Design and performance of a multicentre, randomized controlled trial of teleconsulting.

We have designed and performed a multicentre, randomized controlled trial of teleconsulting. The trial investigated the effectiveness and cost implications in rural and inner-city settings of using videoconferencing as an alternative to general practitioner referral to a hospital specialist. The participating general practitioners referred a total of 3170 patients who satisfied the entry criteria. Of these, 1040 (33%) failed to provide consent or otherwise refused to participate in the trial. Of the patients recruited to the trial, a total of 1902 (91%) completed and returned the baseline questionnaire. Although the trial was successful in recruiting sufficient patients and in obtaining high questionnaire response rates, the findings will require careful interpretation to take account of the limits which the protocol placed on the ability of general practitioners to select patients for referral

A baseline evaluation of oceanographic and sea ice conditions in the Hudson Bay Complex during 2016-2018

In this paper, we examine sea surface temperatures (SSTs) and sea ice conditions in the Hudson Bay Complex as a baseline evaluation for the BaySys 2016–2018 field program time frame. Investigated in particular are spatiotemporal patterns in SST and sea ice state and dynamics, with rankings of the latter to highlight extreme conditions relative to the examined 1981–2010 climatology. Results from this study show that SSTs in northwestern Hudson Bay from May to July, 2016–2018, are high relative to the climatology for SST (1982–2010). SSTs are also warmer in 2016 and 2017 than in 2018 relative to their climatology. Similarly, unusually low sea ice cover existed from August to December of 2016 and July to September of 2017, while unusually high sea ice cover existed in January, February, and October of 2018. The ice-free season was approximately 20 days longer in 2016 than in 2018. Unusually high ice-drift speeds occurred in April of 2016 and 2017 and in May of 2018, coinciding with strong winds in 2016 and 2018 and following strong winds in March 2017. Strong meridional circulation was observed in spring of 2016 and winter of 2017, while weak meridional circulation existed in 2018. In a case study of an extreme event, a blizzard from 7 to 9 March 2017, evaluated using Lagrangian dispersion statistics, is shown to have suppressed sea ice deformation off the coast of Churchill. These results are relevant to describing and planning for possible future pathways and scenarios under continued climate change and river regulation

A baseline evaluation of atmospheric and river discharge conditions in the Hudson Bay Complex during 2016-2018

In this article, we examine atmospheric and river discharge conditions within the Hudson Bay Complex for the BaySys 2016–2018 field program time frame. Investigated in particular is a subset of European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis - Interim (ERA-Interim) atmospheric forcing variables, namely 2-m surface temperature, 10-m surface winds, precipitation, and sea-level pressure, in addition to river discharge. Results from this assessment show that 2016 was characterized by unusually warm conditions (terrestrial and marine) throughout the annual cycle; 2017 by strong cyclone activity in March and high precipitation in January, October, and November; and 2018 by cold and windy conditions throughout the annual cycle. Evaluation of terrestrial conditions showed higher than normal land surface temperatures (the Hudson Bay physical watershed) for all of the 2016–2018 period (excluding a colder than normal spell August–November 2018), particularly in January (2016 and 2017), higher than normal precipitation in October (2016 and 2017), and higher than normal terrestrial discharge to the Hudson Bay Complex in March (2016 and 2017), with drier than average June through October (2016–2018)

Selectivity and stability of N-terminal targeting protein modification chemistries

Protein N-termini provide uniquely reactive motifs for single site protein modification. Though a number of reactions have been developed to target this site, the selectivity, generality, and stability of the conjugates formed has not been studied. We have therefore undertaken a comprehensive comparative study of the most promising methods for N-terminal protein modification, and find that there is no ‘one size fits all’ approach, necessitating reagent screening for a particular protein or application. Moreover, we observed limited stability in all cases, leading to a need for continued innovation and development in the bioconjugation field

Simulated impacts of relative climate change and river discharge regulation on sea ice and oceanographic conditions in the Hudson Bay Complex

In this analysis, we examine relative contributions from climate change and river discharge regulation to changes in marine conditions in the Hudson Bay Complex using a subset of five atmospheric forcing scenarios from the Coupled Model Intercomparison Project Phase 5 (CMIP5), river discharge data from the Hydrological Predictions for the Environment (HYPE) model, both naturalized (without anthropogenic intervention) and regulated (anthropogenically controlled through diversions, dams, reservoirs), and output from the Nucleus for European Modeling of the Ocean Ice-Ocean model for the 1981–2070 time frame. Investigated in particular are spatiotemporal changes in sea surface temperature, sea ice concentration and thickness, and zonal and meridional sea ice drift in response to (i) climate change through comparison of historical (1981–2010) and future (2021–2050 and 2041–2070) simulations, (ii) regulation through comparison of historical (1981–2010) naturalized and regulated simulations, and (iii) climate change and regulation combined through comparison of future (2021–2050 and 2041–2070) naturalized and regulated simulations. Also investigated is use of the diagnostic known as e-folding time spatial distribution to monitor changes in persistence in these variables in response to changing climate and regulation impacts in the Hudson Bay Complex. Results from this analysis highlight bay-wide and regional reductions in sea ice concentration and thickness in southwest and northeast Hudson Bay in response to a changing climate, and east-west asymmetry in sea ice drift response in support of past studies. Regulation is also shown to amplify or suppress the climate change signal. Specifically, regulation amplifies sea surface temperatures from April to August, suppresses sea ice loss by approximately 30% in March, contributes to enhanced sea ice drift speed by approximately 30%, and reduces meridional circulation by approximately 20% in January due to enhanced zonal drift. Results further suggest that the offshore impacts of regulation are amplified in a changing climate

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

<p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt

The Incidence Of Prescribing Errors In An Eye Hospital

BACKGROUND: Relatively little is known about the incidence of prescribing errors and there has been no work on this in a single specialty ophthalmic hospital. Knowing where and when errors are most likely to occur is generally felt to be the first step in trying to prevent these errors. This study is an attempt in, the setting of an eye hospital, to try to identify and attribute these medication errors. METHODS: The study setting was a single specialty eye hospital geographically separated from the main general hospital. Pharmacists prospectively recorded the number of errors of prescribing during a 4 week period at an eye hospital in UK. The errors were categorised as error of prescription writing or drug error. Potential significance of the errors was not addressed. RESULTS: Overall 144/1952 (8%)prescription sheets had errors. 7% of the total errors were errors of prescription writing while 1% were drug errors. The majority of errors were made by junior doctors and no drug errors were made by senior doctors. The outpatients department had by far the highest prevalence of errors. CONCLUSION: Certain areas within the hospital and certain grades of staff are more prone to drug errors. Further study is required to look at the reasons why this is so and what systems can be put in place to reduce these errors

New evidence on Allyn Young's style and influence as a teacher

This paper publishes the hitherto unpublished correspondence between Allyn Abbott Young's biographer Charles Blitch and 17 of Young's former students or associates. Together with related biographical and archival material, the paper shows the way in which this adds to our knowledge of Young's considerable influence as a teacher upon some of the twentieth century's greatest economists. The correspondents are as follows: James W Angell, Colin Clark, Arthur H Cole, Lauchlin Currie, Melvin G de Chazeau, Eleanor Lansing Dulles, Howard S Ellis, Frank W Fetter, Earl J Hamilton, Seymour S Harris, Richard S Howey, Nicholas Kaldor, Melvin M Knight, Bertil Ohlin, Geoffrey Shepherd, Overton H Taylor, and Gilbert Walker

Vitamin D levels as an important predictor for type 2 diabetes mellitus and weight regain post-sleeve gastrectomy

Weight Loss Surgery (WLS), including sleeve-gastrectomy (SG), results in significant weight loss and improved metabolic health in severe obesity (BMI ≥ 35 kg/m2). Previous studies suggest post-operative health benefits are impacted by nutrient deficiencies, such as Vitamin D (25(OH)D) deficiency, while it is currently unknown whether nutrient levels may actually predict post-surgery outcomes. As such, this study investigated whether 25(OH)D levels could predict metabolic improvements in patients who underwent SG. Patients with severe obesity (n = 309; 75% female) undergoing SG participated in this ethics-approved, non-randomized retrospective cohort study. Anthropometry, clinical data, 25(OH)D levels and serum markers were collected at baseline, 6-, 12- and 18-months post-surgery. SG surgery resulted in significant improvements in metabolic health at 6- and 12-months post-surgery compared with baseline, as expected. Patients with higher baseline 25(OH)D had significantly lower HbA1c levels post-surgery (p < 0.01) and better post-surgical T2DM outcomes, including reduced weight regain (p < 0.05). Further analysis revealed that baseline 25(OH)D could predict HbA1c levels, weight regain and T2DM remission one-year post-surgery, accounting for 7.5% of HbA1c divergence (p < 0.01). These data highlight that higher circulating 25(OH)D levels are associated with significant metabolic health improvements post-surgery, notably, that such baseline levels are able to predict those who attain T2DM remission. This highlights the importance of 25(OH)D as a predictive biomarker of post-surgery benefits

Deterioration of Parkinson's disease during hospitalization: survey of 684 patients

Abstract Background A substantial fraction of Parkinson's disease patients deteriorate during hospitalisation, but the precise proportion and the reasons why have not been studied systematically and the focus has been on surgical wards and on Accident & Emergency departments. We assessed the prevalence and risk factors of deterioration of Parkinson's disease symptoms during hospitalization, including all wards. Methods We invited Parkinson's disease patients from three neurology departments in The Netherlands to answer a standardised questionnaire on general, disease and hospital related issues. Patients who had been hospitalized in the previous year were included and analysed. Possible risk factors for Parkinson's disease deterioration were identified. Proportions were analysed using the Chi-Square test and a logistic regression analysis was performed. Results Eighteen percent of 684 Parkinson's disease patients had been hospitalized at least once in the last year. Twenty-one percent experienced deterioration of motor symptoms, 33% did have one or more complications and 26% had received incorrect anti-Parkinson's medication. There were no statistically significant differences for these variables between admissions on neurologic or non-neurologic wards and between having surgery or not. Incorrect medication during hospitalization was significantly associated with higher risk (OR 5.8, CI 2.5-13.7) of deterioration, as were having infections (OR 6.7 CI 1.8-24.7). A higher levodopa equivalent dose per day was a significant risk factor for deterioration. When adjusting for different variables, wrong medication distribution was the most important risk factor for deterioration. Conclusions Incorrect medication and infections are the important risk factors for deterioration of Parkinson's disease patients both for admissions with and without surgery and both for admissions on neurologic and non-neurologic wards. Measures should be taken to improve care and incorporated in guidelines.</p