Population-based screen-detected type 2 diabetes mellitus is associated with less need for insulin therapy after 10 years

INTRODUCTION: With increased duration of type 2 diabetes, most people have a growing need of glucose-lowering medication and eventually might require insulin. Presumptive evidence is reported that early detection (eg, by population-based screening) and treatment of hyperglycemia will postpone the indication for insulin treatment. A treatment legacy effect of population-based screening for type 2 diabetes of about 3 years is estimated. Therefore, we aim to compare insulin prescription and glycemic control in people with screen-detected type 2 diabetes after 10 years with data from people diagnosed with type 2 diabetes seven (treatment legacy effect) and 10 years before during care-as-usual. RESEARCH DESIGN AND METHODS: Three cohorts were compared: one screen-detected cohort with 10 years diabetes duration (Anglo-Danish-Dutch study of Intensive Treatment in People with Screen-Detected Diabetes in Primary care (ADDITION-NL): n=391) and two care-as-usual cohorts, one with 7-year diabetes duration (Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) and Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC): n=4473) and one with 10-year diabetes duration (GIANTT and ZODIAC: n=2660). Insulin prescription (primary outcome) and hemoglobin A1c (HbA1c) of people with a known diabetes duration of 7 years or 10 years at the index year 2014 were compared using regression analyses. RESULTS: Insulin was prescribed in 10.5% (10-year screen detection), 14.7% (7-year care-as-usual) and 19.0% (10-year care-as-usual). People in the 7-year and 10-year care-as-usual groups had a 1.5 (95% CI 1.0 to 2.1) and 1.8 (95% CI 1.3 to 2.7) higher adjusted odds for getting insulin prescribed than those after screen detection. Lower HbA1c values were found 10 years after screen detection (mean 50.1 mmol/mol (6.7%) vs 51.8 mmol/mol (6.9%) and 52.8 mmol/mol (7.0%)), compared with 7 years and 10 years after care-as-usual (MDadjusted: 1.6 mmol/mol (95% CI 0.6 to 2.6); 0.1% (95% CI 0.1 to 0.2) and 1.8 mmol/mol (95% CI 0.7 to 2.9); and 0.2% (95% CI 0.1 to 0.3)). CONCLUSION: Population-based screen-detected type 2 diabetes is associated with less need for insulin after 10 years compared with people diagnosed during care-as-usual. Glycemic control was better after screen detection but on average good in all groups

Do patients with schizophrenia exhibit aberrant salience?

BACKGROUND: It has been suggested that some psychotic symptoms reflect ‘aberrant salience’, related to dysfunctional reward learning. To test this hypothesis we investigated whether patients with schizophrenia showed impaired learning of task-relevant stimulusreinforcement associations in the presence of distracting task-irrelevant cues. METHODS: We tested 20 medicated patients with schizophrenia and 17 controls on a reaction time game, the Salience Attribution Test. In this game, participants made a speeded response to earn money in the presence of conditioned stimuli (CSs). Each CS comprised two visual dimensions, colour and form. Probability of reinforcement varied over one of these dimensions (task-relevant), but not the other (task-irrelevant). Measures of adaptive and aberrant motivational salience were calculated on the basis of latency and subjective reinforcement probability rating differences over the task-relevant and task-irrelevant dimensions respectively. RESULTS: Participants rated reinforcement significantly more likely and responded significantly faster on high-probability reinforced relative to lowprobability reinforced trials, representing adaptive motivational salience. Patients exhibited reduced adaptive salience relative to controls, but the two groups did not differ in terms of aberrant salience. Patients with delusions exhibited significantly greater aberrant salience than those without delusions, and aberrant salience also correlated with negative symptoms. In the controls, aberrant salience correlated significantly with ‘introvertive anhedonia’ schizotypy. CONCLUSIONS: These data support the hypothesis that aberrant salience is related to the presence of delusions in medicated patients with schizophrenia, but are also suggestive of a link with negative symptoms. The relationship between aberrant salience and psychotic symptoms warrants further investigation in unmedicated patients

The CARE accelerator R&D programme in Europe

Published online on JACoWCARE, an ambitious and coordinated programme of accelerator research and developments oriented towards high energy physics projects, has been launched in January 2004 by the main European laboratories and the European Commission. This project aims at improving existing infrastructures dedicated to future projects such as linear colliders, upgrades of hadron colliders and high intensity proton drivers. We describe the CARE R&D plans, mostly devoted to advancing the performance of the superconducting technology, both in the fields of RF cavities for electron or proton acceleration and of high field magnets, as well as to developing high intensity electron and proton injectors. We highlight some results and progress obtained so far

Use of mental health services among disaster survivors: predisposing factors

<p>Abstract</p> <p>Background</p> <p>Given the high prevalence of mental health problems after disasters it is important to study health services utilization. This study examines predictors for mental health services (MHS) utilization among survivors of a man-made disaster in the Netherlands (May 2000).</p> <p>Methods</p> <p>Electronic records of survivors (n = 339; over 18 years and older) registered in a mental health service (MHS) were linked with general practice based electronic medical records (EMRs) of survivors and data obtained in surveys. EMR data were available from 16 months pre-disaster until 3 years post-disaster. Symptoms and diagnoses in the EMRs were coded according to the International Classification of Primary Care (ICPC). Surveys were carried out 2–3 weeks and 18 months post-disaster, and included validated questionnaires on psychological distress, post-traumatic stress reactions and social functioning. Demographic and disaster-related variables were available. Predisposing factors for MHS utilization 0–18 months and 18–36 months post-disaster were examined using multiple logistic regression models.</p> <p>Results</p> <p>In multiple logistic models, adjusting for demographic and disaster related variables, MHS utilization was predicted by demographic variables (young age, immigrant, public health insurance, unemployment), disaster-related exposure (relocation and injuries), self-reported psychological problems and pre- and post-disaster physician diagnosed health problems (chronic diseases, musculoskeletal problems). After controlling for all health variables, disaster intrusions and avoidance reactions (OR:2.86; CI:1.48–5.53), hostility (OR:2.04; CI:1.28–3.25), pre-disaster chronic diseases (OR:1.82; CI:1.25–2.65), injuries as a result of the disaster (OR:1.80;CI:1.13–2.86), social functioning problems (OR:1.61;CI:1.05–2.44) and younger age (OR:0.98;CI:0.96–0.99) predicted MHS utilization within 18 months post-disaster. Furthermore, disaster intrusions and avoidance reactions (OR:2.29;CI:1.04–5.07) and hostility (OR:3.77;CI:1.51–9.40) predicted MHS utilization following 18 months post-disaster.</p> <p>Conclusion</p> <p>This study showed that several demographic and disaster-related variables and self-reported and physician diagnosed health problems predicted post-disaster MHS-use. The most important factors to predict post-disaster MHS utilization were disaster intrusions and avoidance reactions and symptoms of hostility (which can be identified as symptoms of PTSD) and pre-disaster chronic diseases.</p

Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples

Mobile element insertions (MEIs) are a known cause of genetic disease but have been underexplored due to technical limitations of genetic testing methods. Various bioinformatic tools have been developed to identify MEIs in Next Generation Sequencing data. However, most tools have been developed specifically for genome sequencing (GS) data rather than exome sequencing (ES) data, which remains more widely used for routine diagnostic testing. In this study, we benchmarked six MEI detection tools (ERVcaller, MELT, Mobster, SCRAMble, TEMP2 and xTea) on ES data and on GS data from publicly available genomic samples (HG002, NA12878). For all the tools we evaluated sensitivity and precision of different filtering strategies. Results show that there were substantial differences in tool performance between ES and GS data. MELT performed best with ES data and its combination with SCRAMble increased substantially the detection rate of MEIs. By applying both tools to 10,890 ES samples from Solve-RD and 52,624 samples from Radboudumc we were able to diagnose 10 patients who had remained undiagnosed by conventional ES analysis until now. Our study shows that MELT and SCRAMble can be used reliably to identify clinically relevant MEIs in ES data. This may lead to an additional diagnosis for 1 in 3000 to 4000 patients in routine clinical ES

Gender specific age-related changes in bone density, muscle strength and functional performance in the elderly: a-10 year prospective population-based study

Background:&nbsp;Age-related losses in bone mineral density (BMD), muscle strength, balance, and gait have been linked to&nbsp;an increased risk of falls, fractures and disability, but few prospective studies have compared the timing, rate and pattern&nbsp;of changes in each of these measures in middle-aged and older men and women. This is important so that targeted&nbsp;strategies can be developed to optimise specific musculoskeletal and functional performance measures in older adults.&nbsp;Thus, the aim of this 10-year prospective study was to: 1) characterize and compare age- and gender-specific changes in&nbsp;BMD, grip strength, balance and gait in adults aged 50 years and over, and 2) compare the relative rates of changes&nbsp;between each of these musculoskeletal and functional parameters with ageing.Methods: Men (n = 152) and women (n = 206) aged 50, 60, 70 and 80 years recruited for a population-based study had&nbsp;forearm BMD, grip strength, balance and gait velocity re-assessed after 10-years.Results: The annual loss in BMD was 0.5-0.7% greater in women compared to men aged 60 years and older&nbsp;(p &lt; 0.05- &lt; 0.001), but there were no gender differences in the rate of loss in grip strength, balance or gait. From the age&nbsp;of 50 years there was a consistent pattern of loss in grip strength, while the greatest deterioration in balance and gait&nbsp;occurred from 60 and 70 years onwards, respectively. Comparison of the changes between the different measures&nbsp;revealed that the annual loss in grip strength in men and women aged &lt;70 years was 1-3% greater than the decline in&nbsp;BMD, balance and gait velocity.Conclusion: There were no gender differences in the timing (age) and rate (magnitude) of decline in grip strength,&nbsp;balance or gait in Swedish adults aged 50 years and older, but forearm BMD decreased at a greater rate in women than&nbsp;in men. Furthermore, there was heterogeneity in the rate of loss between the different musculoskeletal and function&nbsp;parameters, especially prior to the age of 70 years, with grip strength deteriorating at a greater rate than BMD,&nbsp;balance and gait.</div

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular