptoms, and its myriad manifestations and outcomes, work is underway to understand the root causes of the disorder. Genetic studies, in particular, have focused on finding candidate genes for MDD, and investigating links between these genes and any particular group of people. It is hoped that these studies may shed light on the types of people that are commonly affected, and what factors make a person more or less vulnerable to depressive disorders. Multiple factors have been considered, including socioeconomic status, urban versus rural environments, ethnicity, lifestyle factors such as substance abuse and both pre- and post-natal early traumas. Through various methods, including network analyses and bioinformatics among others, significant links have been found between socioeconomic status, urban living, and MDD. Moreover, epigenetic links have been discovered between the prevalence of MDD and the prevalence of other diseases such as cardiovascular disease and other forms of mental illness, making it clear that environment plays a key role in overall health and wellbeing. While no statistically significant link between ethnicity and MDD has been found in candidate genes thus far despite certain ethnicity-based polymorphisms influencing clinical outcomes with different treatments, it is much more apparent that urban environments and early stress contribute to the prevalence of MDD. © Nair et al.; Licensee Bentham Open.


PubMed | Clinical Research Center and and Ecole Normale Superieure de Paris
Type: Journal Article | Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2015

Autistic traits span a wide spectrum of behavioral departures from typical function. Despite the heterogeneous nature of autism spectrum disorder (ASD), there have been attempts at formulating unified theoretical accounts of the associated impairments in social cognition. A class of prominent theories capitalizes on the link between social interaction and visual perception: effective interaction with others often relies on discrimination of subtle nonverbal cues. It has been proposed that individuals with ASD may rely on poorer perceptual representations of other peoples actions as returned by dysfunctional visual circuitry and that this, in turn, may lead to less effective interpretation of those actions for social behavior. It remains unclear whether such perceptual deficits exist in ASD: the evidence currently available is limited to specific aspects of action recognition, and the reported deficits are often attributable to cognitive factors that may not be strictly visual (e.g., attention). We present results from an exhaustive set of measurements spanning the entire action processing hierarchy, from motion detection to action interpretation, designed to factor out effects that are not selectively relevant to this function. Our results demonstrate that the ASD perceptual system returns functionally intact signals for interpreting other peoples actions adequately; these signals can be accessed effectively when autistic individuals are prompted and motivated to do so under controlled conditions. However, they may fail to exploit them adequately during real-life social interactions.

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