Prevention of delirium (POD) for older people in hospital: study protocol for a randomised controlled feasibility trial

Background: Delirium is the most frequent complication among older people following hospitalisation. Delirium may be prevented in about one-third of patients using a multicomponent intervention. However, in the United Kingdom, the National Health Service has no routine delirium prevention care systems. We have developed the Prevention of Delirium Programme, a multicomponent delirium prevention intervention and implementation process. We have successfully carried out a pilot study to test the feasibility and acceptability of implementation of the programme. We are now undertaking preliminary testing of the programme. Methods/Design: The Prevention of Delirium Study is a multicentre, cluster randomised feasibility study designed to explore the potential effectiveness and cost-effectiveness of the Prevention of Delirium Programme. Sixteen elderly care medicine and orthopaedic/trauma wards in eight National Health Service acute hospitals will be randomised to receive the Prevention of Delirium Programme or usual care. Patients will be eligible for the trial if they have been admitted to a participating ward and are aged 65 years or over. The primary objectives of the study are to provide a preliminary estimate of the effectiveness of the Prevention of Delirium Programme as measured by the incidence of new onset delirium, assess the variability of the incidence of new-onset delirium, estimate the intracluster correlation coefficient and likely cluster size, assess barriers to the delivery of the Prevention of Delirium Programme system of care, assess compliance with the Prevention of Delirium Programme system of care, estimate recruitment and follow-up rates, assess the degree of contamination due to between-ward staff movements, and investigate differences in financial costs and benefits between the Prevention of Delirium Programme system of care and standard practice. Secondary objectives are to investigate differences in the number, severity and length of delirium episodes (including persistent delirium); length of stay in hospital; inhospital mortality; destination at discharge; health-related quality of life and health resource use; physical and social independence; anxiety and depression; and patient experience. Discussion: This feasibility study will be used to gather data to inform the design of a future definitive randomised controlled trial. Trial registration: ISRCTN01187372. Registered 13 March 2014

Detection of Dynamical Instability in Titan’s Thermospheric Jet

Similar to Earth, Saturn’s largest moon, Titan, possesses a system of high-altitude zonal winds (or jets) that encircle the globe. Using the Atacama Large millimeter/submillimeter Array (ALMA) in August 2016, Lellouch et al. (2019) discovered an equatorial jet at much higher altitudes than previously known, with a surprisingly fast speed of up to ∼ 340 m s−1, but the origin of such high velocities is not yet understood. We obtained spectrally and spatially resolved ALMA observations in May 2017 to map Titan’s 3D global wind field and compare our results with a reanalysis of the August 2016 data. Doppler wind velocity maps were derived in the altitude range ∼ 300–1000 km (from the upper stratosphere to the thermosphere). At the highest, thermospheric altitudes, a 47% reduction in the equatorial zonal wind speed was measured over the 9-month period (corresponding to Ls = 82◦–90◦ on Titan). This is interpreted as due to a dramatic slowing and loss of confinement (broadening) of the recently discovered thermospheric equatorial jet, as a result of dynamical instability. These unexpectedly rapid changes in the upper-atmospheric dynamics are consistent with strong variability of the jet’s primary driving mechanism

Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish

10.1371/journal.pone.0068759PLoS ONE87-POLN

Regeneration of the Semitendinosus Tendon Harvested for Anterior Cruciate Ligament Reconstruction. Evaluation Using Ultrasonography

In a prospective study, 40 consecutive patients who underwent anterior cruciate ligament reconstruction with doubled semitendinosus and gracilis tendon autografts were examined pre- and postoperatively by ultrasound to investigate the anatomy of the donor site before and after the harvest of the tendons. The patients underwent ultrasonography at 2 weeks and 1, 2, 3, 6, 12, 18, and 24 months postoperatively. A total of 298 postoperative sonographic evaluations were performed. The semitendinosus tendon was imaged in the sagittal and axial planes: structure and margins were evaluated with the sagittal views; thickness and width were measured with the axial views. In all cases the following sequence of healing was documented: 2 weeks after surgery the semitendinosus tendon site was occupied by an area of increased thickness and decreased echogenicity, suggesting the presence of traumatic edema of the soft tissue surrounding the tenotomy. At 1 month, an irregular hypoechoic structure appeared in a near-anatomic position; at 2 months after surgery, thickness, width, and cross-sectional area of this structure were significantly greater than preoperatively. The amount of regenerated tissue increased up to that seen in the tissue of the 6-month examinations, which also showed a more uniform echostructure. The scans performed at 1 year showed distinct edges and reduction in thickness and width. At 18 and 24 months the echogenicity of the structure occupying the donor site was very similar to that of the normal semitendinosus tendon. However, this structure was clearly identified about 4 cm proximal to the pes anserinus, revealing a more proximal insertion of the regenerated semitendinosus tendon

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Smoking Comorbidity in Alcoholism: Neurobiological and Neurocognitive Consequences

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65249/1/j.1530-0277.2006.00034.x.pd

Prognostic value of radical cystoprostatectomy in men with bladder cancer infiltrating prostate versus co-existing prostate cancer: a research study

<p>Abstract</p> <p>Background</p> <p>The aim of the following study is to evaluate the advancement of incidentally diagnosed prostate cancer in specimen after cystoprostatectomies caused by muscle-invasive bladder cancer. Secondly we assessed the survival in patients after radical cystoprostatectomy whose postoperative specimen was characterized by the presence of co-existing prostate cancer or prostate infiltration by urothelial bladder cancer.</p> <p>Methods</p> <p>Between 1993 and 2009 a total of 320 patients with muscle-invasive bladder cancer underwent cystoprostatectomy. The first analyzed group consisted of 52 patients with bladder cancer infiltrating prostate, while the second group consisted of 21 patients with co-existing prostate cancer. In all patients cancer specific survival and progression were analyzed. Average follow up was 75.2 months (range: 0 - 181).</p> <p>Results</p> <p>Cancer-specific survival was significantly shorter in group I (p = 0.03). Neoplastic progression in patients from group I was observed in 42.2% of patients, while in patients from group II in 23.6% of patients (p = 0.04). No statistical difference was observed in the percentage of positive lymph nodes between the groups (p = 0.22). The median Gleason score in patients with co-existing prostate cancer was equal to 5. The stage of prostate cancer pT₂/pT₃was equal to 20 (96%)/1 (4%) patients. 12 (57%) prostate cancers were clinically insignificant. Biochemical recurrence occurred in 2 (9%) patients.</p> <p>Conclusions</p> <p indent="1">1. Incidentally diagnosed prostate cancer in specimen after cystoprostatectomies is frequently clinically insignificant and characterized by low progression.</p> <p indent="1">2. Patients with bladder cancer infiltrating prostate are characterized by higher percentage of progression and death in comparison with patients with co-existing prostate cancer.</p

Climate change, precipitation and impacts on an estuarine refuge from disease

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e18849, doi:10.1371/journal.pone.0018849.Oysters play important roles in estuarine ecosystems but have suffered recently due to overfishing, pollution, and habitat loss. A tradeoff between growth rate and disease prevalence as a function of salinity makes the estuarine salinity transition of special concern for oyster survival and restoration. Estuarine salinity varies with discharge, so increases or decreases in precipitation with climate change may shift regions of low salinity and disease refuge away from optimal oyster bottom habitat, negatively impacting reproduction and survival. Temperature is an additional factor for oyster survival, and recent temperature increases have increased vulnerability to disease in higher salinity regions. We examined growth, reproduction, and survival of oysters in the New York Harbor-Hudson River region, focusing on a low-salinity refuge in the estuary. Observations were during two years when rainfall was above average and comparable to projected future increases in precipitation in the region and a past period of about 15 years with high precipitation. We found a clear tradeoff between oyster growth and vulnerability to disease. Oysters survived well when exposed to intermediate salinities during two summers (2008, 2010) with moderate discharge conditions. However, increased precipitation and discharge in 2009 reduced salinities in the region with suitable benthic habitat, greatly increasing oyster mortality. To evaluate the estuarine conditions over longer periods, we applied a numerical model of the Hudson to simulate salinities over the past century. Model results suggest that much of the region with suitable benthic habitat that historically had been a low salinity refuge region may be vulnerable to higher mortality under projected increases in precipitation and discharge. Predicted increases in precipitation in the northeastern United States due to climate change may lower salinities past important thresholds for oyster survival in estuarine regions with appropriate substrate, potentially disrupting metapopulation dynamics and impeding oyster restoration efforts, especially in the Hudson estuary where a large basin constitutes an excellent refuge from disease.Funding was provided by the Hudson River Foundation, grant number 00607A, and the New York State Department of Environmental Conservation (MOU 2008)

An Ecological Study of the Determinants of Differences in 2009 Pandemic Influenza Mortality Rates between Countries in Europe

Pandemic A (H1N1) 2009 mortality rates varied widely from one country to another. Our aim was to identify potential socioeconomic determinants of pandemic mortality and explain between-country variation.Based on data from a total of 30 European countries, we applied random-effects Poisson regression models to study the relationship between pandemic mortality rates (May 2009 to May 2010) and a set of representative environmental, health care-associated, economic and demographic country-level parameters. The study was completed by June 2010.Most regression approaches indicated a consistent, statistically significant inverse association between pandemic influenza-related mortality and per capita government expenditure on health. The findings were similar in univariable [coefficient: -0.00028, 95% Confidence Interval (CI): -0.00046, -0.00010, p = 0.002] and multivariable analyses (including all covariates, coefficient: -0.00107, 95% CI: -0.00196, -0.00018, p = 0.018). The estimate was barely insignificant when the multivariable model included only significant covariates from the univariate step (coefficient: -0.00046, 95% CI: -0.00095, 0.00003, p = 0.063).Our findings imply a significant inverse association between public spending on health and pandemic influenza mortality. In an attempt to interpret the estimated coefficient (-0.00028) for the per capita government expenditure on health, we observed that a rise of 100 international dollars was associated with a reduction in the pandemic influenza mortality rate by approximately 2.8%. However, further work needs to be done to unravel the mechanisms by which reduced government spending on health may have affected the 2009 pandemic influenza mortality

Seasonal and annual fluxes of nutrients and organic matter from large rivers to the Arctic Ocean and surrounding seas

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 35 (2012): 369-382, doi:10.1007/s12237-011-9386-6.River inputs of nutrients and organic matter impact the biogeochemistry of arctic estuaries and the Arctic Ocean as a whole, yet there is considerable uncertainty about the magnitude of fluvial fluxes at the pan-arctic scale. Samples from the six largest arctic rivers, with a combined watershed area of 11.3 x 106 km2, have revealed strong seasonal variations in constituent concentrations and fluxes within rivers as well as large differences among the rivers. Specifically, we investigate fluxes of dissolved organic carbon, dissolved organic nitrogen, total dissolved phosphorus, dissolved inorganic nitrogen, nitrate, and silica. This is the first time that seasonal and annual constituent fluxes have been determined using consistent sampling and analytical methods at the pan arctic scale, and consequently provide the best available estimates for constituent flux from land to the Arctic Ocean and surrounding seas. Given the large inputs of river water to the relatively small Arctic Ocean, and the dramatic impacts that climate change is having in the Arctic, it is particularly urgent that we establish the contemporary river fluxes so that we will be able to detect future changes and evaluate the impact of the changes on the biogeochemistry of the receiving coastal and ocean systems.This work was supported by the National Science Foundation through grants OPP-0229302, OPP-0519840, OPP-0732522, and OPP-0732944. Additional support was provided by the U. S. Geological Survey (Yukon River) and the Department of Indian and Northern Affairs (Mackenzie River)