Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study

OBJECTIVES Non-steroidal anti-inflammatory drugs (NSAIDs) may cause kidney damage. This study assessed the impact of prolonged NSAID exposure on renal function in a large rheumatoid arthritis (RA) patient cohort. METHODS Renal function was prospectively followed between 1996 and 2007 in 4101 RA patients with multilevel mixed models for longitudinal data over a mean period of 3.2 years. Among the 2739 'NSAID users' were 1290 patients treated with cyclooxygenase type 2 selective NSAIDs, while 1362 subjects were 'NSAID naive'. Primary outcome was the estimated glomerular filtration rate according to the Cockroft-Gault formula (eGFRCG), and secondary the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formula equations and serum creatinine concentrations. In sensitivity analyses, NSAID dosing effects were compared for patients with NSAID registration in ≤/>50%, ≤/>80% or ≤/>90% of assessments. FINDINGS In patients with baseline eGFRCG >30 mL/min, eGFRCG evolved without significant differences over time between 'NSAID users' (mean change in eGFRCG -0.87 mL/min/year, 95% CI -1.15 to -0.59) and 'NSAID naive' (-0.67 mL/min/year, 95% CI -1.26 to -0.09, p=0.63). In a multivariate Cox regression analysis adjusted for significant confounders age, sex, body mass index, arterial hypertension, heart disease and for other insignificant factors, NSAIDs were an independent predictor for accelerated renal function decline only in patients with advanced baseline renal impairment (eGFRCG <30 mL/min). Analyses with secondary outcomes and sensitivity analyses confirmed these results. CONCLUSIONS NSAIDs had no negative impact on renal function estimates but in patients with advanced renal impairment.

Strategies to increase the use and approval of gender-fair language

When masculine forms are used to refer to men and women, this causes male-biased cognitive representations and behavioral consequences, as numerous studies have shown. This effect can be avoided or reduced with the help of gender-fair language. In this talk, we will present different approaches that aim at influencing people’s use of and attitudes towards gender-fair language. Firstly, we tested the influence of gender-fair input on people’s own use of gender-fair language. Based on Irmen and Linner’s (2005) adaptation of the scenario mapping and focus approach (Sanford & Garrod, 1998), we found that after reading a text with gender-fair forms women produced more gender-fair forms than women who read gender-neutral texts or texts containing masculine generics. Men were not affected. Secondly, we examined reactions to arguments which followed the Elaboration Likelihood Model (Petty &Cacioppo, 1986). We assumed that strong pros and cons would be more effective than weak arguments or control statements. The results indicated that strong pros could convince some, but not all participants, suggesting a complex interplay of diverse factors in reaction to attempts at persuasion. The influence of people’s initial characteristics will be discussed. Currently, we are investigating how self-generated refutations, in addition to arguments, may influence initial attitudes. Based on the resistance appraisal hypothesis (Tormala, 2008), we assume that individuals are encouraged in their initial attitude if they manage to refute strong counter-arguments. The results of our studies will be discussed regarding their practical implications.

Hormonal Contraceptive Use and the Prevalence of Endometriotic Lesions at Different Regions within the Peritoneal Cavity.

Endometriosis is an estrogen-dependent disease that can lead to chronic pain and subfertility. Endometriotic lesions found in different locations are heterogeneous and may represent a collection of related but distinct conditions. Whether there is a relationship between hormonal contraceptive (HC) use and endometriosis is still controversial. The purpose of this study was to determine whether HC use affected the prevalence of endometriotic lesions differently based on lesion location. Data was retrospectively collected from 161 patients presenting to the Berne University Women's Hospital between 2008 and 2012 for laparoscopic investigation. Women with histologically proven endometriosis were included in the study and patients were grouped according to lesion location and HC use. The results of the study indicate that HC users are significantly less likely to have endometriotic lesions on the ovaries, although in contrast, no difference was observed in the incidence of lesions in the rectovaginal septum (RVS) or peritoneal region. In addition, women using HC who were diagnosed with endometriotic lesions on the peritoneum were significantly younger than women with lesions in other locations. In conclusion, women with endometriosis who are currently using HC are less likely to have ovarian endometriotic lesions than in alternate locations.

Valuation of ecosystem goods and services. Part 2: Implications of unpredictable novel change

This is the second part of a two-part paper which offers a new approach to the valuation of ecosystem goods and services. In the first part a simple pre-industrial model was introduced to show how the interdependencies between the three subsystems, society, economy and nature, influence values, and how values change over time. In this second part the assumption of perfect foresight is dropped. I argue that due to novelty and complexity ex ante unpredictable change occurs within the three subsystems society, economy and nature. Again the simple pre-industrial model, which was introduced in part 1, serves as a simple paradigm to show how unpredictable novel change limits the possibility to derive accurate estimates of values.

Shifting cultivation stability and change: Contrasting pathways of land use and livelihood change in Laos

Rural areas in Laos are experiencing a rapid transformation from traditional rice-based shifting cultivation systems to more permanent and diversified market-oriented cultivation systems. The consequences of these changes for local livelihoods are not well known. This study analyzes the impact of shifting cultivation change on the livelihood of rural people in six villages in three districts of northern and central Laos. Focus group discussions and household interview questionnaires were employed for data collection. The study reveals that the shifting cultivation of rice is still important in these communities, but it is being intensified as cash crops are introduced. Changes in shifting cultivation during the past ten years vary greatly between the communities studied. In the northern study sites, it is decreasing in areas with rubber expansion and increasing in areas with maize expansion, while it is stable in the central site, where sugarcane is an important cash crop. The impacts of land use change on livelihoods are also diverse. Cash crop producers hold more agricultural land than non-cash crop producers, and rubber and sugarcane producers have fewer rice shortages than non-producers. In the future, livelihood improvements in the central study site may be replicated in the northern sites, but this depends to a large extent on the economic and agricultural settings into which cash crops and other development opportunities are introduced. Moreover, the expansion of cash crops appears to counteract Lao policies aimed at replacing shifting cultivation areas with forests.

Modelling the effects of land use and climate changes on hydrology in the Ursern Valley, Switzerland

While many studies have been conducted in mountainous catchments to examine the impact of climate change on hydrology, the interactions between climate changes and land use components have largely unknown impacts on hydrology in alpine regions. They need to be given special attention in order to devise possible strategies concerning general development in these regions. Thus, the main aim was to examine the impact of land use (i.e. bushland expansion) and climate changes (i.e. increase of temperature) on hydrology by model simulations. For this purpose, the physically based WaSiM-ETH model was applied to the catchment of Ursern Valley in the central Alps (191 km2) over the period of 1983−2005. Modelling results showed that the reduction of the mean monthly discharge during the summer period is due primarily to the retreat of snow discharge in time and secondarily to the reduction in the glacier surface area together with its retreat in time, rather than the increase in the evapotranspiration due to the expansion of the “green alder” on the expense of grassland. The significant decrease in summer discharge during July, August and September shows a change in the regime from b-glacio-nival to nivo-glacial. These changes are confirmed by the modeling results that attest to a temporal shift in snowmelt and glacier discharge towards earlier in the year: March, April and May for snowmelt and May and June for glacier discharge. It is expected that the yearly total discharge due to the land use changes will be reduced by 0.6% in the near future, whereas, it will be reduced by about 5% if climate change is also taken into account. Copyright © 2013 John Wiley & Sons, Ltd.

Lack of association between dual antiplatelet therapy use and stent thrombosis between 1 and 12 months following resolute zotarolimus-eluting stent implantation.

AIM The optimal duration of dual antiplatelet therapy (DAPT) following the use of new generation drug-eluting stents is unknown. METHODS AND RESULTS The association between DAPT interruption and the rates of stent thrombosis (ST) and cardiac death/target-vessel myocardial infarction (CD/TVMI) in patients receiving a Resolute zotarolimus-eluting stent (R-ZES) was analysed in 4896 patients from the pooled RESOLUTE clinical programme. Daily acetylsalicylate (ASA) and a thienopyridine for 6-12 months were prescribed. A DAPT interruption was defined as any interruption of ASA and/or a thienopyridine of >1 day; long interruptions were >14 days. Three groups were analysed: no interruption, interruption during the first month, and >1-12 months. There were 1069 (21.83%) patients with a DAPT interruption and 3827 patients with no interruption. Among the 166 patients in the 1-month interruption group, 6 definite/probable ST events occurred (3.61%; all long DAPT interruptions), and among the 903 patients in the >1-12 months (60% occurred between 6 and 12 months) interruption group, 1 ST event occurred (0.11%; 2-day DAPT interruption). Among patients with no DAPT interruption, 32 ST events occurred (0.84%). Rates of CD/TVMI were 6.84% in the 1-month long interruption group, 1.41% in the >1-12 months long interruption group, and 4.08% in patients on continuous DAPT. CONCLUSION In a pooled population of patients receiving an R-ZES, DAPT interruptions within 1 month are associated with a high risk of adverse outcomes. Dual antiplatelet therapy interruptions between 1 and 12 months were associated with low rates of ST and adverse cardiac outcomes. Randomized clinical trials are needed to determine whether early temporary or permanent interruption of DAPT is truly safe. CLINICAL TRIALSGOV IDENTIFIERS NCT00617084; NCT00726453; NCT00752128; NCT00927940.

Fluorescence-encoded gold nanoparticles: library design and modulation of cellular uptake into dendritic cells.

In order to harness the unique properties of nanoparticles for novel clinical applications and to modulate their uptake into specific immune cells we designed a new library of homo- and hetero-functional fluorescence-encoded gold nanoparticles (Au-NPs) using different poly(vinyl alcohol) and poly(ethylene glycol)-based polymers for particle coating and stabilization. The encoded particles were fully characterized by UV-Vis and fluorescence spectroscopy, zeta potential and dynamic light scattering. The uptake by human monocyte derived dendritic cells in vitro was studied by confocal laser scanning microscopy and quantified by fluorescence-activated cell sorting and inductively coupled plasma atomic emission spectroscopy. We show how the chemical modification of particle surfaces, for instance by attaching fluorescent dyes, can conceal fundamental particle properties and modulate cellular uptake. In order to mask the influence of fluorescent dyes on cellular uptake while still exploiting its fluorescence for detection, we have created hetero-functionalized Au-NPs, which again show typical particle dependent cellular interactions. Our study clearly prove that the thorough characterization of nanoparticles at each modification step in the engineering process is absolutely essential and that it can be necessary to make substantial adjustments of the particles in order to obtain reliable cellular uptake data, which truly reflects particle properties.

Towards a new model of care: integrating mental health, substance use, and somatic care

Although research and clinical interventions for patients with dual disorders have been described since as early as the 1980s, the day-to-day treatment of these patients remains problematic and challenging in many countries. Throughout this book, many approaches and possible pathways have been outlined. Based upon these experiences, some key points can be extracted in order to guide to future developments. (1) New diagnostic approaches are warranted when dealing with patients who have multiple problems, given the limitations of the current categorical systems. (2) Greater emphasis should be placed on secondary prevention and early intervention for children and adolescents at an increased risk of later-life dual disorders. (3) Mental, addiction, and somatic care systems can be integrated, adopting a patient-focused approach to care delivery. (4) Recovery should be taken into consideration when defining treatment intervention and outcome goals. (5) It is important to reduce societal risk factors, such as poverty and early childhood adversity. (6) More resources are needed to provide adequate mental health care in the various countries. The development of European guidance initiatives would provide benefits in many of these areas, making it possible to ensure a more harmonized standard of care for patients with dual disorders.

Deficit actual tool use in schizophrenia is linked to structural alterations in key regions of planning and executing of tool use and connecting fibers

Introduction: Schizophrenia patients frequently suffer from complex motor abnormalities including fine and gross motor disturbances, abnormal involuntary movements, neurological soft signs and parkinsonism. These symptoms occur early in the course of the disease, continue in chronic patients and may deteriorate with antipsychotic medication. Furthermore gesture performance is impaired in patients, including the pantomime of tool use. Whether schizophrenia patients would show difficulties of actual tool use has not yet been investigated. Human tool use is complex and relies on a network of distinct and distant brain areas. We therefore aim to test if schizophrenia patients had difficulties in tool use and to assess associations with structural brain imaging using voxel based morphometry (VBM) and tract based spatial statistics (TBSS). Methode: In total, 44 patients with schizophrenia (DSM-5 criteria; 59% men, mean age 38) underwent structural MR imaging and performed the Tool-Use test. The test examines the use of a scoop and a hammer in three conditions: pantomime (without the tool), demonstration (with the tool) and actual use (with a recipient object). T1-weighted images were processed using SPM8 and DTI-data using FSL TBSS routines. To assess structural alterations of impaired tool use we first compared gray matter (GM) volume in VBM and white matter (WM) integrity in TBSS data of patients with and without difficulties of actual tool use. Next we explored correlations of Tool use scores and VBM and TBSS data. Group comparisons were family wise error corrected for multiple tests. Correlations were uncorrected (p < 0.001) with a minimum cluster threshold of 17 voxels (equivalent to a map-wise false positive rate of alpha < 0.0001 using a Monte Carlo procedure). Results: Tool use was impaired in schizophrenia (43.2% pantomime, 11.6% demonstration, 11.6% use). Impairment was related to reduced GM volume and WM integrity. Whole brain analyses detected an effect in the SMA in group analysis. Correlations of tool use scores and brain structure revealed alterations in brain areas of the dorso-dorsal pathway (superior occipital gyrus, superior parietal lobule, and dorsal premotor area) and the ventro-dorsal pathways (middle occipital gyrus, inferior parietal lobule) the action network, as well as the insula and the left hippocampus. Furthermore, significant correlations within connecting fiber tracts - particularly alterations within the bilateral corona radiata superior and anterior as well as the corpus callosum -were associated with Tool use performance. Conclusions: Tool use performance was impaired in schizophrenia, which was associated with reduced GM volume in the action network. Our results are in line with reports of impaired tool use in patients with brain lesions particularly of the dorso-dorsal and ventro-dorsal stream of the action network. In addition an effect of tool use on WM integrity was shown within fiber tracts connecting regions important for planning and executing tool use. Furthermore, hippocampus is part of a brain system responsible for spatial memory and navigation.The results suggest that structural brain alterations in the common praxis network contribute to impaired tool use in schizophrenia.