Markov (state) models (MSMs) and related models of molecular kinetics have recently received a surge of interest as they can systematically reconcile simulation data from either a few long or many ...short simulations and allow us to analyze the essential metastable structures, thermodynamics, and kinetics of the molecular system under investigation. However, the estimation, validation, and analysis of such models is far from trivial and involves sophisticated and often numerically sensitive methods. In this work we present the open-source Python package PyEMMA (http://pyemma.org) that provides accurate and efficient algorithms for kinetic model construction. PyEMMA can read all common molecular dynamics data formats, helps in the selection of input features, provides easy access to dimension reduction algorithms such as principal component analysis (PCA) and time-lagged independent component analysis (TICA) and clustering algorithms such as k-means, and contains estimators for MSMs, hidden Markov models, and several other models. Systematic model validation and error calculation methods are provided. PyEMMA offers a wealth of analysis functions such that the user can conveniently compute molecular observables of interest. We have derived a systematic and accurate way to coarse-grain MSMs to few states and to illustrate the structures of the metastable states of the system. Plotting functions to produce a manuscript-ready presentation of the results are available. In this work, we demonstrate the features of the software and show new methodological concepts and results produced by PyEMMA.
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IJS, KILJ, NUK, PNG, UL, UM
Although severe thunderstorms are one of the primary causes of catastrophic loss in the United States, their response to elevated greenhouse forcing has remained a prominent source of uncertainty for ...climate change impacts assessment. We find that the Coupled Model Intercomparison Project, Phase 5, global climate model ensemble indicates robust increases in the occurrence of severe thunderstorm environments over the eastern United States in response to further global warming. For spring and autumn, these robust increases emerge before mean global warming of 2 °C above the preindustrial baseline. We also find that days with high convective available potential energy (CAPE) and strong low-level wind shear increase in occurrence, suggesting an increasing likelihood of atmospheric conditions that contribute to the most severe events, including tornadoes. In contrast, whereas expected decreases in mean wind shear have been used to argue for a negative influence of global warming on severe thunderstorms, we find that decreases in shear are in fact concentrated in days with low CAPE and therefore do not decrease the total occurrence of severe environments. Further, we find that the shift toward high CAPE is most concentrated in days with low convective inhibition, increasing the occurrence of high-CAPE/low-convective inhibition days. The fact that the projected increases in severe environments are robust across a suite of climate models, emerge in response to relatively moderate global warming, and result from robust physical changes suggests that continued increases in greenhouse forcing are likely to increase severe thunderstorm occurrence, thereby increasing the risk of thunderstorm-related damage.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and ...evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.
We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.
From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.
Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chronic heart failure patients typically suffer from tremendous strain and are managed mainly in primary care. New care concepts adapted to the severity of heart failure are a challenge and need to ...consider health-related quality of life aspects. This is the first psychometric validation of the German EQ-5D-5L™ as a generic instrument for assessing health-related quality of life (HRQOL) in a primary care heart failure patient sample.
Confirmatory factor analysis (CFA) was performed on the baseline EQ-5D-5L™ data from the RECODE-HF study (responses to all items from n = 3225 of 3778 patients). Basic CFA models for HRQOL were calculated based on the EQ-5D-5L™ items using the maximum likelihood (ML) and the asymptotic distribution-free method. In an extended CFA, physical activity and depression were added. The basic CFA ML model was verified for the reduced number of cases of the extended CFA model (n = 3064). In analyses of variance the association of the EQ-5D-5L™ visual analogue scale (VAS) and both the German and the British EQ-5D-5L™ crosswalk index with the SF-36 measure of general health were examined. The discriminant validity was analysed using Pearson's chi-squared tests applying the New York Heart Association classification, for the VAS and indices analyses of variance were calculated.
In the basic CFA models the root mean square error of approximation was 0.095 with the ML method, and 0.081 with the asymptotic distribution-free method (Comparative Fit Index > 0.90 for both). Physical activity and depression were confirmed as influential factors in the extended model. The VAS and indices were strongly associated with the SF-36 measure of general health (partial eta-squared 0.525/0.454/0.481; all p < 0.001; n = 3155/3210/3210, respectively), also for physical activity and depression when included together (partial eta-squared 0.050, 0.200/0.047, 0.213/0.051 and 0.270; all p < 0.001; n = 3015/n = 3064/n = 3064, respectively). The discriminant validity analyses showed p-values < 0.001 and small to moderate effect sizes for all EQ-5D-5L™ items. Analyses of variance demonstrated moderate effect sizes for the VAS and indices (0.067/0.087/0.084; all p < 0.001; n = 3110/3171/3171).
The German EQ-5D-5L™ is a suitable method for assessing HRQOL in heart failure patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metamizole is used to treat pain in many parts of the world. Information on the safety profile of metamizole is scarce; no conclusive summary of the literature exists.
To determine whether metamizole ...is clinically safe compared to placebo and other analgesics.
We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and several clinical trial registries. We screened the reference lists of included trials and previous systematic reviews. We included randomized controlled trials that compared the effects of metamizole, administered to adults in any form and for any indication, to other analgesics or to placebo. Two authors extracted data regarding trial design and size, indications for pain medication, patient characteristics, treatment regimens, and methodological characteristics. Adverse events (AEs), serious adverse events (SAEs), and dropouts were assessed. We conducted separate meta-analyses for each metamizole comparator, using standard inverse-variance random effects meta-analysis to pool the estimates across trials, reported as risk ratios (RRs). We calculated the DerSimonian and Laird variance estimate T2 to measure heterogeneity between trials. The pre-specified primary end point was any AE during the trial period.
Of the 696 potentially eligible trials, 79 trials including almost 4000 patients with short-term metamizole use of less than two weeks met our inclusion criteria. Fewer AEs were reported for metamizole compared to opioids, RR = 0.79 (confidence interval 0.79 to 0.96). We found no differences between metamizole and placebo, paracetamol and NSAIDs. Only a few SAEs were reported, with no difference between metamizole and other analgesics. No agranulocytosis or deaths were reported. Our results were limited by the mediocre overall quality of the reports.
For short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics. High-quality, adequately sized trials assessing the intermediate- and long-term safety of metamizole are needed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Global migration trends have led to a more diverse population in health care services everywhere, which in turn has set off a paradigm shift away from medical paternalism toward more patient ...autonomy. Consequently, physicians need to provide a more precise patient-centred healthcare. Professional interpreting appears to play a crucial part in tackling the challenges of language barriers adequately. The aim of this study was to conduct process evaluation through the implementing of video remote interpreting (VR) and telephone remote interpreting (TR) within primary care facilities in the northern German metropolis of Hamburg.
We conducted a three-armed exploratory pilot trial, which compared VR to TR and to a control group (CG) in different primary care settings. We assessed feasibility of implementation, as well as the acceptance of interpreting tools among their users. In addition, we compared the quality of communication as perceived by patients and physicians, as well as the enabling of patient-centred medicine over all three study groups using quantitative questionnaires.
13 practices (7 GPs, 3 Gynaecologists, 3 Paediatricians) took part in this trial. 183 interpreting calls were documented, 178 physicians as well as 127 patients answered their respective questionnaires. The implementation of the VR- und TR-tools went smoothly and they were broadly accepted by their users. However, the tools were used significantly less often than we had anticipated. With regards to quantitative questionnaires, VR scored significantly better than the control group in terms of the perceived quality of communication by both, patients and physicians and enabled of patient-centred medicine.
Our main findings were the discrepancy between the assumed high demand of professional interpreting solutions on the one hand and the low willingness of practices to participate on the other. The rather low utilisation rates were also noteworthy. This discrepancy indicates a lack of awareness concerning the adverse effects of using informal or no interpreter in medical settings, which needs to be rectified. Due to the small sample size, all statistical results must be viewed with caution. However, our results show that remote interpreting represents a promising approach to tackling language barriers in primary care settings.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Our cohort study revealed severe communication deficiencies at graduation. • Inappropriate history taking and communication skills causing costs became evident. • Individual ...communication deficiencies could barely be eliminated over time. • Patient-centeredness and empathy were rather low at graduation. • Graduates are inadequately prepared for clinical practice regarding communication.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Objective To compare the risk of developing Alzheimer’s disease (AD) dementia in late mild cognitive impairment (LMCI), early MCI (EMCI), and subjective memory impairment (SMI) with normal ...test performance. Methods The baseline sample (n = 2892) of the prospective cohort study in nondemented individuals (German Study on Aging, Cognition and Dementia in Primary Care Patients) was divided into LMCI, EMCI, SMI, and control subjects by delayed recall performance. These groups were subdivided by the presence of self-reported concerns associated with experienced memory impairment. AD dementia risk was assessed over 6 years. Results Across all groups, risk of AD dementia was greatest in LMCI. In those with self-reported concerns regarding their memory impairment, SMI and EMCI were associated with a similarly increased risk of AD dementia. In those subgroups without concerns, SMI was not associated with increased risk of AD dementia, but EMCI remained an at-risk condition. Conclusions SMI and EMCI with self-reported concerns were associated with the same risk of AD dementia, suggesting that pre-LMCI risk conditions should be extended to SMI with concerns.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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