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Posted on April 7, 2015 by Maurice Preter MD
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Objective: To examine the effect of cost, a traditionally “inactive” trait of intervention, as contributor to the response to therapeutic interventions.
Methods: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a “cheap” or “expensive” subcutaneous “novel injectable dopamine agonist” placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the “practically defined off” state, before and after each intervention, included the Unified Parkinson’s Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis.
Results: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions.
Conclusion: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies.
Classification of evidence: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 766
Supplemental data at Neurology.org
Joerg Hucklenbroich12, Rebecca Klein23, Bernd Neumaier3, Rudolf Graf3, Gereon Rudolf Fink12, Michael Schroeter123 and Maria Adele Rueger123*
1Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Leo-Brandt-Straße 52425, Jülich, Germany
2Department of Neurology, University Hospital of Cologne, Cologne, Germany
3Max Planck Institute for Neurological Research, Cologne, Germany
Stem Cell Research & Therapy 2014, 5:100 doi:10.1186/scrt500
The electronic version of this article is the complete one and can be found online at: http://stemcellres.com/content/5/4/100
| Received: | 27 May 2014 |
| Revisions received: | 12 August 2014 |
| Accepted: | 12 August 2014 |
| Published: | 26 September 2014 |
© 2014 Hucklenbroich et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Aromatic (ar-) turmerone is a major bioactive compound of the herb Curcuma longa. It has been suggested that ar-turmerone inhibits microglia activation, a property that may be useful in treating neurodegenerative disease. Furthermore, the effects of ar-turmerone on neural stem cells (NSCs) remain to be investigated.
We exposed primary fetal rat NSCs to various concentrations of ar-turmerone. Thereafter, cell proliferation and differentiation potential were assessed. In vivo, naïve rats were treated with a single intracerebroventricular (i.c.v.) injection of ar-turmerone. Proliferative activity of endogenous NSCs was assessed in vivo, by using noninvasive positron emission tomography (PET) imaging and the tracer [18F]-fluoro-L-thymidine ([18F]FLT), as well as ex vivo.
In vitro, ar-turmerone increased dose-dependently the number of cultured NSCs, because of an increase in NSC proliferation (P < 0.01). Proliferation data were supported by qPCR-data for Ki-67 mRNA. In vitro as well as in vivo, ar-turmerone promoted neuronal differentiation of NSCs. In vivo, after i.c.v. injection of ar-turmerone, proliferating NSCs were mobilized from the subventricular zone (SVZ) and the hippocampus of adult rats, as demonstrated by both [18F]FLT-PET and histology (P < 0.05).
Both in vitro and in vivo data suggest that ar-turmerone induces NSC proliferation. Ar-turmerone thus constitutes a promising candidate to support regeneration in neurologic disease.
Paleo-epidemiology. We were simply not designed to sit around a lot.
Background: The magnitude, consistency, and manner of association between sedentary time and outcomes independent of physical activity remain unclear.
Purpose: To quantify the association between sedentary time and hospitalizations, all-cause mortality, cardiovascular disease, diabetes, and cancer in adults independent of physical activity.
Data Sources: English-language studies in MEDLINE, PubMed, EMBASE, CINAHL, Cochrane Library, Web of Knowledge, and Google Scholar databases were searched through August 2014 with hand-searching of in-text citations and no publication date limitations.
Study Selection: Studies assessing sedentary behavior in adults, adjusted for physical activity and correlated to at least 1 outcome.
Data Extraction: Two independent reviewers performed data abstraction and quality assessment, and a third reviewer resolved inconsistencies.
Data Synthesis: Forty-seven articles met our eligibility criteria. Meta-analyses were performed on outcomes for cardiovascular disease and diabetes (14 studies), cancer (14 studies), and all-cause mortality (13 studies). Prospective cohort designs were used in all but 3 studies; sedentary times were quantified using self-report in all but 1 study. Significant hazard ratio (HR) associations were found with all-cause mortality (HR, 1.240 [95% CI, 1.090 to 1.410]), cardiovascular disease mortality (HR, 1.179 [CI, 1.106 to 1.257]), cardiovascular disease incidence (HR, 1.143 [CI, 1.002 to 1.729]), cancer mortality (HR, 1.173 [CI, 1.108 to 1.242]), cancer incidence (HR, 1.130 [CI, 1.053 to 1.213]), and type 2 diabetes incidence (HR, 1.910 [CI, 1.642 to 2.222]). Hazard ratios associated with sedentary time and outcomes were generally more pronounced at lower levels of physical activity than at higher levels.
Limitation: There was marked heterogeneity in research designs and the assessment of sedentary time and physical activity.
Conclusion: Prolonged sedentary time was independently associated with deleterious health outcomes regardless of physical activity.
Primary Funding Source: None.
Background: Vitamin D deficiency has been associated with adverse health outcomes.
Purpose: To systematically review benefits and harms of vitamin D screening in asymptomatic adults.
Data Sources: Ovid MEDLINE (through the third week of August 2014), Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.
Study Selection: Randomized trials of screening for and treatment of vitamin D deficiency and case–control studies nested within the Women’s Health Initiative.
Data Extraction: One investigator abstracted data, a second reviewed data for accuracy, and 2 investigators independently assessed study quality using predefined criteria.
Data Synthesis: No study examined the effects of vitamin D screening versus no screening on clinical outcomes. Vitamin D treatment was associated with decreased mortality versus placebo or no treatment (11 studies; risk ratio [RR], 0.83 [95% CI, 0.70 to 0.99]), although benefits were no longer seen after trials of institutionalized persons were excluded (8 studies; RR, 0.93 [CI, 0.73 to 1.18]). Vitamin D treatment was associated with possible decreased risk for having at least 1 fall (5 studies; RR, 0.84 [CI, 0.69 to 1.02]) and falls per person (5 studies; incidence rate ratio, 0.66 [CI, 0.50 to 0.88]) but not fractures (5 studies; RR, 0.98 [CI, 0.82 to 1.16]). Vitamin D treatment was not associated with a statistically significant increased risk for serious adverse events (RR, 1.17 [CI, 0.74 to 1.84]).
Limitation: Variability across studies in 25-hydroxyvitamin D assays and baseline levels, treatment doses, use of calcium, and duration of follow-up.
Conclusion: Treatment of vitamin D deficiency in asymptomatic persons might reduce mortality risk in institutionalized elderly persons and risk for falls but not fractures.
Primary Funding Source: Agency for Healthcare Research and Quality.
Maurice Preter, MD is a European and U.S. educated psychiatrist, psychotherapist, psychopharmacologist, neurologist, and medical-legal expert in private practice in Manhattan. He is also the principal of Fifth Avenue Concierge Medicine, PLLC, a medical concierge service and health advisory for select individuals and families.
We pride ourselves in providing exceptional quality of care, access, comfort and privacy to our patients.