Inconsistencies in the planning of the duration of anticoagulation among outpatients with acute deep-vein thrombosis. Results from the OTIS-DVT Registry

Three-month anticoagulation is recommended to treat provoked or first distal deep-vein thrombosis (DVT), and indefinite-duration anticoagulation should be considered for patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. In the prospective Outpatient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) Registry of 502 patients with acute objectively confirmed lower extremity DVT (59% provoked or first distal DVT; 41% unprovoked proximal, unprovoked recurrent, or cancer-associated DVT) from 53 private practices and 11 hospitals, we investigated the planned duration of anticoagulation at the time of treatment initiation. The decision to administer limited-duration anticoagulation therapy was made in 343 (68%) patients with a median duration of 107 (interquartile range 91-182) days for provoked or first distal DVT, and 182 (interquartile range 111-184) days for unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. Among patients with provoked or first distal DVT, anticoagulation was recommended for < 3 months in 11%, 3 months in 63%, and for an indefinite period in 26%. Among patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT, anticoagulation was recommended for < 6 months in 22%, 6-12 months in 38%, and for an indefinite period in 40%. Overall, there was more frequent planning of indefinite-duration therapy from hospital physicians as compared with private practice physicians (39% vs. 28%; p=0.019). Considerable inconsistency in planning the duration of anticoagulation therapy mandates an improvement in risk stratification of outpatients with acute DVT.

Multilocus analysis of genetic divergence between outcrossing Arabidopsis species: evidence of genome-wide admixture

P>Outcrossing Arabidopsis species that diverged from their inbreeding relative Arabidopsis thaliana 5 million yr ago and display a biogeographical pattern of interspecific sympatry vs intraspecific allopatry provides an ideal model for studying impacts of gene introgression and polyploidization on species diversification. Flow cytometry analyses detected ploidy polymorphisms of 2x and 4x in Arabidopsis lyrata ssp. kamchatica of Taiwan. Genomic divergence between species/subspecies was estimated based on 98 randomly chosen nuclear genes. Multilocus analyses revealed a mosaic genome in diploid A. l. kamchatica composed of Arabidopsis halleri-like and A. lyrata-like alleles. Coalescent analyses suggest that the segregation of ancestral polymorphisms alone cannot explain the high inconsistency between gene trees across loci, and that gene introgression via diploid A. l. kamchatica likely distorts the molecular phylogenies of Arabidopsis species. However, not all genes migrated across species freely. Gene ontology analyses suggested that some nonmigrating genes were constrained by natural selection. High levels of estimated ancestral polymorphisms between A. halleri and A. lyrata suggest that gene flow between these species has not completely ceased since their initial isolation. Polymorphism data of extant populations also imply recent gene flow between the species. Our study reveals that interspecific gene flow affects the genome evolution in Arabidopsis.

Study design features affecting outcome in antidepressant trials

A key issue in the approval process of antidepressants is the inconsistency of results between antidepressant clinical phase III trials. Identifying factors influencing efficacy data is needed to facilitate interpretation of the results.

Inkonsistenz und psychische Gesundheit: eine Metaanalyse

Consistency within the psychological processes is accepted as a precondition for efficient functioning and good health. Inconsistency in contrast impairs meeting the requirements of environment and therefore impairs the satisfaction of human needs. It is also seen as a stressor and having the potential to increase the vulnerability for mental disorders (Grawe, 1998, 2004). Incongruence is a form of Inconsistency, describing the divergency between the perception of reality and the goals of a person. Discordance as a second form of Inconsistency is the amount of conflict between goals, wishes and motives. According to the Consistency Theory of Grawe, these two forms of Inconsistency together with avoidance goals and satisfaction of human needs play an important role at the emergence and the maintenance of mental disorders, as well as for the wellbeing of humans. This study includes a short overview of the conceptions of Inconsistency in the psychological literature and a metaanalysis about the interrelations between forms of Inconsistency and characteristics of health and disease. The results support mostly the assumptions of Consistency Theory. Almost all forms of Inconsistency are associated with characteristics of subjective wellbeing, health and disease. One has to take into consideration, that most of the results come from correlational studies with only one measuring time. It is therefore not possible to distinguish between cause and effect.

Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Variability in pain response to a non-pharmacological intervention across repeated routine pain exposure in preterm infants: a feasibility study

AIM: To explore the variability in pain response in preterm infants across time who received sucrose during routine heel stick. METHOD: Single group, exploratory repeated measures design. SETTING: Two tertiary level neonatal intensive care units (NICU) in Switzerland. SUBJECTS: Nine preterm infants born between 28 2/7 and 31 4/7 weeks of gestation during their first 14 days of life. MEASUREMENTS: Pain was assessed by the Bernese Pain Scale for Neonates (BPSN), the Premature Infant Pain Profile (PIPP) and the Visual Analogue Scale (VAS). Salivary cortisol was analysed. RESULTS: 72-94% of the variability was within-subject variability, indicating inconsistency of pain responses across the 5 heel sticks. Interrater agreement was highest during heel sticks 1-3 and decreased during heel stick 4 and 5, indicating a possible alteration of pain patterns. No significant differences in the amount of cortisol could be detected before and after the heel sticks (p = 0.55), indicating no stress-induced peak after the painful intervention. However, a general gradual decrease of cortisol levels across time could be detected. CONCLUSION: A high variability in pain response among preterm neonates across time could be described. Consistency of cortisol levels before and after the heel sticks could indicate the effectiveness of sucrose across time.

Target difficulty, intra-year target revisions and firm performance: evidence from business units' targets

Target difficulty is often argued to increase performance. While this association is well established in experimental research, empirical evidence in field research is rather mixed. We attempt to explain this inconsistency by analyzing the importance of intra-year target revisions, which are especially prevalent in real-world field settings. Using survey and archival data from 97 firms, we find that firms with more challenging business unit targets revise targets more often, in line with asymmetric, downward target revisions. Results further show that the degree to which targets are revised during a period results in negative effects on firm performance, as the anticipation of revision negatively affects the business unit management’s performance incentives. Additionally, we find that using targets predominantly for either decision-making or control influences the overall performance effects of target revisions. Our findings may partially explain the mixed field study evidence regarding the effects of target difficulty.

Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis

OBJECTIVES To synthesise the available evidence on pharmacological and non-pharmacological interventions recommended for fibromyalgia syndrome (FMS). METHODS Electronic databases including MEDLINE, PsycINFO, Scopus, the Cochrane Controlled Trials Registry and the Cochrane Library were searched for randomised controlled trials comparing any therapeutic approach as recommended in FMS guidelines (except complementary and alternative medicine) with control interventions in patients with FMS. Primary outcomes were pain and quality of life. Data extraction was done using standardised forms. RESULTS 102 trials in 14 982 patients and eight active interventions (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors (SNRIs), the gamma-amino butyric acid analogue pregabalin, aerobic exercise, balneotherapy, cognitive behavioural therapy (CBT), multicomponent therapy) were included. Most of the trials were small and hampered by methodological quality, introducing heterogeneity and inconsistency in the network. When restricted to large trials with ≥100 patients per group, heterogeneity was low and benefits for SNRIs and pregabalin compared with placebo were statistically significant, but small and not clinically relevant. For non-pharmacological interventions, only one large trial of CBT was available. In medium-sized trials with ≥50 patients per group, multicomponent therapy showed small to moderate benefits over placebo, followed by aerobic exercise and CBT. CONCLUSIONS Benefits of pharmacological treatments in FMS are of questionable clinical relevance and evidence for benefits of non-pharmacological interventions is limited. A combination of pregabalin or SNRIs as pharmacological interventions and multicomponent therapy, aerobic exercise and CBT as non-pharmacological interventions seems most promising for the management of FMS.

Do implicit motives and basic psychological needs interact to predict well-being and flow? Testing a universal hypothesis and a matching hypothesis

Self-Determination Theory (Deci and Ryan in Intrinsic motivation and self-determination in human behavior. Plenum Press, New York, 1985) suggests that certain experiences, such as competence, are equally beneficial to everyone’s well-being (universal hypothesis), whereas Motive Disposition Theory (McClelland in Human motivation. Scott, Foresman, Glenview, IL, 1985) predicts that some people, such as those with a high achievement motive, should benefit particularly from such experiences (matching hypothesis). Existing research on motives as moderators of the relationship between basic need satisfaction and positive outcomes supports both these seemingly inconsistent views. Focusing on the achievement motive, we sought to resolve this inconsistency by considering the specificity of the outcome variables. When predicting domain-specific well-being and flow, the achievement motive should interact with felt competence. However, when it comes to predicting general well-being and flow, felt competence should unfold its effects without being moderated by the achievement motive. Two studies confirmed these assumptions indicating that the universal and matching hypotheses are complementary rather than mutually exclusive.

Solutions to the Chronological Puzzles in Book 1 of the Chronicle of Matthew of Edessa

The chronological inconsistency in the first book of Matthew of Edessa's Chronicle is well-known. Some of his are dates accurate to the day, while others err by up to 50 years, with no immediately apparent pattern of error. In this talk I will examine some of these chronological puzzles, by untangling the five main themes that run through the book. By demonstrating how these chronological errors may have arisen, and why certain events in the chronicle are dated much more accurately than others, light may be shed on the sources and methodologies that Matthew used to compose his chronicle.

Statusinkonsistenz im Lebensverlauf

Sozialbiographische Überlegungen und die Lebensverlaufsperspektive tragen zu einem Fortschritt in der Inkonsistenzforschung bei. Wichtige theoretische und methodische Voraussetzungen sind dabei die Berücksichtigung der Dynamik von Statusinkonsistenz und die Kontrolle der Zeitabhängigkeit von Statuslagen. Dadurch wird es möglich, Entstehen, Verschwinden, Dauer und Folgen von Statusinkonsistenz detailliert zu untersuchen. Die empirischen Befunde des Artikels zeigen, daß die Verortung von Individuen in einer Statushierarchie im Lebenslauf zunehmend mit vergleichbaren Plazierungen in anderen Statusdimensionen übereinstimmt. Dies verstärkt sich in der Abfolge von Geburtskohorten; ferner finden sich eher Frauen als Männer in ungünstigen statusinkonsistenten Lagen. Schließlich hat Statusinkonsistenz deutliche Auswirkungen auf berufliche Mobilität von Männern. Eine ungünstige Statuslage 'erzwingt' Mobilität, wenn, gemessen an der Bildung, unerwartete Statusverluste ausgeglichen werden sollen. Männer mit unerwarteten Statusgewinnen versuchen dagegen, ihre vorteilhafte Statuslage abzusichern, und sind eher immobil.

Solute transport in crystalline rocks at Äspö — II: Blind predictions, inverse modelling and lessons learnt from test STT1

Based on the results from detailed structural and petrological characterisation and on up-scaled laboratory values for sorption and diffusion, blind predictions were made for the STT1 dipole tracer test performed in the Swedish A¨ spo¨ Hard Rock Laboratory. The tracers used were nonsorbing, such as uranine and tritiated water, weakly sorbing 22Na+, 85Sr2 +, 47Ca2 +and more strongly sorbing 86Rb+, 133Ba2 +, 137Cs+. Our model consists of two parts: (1) a flow part based on a 2D-streamtube formalism accounting for the natural background flow field and with an underlying homogeneous and isotropic transmissivity field and (2) a transport part in terms of the dual porosity medium approach which is linked to the flow part by the flow porosity. The calibration of the model was done using the data from one single uranine breakthrough (PDT3). The study clearly showed that matrix diffusion into a highly porous material, fault gouge, had to be included in our model evidenced by the characteristic shape of the breakthrough curve and in line with geological observations. After the disclosure of the measurements, it turned out that, in spite of the simplicity of our model, the prediction for the nonsorbing and weakly sorbing tracers was fairly good. The blind prediction for the more strongly sorbing tracers was in general less accurate. The reason for the good predictions is deemed to be the result of the choice of a model structure strongly based on geological observation. The breakthrough curves were inversely modelled to determine in situ values for the transport parameters and to draw consequences on the model structure applied. For good fits, only one additional fracture family in contact with cataclasite had to be taken into account, but no new transport mechanisms had to be invoked. The in situ values for the effective diffusion coefficient for fault gouge are a factor of 2–15 larger than the laboratory data. For cataclasite, both data sets have values comparable to laboratory data. The extracted Kd values for the weakly sorbing tracers are larger than Swedish laboratory data by a factor of 25–60, but agree within a factor of 3–5 for the more strongly sorbing nuclides. The reason for the inconsistency concerning Kds is the use of fresh granite in the laboratory studies, whereas tracers in the field experiments interact only with fracture fault gouge and to a lesser extent with cataclasite both being mineralogically very different (e.g. clay-bearing) from the intact wall rock.

Resolving Cl and SO4 Profiles in a Clay-Rich Rock Sequence

The chloride and sulfate concentration profiles in a 260 m thick clay-rich Mesozoic sediment sequence have been analyzed by various methods. Chloride data generally indicate a good consistency between different methods if anion exclusion is accounted for in leaching tests. For sulfate, however, there is an apparent inconsistency between leaching data and those obtained from the other methods, which points to the dissolution of a sulfur-bearing mineral. Traces of diagenetic gypsum seem to be a likely source, but other sulfur minerals cannot be ruled out.

Does ‘better’ discounting lead to ‘worse’ outcomes in long-run decisions? The dilemma of hyperbolic discounting

The shortcomings of conventional discounting, especially in the context of long-run environmental problems, have been extensively discussed in the literature. Recently, hyperbolic discounting, i. e. discounting at declining instead of constant discount rates, has attracted a lot of interest among both scientists and politicians. Although there are compelling arguments for employing hyperbolic discounting, there are also pitfalls, which have to be pointed out. In this paper I show that the problem of time-inconsistency, an inherent characteristics of hyperbolic discounting, leads to a potential clash between economic efficiency and intergenerational equity. As an example, I refer to the weak progress in the controlling of greenhouse gas emissions under the Kyoto protocol. As the problem of time-inconsistency cannot be solved on economic grounds alone, there is a need for an intergenerational moral commitment.