Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes

AIMS/HYPOTHESIS: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes. METHODS: We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target ≤6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment. RESULTS: Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (>1%, 5 year number-needed-to-benefit [NNTB5] 200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] 200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients. CONCLUSIONS/INTERPRETATION: Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925

Vitamin D concentration and psychotic disorder:associations with disease status, clinical variables and urbanicity

Background The association between schizophrenia and decreased vitamin D levels is well documented. Low maternal and postnatal vitamin D levels suggest a possible etiological mechanism. Alternatively, vitamin D deficiency in patients with schizophrenia is presumably (also) the result of disease-related factors or demographic risk factors such as urbanicity. Methods In a study population of 347 patients with psychotic disorder and 282 controls, group differences in vitamin D concentration were examined. Within the patient group, associations between vitamin D, symptom levels and clinical variables were analyzed. Group x urbanicity interactions in the model of vitamin D concentration were examined. Both current urbanicity and urbanicity at birth were assessed. Results Vitamin D concentrations were significantly lower in patients (B= -8.05; 95% confidence interval (CI) -13.68 to -2.42;p= 0.005). In patients, higher vitamin D concentration was associated with lower positive (B= -0.02; 95% CI -0.04 to 0.00;p= 0.049) and negative symptom levels (B= -0.03; 95% CI -0.05 to -0.01;p= 0.008). Group differences were moderated by urbanicity at birth (chi(2)= 6.76 andp= 0.001), but not by current urbanicity (chi(2)= 1.50 andp= 0.224). Urbanicity at birth was negatively associated with vitamin D concentration in patients (B= -5.11; 95% CI -9.41 to -0.81;p= 0.020), but not in controls (B= 0.72; 95% CI -4.02 to 5.46;p= 0.765). Conclusions Lower vitamin D levels in patients with psychotic disorder may in part reflect the effect of psychosis risk mediated by early environmental adversity. The data also suggest that lower vitamin D and psychopathology may be related through direct or indirect mechanisms.</p

Modeling match performance in elite volleyball players: importance of jump load and strength training characteristics

In this study, we investigated the relationships between training load, perceived wellness and match performance in professional volleyball by applying the machine learning techniques XGBoost, random forest regression and subgroup discovery. Physical load data were obtained by manually logging all physical activities and using wearable sensors. Daily wellness of players was monitored using questionnaires. Match performance was derived from annotated actions by a video scout during matches. We identified conditions of predictor variables that related to attack and pass performance (p < 0.05). Better attack performance is related to heavy weights of lower-body strength training exercises in the preceding four weeks. However, worse attack performance is linked to large variations in weights of full-body strength training exercises, excessively heavy upper-body strength training, low jump heights and small variations in the number of high jumps in the four weeks prior to competition. Lower passing performance was associated with small variations in the number of high jumps in the preceding week and an excessive amount of high jumps performed, on average, in the two weeks prior to competition. Differences in findings with respect to passing and attack performance suggest that elite volleyball players can improve their performance if training schedules are adapted to the position of a player.Algorithms and the Foundations of Software technolog

Personalized machine learning approach to injury monitoring in elite volleyball players

LIACS-Managemen

Concomitant prednisone may alleviate methotrexate side-effects in rheumatoid arthritis patients

Objectives: To evaluate whether addition of low-moderate dose prednisone to methotrexate (MTX) treatment can alleviate common MTX side-effects in rheumatoid arthritis (RA) patients. Methods: We performed a post-hoc analysis of the CAMERA-II trial which randomized (1:1) 236 early DMARD and prednisone naive RA patients to treatment with MTX + prednisone 10 mg daily, or MTX monotherapy during two years. MTX dose was increased using a treat-to-target approach. We used Generalized Estimating Equations to model the occurrence of common MTX side-effects and of any adverse event over time, controlling for disease activity and MTX dose over time and other possible predictors of adverse events. To assess whether a possible effect was prednisone-specific, we performed the same analysis in the U-ACT-EARLY trial, in which the addition of tocilizumab (TCZ) to MTX was compared to MTX monotherapy in a comparable setting. Results: MTX side-effects were reported at 5.9% of visits in the prednisone-MTX group, compared to 11.2% in the MTX monotherapy group. After controlling for MTX dose and disease activity over time, treatment duration, age, sex, and baseline transaminase levels, addition of prednisone significantly decreased the occurrence of MTX side-effects (OR: 0.54, CI: 0.38–0.77, p = 0.001). Specifically, the occurrence of nausea (OR 0.46, CI: 0.26–0.83, p = 0.009)) and elevated ALT/AST (OR 0.29, CI: 0.17–0.49, p < 0.001) was decreased. There was a trend towards fewer overall adverse events in the prednisone-MTX arm (OR: 0.89, CI: 0.72–1.11, p = 0.30). No difference in MTX side-effects was found between TCZ-MTX and MTX monotherapy in U-ACT-EARLY (OR 1.05, CI: 0.61–1.80, p = 0.87). Conclusion: Addition of 10 mg prednisone daily to MTX treatment in RA patients may ameliorate MTX side-effects, specifically nausea and elevated ALT/AST

The Long-Term Evolution of Social Organization

This chapter outlines how the ‘innovation innovation’ transformed the world of our distant ancestors into that in which we live today. It focuses on the relationship between people and the material world, as it is the material world that has been most drastically, and measurably, transformed over the last several tens of thousands of years. In view of what we know about such distant periods, and in view of the space allot-ted to us here, it will not surprise the reader that we do so in the form of a narrative that is only partly underpinned by substantive data. We emphasize this because we do not want to hide from the reader the speculative nature of the story that follows. Yet we firmly believe that, in very general terms, this scenario is correct, and that further research will vindicate us.We first give examples of the kinds of abstractions, and the hierarchy of conceptual dimensions necessary for prehistoric human beings and their ancestors, to conquer matter, i.e. to conceptually understand, transmit and apply the operations needed to master the making of a range of objects made out of stone, bone, wood, clay and other materials. Some of the abstractions that had to be conceived in this domain re-semble those that Read et al. (http://www.escholarship.org/uc/item/2798j162) refer to, while others apply to this domain alone, and had to be truly ‘invented’. It is then argued that such ‘identification of conceptual dimensions’ is a process that underlies all human activity, and we look a little closer at how that process relates to invention and innovation.Lastly, we shift our attention to the role of innovation, information processing and communication in the emergence of social institutions, and in the structural transformation of human societies as they grow in size and complexity. In particular, we look at the role that problem solving and invention play in creating more and more complex societies, encompassing increasing numbers of people, more and more diverse institutions, and an – ultimately seemingly all-encompassing – appropriation of the natural environment. To illustrate this development we will focus on the origins and growth of urban systems

Pharmacological Modulation of Dopamine Receptor D2-Mediated Transmission Alters the Metabolic Phenotype of Diet Induced Obese and Diet Resistant C57Bl6 Mice

High fat feeding induces a variety of obese and lean phenotypes in inbred rodents. Compared to Diet Resistant (DR) rodents, Diet Induced Obese (DIO) rodents are insulin resistant and have a reduced dopamine receptor D2 (DRD2) mediated tone. We hypothesized that this differing dopaminergic tone contributes to the distinct metabolic profiles of these animals. C57Bl6 mice were classified as DIO or DR based on their weight gain during 10 weeks of high fat feeding. Subsequently DIO mice were treated with the DRD2 agonist bromocriptine and DR mice with the DRD2 antagonist haloperidol for 2 weeks. Compared to DR mice, the bodyweight of DIO mice was higher and their insulin sensitivity decreased. Haloperidol treatment reduced the voluntary activity and energy expenditure of DR mice and induced insulin resistance in these mice. Conversely, bromocriptine treatment tended to reduce bodyweight and voluntary activity, and reinforce insulin action in DIO mice. These results show that DRD2 activation partly redirects high fat diet induced metabolic anomalies in obesity-prone mice. Conversely, blocking DRD2 induces an adverse metabolic profile in mice that are inherently resistant to the deleterious effects of high fat food. This suggests that dopaminergic neurotransmission is involved in the control of metabolic phenotype

Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients

Paraneoplastic cerebellar degeneration (PCD) is a heterogeneous group of disorders characterized by subacute cerebellar ataxia, specific tumour types and (often) associated antineuronal antibodies. Nine specific antineuronal antibodies are associated with PCD. We examined the relative frequency of the antineuronal antibodies associated with PCD and compared the neurological symptoms and signs, associated tumours, disability and survival between groups of PCD with different antibodies. Also, we attempted to identify patient-, tumour- and treatment-related characteristics associated with functional outcome and survival. In a 12-year period, we examined >5000 samples for the presence of antineuronal antibodies. A total of 137 patients were identified with a paraneoplastic neurological syndrome and high titre (> or =400) antineuronal antibodies. Fifty (36%) of these patients had antibody-associated PCD, including 19 anti-Yo, 16 anti-Hu, seven anti-Tr, six anti-Ri and two anti-mGluR1. Because of the low number, the anti-mGluR1 patients were excluded from the statistical analysis. While 100% of patients with anti-Yo, anti-Tr and anti-mGluR1 antibodies suffered PCD, 86% of anti-Ri and only 18% of anti-Hu patients had PCD. All patients presented with subacute cerebellar ataxia progressive over weeks to months and stabilized within 6 months. The majority of patients in all antibody groups had both truncal and appendicular ataxia. The frequency of nystagmus and dysarthria was lower in anti-Ri patients (33 and 0%). Later in the course of the disease, involvement of non-cerebellar structures occurred most frequently in anti-Hu patients (94%). In 42 patients (84%), a tumour was detected. The most commonly associated tumours were gynaecological and breast cancer (anti-Yo and anti-Ri), lung cancer (anti-Hu) and Hodgkin's lymphoma (anti-Tr and anti-mGluR1). In one anti-Hu patient, a suspect lung lesion on CT scan disappeared while the PCD evolved. Seven patients improved by at least 1 point on the Rankin scale, while 16 remained stable and 27 deteriorated. All seven patients that improved received antitumour treatment for their underlying cancer, resulting in complete remission. The functional outcome was best in the anti-Ri patients, with three out of six improving neurologically and five were able to walk at the time of last follow-up or death. Only four out of 19 anti-Yo and four out of 16 anti-Hu patients remained ambulatory. Also, survival from time of diagnosis was significantly worse in the anti-Yo (median 13 months) and anti-Hu (median 7 months) patients compared with anti-Tr (median >113 months) and anti-Ri (median >69 months). Patients receiving antitumour treatment (with or without immunosuppressive therapy) lived significantly longer [hazard ratio (HR) 0.3; 95% confidence interval (CI) 0.1-0.6; P = 0.004]. Patients > or =60 years old lived somewhat shorter from time of diagnosis, although statistically not significant (HR 2.9; CI 1.0-8.5; P = 0.06)

Associations Between Nutrient Intake and Corresponding Nutritional Biomarker Levels in Blood in a Memory Clinic Cohort:The NUDAD Project

Diet is a promising intervention target to prevent or slow Alzheimer's disease (AD). Early (predementia) stages of AD offer a unique opportunity for dietary interventions. Nutritional assessment methods to estimate nutrient intake have, however, not been validated in clinical populations. Hence, we assessed the association between nutrient intake assessed by food frequency questionnaire (FFQ) and nutrient status measured by nutritional biomarkers in blood in a clinical sample of controls, mild cognitive impairment (MCI), and patients with AD

Coronacrisis en kinderen en jongeren in Nederland. Een inventarisatie van de impact van de coronacrisis op kinderen en jongeren in Nederland

Effective Protection of Fundamental Rights in a pluralist worl