Polysomnographic and Subjective Sleep Predictors of Alcoholic Relapse

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65219/1/j.1530-0277.1998.tb03995.x.pd

Noise Reduction by Diffusional Dissipation in a Minimal Quorum Sensing Motif

Cellular interactions are subject to random fluctuations (noise) in quantities of interacting molecules. Noise presents a major challenge for the robust function of natural and engineered cellular networks. Past studies have analyzed how noise is regulated at the intracellular level. Cell–cell communication, however, may provide a complementary strategy to achieve robust gene expression by enabling the coupling of a cell with its environment and other cells. To gain insight into this issue, we have examined noise regulation by quorum sensing (QS), a mechanism by which many bacteria communicate through production and sensing of small diffusible signals. Using a stochastic model, we analyze a minimal QS motif in Gram-negative bacteria. Our analysis shows that diffusion of the QS signal, together with fast turnover of its transcriptional regulator, attenuates low-frequency components of extrinsic noise. We term this unique mechanism “diffusional dissipation” to emphasize the importance of fast signal turnover (or dissipation) by diffusion. We further show that this noise attenuation is a property of a more generic regulatory motif, of which QS is an implementation. Our results suggest that, in a QS system, an unstable transcriptional regulator may be favored for regulating expression of costly proteins that generate public goods

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome

BACKGROUND: Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? METHODS: The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. RESULTS: Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be$62,238 (5% – 95% percentiles $42,259 –$83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost$267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. CONCLUSION: ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS

Protocol for an economic evaluation alongside the University Health Network Whiplash Intervention Trial: cost-effectiveness of education and activation, a rehabilitation program, and the legislated standard of care for acute whiplash injury in Ontario

Background: Whiplash injury affects 83% of persons in a traffic collision and leads to whiplash-associated disorders (WAD). A major challenge facing health care decision makers is identifying cost-effective interventions due to lack of economic evidence. Our objective is to compare the cost-effectiveness of: 1) physician-based education and activation, 2) a rehabilitation program developed by Aviva Canada (a group of property and casualty insurance providers), and 3) the legislated standard of care in the Canadian province of Ontario: the Pre-approved Framework Guideline for Whiplash developed by the Financial Services Commission of Ontario. Methods/Design. The economic evaluation will use participant-level data from the University Health Network Whiplash Intervention Trial and will be conducted from the societal perspective over the trial's one-year follow-up. Resource use (costs) will include all health care goods and services, and benefits provided during the trial's 1-year follow-up. The primary health effect will be the quality-adjusted life year. We will identify the most cost-effective intervention using the incremental cost-effectiveness ratio and incremental net-benefit. Confidence ellipses and cost-effectiveness acceptability curves will represent uncertainty around these statistics, respectively. A budget impact analysis will assess the total annual impact of replacing the current legislated standard of care with each of the other interventions. An expected value of perfect information will determine the maximum research expenditure Canadian society should be willing to pay for, and inform priority setting in, research of WAD management. Discussion. Results will provide health care decision makers with much needed economic evidence on common interventions for acute whiplash management. © 2011 van der Velde et al; licensee BioMed Central Ltd

Prevention of depression and sleep disturbances in elderly with memory-problems by activation of the biological clock with light - a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Depression frequently occurs in the elderly and in patients suffering from dementia. Its cause is largely unknown, but several studies point to a possible contribution of circadian rhythm disturbances. Post-mortem studies on aging, dementia and depression show impaired functioning of the suprachiasmatic nucleus (SCN) which is thought to be involved in the increased prevalence of day-night rhythm perturbations in these conditions. Bright light enhances neuronal activity in the SCN. Bright light therapy has beneficial effects on rhythms and mood in institutionalized moderate to advanced demented elderly. In spite of the fact that this is a potentially safe and inexpensive treatment option, no previous clinical trial evaluated the use of long-term daily light therapy to prevent worsening of sleep-wake rhythms and depressive symptoms in early to moderately demented home-dwelling elderly.</p> <p>Methods/Design</p> <p>This study investigates whether long-term daily bright light prevents worsening of sleep-wake rhythms and depressive symptoms in elderly people with memory complaints. Patients with early Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI) and Subjective Memory Complaints (SMC), between the ages of 50 and 75, are included in a randomized double-blind placebo-controlled trial. For the duration of two years, patients are exposed to ~10,000 lux in the active condition or ~300 lux in the placebo condition, daily, for two half-hour sessions at fixed times in the morning and evening. Neuropsychological, behavioral, physiological and endocrine measures are assessed at baseline and follow-up every five to six months.</p> <p>Discussion</p> <p>If bright light therapy attenuates the worsening of sleep-wake rhythms and depressive symptoms, it will provide a measure that is easy to implement in the homes of elderly people with memory complaints, to complement treatments with cholinesterase inhibitors, sleep medication or anti-depressants or as a stand-alone treatment.</p> <p>Trial registration</p> <p>ISRCTN29863753</p

Relative effectiveness and adverse effects of cervical manipulation, mobilisation and the activator instrument in patients with sub-acute non-specific neck pain: results from a stopped randomised trial

<p>Abstract</p> <p>Background</p> <p>Neck pain of a mechanical nature is a common complaint seen by practitioners of manual medicine, who use a multitude of methods to treat the condition. It is not known, however, if any of these methods are superior in treatment effectiveness. This trial was stopped due to poor recruitment. The purposes of this report are (1) to describe the trial protocol, (2) to report on the data obtained from subjects who completed the study, (3) to discuss the problems we encountered in conducting this study.</p> <p>Methods</p> <p>A pragmatic randomised clinical trial was undertaken. Patients who met eligibility criteria were randomised into three groups. One group was treated using specific segmental high velocity low amplitude manipulation (diversified), another by specific segmental mobilisation, and a third group by the Activator instrument. All three groups were also treated for any myofascial distortions and given appropriate exercises and advice. Participants were treated six times over a three-week period or until they reported being pain free. The primary outcome measure for the study was Patient Global Impression of Change (PGIC); secondary outcome measures included the Short-Form Health Survey (SF-36v₂), the neck Bournemouth Questionnaire, and the numerical rating scale for pain intensity. Participants also kept a diary of any pain medication taken and noted any perceived adverse effects of treatment. Outcomes were measured at four points: end of treatment, and 3, 6, and 12 months thereafter.</p> <p>Results</p> <p>Between January 2007 and March 2008, 123 patients were assessed for eligibility, of these 47 were considered eligible, of which 16 were allocated to manipulation, 16 to the Activator instrument and 15 to the mobilisation group. Comparison between the groups on the PGIC adjusted for baseline covariants did not show a significant difference for any of the endpoints. Within group analyses for change from baseline to the 12-month follow up for secondary outcomes were significant for all groups on the Bournemouth Questionnaire and for pain, while the mobilisation group had a significant improvement on the PCS and MCS subscales of the SF-36_v2. Finally, there were no moderate, severe, or long-lasting adverse effects reported by any participant in any group.</p> <p>Conclusions</p> <p>Although the small sample size must be taken into consideration, it appears that all three methods of treating mechanical neck pain had a long-term benefit for subacute neck pain, without moderate or serious adverse events associated with any of the treatment methods. There were difficulties in recruiting subjects to this trial. This pragmatic trial should be repeated with a larger sample size.</p

Cytoskeletal control of B cell responses to antigens.

The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also have a role in the adaptation of B cell subsets to specialized tasks during antibody responses